Are pickles a source of probiotics? Can you elaborate?

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probiotic

Throughout history cultures the world over developed pickling techniques by trial and error to preserve and prolong nutritive qualities of fruits, vegetables and even meats that otherwise have short natural shelf life. Fermentation is a key anaerobic process in Pickling – Wikipedia.

Fermenting microorganisms, typically lactic acid bacteria (LAB) or ethanol fermenting yeast, convert sugars such as glucose to alcohol while also generating energy for themselves (1; see below from 2). Acidification (by acids such as acetic, lactic, malic) by fermenting microbes is a key part of the preservative process.

Traditional pickling/fermentation is a rare example of being able to have one’s cake and eating it too; not only did it allow people in the pre-refrigeration era to derive the nutritive qualities of fruits and vegetables long past their “sell-by” dates, it also provided them a source of beneficial microorganisms in the form of the fermenters, some of which are now considered probiotics. Home-made kimchi and sauerkraut are famous examples of traditional pickles.

The WHO defines probiotics as ‘live microorganisms which when administered in adequate amounts confer a health benefit on the host‘ (3).

Microbial species found in fermented foods such as traditional home-made pickles may be beneficial for gastrointestinal health (4). However, key to denoting a microorganism a probiotic is proven health benefit (4, 5, 6), which requires rigorous clinical studies such as randomized clinical trials, something not conclusively researched yet for the many types of microorganisms found in different kinds of traditional pickles found in different cultures around the world. Thus, formal recognition of many of traditional pickle-associated microorganisms as probiotics is still work in progress.

Some fermented food-associated probiotics such as Lactobacillus plantarum (a LAB) have been researched extensively.

Such probiotics have been found to provide a variety of practical benefits (7),

• Enhance food flavor and texture.
• Inhibit growth of potential pathogens by lowering the food pH.
• Prevent food spoilage by producing antimicrobial peptides.

They have also been found to provide a variety of health benefits (2, 4),

• Assist in colonization resistance, i.e., help antagonize and prevent pathogens from colonizing the gut.
• Provide valuable vitamins, peptides, and even neurotransmitters in some instances.
• Support digestive processes, i.e., potentially help prevent diarrhea and/or constipation.

Lactobacillus plantarum is indeed a recognized probiotic found in many traditional pickles while microorganisms Leuconostoc mesenteroides and Weisella cibaria are also common pickle-associated microorganisms (2).

Some even go so far as to suggest that traditional food and beverage fermentation practices such as pickling, wine- and beer-making, cheeses and yogurts represent microbial domestication, whereby wild bacteria, mold and yeast were ‘tamed’ into industrial microorganisms such as LAB and Saccharomyces (see below from 8), the point being the microorganisms that provide such fermented foods their distinct tastes and flavors aren’t there by accident or happenstance.

Bibliography

1. Chilton, Stephanie N., Jeremy P. Burton, and Gregor Reid. “Inclusion of fermented foods in food guides around the world.” Nutrients 7.1 (2015): 390-404. Inclusion of Fermented Foods in Food Guides around the World

2. Swain, Manas Ranjan, et al. “Fermented fruits and vegetables of Asia: a potential source of probiotics.” Biotechnology research international 2014 (2014). Fermented Fruits and Vegetables of Asia: A Potential Source of Probiotics

3. Hotel, Amerian Córdoba Park. “Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria.” PREVENTION 5 (2001): 1. http://www.mesanders.com/probio_…

4. Marco, Maria L., et al. “Health benefits of fermented foods: microbiota and beyond.” Current opinion in biotechnology 44 (2017): 94-102. https://www.researchgate.net/pro…

5. Felis, Giovanna E., Franco Dellaglio, and Sandra Torriani. “Taxonomy of probiotic microorganisms.” Prebiotics and probiotics science and technology. Springer, New York, NY, 2009. 591-637.

6. Hill, Colin, et al. “Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic.” Nature Reviews Gastroenterology and Hepatology 11.8 (2014): 506. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic

7. Price, Claire E., et al. “From meadows to milk to mucosa–adaptation of Streptococcus and Lactococcus species to their nutritional environments.” FEMS microbiology reviews 36.5 (2012): 949-971. From meadows to milk to mucosa – adaptation of Streptococcus and Lactococcus species to their nutritional environments | FEMS Microbiology Reviews | Oxford Academic

8. Gibbons, John G., and David C. Rinker. “The genomics of microbial domestication in the fermented food environment.” Current opinion in genetics & development 35 (2015): 1-8. http://wordpress.clarku.edu/jgib…

https://www.quora.com/Are-pickles-a-source-of-probiotics-Can-you-elaborate/answer/Tirumalai-Kamala

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What is the rationale behind the push to vaccinate adults against pertussis to protect babies as research is showing that the acellular version doesn’t stop transmission or carriage nor does it provide herd immunity? Is there a flaw in this research?

The bacterium Bordetella pertussis is the most common cause of pertussis or whooping cough and it spreads from an infected person’s cough or sneeze as airborne droplets.

Some (Australia, Canada, Ireland, Spain, UK, US), not all, countries that switched from whole cell (wP) to acellular (aP) pertussis vaccines saw in subsequent decades (1),

• Protection that turned out to be both weaker and of shorter duration in adolescents.
• Resurgence of pertussis infections, even among those previously vaccinated, i.e., poor herd immunity.

Not only does aP appear to induce weak immunological memory against pertussis in these countries, it even appears to be counter-productive in some age groups. Italy, Japan and Sweden are reported exceptions to these trends (1).

Why did some countries decide to switch from wP to aP in the first place?

In the US, that decision was not rooted in scientific rationale but was instead a knee-jerk reaction by vaccine manufacturers and government regulators to lawsuits in the 1980s.

Developed in the 1930s, wP is just killed Bordetella pertussis bacteria and it does give injection site reactions. This was enough for some US parents in the 1980s to blame it for encephalopathy-associated febrile seizures and intellectual disability in their children. The resulting lawsuits drove most US pertussis vaccine manufacturers out of the market and made it urgent for the US to find a ‘safer’ vaccine alternative.

Simply removing the Bordetella pertussis cell wall component, endotoxin, presumed responsible for the injection site reactions, presented itself as the easy solution, never mind that it wasn’t the source of the febrile seizures, whose cause(s) remained unidentified. The eventual approved product, aP, had some purified pertussis antigens but not the endotoxin.

Meantime, recent discoveries suggest switching from wP to aP was based on a fallacy since a causal link between wP and febrile seizures seems to have been misplaced.

An exhaustive retrospective 2010 analysis concluded that children who had developed such seizures coincident to wP instead had Dravet syndrome – Wikipedia, de novo mutations in the sodium channel gene SCN1A (2). This conclusion was strengthened by the observation that children who got wP before or after their first seizure had similar clinical outcome when consequences of pre-seizure wP should have been worse if it indeed played a role in the syndrome.

Confirmation bias may thus have played a role in implicating wP in these febrile seizures. After all, wP is still standard for large swaths of the world’s population such as India, which haven’t reported febrile seizures after children there get wP.

Nevertheless, naysayers would argue such retrospective studies include small numbers of patients, that they rely on previously recorded clinical data and thus may be subject to recall bias, and that they lack an unvaccinated control group.

Point is the horse is already out of the barn and these days, parents in countries such as the US are less likely or even unlikely to agree to switching back to wP even as data accumulates that it does indeed better protect against pertussis infection compared to aP.

Constituents of effective human anti-pertussis immunity are still unknown

Usually intended for use among the healthy population at large makes vaccines a much more expensive proposition compared to drugs and other medical interventions. Optimal scientific proof that a vaccine indeed prevents a given infection requires comparing infection rates for many years, maybe even lifetimes, in two groups, one that got the vaccine and the other that didn’t, an unimaginably expensive proposition that would make it impossible to get any vaccine approved.

Vaccinologists counter this gap by developing protection measurements assumed to be reliable surrogates. Correlates of immunity/correlates of protection – Wikipedia are immunological assays that hopefully measure the relevant anti-vaccine immune response(s).

Countries such as the US switching from wP to aP relied on such pertussis-related correlates of protection for their decision making. Specifically, they concluded that aP induced equivalent immunity compared to wP since both induced equivalent antibody titers against the pertussis antigens present in aP.

Contrary to anti-vaxxer conspiracy theories, vaccines are actually loss-leaders rather than moneymaking bonanzas for pharma companies. It isn’t by accident that at ~US $17 billion, vaccines represent barely 3% of US pharmaceutical sales (3).

Problem is rodent animal models commonly used in pertussis are poorly predictive of human infection and immunity. Baboons may be a better model but using them is both prohibitively expensive and ethically problematic.

That perverse incentives fuel scientific research doesn’t help matters either, with knowledge about the mouse immune system leaps and bounds ahead of its human counterpart.

Thus, pertussis vaccinologists have been making decisions in the dark, not knowing exactly which human immune responses are relevant and/or critical for preventing infection nor knowing which pertussis antigens are necessary and sufficient to recapitulate effective immunity against the whole organism. Today decades later, such ignorance is proving costly since data shows that antibody titers against aP antigens, assumed to be a reliable correlate of protection, are unable to distinguish between effective (driven by wP) and ineffective (driven by aP) human anti-pertussis immune responses.

What then lies behind the push to vaccinate adults with aP to protect babies?

Maternal pertussis vaccination effectively protects against infant death from pertussis (4, 5), especially when it is given in the 2nd trimester (6).

Since the US switch to aP largely occurred in the late 1990s and early 2000s, the idea is today’s mothers as well as older adults were more likely to have been primed (originally vaccinated) with wP, meaning they should have a more robust and effective pre-existing memory immune response to pertussis. Meantime, studies have shown that even a single aP boost can effectively reactivate memory immune responses initially induced by wP (7).

This is the basis for the rationale that expectant mothers boosted with even a less than optimal aP may passively transfer sufficient levels of anti-pertussis antibodies to vulnerable infants to protect them from pertussis.

Problem is the window of opportunity for such an approach is fast closing as aP-primed girls grow up and become mothers. Given the poor ability of aP to prime strong and effective anti-pertussis immunity, it’s unclear whether an aP boost given during pregnancy to aP-primed mothers would work as well.

Coda

At their core, suspicions about vaccines represent a profound failure of communication and breakdown of trust between scientists and those who harbor such suspicions. Since vaccines affect pubic health, entire populations, not just those individuals, pay the price.

Perversely, science’s successes – not just vaccines but also hygiene and sanitation – set the stage for current doubts about vaccines among some individuals in affluent countries. After all, at least one or more generations of people in affluent countries such as the US have now grown up without facing the scourge of epidemics caused by pathogenic microbes. Such an embarrassment of riches can foster unreasonable expectations.

