The large microbiome

"All disease begins in the gut." - Hippocrates

I'd like to introduce you to my friend John. John began his career working at organizations that generously provided their employees with large healthy meals (breakfast, lunch, and dinner). Eventually he took a new position where meals were not provided. As he wasn't in the habit of packing a lunch, this change of position subsequently led to a change in his dietary habits and an overall reduction in food consumed during the day. Eventually he found that he was experiencing occasional abdominal discomfort. But it wasn't a grumbling stomach, rather it was an aching gut. Because it wasn't his stomach that was telling him to eat, he didn't immediately trace the cause of the problem to his eating habits, after all he was getting enough food right? Instead he suspected something more sinister (appendicitis, cancer?). The wide range of advice he encountered, both online and offline, didn't help narrow down the issue, and instead only exacerbated his hypochondriac tendencies. Eventually he came across some information about gut dysbiosis, the importance of prebiotic foods, and the many "downstream" effects that can result from deviations from healthy eating patterns. Now he knows what his gut was trying to tell him. 

The commonly used expression "empty calories", which suggests that it's possible to consume more than enough energy without the food sufficiently nourishing one's body, has many possible implications. Now we know that empty calories can also mean insufficient nourishment of the "large microbiome", which is perhaps a more appropriate name for the colon than the less informative sounding "large intestine". Sam Possemiers and coauthors wrote in a 2011 paper "For many years, it was believed that the main function of the large intestine was the resorption of water and salt and the facilitated disposal of waste materials... Nowadays it is clear that the complex microbial ecosystem in our intestines should be considered as a separate organ within the body, with a metabolic capacity which exceeds the liver by a factor of one hundred." I'll use the neologism "large microbiome" from here on. 

The obvious structural differences between the small intestine and large microbiome should make it apparent that there's a significant change occurring to the chyme (partially digested food) where it enters the caecum. (Over 99% of the bacteria in the gut are anaerobes, but in the caecum, aerobic bacteria reach high densities.) The small intestine does not have a large number of bacteria most of the time, and so when the chyme mixes with the microorganisms present there it undergoes a dramatic compositional change. Comparative anatomy shows these structures are mirrored across many different species, particularly those whose diets are composed of significant amounts of plant material. 

There's a synergy, a symbiosis, between the organ, the microbes, and the chyme. And it's healthy functioning begins with a concept that was first introduced in 1995 called "prebiotics". These are typically nondigestible fiber compounds that pass undigested through the upper part of the gastrointestinal tract and stimulate the growth or activity of beneficial microorganisms such as bacteria and fungi by acting as substrates for them. Fermentation is the main mechanism of action by which prebiotics are used. When the partially digested chyme containing prebiotics enters the large microbiome, the bacteria get to work and the organ is able to maintain healthy functioning. 

Preliminary research into prebiotics has demonstrated potential effects on calcium and other mineral absorption, immune system effectiveness, bowel acidity, reduction of colorectal cancer risk, inflammatory bowel disease (Crohn's disease or ulcerative colitis), hypertension and defecation frequency. These and other beneficial properties may be due to the increased production of short-chain fatty acids (SCFA) as nourishment for colonic walls, and mitigation of ulcerative colitis symptoms. Recent data have shown that the SCFA acetate, propionate, and butyrate [one of the most beneficial SCFAs and the primary fuel feeding the intestinal epithelium] function in the suppression of inflammation and cancer. In other words, the mechanistic explanation for the beneficial effects of dietary fiber may be largely attributed to fermentation by the microbiota: we feed our microbiome with fiber, and they turn around and feed us right back. When we don't eat enough whole plant foods we are in effect "starving our microbial self" (2014 paper title by Erica and Justin Sonnenburg). The relationship between modern Western lifestyles and the human microbiome is both damaged and causing damage. We should shift attention away from the plant/animal distinction (which dominates most discourse on diet fads) and toward the lifestyle-microbiome dynamic. This suggests some counterintuitive possibilities. Could it be that Western diets that include more meat are healthier because they complement the depleted Western microbiome composition better than plant based diets, which would require the more diverse microbiome more common in the Global South? Is a more diverse microbiome necessary for proper digestion and metabolic function? The Sonnenburgs wrote "the modern microbiota deviates substantially from ancestral states". What consequences might this have for human health?

One of the downstream effects of maintaining a healthy large microbiome is large, healthy bowel movements. The same paper by the Sonnenburgs notes "Denis Burkitt reported that rural Africans passed stool that was up to five times greater by mass, had intestinal transit times that were more than twice as fast, and ate three to seven times more dietary fiber (60 - 140g versus 20g) than their Western counterparts". The bigger our bowel movements, the healthier we may be. For every gram of fiber we eat, we can increase our stool by nearly two grams, due to the fiber fermentation process in our colon. By weight, the bulk of our stool is pure bacteria, trillions and trillions of bacteria. Fiber is what our good gut bacteria thrive on, their fuel source. When we eat whole plant foods, like fruits, vegetables, beans, and whole grains, we are telling our gut flora to be fruitful and multiply. The risk of low stool weight includes colon cancer, diverticular disease, appendicitis, anal diseases, etc. When stool weight gets down to around half a pound, colon cancer rates increase, at a quarter pound the incidence quadruples. The link between stool size and colon cancer is "transit time", the number of hours it takes for food to go from mouth to anus: the larger the stool the quicker the transit time and easier it is for our intestines to move things along. 

