Diet rapidly and reproducibly alters the human gut microbiome

Abstract

Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut1,2,3,4,5, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals2, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses.

Origins of the Human Predatory Pattern: The Transition to Large-Animal Exploitation by Early Hominins

Abstract

The habitual consumption of large-animal resources (e.g., similar sized or larger than the consumer) separates human and nonhuman primate behavior. Flaked stone tool use, another important hominin behavior, is often portrayed as being functionally related to this by the necessity of a sharp edge for cutting animal tissue. However, most research on both issues emphasizes sites that postdate ca. 2.0 million years ago. This paper critically examines the theoretical significance of the earlier origins of these two behaviors, their proposed interrelationship, and the nature of the empirical record. We argue that concepts of meat-eating and tool use are too loosely defined: outside-bone nutrients (e.g., meat) and inside-bone nutrients (e.g., marrow and brains) have different macronutrient characteristics (protein vs. fat), mechanical requirements for access (cutting vs. percussion), search, handling and competitive costs, encounter rates, and net returns. Thus, they would have demanded distinct technological and behavioral solutions. We propose that the regular exploitation of large-animal resources—the “human predatory pattern”—began with an emphasis on percussion-based scavenging of inside-bone nutrients, independent of the emergence of flaked stone tool use. This leads to a series of empirical test implications that differ from previous “meat-eating” origins scenarios.

B12 is too large a molecule to be absorbed in the colon's membrane - it has evolved to be absorbed in the ileum, a segment at the end of the small intestine, and requires an intrinsic factor mediated system. Other apes either need to eat their own feces - coprophagy -  to absorb B12 or eat animal products (insects or small prey). Nutritional requirements for other apes are not well known but B12 deficiency is a well known problem in humans. 

The ileum is the major site of absorption of vitamin B12 analogues

Abstract

Non-cobalamin vitamin B12 analogues constitute a significant percentage of total corrinoids in human serum. The source and means of absorption of analogues and their significance are largely unknown. We studied the sites of production and absorption of B12 analogues by measuring serum vitamin B12 and analogues in 93 patients with various gastrointestinal diseases: pernicious anemia (PA), ileal resections, ileitis, Crohn's colitis, ulcerative colitis, and irritable bowel syndrome (IBS). Patients with PA had normal analogue levels that were unchanged or that rose during cessation of B12 administration. Patients with IBS, Crohn's colitis, ulcerative colitis, and total colectomies had B12 analogues in the normal range. Patients with diseased or resected ileums had low B12 and analogues. These data suggest that serum B12 analogues are absorbed in the ileum by a mechanism independent of intrinsic factor, and that colonic bacteria and endogenous metabolism of vitamin B12 do not contribute significantly to their level.

Vitamin B12 deficiency

Abstract

Vitamin B12 (cobalamin) deficiency is a common cause of macrocytic anemia and has been implicated in a spectrum of neuropsychiatric disorders. The role of B12 deficiency in hyperhomocysteinemia and the promotion of atherosclerosis is only now being explored. Diagnosis of vitamin B12 deficiency is typically based on measurement of serum vitamin B12 levels; however, about 50 percent of patients with subclinical disease have normal B12 levels. A more sensitive method of screening for vitamin B12 deficiency is measurement of serum methylmalonic acid and homocysteine levels, which are increased early in vitamin B12 deficiency. Use of the Schilling test for detection of pernicious anemia has been supplanted for the most part by serologic testing for parietal cell and intrinsic factor antibodies. Contrary to prevailing medical practice, studies show that supplementation with oral vitamin B12 is a safe and effective treatment for the B12 deficiency state. Even when intrinsic factor is not present to aid in the absorption of vitamin B12 (pernicious anemia) or in other diseases that affect the usual absorption sites in the terminal ileum, oral therapy remains effective.

Vitamin B12 synthesis by human small intestinal bacteria

Abstract

In man, physiological amounts of vitamin B12 (cyanocobalamin) are absorbed by the intrinsic factor mediated mechanism exclusively in the ileum. Human faeces contain appreciable quantities of vitamin B12 or vitamin B12-like material presumably produced by bacteria in the colon, but this is unavailable to the non-coprophagic individual. However, the human small intestine also often harbours a considerable microflora and this is even more extensive in apparently healthy southern Indian subjects. We now show that at least two groups of organisms in the small bowel, Pseudomonas and Klebsiella sp., may synthesise significant amounts of the vitamin.