In the case of vaccines, that unreasonable expectation expresses itself as entitlement to paramount safety and zero risk, notwithstanding that being very far from complete, current knowledge of human biology could never hope to meet such a lofty expectation.

In response, vaccine makers and regulators alike feel pressured to make the more risk-averse and biologically impossible decision of prioritizing safety over immunogenicity when designing new vaccines, the decision to switch from wP to aP being a case in point. This ends up violating an essential biological principle since immunogenicity, the ability to drive strong and effective immune responses, requires ‘dirt’.

Needing to make up for this lack of natural ‘dirt’, scientists add Adjuvant – Wikipedia to sub-unit vaccines comprised of pure antigens. However, how adjuvants work is still largely a black box which means outcomes remain unpredictable, especially at a population level. The wP to aP switch embodies these drawbacks.

For more details on the why and consequences of switching from wP to aP: Tirumalai Kamala’s answer to Why is the pertussis vaccine not protecting those vaccinated for pertussis?

Bibliography

1. Gill, Christopher, Pejman Rohani, and Donald M. Thea. “The relationship between mucosal immunity, nasopharyngeal carriage, asymptomatic transmission and the resurgence of Bordetella pertussis.” F1000Research 6 (2017). The relationship between mucosal immunity, nasopharyngeal carriage, asymptomatic transmission and the resurgence of Bordetella pertussis

2. McIntosh, Anne M., et al. “Effects of vaccination on onset and outcome of Dravet syndrome: a retrospective study.” The Lancet Neurology 9.6 (2010): 592-598. Effects of vaccination on onset and outcome of Dravet syndrome: a retrospective study

3. U.S. Vaccine Market – Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 – 2018

4. Amirthalingam, Gayatri, et al. “Effectiveness of maternal pertussis vaccination in England: an observational study.” The Lancet 384.9953 (2014): 1521-1528. http://sys.91sqs.net/mobilenews/…

5. Dabrera, Gavin, et al. “A case-control study to estimate the effectiveness of maternal pertussis vaccination in protecting newborn infants in England and Wales, 2012–2013.” Clinical Infectious Diseases 60.3 (2014): 333-337. https://pdfs.semanticscholar.org…

6. Eberhardt, Christiane S., et al. “Maternal immunization earlier in pregnancy maximizes antibody transfer and expected infant seropositivity against pertussis.” Clinical Infectious Diseases 62.7 (2016): 829-836. Maternal Immunization Earlier in Pregnancy Maximizes Antibody Transfer and Expected Infant Seropositivity Against Pertussis | Clinical Infectious Diseases | Oxford Academic

7. Huang, Li-Min, et al. “Immunogenicity and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine in healthy Taiwanese children and adolescents.” Journal of Adolescent Health 37.6 (2005): 517-e1. https://www.jahonline.org/articl…

https://www.quora.com/What-is-the-rationale-behind-the-push-to-vaccinate-adults-against-pertussis-to-protect-babies-as-research-is-showing-that-the-acellular-version-doesn-t-stop-transmission-or-carriage-nor-does-it-provide-herd-immunity/answer/Tirumalai-Kamala

How do anti-bacterial and germ resistant coated surfaces work?

Tags

Antibacterial, Antimicrobial

Common non-antibiotic anti-bacterials used in surfaces are typically compounds containing the Halogen – Wikipedia, chlorine. Among such compounds, Triclosan – Wikipedia and Triclocarban – Wikipedia are the most prevalent.

According to a 2011 white paper from the Alliance for Prudent Use of Antibiotics (1),

‘Triclosan works by blocking the active site of the enoyl-acyl carrier protein reductase enzyme (ENR), which is an essential enzyme in fatty acid synthesis in bacteria (11). By blocking the active site, triclosan inhibits the enzyme, and therefore prevents the bacteria from synthesizing fatty acid, which is necessary for building cell membranes and for reproducing. Since humans do not have this ENR enzyme, triclosan has long been thought to be fairly harmless to them. Triclosan is a very potent inhibitor, and only a small amount is needed for powerful antibacterial action.’

A 1999 Nature paper (2) presumptively confirmed this mechanism of action.

Such an effect doesn’t discriminate between environmental bacteria, human-associated commensal bacteria and pathogens, which could be quite problematic.

In the US, triclosan use has exploded in recent decades, progressively making its way into increasing numbers of consumer products with the public largely unaware of this happening and even more consequentially, largely unaware of the implications of such widespread exposure.

The range of products that contain triclosan these days is not only eyebrow- but also hair-raising,

• Everyday use items such as cosmetics, deodorants, detergents, hand soaps, hand lotions, mouthwashes, shampoos, toothpastes.
• Household staples such as tablecloths, kitchen cutting boards, furniture, toys, school supplies, sport equipment and even shoe insoles.
• Hospital disinfectants, surgical scrubs, surfaces (plastics and other durables).

These products present several problems,

• There is little convincing evidence they actually do a better job compared to the tried and true method of hand washing with soap and water.
• They could stoke drug resistance in bacteria.
• They could sensitize children to common allergens such as mold and animal dander.
• Animal model studies suggest they could interfere with endocrine function.
  • Block aspects of thyroid and testosterone function.
  • Enhance functions of estrogen.

An older answer of mine delves in a bit more detail about triclosan-containing products and the problems they pose: Tirumalai Kamala’s answer to Does anti-bacterial soap do more harm than good?

Increasing evidence of such problems in recent years has led various national regulatory agencies to restrict or ban triclosan use in specific products (see below from 3).

Bottomline, consumers should pay attention to whether common daily use and household products they choose contain triclosan, and avoid them as much as possible.

Bibliography

1. https://www.google.com/url?sa=t&…

2. Levy, Colin W., et al. “Molecular basis of triclosan activity.” Nature 398.6726 (1999): 383. https://www.researchgate.net/pro…

3. Goodman, Michael, Daniel Q. Naiman, and Judy S. LaKind. “Systematic review of the literature on triclosan and health outcomes in humans.” Critical reviews in toxicology 48.1 (2018): 1-51. https://www.tandfonline.com/doi/…

https://www.quora.com/How-do-anti-bacterial-and-germ-resistant-coated-surfaces-work/answer/Tirumalai-Kamala

Why are some tumors more susceptible to bacterial infection than normal tissue?

Refers to article: http://science.sciencemag.org/content/357/6356/1156.full

This answer

• Summarizes main results from the paper, Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine.
• Explains how bacteria might gravitate towards tumors.
• Summarizes evidence of intriguing links between solid tumors and Mycoplasma, given the study in question found an association of pancreatic cancer with Mycoplasma.
• Contextualizes the contentious history of bacteria in tumors.

Data in the paper, Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine

Gemcitabine – Wikipedia is a Nucleoside analogue – Wikipedia used to treat cancers such as breast, bladder, lung and pancreas.

The authors (1) first explored how some tumor cell lines became resistant to gemcitabine, finding it to be associated with some kind of filter- and antibiotic-susceptible entity, identifying that entity to be Mycoplasma hyorhinis – Wikipedia. Next, the authors found not just Mycoplasma but 13 of 27 different bacterial species tested to be capable of mediating gemcitabine resistance in cancer cell lines, with this capacity mostly but not always matching capacity to express the long form of the Cytidine deaminase – Wikipedia (CDD).

Having established a connection between presence of bacteria and capacity for gemcitabine resistance, the authors then examined whether there were bacteria in human tumors, choosing to focus on Pancreatic cancer – Wikipedia (PDAC) since gemcitabine is a critical Rx for it.

Quantitative Real-time polymerase chain reaction – Wikipedia to detect bacterial 16S ribosomal RNA – Wikipedia detected bacterial rDNA in 86 of 113 (76%) PDAC and 3 of 20 (15%) normal pancreas. Authors confirmed these results with additional assays such as Fluorescence in situ hybridization – Wikipedia (FISH) targeting 16S rRNA as well as Immunohistochemistry – Wikipedia using antibody to detect bacterial Lipopolysaccharide – Wikipedia (LPS).

52% of the bacteria were Gammaproteobacteria – Wikipedia, most belonging to Enterobacteriaceae – Wikipedia and Pseudomonadaceae – Wikipedia families.

Finally, authors cultured bacteria from 15 fresh human PDACs and found 14 of 15 capable of making the RKO and HCT116 human colon carcinoma cells fully resistant to gemcitabine.

Article’s main message is selective association of particular bacteria with the human tumor, PDAC, with such association being capable of conferring tumor resistance to the anti-cancer drug, gemcitabine. More than one other group (2, 3) has previously reported such bacterial (Mycoplasma) ability to alter anti-cancer nucleoside function.

Caveats to the study are mainly technical and don’t negate its main message.

• What is by now a standard refrain in so many biomedical research papers (even those published in high impact factor journals such as Science), shoddy use of statistics to present data, especially from in vivo mouse models, as cleaner and much more dichotomous than they actually are. For example, a lack of consistency in the statistical tools used to summarize the data, being standard deviation in one figure, standard error of the mean in another, as well as the interchangeable use of the terms technical and biological replicates.
• Having gone to some lengths to emphasize that bacterial expression of the long form of CDD was required for gemcitabine resistance, authors provide no explanation for mechanism of gemcitabine resistance in M. hyorhinis, which the authors themselves point out expresses the short, not long, form of CDD. Clearly, different bacteria likely have more than one mechanism for mediating gemcitabine resistance.

How Bacteria Might Home To & Grow Within Cancers

Growth within solid tumors typically entails destructive features. Though Neovascularization – Wikipedia, growth of new, disorganized and leaky blood vessels, crops up to support the ravenous oxygen and nutrient demand of such rapidly proliferating cancer cells, such demand more often than not outpaces supply with two major consequences.

• Rapid, unregulated tumor cell growth creates regions of Hypoxia (medical) – Wikipedia, low oxygen levels.
• Pockets of unplanned tumor cell death, i.e., regions of Necrosis – Wikipedia.

Such leaky and disorganized vasculature could make it possible for circulating bacteria to gain access to tumor tissue while hypoxic tumor tissue, being a favorable growth environment for anaerobic bacteria (both obligate and facultative), becomes a magnet for such bacteria, which enter such regions and get settled there.

Further, more than usual number of cells dying in an unplanned manner within solid tumors typically overwhelms the local scavenging capacity of clean-up cells belonging to the local reticuloendothelial system (Mononuclear phagocyte system – Wikipedia) that would normally clear up the resulting cell carcasses and debris. This makes such areas pools of not only chemical messengers that could attract bacteria but also of nutrients that could sustain them (see below from 4).

Thus, not just one but several studies have reported presence of bacteria within solid tumors (see below from 4).

Link Between Mycoplasma & Solid Tumors

Among the smallest of bacteria and lacking a cell wall, association of Mycoplasma in particular with tumors is of an interesting piece within this sub-field of tumor biology, having been reported as far back as 1970 (5).

