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The human GI tract is largely a long tube stretching from mouth to anus. Largely because the enduring puzzle of the worm-like (vermiform) human appendix mars this tubal regularity near the ileo-cecal junction as a dead-end extension that projects off of the cecum, the bulbous, fleshy, front end of the colon (below from 1).
This answer briefly explains
- The recently described notion that the healthy appendix could be a bacterial ‘safe house’ that helps to quickly re-populate the colon with beneficial microbiota lost during a diarrheal purge.
- How the twinned appearance of Darwin’s idea of vestigiality and the industrialization-associated appendicitis epidemic helped embed the notion that the expendability of the human appendix is cost-free.
The healthy appendix could be a bacterial ‘safe house’ that helps to quickly re-populate the colon with beneficial microbiota lost during a diarrheal purge.
What possible digestive function could this relatively small finger-like structure possess, filled as it is with lymphoid tissue that seems ever so busy as to make it practically impossible to distinguish between its normal and inflamed counterparts, especially considering (below from 1)?,
“The internal diameter of the appendix, when open, has been compared to the size of a matchstick. The small opening to the appendix eventually closes in most people by middle age.”
Though Leonardo da Vinci famously illustrated the human appendix in 1492, his drawings weren’t published until the 18th century, which is why the history of anatomy attributes the discovery of the human appendix to Jacopo Berengario da Carpi – Wikipedia in 1521. In the centuries since, biologists have scratched around in vain trying to decipher the function of this intriguing organ even as it consistently failed to catch a break.
An implicit consensus about the presumed “uselessness” of the appendix prevailed unchallenged until 2007 when in the Journal of Theoretical Biology, a group led by William Parker at Duke University suggested an entirely plausible function for the human appendix, that (below from 2, figure below from 3),
“the human appendix is well suited as a ‘‘safe house’’ for commensal bacteria, providing support for bacterial growth and potentially facilitating re-inoculation of the colon in the event that the contents of the intestinal tract are purged following exposure to a pathogen”
Since then, a few other scientists accept the plausibility of this idea about the human appendix, that it (below from 4),
“may serve as a sort of bacterial “safe house,” allowing for the survival of symbiotic flora during severe bouts of diarrhea.”
Below from 5,
“Current evidence supports the hypothesis that the appendix is more than just an evolutionary vestige. Its location in the intestinal tract, but shielded from peristalsis and transiently passing contaminants in the fecal stream, make the appendix an ideal safe house for commensal bacteria (Figure 1). If the colon is purged following pathogen exposure, infection, and antibiotic treatment, the appendix could aid in reseeding the colon and reinstating a healthy microbiota. The biofilm in this vermiform appendage is thought to protect its members from colonization with pathogens [16,56]. Recent research also pointed towards the close contact between the appendix and lymphatic tissue, rendering the appendix an important secondary immune organ promoting growth of some types of beneficial gut bacteria [56].”
Diarrhea is the way the GI tract deals with perturbations to its equilibrium. Problem is sloughing off of its contents in this precipitous manner rids the colon of not just the bad, the troublemakers du jour, but the good bacteria as well. How does it replenish its beneficial gut microbiota post-diarrhea? The default and tacit consideration was that it would come in from the outside as it did originally – start over from scratch in other words.
Since the human microbiota remained under- or even unstudied until just recently, not much attention was paid to how it takes shape post-birth nor whether this community would or should start over from scratch following each diarrhetic episode over the course of a lifetime, a notion that on its face would seem antithetical from nature’s point of view – surely a lifelong association as essential as one’s gut microbiota couldn’t be left to the whims of chance?
In addition, that 2007 study (2) as well as others since (6, 7) also note that bacterial biofilms are more abundant in the appendix than anywhere else in the human colon. This further reinforces the idea of the healthy human appendix having an important role in actively seeding and shaping the gut microbiota composition.
The twinned appearance of Darwin’s idea of vestigiality and the industrialization-associated appendicitis epidemic helped embed the notion that the expendability of the human appendix is cost-free.
Darwin himself proposed that the appendix was vestigial. During his time, only the great apes and humans were known to have an appendix. Darwin suggested that a larger cecum and associated appendix were specialized for breaking down plant tissues such as leaves, a process now described as colonic/cecal fermentation, and that when human ancestors switched to a more easily digested fruit-based diet, the cecum shrank and the appendix became unnecessary, that it was an evolutionary remnant from a primate ancestor that ate leaves (8).
Any wonder then that in my schooldays, the appendix featured prominently among the list of vestigial organs that we dutifully memorized as structures deemed to have lost their ancestral function, Vestigiality – Wikipedia. We were given to understand that they were essentially useless remnants of the past, still hanging around who knows why even though the commonly used definitions of vestigiality are more nuanced (below from 9, emphasis mine).