Most people may not realize you can have daily bowel movements and still be effectively constipated. So a diet high in fiber has many benefits. Not only can it prevent heartburn, GERD, and lower your risk of developing colorectal cancer by lowering fecal pH, but with enough fiber, one should be able to sit in any position and have a comfortable bowel movement. Colorectal cancer is extremely rare in native African populations (less than one per 100,000 compared with 65 per 100,000 for African Americans). Eating just five times more fiber with a prebiotic diet can result in about a 50 times less incidence of colon cancer, the third most common cause of cancer death in the world! This should probably be understood not as increasing overall quantity, but adjusting relative proportions of the same quantity. Given that food resources are highly variable, and eating opportunities are often unpredictable, creating a food schedule can be very difficult. However simple intermittent fasting combined with a diverse diet can result in a large and complete bowel movement every other day on average (without significantly altering exercise levels, fiber content, or other dietary supplements). Why fasting improves bowel function isn't completely clear. However it may affect the composition of the microbiome and improve intestinal health.

The standard American diet of highly processed food leaves nothing left for our gut flora; it's all absorbed in the small intestine before it makes it down to the colon. As another paper, "The Role of Short-Chain Fatty Acids in Health and Disease" notes, "The biggest issue presented by a Western diet typically high in fat and digestible saccharides is that nutrients are mostly absorbed in the duodenum, leaving very few substrates for the colonic bacteria. [This means a loss in microbial metabolites and the microbes themselves.] Consequently this results in dysbiosis, the impairment of microbiota composition [bad bacteria can take over] and increased susceptibility to inflammatory diseases such as inflammatory bowel diseases (IBDs) or colon cancer", metabolic syndrome, type 2 diabetes, and cardiovascular disease. It's difficult to appreciate all the possible downstream effects. In their paper "Do microbiotas warm their hosts?", the authors write "We estimate that microbial metabolism in the human gut, for example, produces 61 kcal/h, which corresponds to approximately 70% of the total heat production of an average person at rest." But would an altered large microbiome function the same? 

The human gut microbiota is mostly composed by two dominant bacterial phyla, Firmicutes and Bacteroidetes that together represent more than 90% of the total community. The relative abundance of these phyla is highly variable between subjects from the same population, which is probably due to many lifestyle-associated factors, which include diet and physical activity, but also food additives, contaminants, and antibiotic consumption, among others that influence the composition of the microbiota in the gastrointestinal tract. Firmicutes make short chain fatty acids, which help to prevent toxins and inflammation. Inflammation decreases serotonin and dopamine levels, which is what we see in anxiety and depression. The ratio is influenced by factors like (1) diet composition and (2) physical activity levels. Activity levels influence intestinal motility (peristalsis) and the transit time of the chyme through the different segments of the gastrointestinal tract. And all this, in turn, affects the composition of the microbiota. So you can see how these synergistic, "chicken and egg" sort of feedback processes, all go on within a single human holobiont, and can make it hard to distinguish which is a cause and which is an effect. Behavior influences microbiota which influences serotonin which influences... behavior. The biomechanics of gut health is critical. As Robyn Chutkan noted, "If you’re not moving, neither are your bowels." That can mean bloating and gas pressure. Relieving that pressure with increased fluid intake and mobility is best, not by merely increasing abdominal pressure to try to "squeeze" out the gas. Observing that runners have better bowel movements, she added "Get sweaty as often as you can, at least three times a week." So not only is eating greens every day going to help, but so does vigorous movement. Running for bowel health isn't a very common reason, as most people run or jog to improve cardio-pulmonary health, but it makes sense. Recall that James Lovelock, who died at 103, would frequently take long walks at his "signature breakneck speed". Whether that was a conscious decision on his part to maintain a healthy large intestine or not, it is even more essential today given our increasingly sedentary lifestyles. It's so critical, that for some people this is the missing variable. Increasing 'hours spent moving' may do more to improve gut health than anything else. Office workers have even resorted to using "standing desks" and other hacks to reduce time spent sitting. But since running can result in joint damage, vigorous walking can be just as good. The point is simply regular and frequent movement, which is in part the reason for "radio calisthenics". (Perhaps there will come a day when OSHA measures these quality of life indicators such that every job must include X time/distance walking.) The biomechanics of waste elimination suggests that a squatting position promotes a more complete evacuation of bowels. Having discussed the mechanics, let's return again to the psychological aspects of gut health. Numerous studies indicate gastrointestinal (GI) problems, including abdominal pain and chronic constipation, are unusually common among people with autism spectrum disorder (ASD). I find this interesting in light of the rising prevalence of autistic features in contemporary Western culture, something which Iain McGilchrist finds particularly significant. How closely does this rise parallel the rise in GI problems?

The disappearance of beneficial commensals could be addressed by the administration of specific probiotics such as Lactobacillus rhamnosus GG, L. reuteri DSM 17938, L. plantarum DSM 9843, and Bifidobacterium lactis Bb-12. Lactobacillus rhamnosus and L. reuteri are often added to yogurts, cheeses, milk, and other dairy products. Lactobacillus plantarum and Bifidobacterium lactis Bb-12 are present in fermented saurkraut and dairy products. Most people can easily make cabbage saurkraut at home, and buy dairy foods with active cultures (yogurt, cheeses), in addition to eating a plant based diet.

Food security and physical activity are among the top concerns of public health advocates, along with access to basic services. Many people do not have a healthy diet that includes cooked whole grains, vegetables, herbs and spices (and raw fruits). Instead they are eating overly processed foods with high amounts of simple sugars, trans fatty acids, emulsifiers, and low amounts of complex phytochemicals and insoluble fiber. This has consequences for the health of the human microbiome, and the digestive and metabolic health of the holobiont. Much of what is sold as food, and that we store in our pantries and refrigerators, should not be called "food", but rather hyperpalatable "pseudofood", per David Kessler (The End of Overeating). These products are often more readily available, heavily advertised, nonperishable, involve very little preparation to make, and provide a quick hit of dopamine when they hit the tongue. In short, we've made eating pseudofood as frictionless as possible, and as a result (and in combination with other disruptive factors) Americans suffer from some of the highest rates of obesity, diabetes, cancer, and cardiovascular disease. How do we return to healthier food choices and consumption habits?