• Cancer cell lines are notorious for becoming infected with Mycoplasma so much so numerous reviews outline how to prevent and eliminate such contamination (6, 7, 8, 9). Such cancer cell-Mycoplasma associations also have practical cost consequences. Since basic research can and often is sloppy enough that Mycoplasma contaminations may even pass unnoticed in some labs, which published responses pertain to cancer cell and which to the Mycoplasma associated with it is a real issue that remains unresolved (10, 11, 12).
• A 1999 study (13) by researchers at the American Registry of Pathology at the Armed Forces Institute of Pathology showed chronic colonization of cell lines with Mycoplasma fermentans and M. penetrans to be associated with chromosomal instability and malignant transformation, i.e., potentially carcinogenic capacities.
• A 2001 PCR-based study (14) found Mycoplasma consistently and preferentially associated in different types of tumor tissues (see below from 15 using data from 14).

Mycoplasma proclivity for cancer cell lines grown in lab cell cultures is itself an intriguing phenomenon deserving of basic research interest since it occurs in absence of the plausible factors proffered for such association in vivo, such as disorganized and leaky blood vessels messily sprouting up to supply ravenously growing tumor tissue, and the lack of attendant tumor hypoxia and necrosis, factors supposed to make solid tumors a magnet for bacterial (Mycoplasma) growth.

The Contentious History of Bacteria in Tumors

Presence of bacteria in tumors has a particularly contentious past in scientific research. After research by Louis Pasteur – Wikipedia and Robert Koch – Wikipedia, among many others, firmly established a scientific basis for the Germ theory of disease – Wikipedia, several prominent mid-20th century researchers tenaciously pursued presence of bacteria in tumors.

The focus of such research by scientists such as Virginia Livingston – Wikipedia, Eleanor Alexander-Jackson, Irene Diller, Florence B. Seibert – Wikipedia was nothing less than trying to uncover evidence that an infectious disease agent underlay any and all types of cancer, i.e., a germ theory of cancer.

However, while some viral, even bacterial and other microbial causes of cancer are certainly known and accepted, the germ theory of cancer became markedly unfashionable over the course of the latter part of the 20th century in the face of the considerable headwind gained by other mechanisms of Carcinogenesis – Wikipedia, which took increasing precedence, principally mechanisms involving the interplay between overexpression an/or mutations in Oncogene – Wikipedia and mutations in Tumor suppressor gene – Wikipedia.

Bacteria as sole cause of cancer is also difficult to reconcile with the fact that Germ-free animal – Wikipedia do develop cancers. Thus, today only one bacterium, Helicobacter pylori is recognized by the International Agency for Research on Cancer – Wikipedia (IARC) as an established human carcinogen (16).

However, consequence of such single-minded focus by one group of researchers trying to prove a germ theory of cancer and severe repudiation of the same by others that followed them may have been detrimental in the long run, detrimental since it seems to have firmly shut the door for at least several decades on a more open-minded exploration of the association between bacteria and cancer, and consequences thereof. After all, a more open-minded view suggests research and therapeutic utility, be such association cause or effect (see below from 17, emphasis mine),

‘Microbial profiling of cancer is agnostic as to whether bacteria are the cause or the effect, although in each scenario lies clinical utility. If the development of cancer is the underlying reason for shifts in the microbial community, then surveying bacteria becomes a new method for diagnosis. Microbial censuses could be used to diagnose malignancies and in surveillance for recurrence. Of clinical importance is that microbiome sampling, as opposed to blood sampling or tissue biopsies, is generally non-invasive. Such approaches are already revealing insights; for example, specific microbes in saliva have been associated with chronic pancreatitis and tumors of the pancreas [8]. On the other hand, if shifts in the microbial spectrum cause cancer, then not only does microbiome research become a new route into exploring pathogenesis but the microbiome itself becomes a new target for preventative strategies. Microbiomes could be sampled proactively for risk stratification in at-risk populations, and probiotics and microbiome transplants could be considered as strategies for cancer prevention.

Also intriguing is the idea that one might be able to categorize cancers that do or do not have a microbial influence. It has been demonstrated in head and neck cancers that microbes live deep within tumor tissue [9], thus contributing to the intracellular stromal environment. Unless their borders are breached by infection, organs such as the kidney and the pancreas have been thought to be completely sterile. With modern metagenomic profiling, which can identify fastidious and previously unculturable microorganisms, we might find that fewer organ systems are sterile than previously thought, and that the contribution of the microbial microenvironment might have a much more inward reaching influence than currently assumed. Classifying cancers into sterile and non-sterile, if sterile cancers truly exist, might garner increased biological understanding of tumorigenesis, perhaps providing new avenues for diagnosis and even novel treatment modalities for nonsterile cancers’

Bibliography

1. Geller, Leore T., et al. “Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine.” Science 357.6356 (2017): 1156-1160. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine

2. Voorde, Johan Vande, et al. “Nucleoside-catabolizing enzymes in mycoplasma-infected tumor cell cultures compromise the cytostatic activity of the anticancer drug gemcitabine.” Journal of Biological Chemistry 289.19 (2014): http://www.jbc.org/content/289/1…

3. Lehouritis, Panos, et al. “Local bacteria affect the efficacy of chemotherapeutic drugs.” Scientific reports 5 (2015). https://www.ncbi.nlm.nih.gov/pmc…

4. Cummins, Joanne, and Mark Tangney. “Bacteria and tumours: causative agents or opportunistic inhabitants?.” Infectious agents and cancer 8.1 (2013): 11. https://infectagentscancer.biome…

5. Livingston, Virginia Wuerthele‐Caspe, and Eleanor Alexander‐Jackson. “A specific type of organism cultivated from malignancy: bacteriology and proposed classification.” Annals of the New York Academy of Sciences 174.1 (1970): 636-654.

6. Uphoff, Cord C., and Hans G. Drexler. “Comparative antibiotic eradication of mycoplasma infections from continuous cell lines.” In Vitro Cellular & Developmental Biology-Animal 38.2 (2002): 86-89.

7. Drexler, Hans G., et al. “Mix-ups and mycoplasma: the enemies within.” Leukemia research 26.4 (2002): 329-333.

8. Drexler, Hans G., and Cord C. Uphoff. “Mycoplasma contamination of cell cultures: Incidence, sources, effects, detection, elimination, prevention.” Cytotechnology 39.2 (2002): 75-90. https://www.ncbi.nlm.nih.gov/pmc…

9. Razin, Shmuel, and Leonard Hayflick. “Highlights of mycoplasma research—an historical perspective.” Biologicals 38.2 (2010): 183-190. https://www.researchgate.net/pro…

10. Callaway, Ewen. “Contamination hits cell work: Mycoplasma infestations are widespread and costing laboratories millions of dollars in lost research.” Nature 511.7511 (2014): 518-519. https://www.nature.com/polopoly_…

11. Heidegger, Simon, et al. “Mycoplasma hyorhinis-contaminated cell lines activate primary innate immune cells via a protease-sensitive factor.” PloS one 10.11 (2015): e0142523. http://journals.plos.org/plosone…

12. Gedye, Craig, et al. “Mycoplasma infection alters cancer stem cell properties in vitro.” Stem Cell Reviews and Reports 12.1 (2016): 156-161. https://www.researchgate.net/pro…

13. Feng, Shaw-Huey, et al. “Mycoplasmal infections prevent apoptosis and induce malignant transformation of interleukin-3-dependent 32D hematopoietic cells.” Molecular and cellular biology 19.12 (1999): 7995-8002. http://mcb.asm.org/content/19/12…

14. Huang, Su, et al. “Mycoplasma infections and different human carcinomas.” World journal of gastroenterology 7.2 (2001): 266. https://www.ncbi.nlm.nih.gov/pmc…

15. Burke, Jennie. “Changes in direction of cancer research over the 20th century: what prompted change: research results, economics, philosophy.” (2007). http://researchdirect.westernsyd…

16. http://monographs.iarc.fr/ENG/Cl…

17. Funchain, Pauline, and Charis Eng. “Hunting for cancer in the microbial jungle.” Genome medicine 5.5 (2013): 42. https://genomemedicine.biomedcen…

https://www.quora.com/Why-are-some-tumors-more-susceptible-to-bacterial-infection-than-normal-tissue/answer/Tirumalai-Kamala

Why do we develop robust immunity after viral infections, but not bacterial infections?

It’s a truism that strength of immunity depends on many factors such as antigen types and doses, organism’s replicative capacity and evasion strategies, number and types of cells involved, responder’s age and health status, to name a few. Could the type of organism influence the nature and strength of immune response? Sure but if human immunity were as a rule weaker against bacteria and fungi compared to viruses, as this question implies, that would represent a huge open sesame to the former and only humans would have emerged worse off from the ensuing bout.

Certainly, adaptations entail a trade-off but choosing to respond more weakly to entire classes of micro-organisms isn’t a trade-off, it’s more akin to signing one’s own death sentence. After all, micro-organisms mutate at a much faster rate than humans. Thus, the fact that we are still around, all >7 billion of us and counting, suggests human adaptations to evolutionary selection pressures entailed robust immunity against all types of pathogens. What that robust immunity entails differs from organism to organism, not between different classes of organisms.

In case this question implies robust immunity to mean serum antibodies that can transfer protection, this is not the exclusive purview of anti-viral immunity alone but also works against bacteria such as those that cause diphtheria (Corynebacterium diphtheriae – Wikipedia), pertussis (Bordetella pertussis – Wikipedia) and tetanus (Clostridium tetani – Wikipedia).

This answer explains why stronger immune responses to an entire class of micro-organisms such as viruses is unlikely because

• We aren’t specifically more susceptible to bacterial and fungal infections as our immune systems weaken with age.
• Not just viruses but all types of microbes from bacteria to a variety of parasites continue to impose selection pressure on us.
• No single entity within the immune system can perceive an entire organism. This implies evolution proceeds by way of incremental tweaks by human and microbe, the two parties engaged in these evolutionary trade-offs.

We Aren’t More Susceptible To Bacterial & Fungal Infections As We Age

If human immunity to virus is more robust than that to bacteria or fungi, what happens as our immune system weakens with age and Immunosenescence – Wikipedia sets in? Specifically, if ‘we develop robust immunity after viral infections, but not bacterial infections‘, do we become disproportionately more susceptible to the latter as we age, as this question implies? No, rather, the deleterious effects of immunosenescence seem to involve increased susceptibility to infectious diseases per se, not just increased susceptibility to bacteria and fungi but not viruses.