“Vestigiality, in the biological sense, refers to the situation in which organs or organisms have lost all of their original function in a species, but nevertheless have been retained through evolution (they have not been de-selected).”
Wikipedia re-writes this definition as (emphasis mine),
“Vestigiality is the retention during the process of sexual reproduction of genetically determined structures or attributes that have lost some or all of their ancestral function in a given species.”
Note the terms ‘original’ and ‘ancestral’ in these definitions which should give pause and instill curiosity as to whether such structures might have since gone on to acquire new attributes and functions. Wouldn’t that better fit nature’s design, given its well-known proclivity for parsimony? Instead the presumably “useless” aspect of the appendix gained free rein in popular consciousness, helped along as appendectomies became routine over the course of the 20th century and remain even today the most common emergency surgical procedure in countries such as the US.
Inflamed appendix? Snip it out, suture and done – the appendix is clearly presumed an expendable organ now and this has been the case since at least the late 19th century when outbreaks of appendicitis started becoming widely prevalent in rapidly industrializing countries such as the US, something that only helped cement the notion of the vestigial nature of this organ, even though a careful accounting would have suggested that such outbreaks of the inflamed appendix pointed less to its apparent lack of utility per se and more to its usefulness as a harbinger of widespread digestive distress in response to too many unprecedented changes in living conditions that emerged in quick succession in the 19th and 20th centuries – chlorinated water supplies, indoor plumbing, flush toilets and sanitation, antibiotics, urban lifestyles that ever increasingly precluded contact with nature, to mention but a few of the important ones – too many rapid changes that have simply overwhelmed the adaptive capacity of our physiology.
This happenstance quirk of history – the coincidental appearance of Darwin’s vestigiality proposal and appendicitis outbreaks in rapidly industrializing countries – allowed the idea about the expendability of the appendix to get embedded into public consciousness so much so that (below from 1),
“Its major importance would appear to be financial support of the surgical profession.” Alfred Sherwood Romer and Thomas S. Parsons The Vertebrate Body (1986), p. 389.”
No surprise then that a 1990 study noted lifetime appendicitis risk of 8.6% for males and 6.7% for females in the US while lifetime risk of appendectomy was nearly twice as high at 12% for males and more than three times as high at 23% for females (10) – as clear a sign as any that the ‘snip, snip, out with the appendix’ formula has remained unchanged at least in the US since the days of William Osler – Wikipedia in the late 19th century when surgeons first started figuring out how to perform this operation safely (11). After all Osler himself noted how crucial the press of his day was in helping spread the mythical scourge of the so-called appendicitis epidemic (below from 11),
“In Osler’s time the press had extensively publicized appendicitis, extolling the marvelous wonders of surgery, something Osler commented on in the 1896 edition: “There is a well-marked appendicular hypochondriasis (italics mine). Through the pernicious influence of the daily press, appendicitis has become a sort of fad, and the physician has often to deal with patients who have a sort of fixed idea that they have the disease. The worst cases of this class which I have seen have been in members of our profession…”
The easily discarded appendix is thus perfectly emblematic of the throwaway culture we now find ourselves in.
Unfortunately, as we now grasp all too well, since Darwin’s time, a suite of inflammatory diseases (allergies, autoimmunities, cancers, inflammatory disorders such as IBS and IBD to name some prominent examples) have indeed become ever more commonplace in post-industrial societies and their link to the microbiota, specifically to its depletion within our bodies, remained unappreciated until fairly recently.
It took nearly a century to realize that most of these conveniences of present-day life that are so beguilingly addictive that they lend themselves to all too quick and unthinking adaptation by people the world over have also mediated “an epidemic of absence” to quote Moises Velasquez-Manoff; that unbeknownst to us, a large part of the microbiota that lived within our bodies generation after generation over evolutionary time started disappearing over the course of the 20th century, a process that’s only gathering pace as this way of living spreads to other rapidly industrializing countries, an idea embodied by the Hygiene hypothesis – Wikipedia.
In like fashion, it took nearly a century for epidemiologists to uncover data (12, 13) suggesting that these rapid-fire changes in living conditions that accompanied industrialization may also be the quite unnatural impetus (below from 14, emphasis mine) for the now more than century old appendicitis epidemics in countries such as the US and the UK that were industrializing pioneers.
“Barker noticed that epidemics of appendicitis followed the introduction of indoor plumbing into various communities. This observation was followed by epidemiologic studies showing that appendicitis is associated with developed but not with developing countries. Almost at the same time, another epidemiologist, Strachan[15], found that a hyper-active immune system is a consequence of the hygienic environment following the industrial revolution[15]. Strachan’s observations point toward the idea that appendicitis, like many other allergic, autoimmune, and inflammatory diseases, is a result of biome depletion, a consequence of industrialization.”