https://pubmed.ncbi.nlm.nih.gov/16828044/

Abstract

The circumstances of human brain evolution are of central importance to accounting for human origins, yet are still poorly understood. Human evolution is usually portrayed as having occurred in a hot, dry climate in East Africa where the earliest human ancestors became bipedal and evolved tool-making skills and language while struggling to survive in a wooded or savannah environment. At least three points need to be recognised when constructing concepts of human brain evolution : (1) The human brain cannot develop normally without a reliable supply of several nutrients, notably docosahexaenoic acid, iodine and iron. (2) At term, the human fetus has about 13 % of body weight as fat, a key form of energy insurance supporting brain development that is not found in other primates. (3) The genome of humans and chimpanzees is <1 % different, so if they both evolved in essentially the same habitat, how did the human brain become so much larger, and how was its present-day nutritional vulnerability circumvented during 5-6 million years of hominid evolution ? The abundant presence of fish bones and shellfish remains in many African hominid fossil sites dating to 2 million years ago implies human ancestors commonly inhabited the shores, but this point is usually overlooked in conceptualizing how the human brain evolved. Shellfish, fish and shore-based animals and plants are the richest dietary sources of the key nutrients needed by the brain. Whether on the shores of lakes, marshes, rivers or the sea, the consumption of most shore-based foods requires no specialized skills or tools. The presence of key brain nutrients and a rich energy supply in shore-based foods would have provided the essential metabolic and nutritional support needed to gradually expand the hominid brain. Abundant availability of these foods also provided the time needed to develop and refine proto-human attributes that subsequently formed the basis of language, culture, tool making and hunting. The presence of body fat in human babies appears to be the product of a long period of sedentary, shore-based existence by the line of hominids destined to become humans, and became the unique solution to insuring a back-up fuel supply for the expanding hominid brain. Hence, survival of the fattest (babies) was the key to human brain evolution.

https://pubmed.ncbi.nlm.nih.gov/24928072/

Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution

Stephen C Cunnane 1, Michael A Crawford 2

Affiliations expand

• PMID: 24928072

• DOI: 10.1016/j.jhevol.2014.05.001

Abstract

The human brain confronts two major challenges during its development: (i) meeting a very high energy requirement, and (ii) reliably accessing an adequate dietary source of specific brain selective nutrients needed for its structure and function. Implicitly, these energetic and nutritional constraints to normal brain development today would also have been constraints on human brain evolution. The energetic constraint was solved in large measure by the evolution in hominins of a unique and significant layer of body fat on the fetus starting during the third trimester of gestation. By providing fatty acids for ketone production that are needed as brain fuel, this fat layer supports the brain's high energy needs well into childhood. This fat layer also contains an important reserve of the brain selective omega-3 fatty acid, docosahexaenoic acid (DHA), not available in other primates. Foremost amongst the brain selective minerals are iodine and iron, with zinc, copper and selenium also being important. A shore-based diet, i.e., fish, molluscs, crustaceans, frogs, bird's eggs and aquatic plants, provides the richest known dietary sources of brain selective nutrients. Regular access to these foods by the early hominin lineage that evolved into humans would therefore have helped free the nutritional constraint on primate brain development and function. Inadequate dietary supply of brain selective nutrients still has a deleterious impact on human brain development on a global scale today, demonstrating the brain's ongoing vulnerability. The core of the shore-based paradigm of human brain evolution proposes that sustained access by certain groups of early Homo to freshwater and marine food resources would have helped surmount both the nutritional as well as the energetic constraints on mammalian brain development.

• DOI: 10.1002/ajhb.20673

Abstract

Carlson and Kingston ([2007]: Am J Hum Biol 19:132-141) propose that preformed dietary docosahexaenoic acid (an omega-3 fatty acid in fish) did not have a significant role in hominin encephalization. Their position hinges on claiming that humans are able to make sufficient docosahexaenoic acid from the plant-based "parent" omega-3 fatty acid-alpha-linolenic acid. They also suggest that hominin fish consumption occurred too late to have materially influenced encephalization. The authors quantify here a summary of the published data showing that humans cannot make sufficient docosahexaenoic acid to maintain normal infant brain development. The authors also provide evidence that the fossil record shows that some of the earliest hominins were regularly consuming fish. Hence, we reject Carlson and Kingston's position and reiterate support for the concept that access to shore-based diets containing docosahexaenoic acid was necessary for hominin encephalization beyond the level seen in the great apes.

Starvation and survival.