In fact, data from countries like the US suggests immunosenescence represents an equal opportunity vulnerability since it entails impaired ability to control both viruses such as Human cytomegalovirus – Wikipedia (CMV) (1, 2) as well as bacteria such as Streptococcus pneumoniae – Wikipedia (3). Even though pneumonia is common among the elderly, often the trigger remains unknown in ~50% of elderly pneumonia patients even in the US (4). Anybody’s guess if it’s a virus such as influenza or Human respiratory syncytial virus – Wikipedia (RSV), bacteria other than S. pneumoniae or fungus such as Chlamydia pneumoniae. Equal opportunity vulnerability indeed.

Major Human Pathogens Include Not Just Viruses & Bacteria But Also Other Organisms

Both human viral and bacterial pathogens, among others, continue to impose selection pressure (5, 6). Consider two textbook examples, one the bacterium, Vibrio cholerae, and the other the retrovirus, HIV. Cholera remains endemic in the Ganges Delta – Wikipedia of Bangladesh, which has the world’s lowest prevalence of blood group O, probably because it’s associated with an increased risk of severe cholera (7, 8, 9). In the case of HIV, the delta 32 mutation deletes a portion of the CCR5 – Wikipedia gene and renders homozygous carriers resistant to HIV (10, 11). Testament to the central importance of adaptive immunity, specifically T cells, is the fact that the Major histocompatibility complex – Wikipedia (MHC complex) contains more infectious disease susceptibility associations than any other portion of the human genome (5). Major human pathogens include both viruses and bacteria (see below from 5).

Other pathogens too impose selection pressure. One of the most well-known examples is malaria (see table below from 6).

No Single Entity Within The Immune System Can Perceive An Entire Organism

While this question shares no data to support its claim that ‘we develop robust immunity after viral infections, but not bacterial infections‘, it implies that some entity within the human immune system can distinguish viruses from bacteria and fungi. The overarching implication that entire classes of organisms could function as selection units for the immune system to adapt against is inaccurate and cannot be substantiated, and here’s why.

Different cells in the immune system express different kinds of receptors of varying specificity and sensitivity. Those of the Innate immune system – Wikipedia (dendritic cells, macrophages, neutrophils, mast cells, NK cells, Innate lymphoid cells, gamma-delta T cells, etc.) are germline-encoded meaning they stay unchanged within the lifespan of an individual while only those of the Adaptive immune system – Wikipedia (T and B cells) are somatically rearranged, meaning they are derived de novo during the lifespan of each individual. Though this feature vastly expands their range to the order of 10^12 unique receptors each per individual as an estimate, what T and B cell receptors bind are hardly the sizes capable of distinguishing a virus from bacterium or fungus or even host cell-derived material for that matter.

• A B cell’s antigen is estimated in the range of 25 to 30 amino acids in length while CD4 and CD8 T cell receptors recognize even smaller peptides ranging in length a mere 15-20 to 8-10 amino acids, respectively.
• Binding larger molecules of varying sizes, derived not just from microbes but also the body’s own breakdown products including dead and dying cells, obviously germ-line encoded receptors too lack the capacity to discern their source.

Thus, no single cell of the immune system can directly differentiate a virus from bacterium or fungus or even allergen for that matter. Instead, different immune cells recognize and bind different bits and pieces of their targets. Thus, be the source of physiological disruption virus, bacteria, fungus, archaea, protist or helminth and so on, varied responses of all these immune cells and their products to varying bits and pieces need to be in sync to neutralize and/or eliminate the source of their individual targets, typically a whole organism.

The beauty as also the mystery of the human immune system is that this process occurs by rote in a healthy body even as no single element within the system can ‘see’ the entirety of the disruptor that sets the process in motion in the first place. This is also why on the one hand, Autoimmunity – Wikipedia, i.e., sustained and deleterious immune attack on one’s own cells and tissues, occurs when the immune system’s not functioning optimally, and why on the other, Cancer immunotherapy – Wikipedia can even be considered a realistic treatment option for tumors. Regardless the trigger, a common set of rules learned over evolutionary time guide the initiation, maintenance, termination and yes, even strength of immune responses, even as no single entity within this system can discern that trigger in its entirety.

Bibliography

1. Pawelec, Graham, et al. “The impact of CMV infection on survival in older humans.” Current opinion in immunology 24.4 (2012): 507-511. https://www.researchgate.net/pro…

2. Weltevrede, Marlies, et al. “Cytomegalovirus persistence and T-cell immunosenescence in people aged fifty and older: a systematic review.” Experimental gerontology 77 (2016): 87-95.

3. Janssens, Jean-Paul, and Karl-Heinz Krause. “Pneumonia in the very old.” The Lancet infectious diseases 4.2 (2004): 112-124. http://www.pneumonologia.gr/arti…

4. Kaplan, Vladimir, et al. “Hospitalized community-acquired pneumonia in the elderly: age-and sex-related patterns of care and outcome in the United States.” American journal of respiratory and critical care medicine 165.6 (2002): 766-772. https://www.researchgate.net/pro…

5. Karlsson, Elinor K., Dominic P. Kwiatkowski, and Pardis C. Sabeti. “Natural selection and infectious disease in human populations.” Nature Reviews Genetics 15.6 (2014): 379-393. Natural selection and infectious disease in human populations

6. Quach, Hélène, and Lluis Quintana-Murci. “Living in an adaptive world: Genomic dissection of the genus Homo and its immune response.” Journal of Experimental Medicine 214.4 (2017): 877-894. http://jem.rupress.org/content/j…

7. Barua, D., and A. S. Paguio. “ABO blood groups and cholera.” Annals of human biology 4.5 (1977): 489-492.

8. Glass, Roger I., et al. “Predisposition for cholera of individuals with o blood group possible evolutionary significance.” American journal of epidemiology 121.6 (1985): 791-796.

9. Harris, Jason B., and Regina C. LaRocque. “Cholera and ABO Blood Group: Understanding an Ancient Association.” The American Journal of Tropical Medicine and Hygiene 95.2 (2016): 263-264. https://pdfs.semanticscholar.org…

10. Liu, Rong, et al. “Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection.” Cell 86.3 (1996): 367-377. https://www.researchgate.net/pro…

11. Dean, Michael, et al. “Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structual gene.” Science 273.5283 (1996): 1856.

https://www.quora.com/Why-do-we-develop-robust-immunity-after-viral-infections-but-not-bacterial-infections/answer/Tirumalai-Kamala

How might gut bacteria affect the brain function in humans?

Tags

Psychobiotic

Animal models show gut microbiota (bacteria, viruses, fungi, archaea and eukaryotes such as helminths) influence various aspects of physiology including brain function. Though data on their effect on human physiology is sparse, gut-associated pathologies and mental health issues such as depression (1) are strongly linked. Reverse also applies. For example, strong correlations between autism severity and gastrointestinal (GI) symptoms (2, 3).

Physicians have for long recognized the link between ‘melancholia’ and constipation and other GI tract disturbances, and attempted to treat their symptoms with GI tract interventions (4). Though ideas such as autointoxication, the notion that psychiatric symptoms owed their genesis to GI tract disturbances (Colon cleansing – Wikipedia), faded over the 20th century, renewed research interest in gut-microbiota-brain link is helping move an idea that relied more on pseudoscience onto a firmer scientific footing.

Recently the term psychobiotic was coined for, ‘a live organism that, when ingested in adequate amounts, produces a health benefit in patients suffering from psychiatric illness‘ (5). Could such outcomes be engineered reproducibly and if yes, exactly how do they work? Here the story gets much murkier because so far little can be stated unequivocally and even less claimed as a replicable therapeutic approach capable of manipulating human neuropsychiatric outcomes at will (6).

This answer briefly explores

1. Physical and neurochemical links between gut, gut bacteria and brain: Vagus nerve, Serotonin, other neurochemicals.
2. Human studies on gut bacteria and brain: too few, poorly done, contradictory results.
3. Antibiotics could affect brain function: Could harm (insomnia, mood alterations, psychosis, mania, depression, autism) or help (treatment-resistant depression, schizophrenia).

1. Physical & Neurochemical Links Between Gut, Gut Bacteria & Brain

Vagus nerve – Wikipedia

Major nerve of the parasympathetic division of the autonomic nervous system, the vagus nerve physically connects the ~100 million neurons of the enteric (gut) nervous system to the base of the brain at the medulla (7) with projections into many other parts of the brain including the thalamus, hypothalamus, amygdala (8). Gut inflammation and brain are theorized to connect via the vagus nerve, i.e., Inflammatory reflex – Wikipedia (9).

• Enteric nerves could directly sense bacteria (10).
• Vagus expresses receptors for many gastrointestinal hormones such as Ghrelin – Wikipedia, which regulate food intake (11), which may explain why blocking it can cause drastic weight loss (12, 13).
• Vagus nerve stimulation – Wikipedia is a procedure that increases parasympathetic tone. Its utility for https://en.wikipedia.org/wiki/Ep… and https://en.wikipedia.org/wiki/Tr… strengthens the link between gut-associated inflammation and brain function.

https://en.wikipedia.org/wiki/Se…

• Influencing brain states from appetite to circadian rhythms to moods, Serotonin is one of the clearest tangible links between gut microbiota and brain function. Major target of antidepressants, it’s also the most studied neurotransmitter in psychiatric illnesses. Rather than the brain, the https://en.wikipedia.org/wiki/En… in the gut are the body’s major source of serotonin (14), and mouse gut microbiota were found to play a role in its synthesis (15). Gut being abundant in both microbiota and serotonin, the latter in turn playing a major role in brain states, makes this a credible link though how serotonin, densely packed inside platelet granules, makes its way into the brain is still a mystery.

Bacteria As Source Of Other Neurochemicals

Many microbes can not only abundantly secrete neurochemicals such as Acetylcholine, Dopamine, Epinephrine, GABA, Norpeinephrine, Serotonin in culture (16) but also respond to them (17). Sheer quantity of such neurochemicals suggests they may be of physiologic importance.

• For example, fermented foods such as Japanese funa-sushi (18) and Chinese paocai (19) use lactobacilli in their making and have millimolar levels of GABA in the final product.
• Bacteria that contaminate fish or shellfish products can secrete such large amounts of the neurotransmitter, histamine, testing is necessary to ensure levels don’t exceed government guidelines for food poisoning (20).
• Gut bacteria are also an important source of vitamins important for CNS (https://en.wikipedia.org/wiki/Ce…) function. For example, Lactobacillus reuteri, a normal human gut inhabitant, is a rich source of https://en.wikipedia.org/wiki/Vi… (21), whose deficiency is implicated in https://en.wikipedia.org/wiki/Ne… in fetuses (22, 23).

2. Human Studies On Gut Bacteria & Brain

Too many fundamentals yet lack answers. No consensus definition of what constitutes a healthy human gut microbiota. Gut bacteria alone are estimated to be >1000 species. Add how confounding variables such as age, diet, ethnicity, gender, location influence gut microbiota composition and the picture gets fuzzier rather than clearer. While proper understanding of gut microbiota-brain link requires an ecological approach, many studies assess gut microbiota-brain link in reductionist inbred rodent models whose results are hard if not impossible to extrapolate to human brain function.