One could plan for a “high fiber, high exercise, sleep hygiene” plan. The sleep hygiene '3,2,1 formula' means no food three hours, no drink two hours, and no computer use one hour before bed. That promotes the intermittent fasting time allowing the gut to periodically rest. High exercise means incorporating Dr. Paul Cotter's research on the connection between microbial diversity and exercise. And high fiber means incorporating the Sonnenburg's research. In The Good Gut they write "The tubers that the Hadza eat are so fibrous that after a period of chewing diners spit out a cud of the toughest fibers... they consume between 100 to 150 grams of fiber per day." (17) They also write "Perhaps the lack of dirt in the diet of people living in the hygienic industrialized world is problematic. There is some evidence that the consumption of soil bacteria can ameliorate symptoms associated with IBS." (106) They note that Dr. Denis Burkett said "If you pass small stools, you have to have large hospitals." (119) Relatedly, foods with a high glycemic index should be avoided. And "Once you reach an optimal level of fiber, it is important to continue to maintain homeostasis." (223) Decreased fiber consumption and less exercise can, over time, tilt the immune system toward the chronic pro-inflammatory side that feeds ‘inflammaging’. (194) There may be a sort of circadian optimization in play here, where several pairs of opposites (syzygies) are brought together physically and/or psychologically for maximum benefit: Processed (cooked or fermented)/raw, fast/feast, fiber/fat, exercise/rest, relax/contract (anismus), flow/stasis, acid (vinegar)/base... Hot cooked food improves digestion while cool nights improve sleep. High fiber foods improve stool bulk and intestinal transit while low fiber fats provide high energy. Physical exertion and activity during the day contrasts with still, quiet, restful nights. Cooking food makes it more digestible, and (as with ectotherms) a higher body temperature enables us to digest better. Temperature varies according to circadian and reproductive cycles, age, sex, activity levels, and what we eat or drink. These cycles also influence the composition and regulation of the large microbiome. 

Add to this that "mindset" is also a causal mechanism in eliciting physiological changes, in some cases as significant as genetic propensity. Both placebo and nocebo effects are presumably psychogenic, which implies that psychological rather than a physiological factors can play a key causal role. Tibetan monks are famously known to practice a sort of meditation call "tummo" in which they can raise their body temperature, especially that of hands and feet, to the point where they can stay outside in the cold, even drying wet sheets draped over their bodies. (Wim Hof gained worldwide attention for his exceptional endurance in extreme cold using similar methods.) The science may not yet be entirely clear, but controlling physiological states through greater awareness and conscious regulation of the affective quality of expectations and beliefs has been demonstrated. In his book, Suggestible You, Erik Vance talked to scientists around the world who investigate placebos, internal pharmacies, hypnosis, and the power of belief on the body and mind. One of his favorite quotes came from Alia Crum, a psychologist at Stanford. “I don’t think the power of mind is limitless,” she said. “But I do think we don’t yet know where those limits are.” Applying psychogenic methods to enhance the effects of the above strategies to improve digestive health is an interesting proposition to consider. 

The Three Vinegar Tasters

Prebiotics and dual inheritance theory

A speculative note on human evolution, diet, exercise, and diseases of affluence. Samin Nosrat wrote a book titled "Salt Fat Acid Heat", a name that reflects what she considers the four elements of successful cooking. It’s very insightful, particularly in regard to 'heat'. Many debates have emerged over identifying the source of the main diseases of affluence. For example, proponents of diets based on animal products have noted that "plants are trying to kill you". And taken at face value, they are not wrong! Most of the plant foods we eat today are substantially indigestible or even toxic when raw, this includes many tubers and legumes, which are staple foods. They must be cooked. So either humans were not 'meant' to eat plants, or we co-evolved with cooking technology to the extent that, over a million years ago (two million by some estimates), we decided (though at the time we couldn’t have known the long term consequences) to choose an evolutionary path where, today, we are indeed 'meant' to cook or in some way process most of our foods to receive the most nutritional benefit from them. Cooking technology made a wide range of difficult to digest plants more easily digestible, liberating more energy for brain growth and development. Changes in diet in turn produced changes in our intestinal microbiota, which became adapted to a diverse diet of cooked, though still high fiber plant products, and a wide range of supplemental animal products (though the relative amounts of these necessarily fluctuate widely, depending on availability).

Contrast this with the extremely narrow range of animals in Western (and particularly American) diets and the over processed plant products that tend to define it. It has been noted that "When humans have vanished from the planet, one of the most enduring marks of our impact on Earth will be the sudden appearance in the fossil record of copious chicken bones." Aside from the ethical questions that this raises, it is interesting to view this in light of our evolutionary trajectory thus far. As noted, over a million years ago we became dependent upon our cooking technologies for optimal nutrition, and our very biology adapted to these processes, becoming virtually inseparable and dependent upon them. In all this time, we cooked and ate many different foods, transforming indigestible raw materials into more digestible materials. But we didn’t, and likely couldn’t, completely eliminate the indigestible portions, and these characteristics (whether called dietary fiber or 'prebiotics') influenced the evolution of our intestinal microbiota as they symbiotically adapted to our new cooked, though still fiber rich, diets. Fast forward to the twentieth century. Now we have succeeded in not only making food highly digestible (liquid sugar is cheap and plentiful) but we have also eliminated most fiber. Given another million years of human evolution, perhaps the human digestive system will shrink further in size as we become increasingly dependent on these newer food processing technologies. Sedentary behavior patterns that revolve around visual information, accessed on various screen interfaces, are also replacing more physically engaged and active lifestyles. 