G. F. Cahill, Jr and O. E. Owen 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2441175/

Starvation in man

https://pubmed.ncbi.nlm.nih.gov/4915800/

Long-term effects of a ketogenic diet in obese patients -https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716748/

Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.

Comparative Analyses of Chromatin Landscape in White Adipose Tissue Suggest Humans May Have Less Beigeing Potential than Other Primates

Abstract

Humans carry a much larger percentage of body fat than other primates. Despite the central role of adipose tissue in metabolism, little is known about the evolution of white adipose tissue in primates. Phenotypic divergence is often caused by genetic divergence in cis-regulatory regions. We examined the cis-regulatory landscape of fat during human origins by performing comparative analyses of chromatin accessibility in human and chimpanzee adipose tissue using rhesus macaque as an outgroup. We find that many regions that have decreased accessibility in humans are enriched for promoter and enhancer sequences, are depleted for signatures of negative selection, are located near genes involved with lipid metabolism, and contain a short sequence motif involved in the beigeing of fat, the process in which lipid-storing white adipocytes are transdifferentiated into thermogenic beige adipocytes. The collective closing of many putative regulatory regions associated with beigeing of fat suggests a mechanism that increases body fat in humans.

Keywords: adipose; chromatin accessibility; comparative genomics; primates.

Evolutionary change in physiological phenotypes along the human lineage 

Several traits contain an adaptive regime shift on the Homo branch at high frequencies: monocytes (60.3%), amylase (52.1%), lipase (48.8%) and haematocrit (48.2%). For amylase and lipase, the Homo branch contains an optimum change in a greater proportion of models than any other branch in the primate tree; for monocytes, haematocrit, neutrophilic bands, blood urea nitrogen, phosphorus, carbon dioxide and MCHC, the Homo branch is in the top five branches.

Focusing on the traits supported in both analyses, we find that the following five traits reached our criteria for undergoing substantial evolution along the human lineage: amylase, haematocrit, phosphorus, monocytes and neutrophilic bands. Some additional traits were supported as outliers in one analysis, but not the other, including MCHC, creatine phosphokinase, alkaline phosphatase and lipase. More generally, we found a striking pattern that humans have more traits identified as outliers in the phylogenetic prediction model than other primates (where twelve species were identified as having no exceptional traits). This pattern suggests that broad physiological changes are more common in recent human evolution than for any other primate analysed. Alternatively, the large number of outlier traits for humans may be attributable to obtaining our human data from a different source than the other primates, and may reflect effects of captivity on physiology in non-human primates.

https://pubmed.ncbi.nlm.nih.gov/29321682/

Abstract

During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease.

https://www.frontiersin.org/articles/10.3389/fevo.2020.00025/full

The Intestines

At some point in the last six million years, in addition to the potential changes in stomach acidity, the guts of our ancestors changed in other ways. The large intestine became shorter relative to the small intestine, while total intestine length also declined relative to body size. That this shift and shortening happened is suggested based on comparisons between the guts of chimpanzees, bonobos, and humans as well as the relatively smaller rib cage (and hence space available for the intestines) in the genus Homo compared to earlier hominin species (Aiello and Wheeler, 1995). However, it is worth noting that even within humans that the length of the large intestine varies even among individuals with similar genetic backgrounds. In one study of one hundred individuals, the shortest small intestine observed in any individual was half the length of the longest small intestine. Similarly, the ratio of small intestine to large intestine varied from 2.6 to 4.5. Given that gut morphology differs within populations of modern humans, it is possible (indeed likely) that variation among modern human populations is even greater (Underhill, 1955). To date no studies have considered such variation. The mean ratio of the small to large intestine length for chimpanzees is 1.0 (such that the chimpanzee large intestine is equal in length, on average) to the small intestine (Chivers and Hladik, 1984). But undoubtedly this value varies among chimpanzees as well, such that it is not inconceivable that some human populations and some chimpanzee populations actually have far more similar gut morphologies than tends to be assumed.

