11. The Human Mutualist: This is an evolutionary imperative!

Probably the most well-known and oft-repeated themes of evolutionary biology are the phrases “adapt or die” and “only the strong survive”. That is, 160 years after Charles Darwin defined Natural Selection, there is a nearly universal understanding that species and populations must respond to stress by adapting (in the genetic sense) or they will likely cease to exist as a result.

However, with the emerging research in microbiomes and a greater (but definitely incomplete) understanding of the complexities of genetics, that phrase may not represent an absolute condition for all species. That is, adaptations to changing conditions, to environmental stresses, are necessary for survival in the long term, but in a symbiotic relationship where there is an intense level of interaction between two organisms, the need to adapt may depend on the role each organism plays in the response to environmental stress.

When two different species have formed a mutualistic (symbiotic) relationship, they have done so as a response to environmental stress. If we think of stress as a “cost” in the sense that the individuals in a population are losing energy or have lower reproduction, then the adaptation is a change that reduces those losses and increases reproduction. When we see a mutualism between two species, we often observe one species experiencing reduced stress (a benefit) while the other species experiencing more favorable living conditions (a benefit).

The two species have adapted to each other in the sense that each develops a genetic predisposition to associate with the other and by doing so continues to receive the benefit of the association, which is the same as saying that being together reduced the stress they were experiencing when they were not together.

When viewed from a different angle, it is highly likely that the species experiencing the original stress did not have to adapt to the stress itself, but adapted instead to another species that helped reduce that stress. In this sense, the stressed species did “adapt or die”, but not quite in the manner we have come to think about such adaptations. That is, the genome of that species might not contain a gene for reducing the environmental stress, but it will contain a gene for associating with the other species.

In the course of millions of years of experiencing uncountable environmental stressors, any response that predictably lowers the intensity of the stress will be favored. Unfortunately, rapid evolution can be hampered by the fact that genetic mutations that may provide tolerance or resistance to a stress are essentially random and have to be rather specific to the stress. In contrast, the ability to form alliances with other species may represent a genomic flexibility rather than specific mutations and this may be a much more adaptive characteristic in the long run.

We should certainly expect to see both beneficial adaptations to specific stressors and beneficial associations with other species, but perhaps more of the latter. And over the course of thousands of generations and millions of years, the beneficial symbioses will become so integral to everyday functioning that life without them becomes impossible.

Consider a population of people. Each person is an individual, each has their own genetic makeup, and we now know each has their own microbiome. Each of us walks through life thinking we are individuals when in truth we are vast and complicated, but somewhat isolated, ecosystems of beneficial and commensal associates (that is, us and our bacteria).

Many of these beneficial organisms have formed obligate relationships with us; we cannot live without each other. Obligate relationships are assumed to have developed over long periods of time and to the point that the two species have become co-dependent and each species provides a benefit that the other species cannot provide for itself and cannot live without. In fact, part of that close dependence can mean that one species has lost a function because the other species is more efficient at providing it. For example, a bacterium could provide a needed vitamin to us and over a long period of time we lose the ability to provide it for ourselves. On the other hand, the bacterium may become wholly dependent on the environment of the colon and lose the ability to live anywhere else.

Others, perhaps newer mutualist species, have formed facultative relationships with us; we don’t need them all the time, but they are beneficial under certain circumstances. An example might be a gut bacterium that is capable of digesting a certain kind of food material that we eat only occasionally.

Even commensal organisms that appear to benefit from being in and on us, but which don’t seem to confer a benefit to us, may actually be beneficial, but only under certain circumstances. For example, if the presence of a non-beneficial (commensal) bacterium prevents the colonization of a pathogenic bacterium, that commensal species has provided an indirect benefit to the host. Currently, we know very little (actually, almost nothing) about direct and indirect benefits, and about frequent vs occasional benefits from different members of our microbiome.

Because of the presence of thousands of other species, both mutualistic and commensal, both in and on our bodies, researchers are now describing humans as superorganisms. We move through the environment like individuals, we behave as individuals, and we are not dependent on the actions of any particular other individual, but we all, as Ed Yong[i] says, contain multitudes.

What we do not have to consider every moment of the day is that we, as humans, are the transportation vehicle and housing system for thousands of other species with trillions of individuals both on us and in us. The other species interact with the environment as we humans, their hosts and vehicles, move them through the environment and bring the environment to them. The simplicity or complexity of those interactions and the direct or indirect consequences to our health are also almost completely unknown.

This is a difficult and exciting conundrum to consider and explore. As humans, we think we are interacting with the external environment, but are we interacting with the environment as individuals or as ecosystems? Is it our microbiome that is interacting and we just the beneficiaries of that interaction? A delightful and squishy example of what I mean is the cow. Everyone knows cows eat grass (or are supposed to), but do they really eat grass in the same sense that we eat our food? Actually, no, they don’t.

The cow consumes grass by chewing and swallowing, but the grass goes into that 25-gallon fermentation vat called the rumen, the first of the four stomach chambers. In the rumen, trillions of bacteria digest the nutrients contained in the grass and provide energy molecules for the cow (called short-chain fatty acids or SCFA). In other words, the cow feeds its bacteria with grass and the bacteria feed the cow with SCFA. Thus, the daily chore of a cow is to move through the large external biome collecting and fragmenting grass to keep its microbiome healthy and happy, which in turn keeps the cow healthy and happy.