Nothing is a foregone conclusion. But what this should tell us is that, as many have noted, culture and cultural technologies are often capable of evolving faster than biology. Our bodies have not yet caught up to the new highly processed (and often nutritionally deficient) diets we have created. This results in a misaligned (or disharmonious) relationship, and we can clearly see it in the prevalence of diseases of affluence today. Our current response appears to be one of trying to accelerate our cultural and biological evolution to adapt to a more sedentary lifestyle and highly processed diet, often with the aid of pharmacological and/or surgical interventions. The less invasive option is to simply increase mobility and reduce the proportion of these refined foods, and recognize the complex dynamics that evolved between our use of heat, which expanded the selection of edible foods, and the changes that occurred within our larger 'holobiont' as a result. In The Good Gut, Justin and Erica Sonnenburg make it clear just how much remains to be learned about intestinal microbial diversity and (to a lesser extent) how technologies of cooking, fermentation, and food storage influence this as well. Even where dietary fiber is absent and therefore unavailable for fermentation by intestinal microbiota, external fermentation (used for food storage) could have served in a surrogate capacity. 

Since much of the above focuses on how cooking did not fully eliminate the indigestible portions of food, a further note should be made about the 'carnivore diet' which comes much nearer to that, and apparently provides relief for some chronic problems. Cooking technologies didn't just make it easier to digest plants, but animals too. But the resurgence in popularity today for a 'meat only' diet may be primarily because sometimes, even well cooked plants are still not tolerated. According to Sten Ekberg, "the 'carnivore diet' is essentially the 'ultimate elimination diet'. You cut out everything until you just have one food remaining. Along the way you eliminate various different things, starting with the really bad stuff like sugar. Then you fine tune and tweak it until you don't even have the leafy greens anymore. You just eat one food, and what meat has going for it is that it's basically the most 'neutral' food. The lowest number of allergies to any food is probably meat. Most of the problems that are caused by food are not due to the substance itself, but rather your body's reaction to it. When your body responds to food as an enemy, it creates inflammation. It’s that inflammation which causes all the problems. Meat being the most neutral food means that it is least likely to cause inflammation." The carnivore diet can be a somewhat misleading name however. Most people associate meat with protein, but protein can’t be the sole source of energy for humans. Loren Cordain, a professor of evolutionary nutrition, noted that "Anyone eating a meaty diet that is low in carbohydrates must have fat as well." Perhaps the majority of the energy in a carnivore diet actually comes from fats, and not all fats are equal. Many of the fats in the contemporary American or Western diet are not of the healthy kind. So the type of fat we eat matters a lot. While the 'ultimate elimination diet' can provide welcome relief to people experiencing chronic inflammation and other digestion problems, it still requires care to be done right. 

Richard Wrangham (author of Catching Fire) and Amber O'Hearn both looked at the development of cooking technology and its effects on human evolution, coming to somewhat different conclusions. O'Hearn is convinced by the importance of a carnivore diet for ketosis, which she believes is essential for adequate nutrition (this occurs when fasting as well). She also suggests that early humans were scavengers and may have eaten a lot of fermented foods: "Our digestive system in some ways seems to be even more like scavengers than carnivores. Because we lost our cecum, we kind of had to outsource fermentation if we wanted to have that digestive process, which in other animals is taking place on the inside. So you could think of fermentation technologies as having an 'exterior gut', letting some of the nutrients get fermented out that we otherwise wouldn't have done, and then you can just have the product of that." Perhaps we are opportunistic scavengers who lost our cecum while eating leftovers, and later we invented cooking and other ways to process energy dense foods. O'Hearn also writes, "The assumption is that starch was the evolutionary reason for our brains. The only way we would could have eaten starch was by cooking, and since our brains changed around two million years ago, Wrangham infers that we must have had the use of fire at that time." In fact, recent evidence is backing him up on this point, that 'obligate cooking' was a point of origin in hominin phylogeny. Indeed, eating food 'while it's hot' may be much more than just a cultural preference. Michael Pollan captured some of the best nutrition advice when he wrote in his 2008 book In Defense of Food: An Eater's Manifesto, “Eat food. Not too much. Mostly plants.” But in light of the evidence, I think the first sentence should’ve been “Eat hot food.” No matter what we eat, and we eat a bewildering array of foods, as a general rule heat is important. (In Pollan's defense, his later book was titled Cooked.) Of course there will always be those who would claim the opposite, that cold raw food is preferable, and sometimes it is, but it’s arguable that these are the exceptions that prove the rule. Coincidentally, for those advocating for a carnivore (exclusion) diet, cooking may be even more important. And in many forms of traditional Chinese medicine and Indian Ayurveda, heat has long been the key to good eating, which has been called “digestive fire”. For poor digestion, the higher the temperature the better. However there are limits; scalding hot food and drink (temperatures above 60°C or 140°F) can cause thermal injuries and lead to chronic inflammation and the formation of cancer cells in the lining of the throat or esophagus. Hot is good, but not too hot.