The shortening in the relative size of the human large intestine, whatever its consistency and magnitude, raises two questions: why the shortening occurred and what its consequences might have been for digestive physiology and the gut microbiome. In general there seems to be an emerging consensus that the use of tools, especially stick and stone kitchen tools of various sorts, to obtain and process foods made our ancestors less reliant on the fermentation that occurs in the large intestine. Cooking is likely one of the tools that our ancestors had at their disposal. Recent work has shown that cooking plant food reshapes the gut microbial environment (Carmody et al., 2019), suggesting that the use of fire, despite mixed evidence for its impact on starch digestibility (Schnorr et al., 2016), may have made nutrients in some types of food more available and also eased the chewing necessary to break down food (Wrangham, 2009). Fire may have also made it possible to smoke hives and therefore easier to harvest large quantities of honey with its easy to digest calories (which do not necessarily require gut microbes; Marlowe et al., 2014). In addition, fishing techniques and tools might have made fish and shellfish protein available which, even raw, is very easy to digest. Pounding tools, such as those employed by chimpanzees, would have made roots and tubers also easier to digest (Crittenden, 2016). Similar tools are used by many small-scale societies around the world, including contemporary subsistence foragers (Benito-Calvo et al., 2018) as well as by chimpanzees (and hence likely our LCA; Figure 2). All of this is to say that as our ancestors invented more kitchen implements they would have been able to pre-digest and pre-process some of their foods, allowing them to rely less on microbes in their guts to break down recalcitrant components of their diets, such as cellulose. They could get by with smaller guts and invest their bodily energy elsewhere, for example in big brains (an idea called the expensive tissue hypothesis; Aiello and Wheeler, 1995).

The shorter average large intestine length of species of Homo compared to those of their ancestors would have had at least two potential consequences for microbiomes. The shorter larger intestine would have sustained a smaller biomass of microbes relative to their body mass (simply because of the reduction in volume). In addition, the retention time of foods in the gut may have been reduced (Ragir et al., 2000). Some features of microbiomes, however, seem likely to have been similar between hominins and our LCA with chimpanzees despite changes in gross intestinal morphology. For example, the taxonomic classes of bacteria found in the guts of both chimpanzees and humans (from urban and rural settings) tend to overlap. What is more, the same families and genera of bacteria tend to occur in similar proportions (Moeller et al., 2012). This overlap is hypothesized to pre-date the human-chimpanzee split (and hence to be characteristic of our LCA). Furthermore, humans in small-scale, non-industrialized populations host a handful of microbial taxa that appear to be genetically equivalent to those in great apes at the level of operational taxanomic units (OTUs) or strains (Amato et al., 2019b). The same humans also share a range of bacterial metabolic pathways with other extant apes, including those involved in vitamin and amino acid synthesis. These results suggest that despite the reduction in length of the human intestines, enough physiological similarities remain between humans and apes such that the composition and function of their microbiomes is similar.

Nevertheless, despite these similarities, it is important to point out that the gut microbiomes of modern humans diverge in important ways from those of extant apes. These differences do not, however, appear to relate to gross morphological features of the gut but instead to diet. The gut microbiomes of humans, while similar to those of modern chimpanzees, appear to be even more similar to those of cercopithecine monkeys, such as baboons (genus Papio; Amato et al., 2019b; Figure 3). Differences in gut microbiome composition are greater between humans and apes (PERMANOVA F1,55 = 14.4, r2 = 0.21, p < 0.01) than between humans and cercopithecines (PERMANOVA F1,57 = 10.0, r2 = 0.15, p < 0.01). Differences in gut microbiome functional potential are similar between humans and apes (PERMANOVA F1,35 = 5.4, r2 = 0.16, p < 0.01) and humans and cercopithecines (PERMANOVA F1,35 = 7.4, r2 = 0.18, p < 0.01). While humans are genetically far more similar to chimpanzees than to baboons, baboons are more similar in diet (and habitat use) to ancestral Homo species than are chimpanzees. Baboons eat diets that are highly omnivorous and relatively high in starch content. Since the gut microbiome plays an important role in processing host dietary compounds, particularly resistant carbohydrates (and in some cases, specifically fibrous plant foods, see Schnorr et al., 2014) it is likely that the same microbial lineages and metabolic pathways nutritionally benefited both our hominin ancestors and extant cercopithecines. Given that the human shift toward habitats and diets like those of modern baboons are often linked to tool use, cooking, and ultimately, reductions in human intestinal length, it seems reasonable to suggest that this suite of changes altered the human gut microbiome. The result appears to be a “characteristic” human microbiome composed of both “ape” and “cercopithecine” traits.

It has long been known that humans have a very acidic stomach but some will be surprised to learn just how acidic it is - as acidic as other carnivores and scavengers.

