Gut bugs and human health: A tale of two evolutionary trajectories

In the wonderful Pixar film WALL-E, 29th century humans are depicted as helpless, indolent, obese creatures. Generations of exposure to microgravity, and total reliance on machines to service their every need, have acted as evolutionary selection pressures. With no requirement to think for themselves, navigate adversity or perform any actions on their own behalf, both the bodies and minds of these future humans have been weakened. Only a return to self-reliance on Earth (depicted in the movie credits, as they relearn to move their bodies and grow their own food) can restore their physical and psychological well-being by presenting them with a healthy level of challenge.

According to a paper published by prominent gut microbiome researchers Erica and Justin Sonnenburg in the journal Nature Reviews Microbiology in June 2019, the epidemic of chronic diet- and lifestyle-related illness that is engulfing 21st century humans is both the result of a mismatch between the speed of evolutionary adaption of the human genome versus our resident microbiota’s genome; and an evolutionary force in itself that may eventually select for individuals whose genes are resistant to the disease-inducing elements of the industrialised diet and lifestyle.

The paper, titled ‘The ancestral and industrialized gut microbiota and implications for human health‘, lays out a thought-provoking hypothesis – the post-industrial diet and lifestyle has uncoupled the previously harmonious relationship between humans and our microscopic inhabitants:

Our human genome – dependent on vertical transmission of genes from parent to offspring – evolves slowly, only capable of adapting to shifts in the environment over the course of decades to centuries.

Adaptation occurs when a chance mutation in a gene, occurring at conception, happens to confer a survival and reproductive advantage upon the offspring in the particular environment in which it finds itself. Such mutations can only occur once in a generation – that is, approximately every 20 years.

This pace of evolution is well suited to a slow-paced change in environment or lifestyle, such as the gradual diaspora of humans out from Africa, where our species evolved, into Asia and beyond.

For example, as our ancestors migrated from equatorial regions into higher latitudes, individuals with mutations resulting in paler skin would have had a survival and reproductive advantage over their dark-skinned peers, because they could produce more vitamin D from reduced or intermittent sun exposure.

If two individuals with this mutation mated, their children would have even fairer skin and greater survival and reproductive chances, allowing them to push even further north without suffering from vitamin D deficiency.

Over centuries and then millennia, the trait of fair skin came to dominate groups of people who lived in northern latitudes, as can easily be seen if you visit Scandinavian countries!

But our resident microbes have far fewer constraints on their adaptation. Firstly, they replicate much more rapidly than us, doubling every 20 to 30 minutes in ideal conditions, which allows for far more frequent occurrence of chance mutations that confer survival advantages.

Secondly, they are capable of horizontal gene transfer – that is, one bacterium can pass DNA that confers an adaptive trait directly to another bacterium.

Consequently, bacteria and certain other single-celled organisms can adapt far more rapidly to shifts in environmental conditions such as changes in temperature, pH and nutrient availability than humans.

For millennia, this metabolic flexibility of our resident microbes played to our advantage. We harnessed their fast rate of adaptation to compensate for our relatively slow rate – especially when it came to nutrition.

The foraging lifestyle of our ancient ancestors presented them with frequent fluctuations in the availability of particular foods. Fruits ripened only in certain seasons; hunting was only occasionally successful resulting in sporadic intake of large amounts of meat followed by weeks of subsisting on foliage and on starchy plant foods such as tubers and corms, perhaps with a side order of insects.

The ability of our gut microbiota to adapt to such a diverse and ever-changing range of foodstuffs was crucial to our survival. Within hours of a novel food arriving in our gastrointestinal tract, bacteria with the capability of utilising it start to replicate. Abrupt changes in dietary intake result in rapid shifts in the composition and metabolic activity of our gut microbiota.

