Among the ramifications of current human microbiota research perhaps nothing could be more important than to reconsider what it even means to be a human being, to acknowledge that our individual identity isn’t quite what we’ve thought all along, that instead of autonomous entities we’re each an ecosystem, i.e., super-organisms, entities so dynamic as to even fundamentally alter, albeit temporarily, when we just change our diet or even just travel, perhaps even a. And who knows when some of these changes we’re used to making without a second thought actually end up altering us just a bit more permanently simply because they permanently alter our microbial components?
For example, does a person who switches permanently from a meat-eating to a vegetarian diet or vice-versa remain the same person with the same kinds of thoughts and feelings or does the microbiota change accompanying their diet change also alter them more fundamentally? When two flu-naive persons (neither previously exposed nor vaccinated) get equally exposed to seasonal flu and only one becomes sick, is one better protected than the other because their respiratory microbes were better suited to joining battle with their human cell partners to fend off the flu strain ()?
We aren’t used to asking such questions of ourselves. After all, the notion we’re each an autonomous entity is so ingrained in us, it may seem more than a bit bizarre initially to ask such ecological questions of ourselves. To acknowledge and reconcile that the multitude others we each harbor within our selves at all times influence just about every aspect of our physiology and thereby our identity is thus perhaps the most important ramification of human microbiota research. We are only beginning to understand just how much of who we are is outcome of not just the bacteria but also the varieties of viruses () and eukaryotes (fungi ( ) and helminths ( )) we harbor within our bodies.
The focus of so much research attention in recent years, it would take several theses to lay out all the ramifications in detail. Perhaps the best one could do in one answer on an issue so revelatory and essentially revolutionary is to just take a bird’s eye view of some key findings and their implications for not just human health but also identity, the latter in terms of pondering how much of what we do, and who and how we are may be actually for the benefit of our microbial partners, for their nourishment, survival and transmission.
- We’re used to thinking of our skin as a barrier protecting us from outside threats. The largest organ in the body, the skin doesn’t lack for microbial cohabitants. That a microbial multitude inhabits the top dead cell skin layer isn’t novel. What is remarkable is a select few actually penetrate below to reside within the living dermis ( ), yes, even in healthy skin. Thus appearing more than a little passe, the notion of the skin as a barrier instead cedes ground to the idea it’s a dynamic filter engaged in interactions with microbial multitudes, constantly negotiating for peaceful co-existence ( ).
- Cumulative evidence suggests skin microbial imbalance accompanies many skin diseases such as , , (7). Whether such is cause or effect of such diseases is the subject of ongoing research (8). Implication: skin diseases may be outcome of discord between skin cells and their microbial neighbors.
- Ever noticed how some people seem to be the disproportionate targets of mosquitoes and other biting insects? What is it about them? Do they release different scents more attractive to such insects? Turns out people preferentially targeted by mosquitoes and other biting insects emit different volatile scents from those who aren’t and this mostly boils down to differences in skin microbial composition ( ).
- Gut microbes not only help digest food but also expand our base of what’s digestible by providing calories from material human gut epithelial cells can’t digest, a salient example being ( ).
- The fact that such microbial digestion entails fermentation which yields not only calories but also nutrients such as butyrate essential for gut epithelial cell health and maintenance ( , , ) begs the question whether over evolutionary time we ate for our health or rather to nurture the microbes necessary for our health.
- A quick glance at cultures the world over suffices to confirm fermentation practices for making a variety of foods (breads, cheeses, pickled foods), and drinks (beers, wines, toddies) developed globally ( , 14). Over evolutionary time, what drove our global propensity for fermented foods, our taste buds or the microbes we harbor that depend on such foods for nutrition?
- Gut microbes synthesize key vitamins such as B and K ( , ), catabolize , drugs and toxins ( ) and mediate cholesterol and bile acid synthesis ( ).
- Gut microbes are also immensely important in training neonatal immune responses ( , ).
- Gut microbes synthesize ( , , ). Through circulation and through their effect on the , gut microbes may thus influence physiological states ranging from anxiety to mood and stress ( , ). In short, much of our behavior may be the outcome of interactions with the microbes we harbor. Seen in this light, it may be justified to speculate whether we evolved social behaviors such as kissing, social grooming and other social traditions to maximize chances of transmitting our microbial partners ( ).
- Only recently has consensus coalesced around the notion that many cognitive and behavioral disorders also involve gastrointestinal disturbances (26, 27, ). This is especially so in the case of disorders ( ).
Mother & Child
- Initial microbial colonization starts with the process of birth as the baby passes through the mother’s birth canal and vagina. Thus vertical (mother-to-child) transmission of microbes is a fundamental feature of human life and epidemiological studies suggest interfering with this process through procedures like C-section may also interfere with long-term health, given lifelong higher risk of allergies and autoimmunities among C-section babies compared to vaginal births ( ).
- Specific microbial species preferentially colonize infant gut during breast feeding ( ) while breast milk itself is rich in specific sugars, oligosaccharides that act as , i.e., nutrient beds that create a milieu to specifically promote growth of human infant gut beneficial microbes such as bifidobacteria ( ).
- In fact, so specialized does human breast milk seem to be in promoting colonization by specific infant gut microbes that scientists are even coming around to the idea that rather than provide nutrition to newborns, breastmilk’s true purpose may be as a prebiotic to promote infant gut colonization by specific microbial species ( , , , ).
- One of the most compelling examples is of mothers capable of secreting 2′-fucosylated glycans in their breast milk. People with active alleles are called secretors. One study ( ) found nursing infants of such secretors (n=32) were colonized much earlier by colonic bifidobacteria, specifically Bifidobacterium longum, compared to infants nursed by FUT2 non-secreting mothers (n=12), who were instead colonized by a different bifido, B. breve. Relevance of this difference? Infants nursing from FUT2 secretor mothers had lower fecal levels of lactate, suggesting they better utilized milk sugars.
Female Reproductive Tract
- Reinforcing the body-as-ecosystem idea, a study suggests vaginal microbiota influence risk of contracting sexually transmitted infections ( ).
- Importance of urinary tract ( ), cervical, vaginal microbiota in maintaining reproductive health (38, ) obviously begs the question of their role in birth, and especially how it’s different in preterm and still births ( , ).
- Healthy human placenta seems to specifically promote residence of a unique subset of microbes that most closely resemble those in healthy mouths ( ). Microbes specifically residing in the placenta! As research continues to plumb the depths of our microbial partnership, will any tissue turn out to be microbe-free?
Obviously microbes predate us. Patterns of genetic variations of microbes such as Mycobacterium tuberculosis () and Helicobacter pylori ( , , ) suggest they’ve evidently also accompanied us on our global migrations ( , ), i.e., that human-microbial associations may not be happenstance but rather evolutionarily conserved. No longer autonomous entities but rather each human a unique ecosystem, proof positive that we’re also holobionts awaits the discovery that each one of us invariably harbors the same specific microbial species or two or three or more.
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