• Often studies on effect of probiotics on brain function are poorly done, have few subjects and use questionnaires or scale-based assessments plagued by subjective bias.
• There are few RCT (https://en.wikipedia.org/wiki/Ra…).
• No wonder a 2015 systematic review found ‘very limited evidence for the efficacy of probiotic interventions in psychological outcomes‘ (24) while a 2016 meta-analysis of RCTs could only provisionally conclude probiotics might improve CNS function but couldn’t rule out https://en.wikipedia.org/wiki/Pu… towards positive results (25).
• No surprise that studies so far (26, 27, 28, 29, 30) comparing gut microbiota between MDD (https://en.wikipedia.org/wiki/Ma…) patients and healthy controls yield contradictory data.
• OTOH, a small study when well-designed and controlled can yield useful pointers for future studies. In one such (31), healthy women were given fermented milk product with probiotic (n=12), non-fermented milk product (n=11), or nothing (n=13) twice daily for 4 weeks. The probiotics included Bifidobacterium animalis subsp lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, Lactobacillus lactis subsp lactis. fMRI (https://en.wikipedia.org/wiki/Fu…) suggested such probiotics might reduce stress responses and enhance cognition in healthy subjects.

3. Antibiotics Could Affect Brain Function

Do antibiotics influence neuropsychiatric symptoms? Since antibiotics wipe out gut bacteria, this offers another avenue to explore gut bacteria-brain link. Case-reports, epidemiological studies, clinical trials, a variety of such studies suggest antibiotics could either harm or help brain function, distinction depending on the antibiotic and kinds of bacteria it targets.

Harm

• One of the clearest examples is from case reports of antibiotics inducing insomnia, mood alteration (32), psychosis (33, 34, 35), even mania, antibiomania, especially in the elderly (36). Antibiotics most commonly implicated in these unusual behavior changes are clarithromycin, ciprofloxacin and ofloxacin.
• A retrospective medical records-based study (37) of 202974 patients with depression, 14570 with anxiety, 2690 with psychosis with 803961, 57862 and 10644 matched controls, respectively, concluded recurrent antibiotic Rx increased risk for depression and anxiety but not psychosis.
• Link between prior heavy antibiotic use and autism is quite strong (38, 39, 40), especially use of trimethoprim/sulfamethoxazole (41).

Help

https://en.wikipedia.org/wiki/Mi…, a semi-synthetic https://en.wikipedia.org/wiki/Br… https://en.wikipedia.org/wiki/Te…, is usually used to treat acne and other skin conditions. It’s been suggested as a possibility for treatment-resistant depression (42) and schizophrenia (43).

• A small, open-label study found minocycline effective and well-tolerated in treatment-resistant depression (44).
• A pilot study by King’s College, London, is completed but no results posted yet (45, 46).
• A couple of clinical trials are underway, one a phase II in Germany (47) and another in Thailand/Australia (48).

Thus, accumulating circumstantial data suggests gut microbiota influence human brain function but little of it is as yet tangible and reproducible.

Bibliography

1. Foster, Jane A., and Karen-Anne McVey Neufeld. “Gut–brain axis: how the microbiome influences anxiety and depression.” Trends in neurosciences 36.5 (2013): 305-312. http://neuroscienceresearch.wust…

2. Adams, James B., et al. “Gastrointestinal flora and gastrointestinal status in children with autism–comparisons to typical children and correlation with autism severity.” BMC gastroenterology 11.1 (2011): 22. http://download.springer.com/sta…

3. de Theije, Caroline GM, et al. “Pathways underlying the gut-to-brain connection in autism spectrum disorders as future targets for disease management.” European journal of pharmacology 668 (2011): S70-S80. https://www.researchgate.net/pro…

4. Phillips, J. George Porter. “The treatment of melancholia by the lactic acid bacillus.” The British Journal of Psychiatry 56.234 (1910): 422-NP.

5. Dinan, Timothy G., Catherine Stanton, and John F. Cryan. “Psychobiotics: a novel class of psychotropic.” Biological psychiatry 74.10 (2013): 720-726.

6. MacQueen, Glenda, Michael Surette, and Paul Moayyedi. “The gut microbiota and psychiatric illness.” J Psychiatry Neurosci 42.2 (2017): 75. http://jpn.ca/wp-content/uploads…

7. Alcock, Joe, Carlo C. Maley, and C. Aktipis. “Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms.” Bioessays 36.10 (2014): 940-949. http://onlinelibrary.wiley.com/d…

8. Kennedy, Paul J., et al. “Microbiome in brain function and mental health.” Trends in Food Science & Technology 57 (2016): 289-301. http://download.xuebalib.com/xue…

9. Tracey, Kevin J. “The inflammatory reflex.” Nature 420.6917 (2002): 853-859. https://www.researchgate.net/pro…

10. Raybould, Helen E. “Gut chemosensing: interactions between gut endocrine cells and visceral afferents.” Autonomic Neuroscience 153.1 (2010): 41-46. https://www.ncbi.nlm.nih.gov/pmc…

11. Strader, April D., and Stephen C. Woods. “Gastrointestinal hormones and food intake.” Gastroenterology 128.1 (2005): 175-191. http://www.siumed.edu/~astrader/…

12. Camilleri, Michael, et al. “Intra-abdominal vagal blocking (VBLOC therapy): clinical results with a new implantable medical device.” Surgery 143.6 (2008): 723-731. https://www.researchgate.net/pro…

13. Sarr, Michael G., et al. “The EMPOWER study: randomized, prospective, double-blind, multicenter trial of vagal blockade to induce weight loss in morbid obesity.” Obesity surgery 22.11 (2012): 1771-1782.

14. Tirumalai Kamala’s answer to How do SSRIs affect the microbiome?

15. Wikoff, William R., et al. “Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites.” Proceedings of the national academy of sciences 106.10 (2009): 3698-3703. https://www.researchgate.net/pro…

16. Lyte, Mark. “Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics.” Bioessays 33.8 (2011): 574-581. http://insanemedicine.com/wp-con…

17. Iyer, Lakshminarayan M., et al. “Evolution of cell–cell signaling in animals: did late horizontal gene transfer from bacteria have a role?.” TRENDS in Genetics 20.7 (2004): 292-299. https://www.researchgate.net/pro…

18. Komatsuzaki, Noriko, et al. “Production of γ-aminobutyric acid (GABA) by Lactobacillus paracasei isolated from traditional fermented foods.” Food microbiology 22.6 (2005): 497-504.

19. Li, Haixing, et al. “A high γ-aminobutyric acid-producing Lactobacillus brevis isolated from Chinese traditional paocai.” Annals of Microbiology 58.4 (2008): 649-653.

20. Ieniştea, C. “Bacterial production and destruction of histamine in foods, and food poisoning caused by histamine.” Molecular Nutrition & Food Research 15.1 (1971): 109-113.

21. Santos, Filipe, et al. “High-level folate production in fermented foods by the B12 producer Lactobacillus reuteri JCM1112.” Applied and environmental microbiology 74.10 (2008): 3291-3294. http://library.wur.nl/WebQuery/w…

22. Smithells, R. W., S. Sheppard, and C. J. Schorah. “Vitamin dificiencies and neural tube defects.” Archives of Disease in Childhood 51.12 (1976): 944-950. https://www.ncbi.nlm.nih.gov/pmc…

23. Dror, Daphna K., and Lindsay H. Allen. “Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms.” Nutrition reviews 66.5 (2008): 250-255. https://pubag.nal.usda.gov/pubag…

24. Romijn, Amy R., and Julia J. Rucklidge. “Systematic review of evidence to support the theory of psychobiotics.” Nutrition reviews 73.10 (2015): 675-693. https://www.researchgate.net/pro…

25. Wang, Huiying, et al. “Effect of probiotics on central nervous system functions in animals and humans: A systematic review.” Journal of Neurogastroenterology and Motility 22.4 (2016): 589-605. https://pdfs.semanticscholar.org…

26. Naseribafrouei, A., et al. “Correlation between the human fecal microbiota and depression.” Neurogastroenterology & Motility 26.8 (2014): 1155-1162. https://www.researchgate.net/pro…

27. Jiang, Haiyin, et al. “Altered fecal microbiota composition in patients with major depressive disorder.” Brain, behavior, and immunity 48 (2015): 186-194. https://pdfs.semanticscholar.org…

28. Zheng, P., et al. “Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism.” Molecular psychiatry 21.6 (2016): 786-796.

29. Aizawa, Emiko, et al. “Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder.” Journal of affective disorders 202 (2016): 254-257. https://www.researchgate.net/pro…

30. Kelly, John R., et al. “Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat.” Journal of Psychiatric Research 82 (2016): 109-118.

31. Tillisch, Kirsten, et al. “Consumption of fermented milk product with probiotic modulates brain activity.” Gastroenterology 144.7 (2013): 1394-1401. http://ac.els-cdn.com/S001650851…

32. Sternbach H & State R. (1997). Antibiotics: neuropsychiatric effects and psychotropic interactions. HarvRevPsychiatry 5, 214-226.

33. Mehdi S. (2010). Antibiotic-induced psychosis: a link to D-alanine?. MedHypotheses 75, 676- 677.

34. Bercik, Premysl, and Stephen M. Collins. “The effects of inflammation, infection and antibiotics on the microbiota-gut-brain axis.” microbial endocrinology: the microbiota-gut-brain axis in health and disease. Springer New York, 2014. 279-289.

35. Ly, Duy, and Lynn E. DeLisi. “Can antibiotics cause a psychosis?: Case report and review of the literature.” Schizophrenia Research (2017).

36. Abouesh, A., Stone, C. & Hobbs, W. R. Antimicrobial‐ induced mania (antibiomania): a review of spontaneous reports. J. Clin. Psychopharmacol. 22, 71–81 (2002).

37. Lurie, Ido, et al. “Antibiotic exposure and the risk for depression, anxiety, or psychosis: a nested case-control study.” The Journal of clinical psychiatry 76.11 (2015): 1522.

38. Niehus, Rebecca, and Catherine Lord. “Early medical history of children with autism spectrum disorders.” Journal of Developmental & Behavioral Pediatrics 27.2 (2006): S120-S127.