The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome - DeAnna E. Beasley , Amanda M. Koltz, Joanna E. Lambert, Noah Fierer, Rob R. Dunn Published: July 29, 2015

Gastric acidity is likely a key factor shaping the diversity and composition of microbial communities found in the vertebrate gut. The study conducted a systematic review to test the hypothesis that a key role of the vertebrate stomach is to maintain the gut microbial community by filtering out novel microbial taxa before they pass into the intestines. The study proposes that species feeding either on carrion or on organisms that are close phylogenetic relatives should require the most restrictive filter (measured as high stomach acidity) as protection from foreign microbes. Conversely, species feeding on a lower trophic level or on food that is distantly related to them (e.g. herbivores) should require the least restrictive filter, as the risk of pathogen exposure is lower. Comparisons of stomach acidity across trophic groups in mammal and bird taxa show that scavengers and carnivores have significantly higher stomach acidities compared to herbivores or carnivores feeding on phylogenetically distant prey such as insects or fish. In addition, the study found when stomach acidity varies within species either naturally (with age) or in treatments such as bariatric surgery, the effects on gut bacterial pathogens and communities are in line with our hypothesis that the stomach acts as an ecological filter. Together these results highlight the importance of including measurements of gastric pH when investigating gut microbial dynamics within and across species.

Because maintaining an acidic pH environment is costly, acidic stomachs should be present primarily in those cases where it is adaptive (or where it was adaptive in a recent ancestor). The cost of stomach acidity is twofold. The host must invest significant energy for both acid production and protecting the stomach from acid-related damage [17]. In addition, the acidity of the stomach may preclude, or at least make more difficult, chance acquisition of beneficial microbes. At the opposite extreme are those specialized herbivores in which stomach morphology is derived to include an alkaline chamber (forestomach or pre-saccus) that house microbes critical for fermenting a plant diet [18–22]. In these animals, an acidic stomach is not only of limited value (because the risk of foodborne pathogens in plant material is low), it may also remove those microbes that aid in the breakdown of plant material. Broadly then, we expect stomach acidity to mirror animal diets in ways that reflect pathogen risk. We expect that animals feeding on carrion will have the most restrictive filter, i.e. higher stomach acidity. Carrion has the potential to sustain high pathogen loads because the dead host’s body has stopped suppressing bacterial growth. Similarly, carnivores and omnivores would be expected to have higher stomach acidities than herbivores with specialized fermenting forestomachs because pathogens found in prey are more likely to be capable of infecting the predator than plant-associated microbes [23]. However, we would also expect the acidity of the carnivore and omnivore stomach to also depend on the phylogenetic distance between predator and prey. Pathogens are far more likely to be able to infect related hosts [23], such that a bird consuming an insect should face a lower risk of a foodborne infection than a bird consuming a bird. To test these hypotheses, we compare the stomach acidity of mammals and birds across a diversity of diet types.

In light of the results, we then revisit the ecology of the human stomach, its role as a filter and the likely consequences of this role within the context of modern human lifestyles and medical interventions. If stomach acidity acts as a strong filter, we expect that when acidity levels are reduced, the influence of diet-associated microbes on the intestinal microbiota will be greater. It is known that stomach acidity decreases with age and as a consequence of some medical treatments [24–26]. Thus, as acidity decreases and the filter’s effectiveness is reduced, we would expect to see increases in both the diversity of microbial lineages and pathogen loads in the gut. We also expect that animals, such as humans, with very acidic filters should be particularly predisposed to negative consequences of the loss of gut symbionts because the odds of chance re-colonization are low.

Based on the available data, our analysis illustrates a general pattern in which species feeding on carrion and animals have significantly higher stomach acidities compared to species feeding on insects, leaves, or fruit. On their own, the patterns are in line with the hypothesis that one role of the stomach is to inhibit microbial entry into the gut, though these patterns might also be explained by other phenomena. Carnivores need more acidic stomachs in order to lyse the protein in their meat-based diets. For example, secretion of pepsinogen and its activation to pepsis in the stomach is modulated by an acid pH (2–4) [30]. Also, activity of proteases in a simple acid stomach depends on an acidic environment (pH 2–4) [31]. However, while this might explain differences between predators and herbivores, it does not account for the very high acidity in the stomachs of scavengers, especially considering that the meat consumed by scavengers is not likely to be much harder to digest than that of predators. We suggest that these scavengers rely on the high acidity of their stomach to prevent colonization of their guts by foodborne pathogens [32]. Omnivores and piscivores were most variable in stomach acidities, which is to be expected as both diets differ greatly from species to species. Insectivores may use diverse means to digest insect chitin, with acidity playing a role in some but not other cases.