Taking a systemic perspective, Ekberg concludes "I don't think that [the carnivore diet] is necessarily the best thing forever. There is something to be said for variety. I think your microflora tends to be more varied (I believe that is a good thing) if you eat more varied food." Essentially, these are all different routes toward the same destination, which is to provide nutrition while both avoiding pseudofoods with a high glycemic index and, most importantly, preventing inflammation and feedbacks that could sustain or exacerbate an inflammation response to toxins. While one route primarily focuses on reducing the ingestion of toxins, another focuses on increasing defenses against toxins from unprocessed or processed foods. The carnivore (elimination) diet takes the first and most direct path by avoiding the consumption of toxins in the first place, which are largely absent from meat (in any form). Logically, if they aren't there, you cannot absorb them. Defensive methods include various food processing methods, primarily cooking food (which breaks down toxins), or fermenting food, both of which essentially 'predigest' it making it easier to assimilate. Other defensive mechanisms include staying physically active and well rested. This advice can be used by anyone regardless of food preferences. Another defensive mechanism that may not be utilized depending on dietary restrictions is increasing fiber intake. Like exercise, this also reduces intestinal transit time, but unlike exercise, it uniquely increases stool volume, and thereby moves material through the body faster, reducing exposure to toxic compounds and metabolic byproducts, which are quickly passed. Individual sensitivity to fiber and fiber containing foods will decide if this defensive strategy is appropriate or not. For many people it is, but for some it may not be.

Returning again to the topic of human co-evolution with the development of new food processing technologies, it’s interesting to note that there are now many people, including environmentalist George Monbiot, who are proponents of technologies variously termed ‘cellular agriculture’, ‘precision fermentation’, and ‘lab-grown meat’. Attention will need to be given to the nutrient profile of these novel food products, the form of fats that they contain, and their interactions with our microbiota, if they are not to be just another overly processed and hyperpalatable 'pseudofood' (a term David Kessler uses). The potential for creating foods that are tailored to an individual's personal dietary needs and microbiome, with sufficient levels of micronutrients, fiber, fat, and protein, has its attraction. And while it wouldn't be needed by the majority of people, it could find niche applications for people experiencing compromised health. The job of tailoring our diets to our individual needs remains for the time being a process of trial and error, and one that is both enabled and limited by our understanding of the systemic components of health. 

FODMAPs

Both Hossenfelder and Mason seem to be in broad agreement on FODMAPs. Mason is focusing on all of them, while Hossenfelder is only looking at the Polyols (sugar alcohols). So which of those four (oligosaccharides, disaccharides, monosaccharides, polyols) is the problem? All of them? Or are some more than others? I think Hossenfelder is just trying to eliminate the fewest foods as possible from her diet. Would she feel even better if she eliminated all FODMAPs? It may be that many of these are associated with each other such that by focusing on just one the others are reduced as well. Anecdotally, following the bowel prep for a colonoscopy the microbiome is dramatically changed and bowel symptoms often disappear for a time. If a low FODMAP diet is maintained afterwards, it might be possible to eliminate symptoms altogether. However merely changing dietary habits may be sufficient, per Mason. 

Fermentation technology as a driver of human brain expansion

Digestion is the result of a complex interaction between numerous variables. Several of these include: the amount of fluid and food consumed (separately), the time and frequency of eating it, the length of residence within the large intestine, amount of sleep and exercise, inflammation, body temperature, and the fraction of this food that has been externally fermented. Katherine Bryant and Erin Hecht's 'External Fermentation Hypothesis' argues that the offloading of gut fermentation into an external cultural practice could have provided the caloric boost that allowed our brains to expand. They write:

"The emergence of meat-eating, tuber-harvesting, and cooking have all been proposed to account for human brain expansion; why should our just-so story be given any additional credence? ...Unlike other proposed dietary modifications, a transition to eating fermented foods does not require great leaps in cognitive ability. It does not require advanced planning, as hunting, particularly hunting in groups, would. It does not require the acquisition of a difficult technology, as in fire for cooking. It can more directly explain, than tubers, meat, or cooking, how colon fermentation could be replaced through dietary changes. Fermentation accounts for all the benefits that cooked food offers... the ingestion of externally fermented foods provides four critical components to digestion and absorption. First, it increases the digestibility of foods; second, it increases the bioavailability of micronutrients; third, it supports gut fermentation by contributing to host microfloral diversity; and lastly, it supports immune function and resistance to disruption of the gut microbiome. These benefits would have been adaptive advantages for our early ancestors and could have played a key role in human brain evolution... These benefits have led public health scholars to recommend increasing the consumption of fermented foods...

"Humans deliberately ferment foods of nearly every kind, including fruits, vegetables, grains, legumes, animals (muscle meat, organs, fat and bones), dairy, fish, and shellfish. Fermentation is practiced successfully in a diversity of climatic contexts, from tropical humid conditions to arctic environments. It is accomplished with a wide variety of microorganisms, including bacteria, filamentous fungi, and yeasts. Moreover, fermentation works on a range of timescales from hours to years, effectively acting as a short-term flavor enhancer or a long-term storage technique. ...Notably, many fermented foods such as fish sauce, soy sauce, and vinegar, are condiments—i.e., substances added to other food items mainly for the purpose of improving palatability... preferences for sour or acidic foods are relatively rare in the animal kingdom."