39. Atladóttir, Hjördis Ósk, et al. “Autism after infection, febrile episodes, and antibiotic use during pregnancy: an exploratory study.” Pediatrics 130.6 (2012): e1447-e1454. http://pediatrics.aappublication…;

40. Mezzelani, Alessandra, et al. “Environment, dysbiosis, immunity and sex-specific susceptibility: a translational hypothesis for regressive autism pathogenesis.” Nutritional neuroscience 18.4 (2015): 145-161. https://pdfs.semanticscholar.org…

41. Finegold, Sydney M., et al. “Gastrointestinal microflora studies in late-onset autism.” Clinical Infectious Diseases 35.Supplement 1 (2002): S6-S16. https://www.researchgate.net/pro…

42. Soczynska, Joanna K., et al. “Novel therapeutic targets in depression: minocycline as a candidate treatment.” Behavioural brain research 235.2 (2012): 302-317. http://www.medicinabiomolecular….

43. Chaudhry, Imran B., et al. “Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment.” Journal of psychopharmacology 26.9 (2012): 1185-1193. https://www.researchgate.net/pro…

44. Miyaoka, Tsuyoshi, et al. “Minocycline as adjunctive therapy for patients with unipolar psychotic depression: an open-label study.” Progress in Neuro-Psychopharmacology and Biological Psychiatry 37.2 (2012): 222-226.

45. https://clinicaltrials.gov/ct2/s…

46. Husain, Muhammad I., et al. “Minocycline as an adjunct for treatment-resistant depressive symptoms: study protocol for a pilot randomised controlled trial.” Trials 16.1 (2015): 410. http://download.springer.com/sta…

47. https://clinicaltrials.gov/ct2/s…

48. Dean, Olivia May, et al. “Protocol and rationale-the efficacy of minocycline as an adjunctive treatment for major depressive disorder: a double blind, randomised, placebo controlled trial.” Clinical psychopharmacology and neuroscience 12.3 (2014): 180-188. http://www.cpn.or.kr/journal/dow…

https://www.quora.com/How-might-gut-bacteria-affect-the-brain-function-in-humans/answer/Tirumalai-Kamala

Why does the same virus cause one symptom in one person and another in a different one?

Tags

Gastrointestinal (GI) tract, Symptom

Question details: For example, for a GI bug, some of my kids will have vomiting, others will have diarrhea, or one unfortunate one will end up with both.

Differences in either genetics and/or exposure (dose) might lead siblings to have different symptoms to the same illness and the two reasons aren’t mutually exclusive.

No two individuals have the exact same biomedical profile, not even identical (monozygotic) twins*.

• The process of Genetic recombination – Wikipedia during Meiosis – Wikipedia in germ cells (ova, sperm) ensures children are born with combinations of traits different not only from their parents but also from each other.
• At greater granularity individuals also differ in Single-nucleotide polymorphism – Wikipedia (SNPs), i.e., differences in single letters of the genetic code.
• Epigenetics – Wikipedia helps further differentiate individuals in the course of their life since each sibling’s interaction with their environment is more or less unique and it leaves singular imprints on their genome even though they are genetically related.
• The process of Somatic recombination – Wikipedia creates a unique Adaptive immune system – Wikipedia in each individual and some or much of this may even have to do with the unique Microbiota – Wikipedia each individual harbors though this is pure speculation at present since we’re currently far from knowing much about this.

These differences form the essential basis for differences in symptoms and severity for the same illness among individuals. However, apart from genetic and immunity differences between hosts, differences in severity of exposure could also explain why this happens, with the sibling with greatest exposure, i.e., dose, more likely to suffer the most severe symptoms. The same sibling repeatedly suffering more severe outcomes for shared illnesses would suggest greater likelihood of underlying genetic difference(s) being at play.

To successfully infect means to first successfully enter a cell, replicate inside it and finally spread to neighboring cells and beyond. Each disease-causing microbe thus evolves to express molecules that mimic those that bind certain cell-surface receptors and this process then serves as its entryway into a particular cell. This preference of a particular microbe to infect certain tissues is its Tissue tropism – Wikipedia. For e.g., the cold virus, Rhinovirus – Wikipedia, and Influenza – Wikipedia primarily target the epithelial cells of the upper respiratory tract, Viral hepatitis – Wikipedia the liver, etc.

Though cells obviously differ in the panoply of what they express on their surface, there’s also considerable overlap between different tissues and these overlaps differ between individuals, both in strength and variety. Thus, given the processes of genetic and somatic recombination, and epigenetics, even related individuals differ in their relative susceptibility to various disease-causing microbes.

This is why some people might get Zika fever – Wikipedia and never know since their symptoms stayed so mild while others may get fever (systemic involvement), joint pain (musculoskeletal) and rashes on their torso (skin) while still others could develop debilitating muscle weakness and pain, Guillain–Barré syndrome – Wikipedia, symptoms that could even be life-threatening.

With a GI tract illness, only vomiting suggests a stringently self-limiting infection that stayed restricted to the upper GI tract, diarrhea suggests a spread into the lower GI tract while both vomiting and diarrhea suggest the most severe outcome, i.e., persistent infection effects in both upper and lower GI tract. Again, simple dose differences in initial exposure could be a trivial explanation for a one-off outcome difference of this kind.

* Tim D. Spector’s long-term studies on identical and fraternal twins show that ‘twins rarely die of the same disease‘ (Why do identical twins end up having such different lives?).

https://www.quora.com/Why-does-the-same-virus-cause-one-symptom-in-one-person-and-another-in-a-different-one/answer/Tirumalai-Kamala

What are some ways to test if you have good gut bacteria?

What constitutes good gut bacteria? What’s their benchmark? We have no clue. Economics of gene sequencing technology means fecal microbiome sequencing costs (1) a fraction of what it did just a few years back. Predictably, companies offering to sequence them have mushroomed, for a price of course. Anyone with a handful of disposable US dollars can get their poop bacteria sequenced but what do those results even mean?

• Should poop contain ~55% Firmicutes, apparently the same as Michael Pollan or 74%, same as the author of this Newsweek piece (2)?
• What’s the value of a one-time poop bacteria sequencing? Isn’t that just a snapshot?
• Studies show poop bacterial composition changes rapidly not just with diet (3) but also seasonally (4) so what’s the predictive value of such a snapshot anyway?
• What does poop bacteria even represent?
  • Isn’t poop bacteria sequenced so much just because it’s easier to access?
  • Doesn’t it really only represent distal colon bacteria supported by current diet?
  • What about what’s in the stomach, duodenum, jejunum, ileum, and proximal and transverse colon, and how they relate to gut and overall health? Don’t we need invasive biopsies to accurately access bacteria in other GI tract compartments?
  • What can we extrapolate from what’s in poop to what should be in other parts of the GI tract? Anything? Nothing?

All this to say a lot of data on poop microbiome’s being generated simply because it can be, not because anyone has a clue what any of it means nor a clue what constitutes good gut bacteria.

To top this litany of shortcomings and dubious value of current attempts to benchmark gut bacteria using fecal microbiome sequencing, at least one randomized placebo-controlled study (5, 6) not only reveals novel, incalculable curative powers of Placebo but also casts doubt on currently accepted notions of ‘good’ and ‘bad’ gut bacteria.

• A study across two US academic medical centers, Montefiore Medical Center in the Bronx, New York and the Miriam Hospital, Providence, Rhode Island, both well-known for their expertise in Fecal microbiota transplant (FMT) (5, 6).
• 46 patients with recurrent Clostridium difficile infection (CDI) were randomly assigned to receive either donor or autologous (their own) poop microbiota, i.e., Placebo.
• 91% (20/22) of those who got donor poop were durably cured based on a standard definition. Expected so no surprise.
• The absolute shocker? 63% (15/24) who got their own poop microbiota transplanted back also had durable cure. Rub eyes and read again. What? Patients with a serious GI tract infection were given back their own presumably disease-associated gut bacteria and they got cured?
• Though there were striking inter-center differences in this Placebo effect, 9/10 (90%) placebo cases in the New York center cured versus only 6/14 (~43%) in the Rhode Island center, and perhaps associated patient population differences between these two centers, those aren’t germane to the central issue, namely, a GI tract disease cured from simply taking out and putting fecal bacteria back into C.diff patients.

Thus, even so-called ‘bad’ gut bacteria turn out to be not so cut and dry, a result that only underlines how little we currently know about gut bacteria, good, bad or anything in between. Best one could then say is absence of persistent and serious health problems, especially gastrointestinal, is evidence of having good gut bacteria. Absence of skin problems, no autoimmunities or mental health issues would be icing on the cake.

Bibliography

1. 16S rRNA sequencing

2. Newsweek, Roxane Khamsi, July 17, 2014. Gut Check

3. David, Lawrence A., et al. “Diet rapidly and reproducibly alters the human gut microbiome.” Nature 505.7484 (2014): 559-563. Diet rapidly and reproducibly alters the human gut
microbiome

4. Davenport, Emily R., et al. “Seasonal variation in human gut microbiome composition.” PloS one 9.3 (2014): e90731. http://www.plosone.org/article/f…

5. Kelly, Colleen R., et al. “Effect of Fecal Microbiota Transplantation on Recurrence in Multiply Recurrent Clostridium difficile Infection: A Randomized Trial.” Annals of Internal Medicine (2016).

6. Fecal Transplant for Relapsing C. Difficile Infection

https://www.quora.com/What-are-some-ways-to-test-if-you-have-good-gut-bacteria/answer/Tirumalai-Kamala

What is the function of bacteria in the human mouth?

Tags

Colonisation resistance, Dental caries, Food web, Gum diseases, oral cavity, Periodontal pathology, tooth decay

Most of the data available so far identifies bacterial species that tend to be associated with healthy versus diseased oral cavities but not much is known about exactly what health-associated ones do apart from keeping out the disease-associated ones.

Oral Cavity, A Complex Ecosystem Of Several Specialized Ecological Niches

Gaining insight begins with the appreciation that the oral cavity is a complex habitat further sub-divided into distinct smaller ones ranging from the non-keratinized Oral mucosa to the keratinized Tongue and gingiva, i.e., Gums, as well as Tooth enamel and a variety of dental implants. Thus, depending on its proximity to the gum line, dental plaque is either supra- or subgingival, and the bacteria that inhabit these two regions are different, supragingival plaque dominated by gram-positive Streptococci while subgingival by gram-negative anaerobic bacteria (1).

Since the oral cavity is exposed to the outside world, these surfaces are colonized soon after birth, with some evidence suggesting vertical (mother-to-baby) transmission (2) as well as similarities between family members (3). Stable inhabitants, formally called autochthonous, establish Biofilm, a kind of super-organism consisting of cooperating microbes. Being open, oral cavity also gets plenty of visitors, transients, formally called allochthonous.

Older studies suggested oral cavity diseases are associated with changes in microbial diversity (1).

Gum diseases, i.e., Periodontal pathology, and tooth decay, i.e., Dental caries, are associated with increase (4, 5, 6) and decrease (7), respectively, in microbial diversity. More recent state-of-the-art molecular approaches (8, 9) confirm these decades-old findings. This implies oral cavity disease isn’t so much a matter of presence or absence of certain microbes since those with disease-causing potential, i.e., pathobionts, are present even in health (10) but rather about their relative proportions in complex biofilms.