Human evolution and stomach pH

It is interesting to note that humans, uniquely among the primates so far considered, appear to have stomach pH values more akin to those of carrion feeders than to those of most carnivores and omnivores. In the absence of good data on the pH of other hominoids, it is difficult to predict when such an acidic environment evolved. Baboons (Papio spp) have been argued to exhibit the most human–like of feeding and foraging strategies in terms of eclectic omnivory, but their stomachs–while considered generally acidic (pH = 3.7)–do not exhibit the extremely low pH seen in modern humans (pH = 1.5) [38]. One explanation for such acidity may be that carrion feeding was more important in humans (and more generally hominin) evolution than currently considered to be the case (although see [39]). Alternatively, in light of the number of fecal-oral pathogens that infect and kill humans, selection may have favored high stomach acidity, independent of diet, because of its role in pathogen prevention.

The special risk to juvenile and elderly humans

If, in carnivores and carrion-feeders, the stomach’s role is to act as an ecological filter then we would also expect to see higher microbial diversity and pathogen loads in cases where stomach pH is higher. We see evidence of this in age-related changes in the stomach. Baseline stomach lumen pH in humans is approximately 1.5 (Table 1). However, premature infants have less acidic stomachs (pH > 4) and are susceptibility to enteric infections [40]. Similarly, the elderly show relatively low stomach acidity ([41], pH 6.6 in 80% of study participants) and are prone to bacterial infections in the stomach and gut [42]. It is important to note that these differences may be related to differences in the strength of the immune system however we argue here that the stomach needs more consideration when studying these patterns.

​

Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals (ePDF)

The gastric acid and fluid secretion rates, gastric volume, and pH values for humans, beagle dogs, pigs, and Rhesus monkeys are given in Table 4. In dogs, the gastric acid secretion rate at the basal state is low. Therefore, the stomach pH of the dog can be as high as its duodenal contents in the unstimulated state.I9 Following stimulation (i.e., food, histamine), gastric acid secretion rates in dogs exceed those of the human and pig (Table 4). In humans, the stomach pH after food is initially higher due to the strong buffering action of food. However, the pH returns to a low value after about one hour (Table 4).

The Internal, External and Extended Microbiomes of Hominins

We hypothesize that the stomachs of chimpanzees are likely somewhat acidic, but less so than those of humans. We also propose that the extreme acidity of human stomachs evolved after our split with the LCA with chimpanzees. If this is the case, it raises the question of what factors favored such acidity. One possible explanation is scavenging prey items abandoned by carnivores and/or the consumption of prey items too big to eat all at once. Chimpanzees in all habitats where they are found in the wild eat meat (Moore et al., 2017), as do bonobos (Wakefield et al., 2019), leading many to think that the LCA did as well. Sometimes the meat chimpanzees consumed Is scavenged (Nakamura et al., 2019) but relatively rarely (compared to other foods in their diet). More often the meat is eaten fresh from kills, though chimpanzees exhibit great variability between communities in success, technique, and seasonality of hunting behavior (Moore et al., 2017; Figure 2). Given that several chimpanzee communities target mammalian prey, and may do so using tools (Pruetz and Bertolani, 2007; Nakamura and Itoh, 2008), it is likely that species of Australopithecus, Homo habilis or Homo erectus also targeted and consumed meat, but also that how much meat they consumed, how fresh the meat was and how much was excess varied. While there is broad consensus among paleoanthropologists and evolutionary anthropologists that meat-eating played a role in the evolution of Homo, the relative importance of hunted and scavenged meat is contested. At least some of the meat that early hominins were eating was carrion (Pante et al., 2018). Some bones, for example, from the time during which H. erectus was extant, show evidence both of cut marks by stone tools and, in a layer beneath the cuts from those tools, tooth marks from hyenas (Blumenschine, 1995). The obvious inference is that such bones were scavenged by our ancestors after being killed by another mammal (maybe hyena, maybe something else). Any hominins that scavenged for prey before the advent of fire may have avoided food borne pathogens if their stomachs were acidic. As a result, it is possible that the acidity of the hominin stomach may have played a role in human foraging behavior and diet. That said, we note that the question of how much hominins scavenged, and how central it was to social evolution, is the subject of intense debate (Dominguez-Rodrigo and Pickering, 2017). An alternate (but not mutually exclusive) hypothesis is that acidic stomachs became advantageous once our ancestors began to hunt large prey. This might be expected if the meat from such a prey items was often more than could be eaten in a sitting such that meat was eaten later (after it had begun to rot) even though it had not been scavenged.