"Fermentation technology as a driver of human brain expansion" as featured in "Fermentation, fire, and our big brains"   

Coda: Jeff Krasno's approach to diet and health

In an interview with Sonja Manning, Jeff Krasno said:

"Over decades I had built up insulin resistance through stress, alcohol, diet, overworking, and poor sleep hygiene. To become more insulin sensitive and 'reconfigure' my cells such that they were more welcoming to macronutrients (whether that would be glucose, ketones, or free fatty acids for the production of energy) I needed to down regulate the production of insulin from my pancreas. What's the way to do that? I adopted three protocols conjoined that really kind of set me on my way to a more optimal health: ketotarian diet, intermittent fasting, and cold exposure. The low glycemic, high fiber, 'ketotarian' (plant focused keto) diet allows me to achieve low glycemic states. I also adopted a '16-8 intermittent fasting' protocol in which I consolidated my eating window into eight hours. I'm not neurotic or fundamentalist about it, but generally try to use those goal posts to demarcate my feeding window and try to delineate between a biological need for food to create energy versus a psychological desire for comfort or pleasure with food. The result of this is in some ways the same as the ketotarian diet. Essentially after 16 hours of not consuming food your blood glucose levels go way down and you start to burn fat for energy. The last protocol is cold water therapy, or hydrotherapy, to lower my body temperature. Right before breaking my fast I take a cold shower. (Sometimes I would take a sauna on the front end of that to make it a little easier for me, but oftentimes not.) I just take a 60-second cold shower and then let myself shiver without drying off right away. After my body temperature is lowered my cells need to raise it back up. Most of life is really just about burning energy to stay warm. Our mitochondria need to create that heat, but since I've adopted a low glycemic diet and I'm in a fasted state, they don't have any glucose to burn. They can only burn stored fat. 

I'm currently in the experience of metabolic flexibility, which allows me to switch relatively seamlessly between burning fat and burning carbohydrates (or glucose) for energy. I can then cheat a little bit around the edges and be okay. But there are things I do to keep myself on some form of protocol, including getting some form of exercise after eating, which is an amazing way to control glucose spikes. One other thing is developing some kind of mindful practice before eating. In contemporary culture we are extremely rushed, but you are what your body can absorb. If you are consuming food while you're in a distracted state, where you might be in your sympathetic nervous system, then your energy is being diverted from your gut and immune system to your extremities and muscles. Your heart rate and your respiratory rate are going up, your pupils are dilating, and essentially all of the energy allocation is moving away from digestion and metabolism. So what you really want to do before you eat and consume food is to move yourself out of that sympathetic nervous system, out of that cortisol infused, amygdala hijacked state of being into your parasympathetic 'rest and digest' state. Then you are in a better place to digest and absorb as much nutrients as possible from your food. 

One of the best measures of self-reported well-being or happiness is one's ability to align thoughts with actions. Yoking your intention and what you're thinking about to what you're actually doing. If there is a gap or separation between your intention and your thoughts and your actions, that creates quite a lot of frustration and dissatisfaction. 'A wandering mind is an unhappy mind.' We have every opportunity in the attention economy to be distracted. It's very easy. Everyone and everything is vying for your conscious attention at every possible moment. So one of the targets of meditation is to align yourself with what you are actually doing in the present moment. Thoughts will of course come in and out of consciousness, but that's a good thing. Happiness is not just the ability to hold focus, but the ability to leave and then come back. To always come back, observing phenomena arising and subsiding in consciousness moment to moment without fixating or identifying with anything. To the degree that meditation has a goal, it might be the relief of anxiety by bringing us back to the present."

Here's another way in which I might describe some of this: There are relationships and feedbacks between gut microbiota, transit time, and stress. Healthy microbiota ecologies create large stools. However chronic stress can lead to diarrhea like symptoms with more frequent bowel movements. If this occurs over a long enough time, it can irritate the colon and perturb the microbiota sufficiently that it shifts into an "alternative stable state", with symptoms of irritability and smaller, more frequent stools. There are several ways to return to the former healthier microbial ecologies. And this can perhaps best be explained through using the example of fermentation, as when making sauerkraut. The bacteria goes through several shifts as the culture ages, each dominated by different species and strains of bacteria. The same occurs in the gut. To return to the healthier ecology, bowel elimination frequency needs to be intentionally reduced (as was the former condition) so that these other bacterial species can return to play their important roles. Their added diversity leads to larger and more well formed bowel movements. A very effective way to promote this is through time restricted eating, otherwise called intermittent fasting. This gives the gut time to rest and digest between eating periods and diversifies the gut microbiota. The stool consistency and bowel movements change, and symptoms of irritability reduce as well. Toilet habits change. When the urge arrives, one merely relaxes the lower abdomen, breathes deeply, visualization exercises might help. This is progressive muscle relaxation. Minor positional adjustments can support and enhance the action of peristalsis in the colon. How to achieve this psychological state? McGilchrist recounts one possible meditation practice, "focus your attention very narrowly, and at the same time broaden it as broad as you can. Both hold the focus and be aware of the periphery. It’s a very good exercise." The mind balks at the incomprehensibility of such a task. It sounds like a paradoxical koan, like simultaneously relaxing and contracting one’s muscles. But this is precisely what peristalsis is. A large and clean bowel movement should result. Rise and finish. No Valsalva maneuver is necessary, nor should one try to forcefully eliminate any more material than is quickly and automatically passed at this time. ...I should note that the key isn't a reduction in transit time, but a reduction in bowel movement frequency. In fact, transit time may paradoxically increase due to larger, more complete elimination. (Constipation is often characterized by frequent movements.) Why do larger more infrequent bowel movements promote a healthier microbiome? It's speculation, but perhaps it may have something to do with the "culture" aging all at once together and completely, in a full rhythmic cycle without interruption (continuous snacking, providing an ever present stream of nutrients at all hours, might prevent this succession of bacterial species from occuring). When fermenting vegetables, they should not be disturbed until the moment that they are done. 