Colonisation resistance Is A Key Feature Of Healthy Oral Cavity Microbiota

Like other microbe-associated body sites, the oral cavity too is a series of specialized niches occupied by specific microbes capable of specialized functions both necessary and predicated on some inherent properties of these niches. The ones who establish stable presence in the form of complex, multi-species biofilms dominate their specific niches by preventing others, including pathogens, from establishing themselves, i.e., Colonization Resistance (11). When the oral cavity is stably colonized by beneficial microbe biofilms, it’s healthy. Instability in beneficial microbe colonization is a weakness that’s then exploited by more harmful and even pathogenic species to dominate oral cavity biofilms, with the outcome either tooth decay (Dental Caries) or gum disease (Periodontitis).

Tooth decay (Dental caries) is associated with certain species of Streptococci such as Streptococcus mutans and species of Lactobacilli (12) while subgingival anaerobes establish their communities within periodontal pockets, some of whom such as Porphyromonas gingivalis are associated with gum disease (Periodontitis) (13, 14).

Obviously diet profoundly influences not only which bacterial species stably establish within oral biofilms but also dominate.

• Thus though S. mutans is part of normal oral microbiota (15), it doesn’t dominate in healthy oral cavities.
• However, its capacity to metabolize sucrose more efficiently compared to other oral bacteria (16) gives it a competitive advantage in the oral cavities of those who predominantly consume the highly processed, sucrose-heavy ‘Western’ diet.
• S. mutans can also convert sucrose to adherent glucans, which helps it to attach more strongly to teeth (17).
• S. mutans also rapidly converts sucrose to lactic acid, giving it an added selective advantage owing to its intrinsic capacity to withstand such acidic environments (18, 19).
• These properties may help S. mutans and Lactobacilli dominate in tooth decay, i.e., dental caries, the latter because they metabolize lactic acid generated by S.mutans.

Similar studies done decades apart, scraping plaques from people with or without gum disease and culturing the bacteria that grew out with bacterial species associated with gum disease showed plaques from people without gum disease can inhibit growth of gum disease-associated bacterial species (20, 21). How?

• Streptococcus sanguinis is considered an inhabitant of normal dental plaque. Less acid-tolerant than its presumed niche competitor, S. mutans, S. sanguinis produces Hydrogen peroxide, toxic for S. mutans, which typically lacks capacity to effectively neutralize it (22, 23). Thus, dental plaques rich in S. sanguinis contain relatively lower proportions of dental caries-associated S. mutans and periodontitis-associated P. gingivalis (20).
• Veillonella species (24) and S. oligofermentans (25) readily metabolize lactic acid secreted by S. mutans. A revealing window into how inter-species competition can engender colonization resistance, S. oligofermentans not only utilizes S. mutans-generated lactic acid but converts it into hydrogen peroxide, highly toxic to the latter (26).
• Streptococcus gordonii offers another plausible example of colonization resistance tactic. Another inhabitant of healthy oral cavities, in vitro it could prevent stable S. mutans colonization by inactivating one of its important resistance mechanisms , ability to synthesize a Quorum sensing molecule, CSP (competence-stimulating peptide) (27). When thus hobbled, S. mutans is much less capable of resisting natural salivary antimicrobial peptides such as Histatin (1).
• Oral cavity bacteria also secrete Bacteriocin. Proteinaceous toxins, bacteriocins differ from antibiotics, having a much narrower killing spectrum and acting on related organisms (1).

Thus, as long as diet is varied enough to also allow stable plaque colonization by base-producing microbes, acid-producing S. mutans wouldn’t be able to predominate and take over local plaque ecosystem.

Food web Relationships Between Normal Oral Cavity Microbes Help Maintain Their Stability

As is the hallmark of ecosystems consisting of mutually dependent residents, the healthy oral cavity too contains microbes engaged in Food web activities, i.e., metabolic end products of one species used by others.

• Oral biofilm Streptococci synthesize lactate that Veillonella use (1).
• S. sanguis and S. oralis are inhabitants of healthy oral biofilms. In vitro culture studies suggest their mutually helpful, i.e., synergistic, capacity to digest mucins helps them more efficiently use such complex host sugars as nutrition (28).
• Oral cavity is constantly bathed in saliva and gingival crevicular fluid. Composite of products of not just human tissue cells but also microbes, some microbial inhabitants appear to engage in synergistic/mutualistic interactions to overcome inherent handicaps to colonize. This seems to be the case with Actinomyces naeslundii and S. oralis that alone colonize saliva-coated surfaces poorly and yet can form extensive biofilms together by presumably combining their metabolic activities (29).

However, food web processes can also help shift oral biofilms to dominance by more pathogenic species. Though inhabitants of normal oral cavity, P. gingivalis, Fusobacterium nucleatum, Treponema denticola and Tannerella forsythia are also implicated in periodontal disease.

• In vitro culture studies show P. gingivalis can metabolize succinate produced by T. denticola (30) while the latter can use isobutyric acid secreted by the former (31).
• Both F. nucleatum and T. forsythia seem to secrete factors that stimulate growth of P. gingivalis (1).

Thus, whether mutualistic interactions of beneficial or harmful bacteria dominate in a given oral cavity is outcome of diet, oral hygiene and host genetic polymorphisms.

Why Knowledge Of Bacteria Function In Healthy Oral Cavity Is Better Gleaned From Older, Not Newer, Studies

Since the 2000s an explosion in molecular biological tools, so-called Omics, has led to a similar explosion in human microbiome studies. Since the oral cavity is one of the most easily accessible of all the GI tract niches, human oral cavity microbiome has become the best characterized in terms of the kinds of bacteria present in healthy versus unhealthy mouths.

• Since such typically technocratically driven processes focus primarily on generating an avalanche of data and explore no underlying hypotheses, one may wonder whether the healthy human oral cavity microbiome’s function is simply absence of disease. That is to say, given the monumental scale of molecular biology data generated on this topic since at least the mid-2000s, it’s shocking how little is known about what any of it even means.
• With older prejudices implicitly carried forward, there’s also been no attempt so far to synthesize the roles of bacteria and fungi in healthy oral cavities since fungi like Candida albicans were previously assumed to only represent disease states. Their repeated presence in healthy oral cavities suggests this idea needs revising (32).
• Even less is known about role of Archaea such as Methanobrevibacter species frequently found in healthy oral cavities. Their increasing identification in gum disease (Periodontal pathology) suggests they too may be involved in such disease processes but how? Only in promoting growth of pathogenic bacterial species (33) or as initiators and perpetuators themselves?
• Meantime overweening allegiance to novel technologies is powering this entire absurd process forward with the implicit hope that Data mining will uncover hidden patterns allowing certain predictive hypotheses to be made.
• If past is any predictor of future, the failure of past dependence on novel molecular biological approaches alone to yield predictive insight into complex biological phenomena suggests a similar fate awaits the current giddy immersion in the latest molecular biological toys. A useful and telling example from the recent past is Microarray analysis techniques, the focus of tens of thousands of papers since the late 1990s, which nevertheless yielded little or no improved insight into disease processes nor did they much illuminate possible future predictive approaches to better understand them.
• Necessity of extrapolating data from in vitro culture studies referenced in this answer is their major caveat. Nevertheless, we’d understand oral cavity-bacteria interactions better with more such experiments, especially in vitro co-cultures of human oral epithelial cells with candidate oral cavity commensals, more so co-cultures with commensal biofilms but such experimental approaches are technically much more challenging compared to powering a few cheek swab or saliva samples through the latest molecular biology apparatus. Hence the current absurd status quo.

Bibliography

1. Kuramitsu, Howard K., et al. “Interspecies interactions within oral microbial communities.” Microbiology and molecular biology reviews 71.4 (2007): 653-670. Interspecies Interactions within Oral Microbial Communities

2. Kobayashi, N., et al. “Colonization pattern of periodontal bacteria in Japanese children and their mothers.” Journal of periodontal research 43.2 (2008): 156-161. https://www.researchgate.net/pro…

3. Steenbergen, TJM van, et al. “Intra‐familial transmission and distribution of Prevotella intermedia and Prevotella nigrescens.” Journal of periodontal research 32.4 (1997): 345-350.

4. Löe, Harald, Else Theilade, and S. Börglum Jensen. “Experimental gingivitis in man.” Journal of periodontology 36.3 (1965): 177-187.

5. Listgarten, M. A. “Structure of the Microbial Flora Associated with Periodontal Health and Disease in Man: A Light and Electron Microscopic Study*.” Journal of periodontology 47.1 (1976): 1-18.

6. Syed, S. A., and W. J. Loesche. “Bacteriology of human experimental gingivitis: effect of plaque age.” Infection and immunity 21.3 (1978): 821-829.

7. Simon-Soro, A., et al. “A tissue-dependent hypothesis of dental caries.” Caries research 47.6 (2013): 591-600.

8. Diaz, P. I., A. Hoare, and B. Y. Hong. “Subgingival Microbiome Shifts and Community Dynamics in Periodontal Diseases.” Journal of the California Dental Association 44.7 (2016): 421. http://www.cda.org/Portals/0/jou…

9. Tanner, A. C., C. A. Kressirer, and L. L. Faller. “Understanding Caries From the Oral Microbiome Perspective.” Journal of the California Dental Association 44.7 (2016): 437. http://www.cda.org/Portals/0/jou…

10. Jiao, Y., M. Hasegawa, and N. Inohara. “The role of oral pathobionts in dysbiosis during periodontitis development.” Journal of dental research 93.6 (2014): 539-546. https://www.researchgate.net/pro…

11. Van der Waaij, D., J. M. Berghuis-de Vries, and J. E. C. Lekkerkerk-Van der Wees. “Colonization resistance of the digestive tract in conventional and antibiotic-treated mice.” Journal of Hygiene 69.03 (1971): 405-411. https://www.researchgate.net/pro…

12. Chhour, Kim-Ly, et al. “Molecular analysis of microbial diversity in advanced caries.” Journal of clinical microbiology 43.2 (2005): 843-849. Molecular Analysis of Microbial Diversity in Advanced Caries

13. ÖSterberg, Stic K‐Å., Sara Z. Sudo, and Lars EA Folke. “Microbial succession in subgingival plaque of man.” Journal of periodontal research 11.5 (1976): 243-255.