However, industrialisation of our food supply has wrought changes in our diets never before seen in human history. Ultraprocessed foods that are deficient in what the Sonnenburgs dub microbiota-accessible carbohydrates, or MACs, high intake of animal products, and dramatic reduction in the diversity of our food supply has resulted in significant declines in microbiota diversity and loss of entire taxa (genetically-related groups of bacteria) in urban humans compared to those living in rural settings, and even more so when compared to the few remaining populations of foragers.

Antibiotics, both as prescribed drugs and as feed additives to farmed animals; use of antibacterial products in homes, workplaces and hospitals; caesarean section births and insufficient breastfeeding, all compound the loss of species diversity.

We are now faced with a situation in which our resident microflora have adapted to the modern environment, but for the first time in our long co-evolution with these microbes, their adaptations are detrimental to our health.

For example, the Sonnenburgs point to the dominance of members of the Bacteroides genus and the depletion and even loss of Prevotellaceae, Spirochaetaceae and Succinivibrionaceae families in the microbiotas of Westernised populations compared to foragers.

This dysbiotic pattern is linked with increased inflammatory activity, which in turn is the driving force behind all chronic lifestyle diseases including coronary artery disease, type 2 diabetes, autoimmune conditions and cancer – conditions that are notably absent among forager populations, even in the elderly, but are the major causes of disability and premature death in industrialised countries.

While Bacteroides species thrive on a diet high in fat and protein, the other 3 bacterial groupings are adapted to live off the types of carbohydrates found in unprocessed plant foods.

Remove such foods from our diet, and we lose the bacteria that feed on them.

We have been cohabiting with these bacteria for hundreds of thousands of years, with mutual interaction between our genome and theirs. The Sonnenburgs propose that the loss of bacterial signalling may be contributing to the dramatic increase in autoimmune disease observed in every industrialised country over the last few decades.

Furthermore, we are dependent on byproducts of microbial fermentation such as short chain fatty acids for a host of functions, including fuelling the cells that line our colons, regulating muscle contraction throughout our intestines, optimising insulin activity, and even regulating production of brain-derived neurotrophic factor, which prompts the birth of new neurons (brain cells) and increased connectivity between existing neurons.

Depletion of bacteria that produce vital compounds such as butyrate is implicated in numerous chronic illnesses including Crohn’s disease, type 2 diabetes and colorectal cancer.

Eventually, the Sonnenburgs suggest, individuals whose genes make them particularly susceptible to pathological interactions between Western diet and lifestyle patterns and the ‘industrialised’ gut microbiota may be selected out of the gene pool due to shortened lifespan and diminished reproductive capacity; such is the nature of evolutionary pressure.

‘Survival of the fittest’ refers to being the best fit for one’s environment; in a a toxic environment, ‘fitness’ means being able to withstand that toxicity without succumbing to disease for the longest possible time.

But what about those who are least ‘fit’ for the industrialised diet and lifestyle and its resultant microbiome, and are currently manifesting this evolutionary mismatch in the form of chronic disease?

The Sonnenburgs propose ‘rewilding’ our depleted microbiota by dramatically curtailing our use of antibiotics and antiabacterial products, adding MACs from unprocessed plant foods back into our diet; and perhaps even reintroducing lost species of bacteria from populations of humans who still retain them due to traditional diet and lifestyle practices.

Just like the ‘rewilding’ of 29th century humans depicted at the end of WALL-E, the restoration of the health of 21st century humans may depend on us being willing to accept some key challenges: not resorting to caesarian sections and formula feeding unless there is literally no alternative that preserves the health of mother and baby; relearning how to nurse ourselves and our children through non-life-threatening infections rather than begging the doctor for an antibiotic to treat every sniffle; reacquainting ourselves with the joys of growing our own food, even if it’s just a pot of herbs on the kitchen windowsill; and restoring the lost art of preparing our own food from scratch rather than microwaving a box of industrial goop or ordering Uber Eats.

Let’s hope we can rise to the challenge sooner rather than later.

Struggling with chronic disease? Need help to get your health back on track? Apply for a Roadmap to Optimal Health Consultation today.

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