We too interact with our environment and some aspects of our microbiome are interacting directly and more intimately with the world around us than we are. Undoubtedly, our primary interaction with the external environment is through the food we eat and the water we drink as we move materials from the external ecosystem to the internal ecosystem. However, when we are eating a “healthy” diet, to what extent are we feeding the internal ecosystem which in turn feeds us and protects us? How important is it to eat certain foods and thereby feed certain species of bacteria?

The majority of our direct interactions with the environment largely involve protecting our insides from the outside. However, the microbiome does not necessarily distinguish direct and indirect and inside and outside according to the same criteria. So, a more important question may be to ask how important is that flow of information (mostly food) from the outside world to the denizens of the inside world?

Our movement through the environment results in direct encounters for some microbiome species because of changes in the heat, moisture, and chemicals on the skin of the human transport system. Our skin is both our first line of defense and home to a vast array of microscopic organisms populating our outer surfaces. They experience what our skin experiences yet the skin is their home habitat rather than merely a protective layer. The species populating our skin are able to tolerate the conditions that humans are able to tolerate because they are adapted to that range of conditions. Nonetheless, humans experiencing different habitats and climates around the world are likely to possess small subsets of the much larger possible microbial community. For example, a person living on the coast will have a different skin microbiome than a person living around farmlands or in the mountains.

How geographic variation interacts with human genetics, particularly ethnicity, has been described in a small number of studies, but we have little to no understanding of the possible implications. It may turn out that the skin microbiome does very little else than to prevent unwanted species from landing and establishing. If certain species are well adapted to life on our skin, new arrivals will have a hard time displacing the residents. If a new arrival is a potential pathogen, but is displaced by the local fauna, this is an unquestionable beneficial consequence of a healthy skin microbiome. In contrast, some forms of dermatitis may reflect an inability to protect ourselves from invasive and dangerous new species of microbes.

In contrast to the skin microbiome, the bacteria community in the large intestine will experience the external environment through the food we eat as well as the antibiotics, pharmaceuticals, preservatives, and other chemicals we consume. A person with a very stable and unwavering diet, particularly one low in plant materials, will have a less diverse community than a person with a variable diet that includes a diversity of plants. Many of the bacteria that favor particular food items are predicted to be carried into the digestive tract by that food.[ii]

Certain foods will favor very specific bacteria while other bacteria are generalists and can live on a variety of food items. For example, foods with lactose sugar are rather specific and favor the growth of Lactobacillus species in our digestive system whereas cellulosic foods are rather common and favor Bacteroides species capable of fermentation and the breakdown of complex plant molecules.

When a diet changes dramatically from one food type to another, say from high carbohydrate foods to high-fiber plant foods, the composition of the bacterial community will shift rapidly. Those species that favor the new foods will grow in abundance and those that are less competitive for that food type will decrease. These shifts increase digestive efficiency and the changes to the composition of the community can take as little as 24 hours.

Of course, these responses to changes in diet are complicated by the drugs we take and other chemicals we consume. We certainly know that antibiotics are more or less specific to bacteria and may greatly diminish our microbiome populations. Much less is known about how other non-antibiotic yet powerful drugs intended for managing, for example, depression, blood pressure, or inflammation may affect all or part of the microbial community.

There are many aspects of food quality that can influence bacterial-assisted digestion and some may be very subtle. We provide food sources for our microbiome with every meal, but we may also introduce new genetic strains or species of Lactobacillus that may compete with the ones already in our system. The newcomers may be better for us by being more efficient at converting lactose sugar. If they are better competitors, we would expect them to take over.

Research on obesity is now indicating that the microbiome of obese people differs from that of non-obese people. In particular, the “obese microbiome” appears to be more efficient at extracting calories from food. That is, obese people may be getting more calories from the same food as non-obese people. This research clearly suggests that the different strains or species of bacteria being favored in different people is contextual and this has consequences for human health.

The bacterial community is responsive and dynamic and that is also an important trait of diverse communities because of the constant interactions with the environment that lead to adjustments of one kind or another. Truly, if we experience or even encourage shifts in food quality, we need a shift in bacterial composition to accommodate the digestive requirements of those new foods.

Historically, the regular shift in food quality from one season to another was a definitive aspect of human life, especially for hunters and gatherers, and the possession of a microbiome capable of accommodating such dietary variation, particularly for an omnivorous diet, is perhaps the single most important adaptation for the human species. Such a microbiome, by necessity, must be very complex and capable of rapid shifts in the abundance of bacterial species.

Herbivores also, by necessity, must have complex digestive systems to deal with slow-to-digest food stuffs, but under normal conditions one would expect the bacterial communities to be very stable and consistent over time. In contrast, animals adapted for a carnivorous diet have simpler microbiomes because of the relative ease with which meat and other animal proteins can be digested.

The omnivorous human must possess digestive flexibility and this is accomplished not with a diversity of digestive enzymes, but with a diversity of digestive assistance from bacteria. By possessing such digestive flexibility, and by carrying our highly diverse digestive community with us, our ability to move from place to place through the seasons and over the years must have been greatly facilitated. Thus, we have to think that the possession of a highly diverse microbiome is an essential adaptation for the omnivorous human.

[i] Ed Yong. 2016. I Contain Multitudes. Ecco, HarperCollins Publishers. [ii] This avenue of research is just getting underway. To learn MUCH more, the Human Food Project/American Gut is a good starting point (http://humanfoodproject.com/americangut/)