14. Ximénez‐Fyvie, Laurie Ann, Anne D. Haffajee, and Sigmund S. Socransky. “Microbial composition of supra‐and subgingival plaque in subjects with adult periodontitis.” Journal of clinical periodontology 27.10 (2000): 722-732. https://www.researchgate.net/pro…

15. Aas, Jørn A., et al. “Defining the normal bacterial flora of the oral cavity.” Journal of clinical microbiology 43.11 (2005): 5721-5732. Defining the Normal Bacterial Flora of the Oral Cavity

16. Hamada, Shigeyuki, and HUTTON D. Slade. “Biology, immunology, and cariogenicity of Streptococcus mutans.” Microbiological reviews 44.2 (1980): 331. http://www.ncbi.nlm.nih.gov/pmc/…

17. Gibbons, R. J., and M. Nygaard. “Synthesis of insoluble dextran and its significance in the formation of gelatinous deposits by plaque-forming streptococci.” Archives of oral biology 13.10 (1968): 1249-IN31.

18. Grenier, Daniel. “Antagonistic effect of oral bacteria towards Treponema denticola.” Journal of clinical microbiology 34.5 (1996): 1249-1252. Antagonistic effect of oral bacteria towards Treponema denticola.

19. Doran, A., S. Kneist, and Joanna Verran. “Ecological control: in vitro inhibition of anaerobic bacteria by oral streptococci.” Microbial Ecology in Health and Disease 16.1 (2004): 23-27. https://www.researchgate.net/pro…

20. Hillman, J. D., S. S. Socransky, and Myra Shivers. “The relationships between streptococcal species and periodontopathic bacteria in human dental plaque.” Archives of Oral Biology 30.11-12 (1985): 791-795.

21. van Essche, Mark, et al. “Bacterial antagonism against periodontopathogens.” Journal of periodontology 84.6 (2013): 801-811.

22. Carlsson, Jan, and May‐Britt K. Edlund. “Pyruvate oxidase in Streptococcus sanguis under various growth conditions.” Oral microbiology and immunology 2.1 (1987): 10-14.

23. Kreth, Jens, et al. “Competition and coexistence between Streptococcus mutans and Streptococcus sanguinis in the dental biofilm.” Journal of bacteriology 187.21 (2005): 7193-7203. Competition and Coexistence between Streptococcus mutans and Streptococcus sanguinis in the Dental Biofilm

24. Mikx, F. H. M., and J. S. Van der Hoeven. “Symbiosis of Streptococcus mutans and Veillonella alcalescens in mixed continuous cultures.” Archives of Oral Biology 20.7 (1975): 407-410.

25. Tong, Huichun, et al. “Streptococcus oligofermentans inhibits Streptococcus mutans through conversion of lactic acid into inhibitory H2O2: a possible counteroffensive strategy for interspecies competition.” Molecular microbiology 63.3 (2007): 872-880. https://www.researchgate.net/pro…

26. Bao, Xudong, et al. “Streptococcus oligofermentans inhibits Streptococcus mutans in biofilms at both neutral pH and cariogenic conditions.” PloS one 10.6 (2015): e0130962. http://journals.plos.org/plosone…

27. Wang, Bing-Yan, and Howard K. Kuramitsu. “Interactions between oral bacteria: inhibition of Streptococcus mutans bacteriocin production by Streptococcus gordonii.” Applied and environmental microbiology 71.1 (2005): 354-362. Inhibition of Streptococcus mutans Bacteriocin Production by Streptococcus gordonii.

28. Van der Hoeven, J. S., and P. J. M. Camp. “Synergistic degradation of mucin by Streptococcus oralis and Streptococcus sanguis in mixed chemostat cultures.” Journal of dental research 70.7 (1991): 1041-1044. http://citeseerx.ist.psu.edu/vie…

29. Palmer, Robert J., et al. “Mutualism versus independence: strategies of mixed-species oral biofilms in vitro using saliva as the sole nutrient source.” Infection and immunity 69.9 (2001): 5794-5804. Strategies of Mixed-Species Oral Biofilms In Vitro Using Saliva as the Sole Nutrient Source

30. Grenier, D., and D. Mayrand. “Nutritional relationships between oral bacteria.” Infection and immunity 53.3 (1986): 616-620. Nutritional relationships between oral bacteria.

31. Grenier, D. “Nutritional interactions between two suspected periodontopathogens, Treponema denticola and Porphyromonas gingivalis.” Infection and immunity 60.12 (1992): 5298-5301. Nutritional interactions between two suspected periodontopathogens, Treponema denticola and Porphyromonas gingivalis.

32. Krom, B. P., S. Kidwai, and J. M. Ten Cate. “Candida and Other Fungal Species Forgotten Players of Healthy Oral Microbiota.” Journal of dental research 93.5 (2014): 445-451. https://www.researchgate.net/pro…

33. Bang, Corinna, and Ruth A. Schmitz. “Archaea associated with human surfaces: not to be underestimated.” FEMS microbiology reviews (2015): fuv010. http://femsre.oxfordjournals.org…

https://www.quora.com/What-is-the-function-of-bacteria-in-the-human-mouth/answer/Tirumalai-Kamala

Microbiology: What different kinds of symbioses do humans have with bacteria?

Tags

colonic butyrate, Faecalibacterium (formerly Fusobacterium) prausnitzii

Since human microbiota study’s still in its infancy, strong, conclusive proof of symbiotic associations aren’t yet available. Rather, strong correlations are. Proof of symbiosis requires

1. A specific bacterial species consistently associated with several humans across time.
2. Abundance in health versus reduction in disease.
3. Successful re-planting of such a species into a diseased body should fully or partially restore health.

Further, being genetically diverse, geographically widespread, and having extremely varied diets, human-microbe symbioses are probably redundant between bacterial species and even across genera. This makes the 3rd proposition difficult to prove. Decisive proof becomes even more difficult given bacterial species associated with humans are being identified at exponential pace. For e.g., in the GI tract alone, bacterial species identified have increased from ~300 in 1980 to ~1000 by 2010 due to molecular technologies  (see figure below from 1).

Substantial data supports at least the first two conditions in the example of Faecalibacterium (formerly Fusobacterium) prausnitzii, associated with the colon.

• Presence confirmed by both culture (2) and 16SrRNA (3, 4, 5, 6), F. prausnitzii is one of the most abundant anaerobic bacteria in human colon and feces.
• Possible symbiotic function? One of the main sources of colonic butyrate (3, 7), generally considered beneficial to intestinal health as well as a preferred energy source for colonic epithelial cells, the colonocytes (8, 9, 10).
• Reduced presence in a variety of inflammatory bowel diseases (11, 12, 13, 14) including Crohn’s disease (15, 16, 17) and colorectal cancer (18, 19).

Bibliography

1. Rajilić-Stojanović, Mirjana, and Willem M. de Vos. “The first 1000 cultured species of the human gastrointestinal microbiota.” FEMS microbiology reviews 38.5 (2014): 996-1047. http://femsre.oxfordjournals.org…

2. Moore, W. E., and Lillian H. Moore. “Intestinal floras of populations that have a high risk of colon cancer.” Applied and environmental microbiology 61.9 (1995): 3202-3207. Intestinal floras of populations that have a high risk of colon cancer.

3. Hold, Georgina L., et al. “Oligonucleotide probes that detect quantitatively significant groups of butyrate-producing bacteria in human feces.” Applied and environmental microbiology 69.7 (2003): 4320-4324. Oligonucleotide Probes That Detect Quantitatively Significant Groups of Butyrate-Producing Bacteria in Human Feces

4. Suau, Antonia, et al. “Direct analysis of genes encoding 16S rRNA from complex communities reveals many novel molecular species within the human gut.” Applied and environmental microbiology 65.11 (1999): 4799-4807. Direct Analysis of Genes Encoding 16S rRNA from Complex Communities Reveals Many Novel Molecular Species within the Human Gut

5. Suau, Antonia, et al. “Fusobacterium prausnitzii and related species represent a dominant group within the human fecal flora.” Systematic and Applied Microbiology 24.1 (2001): 139-145. https://www.researchgate.net/pro…

6. Walker, Alan W., et al. “Dominant and diet-responsive groups of bacteria within the human colonic microbiota.” The ISME journal 5.2 (2011): 220-230. http://www.nature.com/ismej/jour…

7. Barcenilla, Adela, et al. “Phylogenetic relationships of butyrate-producing bacteria from the human gut.” Applied and environmental microbiology 66.4 (2000): 1654-1661. Phylogenetic Relationships of Butyrate-Producing Bacteria from the Human Gut

8. Hamer, Henrike M., et al. “Review article: the role of butyrate on colonic function.” Alimentary pharmacology & therapeutics 27.2 (2008): 104-119. http://onlinelibrary.wiley.com/d…

9. Pryde, Susan E., et al. “The microbiology of butyrate formation in the human colon.” FEMS microbiology letters 217.2 (2002): 133-139. http://femsle.oxfordjournals.org…

10. Roediger, W. E. W. “The colonic epithelium in ulcerative colitis: an energy-deficiency disease?.” The Lancet 316.8197 (1980): 712-715.

11. Sartor, R. Balfour. “Therapeutic correction of bacterial dysbiosis discovered by molecular techniques.” Proceedings of the National Academy of Sciences 105.43 (2008): 16413-16414. http://www.pnas.org/content/105/…

12. Cucchiara, Salvatore, et al. “The microbiota in inflammatory bowel disease in different age groups.” Digestive Diseases 27.3 (2009): 252-258.

13. Sokol, H., et al. “Low counts of Faecalibacterium prausnitzii in colitis microbiota.” Inflammatory bowel diseases 15.8 (2009): 1183-1189. https://www.researchgate.net/pro…

14. Schwiertz, Andreas, et al. “Microbiota in pediatric inflammatory bowel disease.” The Journal of pediatrics 157.2 (2010): 240-244. https://www.researchgate.net/pro…

15. Sokol, Harry, et al. “Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients.” Proceedings of the National Academy of Sciences 105.43 (2008): 16731-16736. http://www.pnas.org/content/105/…

16. Willing, Ben, et al. “Twin studies reveal specific imbalances in the mucosa‐associated microbiota of patients with ileal Crohn’s disease.” Inflammatory bowel diseases 15.5 (2009): 653-660. https://www.researchgate.net/pro…

17. Kang, Seungha, et al. “Dysbiosis of fecal microbiota in Crohn’s disease patients as revealed by a custom phylogenetic microarray.” Inflammatory bowel diseases 16.12 (2010): 2034-2042. https://www.researchgate.net/pro…

18. Balamurugan, Ramadass, et al. “Real‐time polymerase chain reaction quantification of specific butyrate‐producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer.” Journal of gastroenterology and hepatology 23.8pt1 (2008): 1298-1303. https://www.researchgate.net/pro…

19. Chen, Weiguang, et al. “Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer.” PloS one 7.6 (2012): e39743. http://www.plosone.org/article/f…

https://www.quora.com/Microbiology-What-different-kinds-of-symbioses-do-humans-have-with-bacteria/answer/Tirumalai-Kamala