There’s a need to understand distal causes of digestive problems, and without this understanding we get apparent paradoxes. If you eat a bunch, you feel bloated, gassy, unable to sleep, and the need to have more frequent bowel movements for these reasons. That in turn leads to greater use of the Valsalva maneuver to urge things along. But intentionally raising our abdominal pressure in this way can cause many other problems, and it doesn’t address the root of the problem: stress eating. Of course, if you eat less you, most of the problems are resolved, and instead of using the Valsalva maneuver one can just relax the pelvic floor muscles and let “the bottom of the tub fall out” (as the Buddhists say). It becomes more natural. 

Retain a habit of time restricted eating and the diversity of the microbiome culture should retain the healthful characteristics described here. One may encounter some problems if this process isn't well understood. During initial stages of this condition the microbial ecology may autonomously try to return to the healthier state, however the individual fights the system and prevents this from occurring. When this happens usually the individual has become habituated to more frequent bowel movements and now imagines longer duration between movements is unhealthy or constipated. Ironically, instead of reducing intake of food and water, they may instead increase intake (binge eating) in order to increase the necessity of bowel movements. When this doesn't produced the desired results, such individuals tend to strain with defecation more often. This highlights the importance of time restricted eating. In short, managing stress, food consumption amount and frequency (though this must be correlated to age and activity levels), and understanding the role of the large microbiome are all critical to health. 

Some common recommendations evaluated in light of prebiotics:

Hydration - large bulky indigestible material helps moderate and store water in the body. 
Chew your food - proper mastication promotes digestion. And remember that satiety is delayed, so stopping before feeling full can prevent bloating later. 
Sleep/exercise - Circadian routines of sleep and exercise influence the composition and regulation of the large microbiome. Michael Pollan famously said "eat food, not too much, mostly plants". To this I would add "not at night, and walk". We know that during fermentation a succession of microbial species will rise and fall in dominance. Does this occur in the large microbiome as well? The GI tract digests food during the morning and afternoon when needed most, and completes a circadian bacterial cycle through the evening and night. Moderate exercise facilitates the process. Strengthen the core with crunches, reverse crunches, and planks.
Vegetarianism - Maybe the carnivore/ herbivore/ omnivore framing relegates the microbiome to the position of “second fiddle” when it might really play a much larger role in health. Maybe plant/animal isn’t the relevant distinction. Maybe we just need to pay more attention to having a balanced microbiome. Clearly food source and quality is a part of that balance, but so might be consumption patterns, sleep, exercise, stress, and other interactions. What is the dietary effect of prebiotic food on the large microbiome? Evaluate diets from the perspective of prebiotic content rather than the fractional contribution from animal or plant products. That's the real common denominator for dietary health. As individuals develop from youth to old age (and their large microbiome develops with them), relative dietary contribution from either animals or plants may also change. 
Leaky gut -  A hypothetical, medically unrecognized condition (that may confuse correlation for causation) which does however describe very real symptoms. Advice to address these symptoms may include: deep breathing, moderate exercise (walking 4-5 miles), periodically allow the GI tract to rest from the burden of digestion (occasional fasting), and reduced use of certain drugs while increasing various micronutrients. 
Intermittent fasting - There's no need to set specific times for eating and fasting, simply refrain from "snacking", maximize the length of time between meals, and moderate consumption during meals. You may not want to undertake the "acute stress" of fasting if you are already operating under the condition of "chronic stress" from a poor diet. Address the chronic stress first. Hormesis doesn't work well with sick people. This is an area with few clear outcomes. OTOH, caloric restriction may lead to "starvation" of the large microbiome, especially if one already has a typical Western diet (as described above), exacerbating the potential for gut dysbiosis symptoms (constipation, inflammation, etc.). But on the other hand, "letting the gut rest" and take a break from accessing easily metabolized food could improve the microbiome, reduce inflammation, etc. See also Michael Mosley, Jeff Krasno, and reference to fasting (above). Paradoxically, sometimes eating increases appetite rather than satisfying it. 
Fiber content - Increasing raw fiber content alone has mixed results as a treatment if dysbiosis is pre-existing. "Fiber content" is low resolution information. What should be measured is "prebiotic content". We know that leguminous, cruciferous, or alliaceous vegetables, whole grains and resistant starch, and fresh fruits all have many more qualities than just "raw fiber" that contribute to their qualities as prebiotic foods. For another example, prunes were found to be more effective than fiber supplements in increasing spontaneous bowel movements. There's a qualitative difference between fiber additives and fresh food. (A "raw food" diet is more diverse and healthier than just upping your psyllium fiber supplements.) Worried you'll fart more? Maybe you will, but that's both healthy and normal. Eating just half a can of chickpeas a day has "the potential to modulate the intestinal microbial composition to promote intestinal health by increasing potentially good bacteria and decreasing pathogenic and putrefactive bacteria". 