Any wonder that the appendix figures in public consciousness in terms of what goes wrong with it so often in industrialized countries – excruciating pain that drives a person to seek emergency services that ends up with an emergency appendectomy? Doctors in the post-Darwin era are all too familiar with an appendix that can get inflamed in a life-threatening manner even as knowledge of the healthy appendix remains truly vestigial (pun intended).
Coming full circle on the need to overhaul age-old ideas about the human appendix, more recent studies also suggest Darwin was mistaken about the basis for its vestigiality itself. Comparative analysis not only suggests no simple direct relationship between cecum and appendix in terms of presence or size (below from 3 and 1), in a series of studies (6, 15), Parker and his colleagues plotted the diets of 361 living mammals on a mammalian evolutionary tree and found 50 appendix-bearing species to be so widely dispersed as to suggest the appendix may have evolved independently as many as 32 to 38 times (16) – if true, the fact that nature saw fit to evolve the appendix so many times over suggests its function remains wide open.
Finally, in another quirk of fate that can only make one shake one’s head in exasperation, today the research mouse is perhaps the biggest obstacle that prevents an improved understanding of the human appendix. After all, mice are today the mainstay of biomedical research and yet they can yield no insight into the appendix since they entirely lack one, just one in an ever-increasing list of fundamental differences that refute the laughably simplistic notion that the mouse is in any way, shape or form an appropriate or reasonable surrogate for human physiology.
Bibliography
1. Vestigiality of the human appendix
2. Bollinger, R. Randal, et al. “Biofilms in the large bowel suggest an apparent function of the human vermiform appendix.” Journal of theoretical biology 249.4 (2007): 826-831. http://www.mbio.ncsu.edu/mjc/old/20072008/Trent_paper.pdf
3. Laurin, Michel, Mary Lou Everett, and William Parker. “The cecal appendix: one more immune component with a function disturbed by post‐industrial culture.” The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology 294.4 (2011): 567-579. https://onlinelibrary.wiley.com/doi/pdf/10.1002/ar.21357
4. Barlow, Andrew, et al. “The vermiform appendix: A review.” Clinical Anatomy 26.7 (2013): 833-842.
5. Tytgat, Hanne LP, et al. “Bowel biofilms: tipping points between a healthy and compromised gut?.” Trends in microbiology (2018). Bowel Biofilms: Tipping Points between a Healthy and Compromised Gut?
6. Smith, H. F., et al. “Comparative anatomy and phylogenetic distribution of the mammalian cecal appendix.” Journal of evolutionary biology 22.10 (2009): 1984-1999. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1420-9101.2009.01809.x
7. Im, Gene Y., et al. “The appendix may protect against Clostridium difficile recurrence.” Clinical gastroenterology and hepatology 9.12 (2011): 1072-1077.
8. Darwin, Charles. The descent of man and selection in relation to sex. Vol. 1. D. Appleton, 1896.
9. Grimson, William, and Mike Murphy. “An evolutionary perspective on engineering design.” (2009). https://arrow.dit.ie/cgi/viewcontent.cgi?article=1002&context=engineducbks
10. Addiss, David G., et al. “The epidemiology of appendicitis and appendectomy in the United States.” American journal of epidemiology 132.5 (1990): 910-925. https://pdfs.semanticscholar.org/0cfc/1ff3a15ff1a226918375489a0870614bbd98.pdf
12. Barker, D. J. P., and Julie Morris. “Acute appendicitis, bathrooms, and diet in Britain and Ireland.” Br Med J (Clin Res Ed) 296.6627 (1988): 953-955. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2545432/pdf/bmj00279-0009.pdf
13. Barker, D. J., et al. “Appendicitis epidemic following introduction of piped water to Anglesey.” Journal of Epidemiology & Community Health 42.2 (1988): 144-148. https://jech.bmj.com/content/jech/42/2/144.full.pdf
14. Sanders, Nathan L., et al. “Appendectomy and Clostridium difficile colitis: relationships revealed by clinical observations and immunology.” World Journal of Gastroenterology: WJG 19.34 (2013): 5607. Appendectomy and Clostridium difficile colitis: Relationships revealed by clinical observations and immunology
15. Smith, Heather F., et al. “Morphological evolution of the mammalian cecum and cecal appendix.” Comptes Rendus Palevol 16.1 (2017): 39-57. http://www.academia.edu/download/50751849/Smith_et_al._2017_CRP.pdf
16. Smith, Heather F., et al. “Multiple independent appearances of the cecal appendix in mammalian evolution and an investigation of related ecological and anatomical factors.” Comptes Rendus Palevol 12.6 (2013): 339-354. Multiple independent appearances of the cecal appendix in mammalian evolution and an investigation of related ecological and anatomical factors
https://www.quora.com/What-is-the-function-of-the-appendix-in-our-body-1/answer/Tirumalai-Kamala
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