The gelada (Theropithecus gelada) is one of the primate species without an appendix referenced in this research. ©Vallée des singes

Although the cecal appendix is no longer considered a vestige of evolution with no particular role, its exact function remains to be discovered and several hypotheses are currently being explored. A research team from Inserm, CNRS, the French National Museum of Natural History (MNHN), Université de Rennes, Sorbonne Université and the Eugène Marquis Center looked at how the presence of an appendix affects the onset and severity of infectious diarrhea in primates, an animal order that is particularly affected by these diseases. Its research shows that the primate species with an appendix are less affected by infectious diarrhea and that it is less severe than in those without an appendix. They are also better protected against these infections during the first part of their lives, a period that is more vulnerable to severe diarrhea and crucial for reproduction. These findings, published in Scientific Reports provide new evidence supporting the advantageous role of the appendix in evolution.

The cecal appendix (more commonly referred to as the “appendix”) is a small blind-ended tube located in the lower part of the cecum, the first part of the large intestine. It is found in some mammals and particularly in some primate species, including humans. While it has long been considered an unnecessary vestige of evolution, research over the past decade has challenged this paradigm with scientists now tending to view it as a potential evolutionary advantage, although its function remains poorly understood.

One hypothesis concerning the role of the appendix is based on its composition of microorganisms. Different from that of the rest of the gut microbiota, it could constitute a reservoir of healthy flora safeguarded from the fecal flow, likely to recolonize the gut after a gut infection and enable faster remission. And it just so happens that primates are an animal order particularly affected by infectious diarrhea. In humans, mortality related to these infections was identified in 2015 as being the second leading cause of mortality in children between 1 month and 5 years of age. More specifically, in patients who have had their appendix removed (appendectomy), there has been an increased risk of the occurrence and/or severity of certain forms of infectious diarrhea, although no direct link has been demonstrated at this time.

A research team led by Éric Ogier-Denis, Inserm research director at the Oncogenesis Stress Signaling unit Inserm/Université de Rennes/Eugène Marquis Center), and Michel Laurin, CNRS research director at the Center for Research on Paleontology – Paris (CNRS/MNHN/Sorbonne Université), had shown in previous research that the mammalian species with an appendix had longer longevity than those without one[1]. As a continuation of this research, the team looked at how the presence of a cecal appendix could affect the frequency and severity of diarrhea in primates and thus be a determining factor in the life span of each species.

To do this, the researchers examined the veterinary records of 1 251 primates of 45 different species – 13 with an appendix, 32 without – living in semi-liberty in “La Vallée des Singes” zoological park in Romagne, France. They listed the frequency and severity of the diarrhea episodes that occurred between 1998 and 2018 in these animals.

The gorilla (Gorilla gorilla gorilla) is one of the species of primates with an appendix referenced in this research. ©Vallée des singes

Half of the primates had experienced at least one episode of diarrhea during the 20-year follow-up period, with 13% of the episodes qualifying as “severe”.

In the primates with an appendix, the frequency of diarrhea episodes was very much lower (by around 85%) than in those without one. The cases of severe diarrhea were also much less frequent, particularly during the first quarter of life when the risk is highest (but then gradually decreases throughout life).

In addition, in the species with an appendix, the median age of onset of diarrhea, whether severe or not, was significantly higher.

“These findings support the hypothesis of a protective role of the cecal appendix against infectious diarrhea in primates, comments Jérémie Bardin, co-first author of the study. The observation of a particularly high protective effect in the first part of life, the period most vulnerable to severe diarrhea, but also the most optimal in terms of reproductive capacity, argues in favor of a selective advantage role in evolution”, adds Ogier-Denis.

The research should therefore be continued in order to gain deeper insights into the cecal appendix and a better understanding of the role of its specific flora. One of the next steps could be to compare the composition of the appendix microbiota between primate species in order to highlight possible similarities.

Finally, the last interesting observation in this study was that none of the primates with an appendix had been diagnosed with acute appendicitis over the 20-year period.

“Although this is more common in humans than in other primate species, if the protection associated with the presence of the appendix in humans is of the same level as that observed in primates, it would very much counterbalance the risk related to fatal appendicitis“, concludes Maxime Collard, co-first author of the study.

[1]See our August 3, 2021 press release: https://presse.inserm.fr/en/the-appendix-is-not-an-unnecessary-organ-but-is-in-fact-correlated-with-a-longer-lifespan/60347/

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