Probiotics - It should be noted that the colonization of the large microbiome by bacteria is relatively easy. Unless one lives in a sterilized (or sterilizing) environment they will have frequent opportunities to contact many probiotic organisms. Fermented food is very healthy, but probiotics are strictly speaking not necessary dietary additions in most cases. Rather it is the prebiotic foods that feed the large microbiome and help it to maintain a healthy population which tends to be lacking.
Gut-brain axis (enteric nervous system) - "The gut and the psyche have close connexions. Anxiety, depression, and other disorders have characteristic expressions in gut behaviour – and the associations work both ways: diseases of the gut affect mind and mood... most of the neural traffic is from the gut to the brain, not the other way round." (Iain McGilchrist)
Meditation: Meditation and other practices that work on the gut-mind connection have been shown to be effective at reducing IBS symptoms, by assisting in regulation of neurotransmitters and stress, it may help to decrease inflammation and improving the gut microbiome.
Reactance - This may be useful for understanding various functional problems like anismus, the result of a dysfunction between the opposites of contraction and relaxation. That may be usefully addressed by positional changes, but also it's useful to understand how psychologically, in order to relax, one perhaps must understand the opposite action. In Chinese philosophy this is the logic behind "wu wei", that in order to effectively act one must paradoxically know when not to act, and even how moving in the opposite direction can bring us closer to the desired outcome. This has also been popularly referred to as "reverse psychology" and in various ways has been used to elicit a desired response for oneself or others, irrespective of the behavioral domain. It's that familiar aphorism: Tell someone not to do something (eat/act/desire), and what's the first thing they will want to do?
In conclusion - Feed the large microbiome enough prebiotics (fresh fruits and vegetables, etc.) to keep it healthy, get enough exercise and sleep, and if you are able, grow lots of prebiotics in your garden. Cooking vegetables makes them easier to digest, so the large microbiome may benefit more from uncooked plant material. In general, the more fresh your food is, the higher the prebiotic value to your large microbiome. 

Keywords: probiotics, prebiotics, synbiotics, zymurgy, fermentation. 

The majority of the information contained in this post was taken from Michael Greger's "Nutrition Facts" website (social media):
Gut Dysbiosis: Starving Our Microbial Self
Stool Size Matters

Additional Resources:
• Steven Gundry. Unlocking the Keto Code. (2022) Role of ketones in "mitochondrial uncoupling".
• Will Cole. Ketotarian. (2018)
• Justin & Erica Sonnenburg. The Good Gut. (2016) The human is a "bacteria filled tube".
• Robyn Chutkan. The Microbiome Solution. (2015) "You are what your gut bacteria eat." Resistant starches (green bananas, green peas, lentils, uncooked rolled oats, white beans).
• Robyn Chutkan. Gutbliss. (2013) Very comprehensive book. Reviews numerous symptoms, including dysbiosis, diverticulosis, thickening in the sigmoid colon, and anismus (inability to relax pelvic floor muscles for bowel movement) which can respond to using a squatting position during bowel movements. Recommends at least 30g fiber per day. "If you’re not moving, neither are your bowels." Runners have better bowel movements. "Get sweaty as often as you can, at least three times a week." Eat greens every day.
• Michael Mosley. The Clever Gut Diet (2017) Mosley is known for his books and TV shows on intermittent fasting which, with high fiber intake, "gives your gut a rest from having to constantly digest food allows the lining to regenerate... [but] for optimal health you also need some high intensity training (HIT)." Dr. Paul Cotter's research has shown that exceptional athletes have a "hugely diverse microbiota only comparable to people living in the Amazon rainforest or hunter-gatherers like the Hadza". Inulin is one of the best prebiotics and found in dandelion leaves, Jerusalem artichoke, barley, oats, flaxseed, apples, and seaweed.
• Scott Anderson. The Psychobiotic Revolution. (2017) A list of common foods with most to least inulin: artichokes, chicory/ endive, lentils, asparagus, beans (especially lentils, but not canned since cans may contain BPA), onions, garlic, leeks, bananas, beets, broccoli, fennel root.
• David Perlmutter. Brain Maker. (2015) “The effects of dietary fiber on the growth of healthy bacteria in the gut may well be fiber’s most important aspect… It has been estimated that the typical hunter-gatherer in our distant past consumed as much as 135g of inulin each day (found in yams too). Raw foods contain more.”
• Kristina Campbell. The Well-Fed Microbiome Cookbook (2016) Lots of great food advice.
• Moises Velasquez-Manoff. How the Western Diet Has Derailed Our Evolution. (2015) The Sonnenburgs think fiber is so important that they’ve given it a new designation: microbiota-accessible carbohydrates, or MACs. Sonnenburg discovered that when MAC-loving microbes go hungry they start eating mucus. “This is the stage where you say, Oh my God. They’re eating me.” Sonnenburg said. “You can see it. We need that mucus."
• Gina Kolata. You’re Missing Microbes. But Is ‘Rewilding’ the Way to Get Them Back? (2021) "Trying to manipulate the microbiome to improve human health is premature."
• Julia Belluz. Processed foods are a much bigger health problem than we thought. (2020) "Antagonizing the microbiota by highly processed diets — starving it by removing fiber and attacking it with emulsifiers — promotes inflammation. Inflammation interferes with the hormone leptin, which quells hunger.
• Yasemin Saplakoglu. 70,000 never-before-seen viruses found in the human gut. (2021) "Although the microbiome includes a variety of microorganisms — including bacteria and viruses — previous studies have focused mainly on gut bacteria because they are easier to detect."
• Nova. Edible Insects. (2021) "It’s unclear if humans can digest chitin fiber. But when ingested, chitin appears to stimulate the growth of good gut bacteria in a way that other dietary fiber may not. In our past, chitin from insects was probably part of the basic human diet that was used to keep a healthy and balanced digestive system with abundant and variable populations of bacteria. Chitin may be a missing ingredient."
• Lina Zeldovich. The Man Who Drank Cholera and Launched the Yogurt Craze. (2015)
• Rahul Sachitanand. Eight countries that have declared war on junk food. (2016)
• Popkin et al. Towards unified and impactful policies to reduce ultra-processed food consumption and promote healthier eating. (2021) Suggests developing effective package labelling, marketing controls, and creating a "mutually reinforcing set of policies".
• BBC. The world’s most nutritious foods. (2018) After analysing more than 1,000 raw foods, researchers ranked the ingredients that provide the best balance of your daily nutritional requirements.
• Bristol stool chart. A very helpful guide.