From hunter-gathering to industrialization, our gut microbiome has adapted and evolved under environmental pressures. The current period of modernization is seeing changes in dietary patterns and medical practices that have driven a deterioration of gut microbial communities over generations. And this, in turn, contributes to explaining the current rise in chronic diseases in industrialized societies.

A new opinion article from Erica D. Sonnenburg and Justin L. Sonnenburg from the Stanford University School of Medicine explores the implications for human health of the changes related to modern lifestyle that are reflected in the gut microbiome of different populations.

Humans have co-evolved with our microbiota over time. The ancestral human communities who mainly consumed plant-based diets harbored a gut microbiota profile that was well adapted to consuming microbiota-accessible carbohydrates (MACs) and a human genome that had similarly adapted to this microbiota profile.

However, a low-MAC diet and antibiotics secondary to industrialization have led to an altered gut microbiota, with a decrease in species that degrade fibers and an enrichment of mucus-degrading microorganisms and bacterial species that harbor antibiotic-resistant genes. These modern changes in the gut microbiota—called “microbiota insufficiency syndrome” by the authors—can lead to the loss of our ancestral microbial heritage, with any recovery of the microorganisms that have disappeared being highly unlikely.

Several drivers of gut microbiome alterations in modern populations include delivery type, antibiotic use, diet and sanitation. For instance, the effects of a Western-style diet low in MACs on gut bacterial species have been well documented across geographically and culturally diverse human populations, leading to a compositional shift in the gut microbiota that varies depending on the degree of transition from a foraging lifestyle to industrialization. In addition, and even more dramatically, these shifts are still apparent and irreversible over four generations of mice.

Although the genes of the microbiota can easily and rapidly adapt to short-term exposure to an environmental stimulus (e.g. Western diet and the indiscriminate use of antibiotics), the human genome may need several generations to adapt. The authors suggest that this incompatibility may contribute to explaining the rise in modern health diseases, such as inflammation-related conditions and non-communicable chronic diseases. For instance, genes that promote calorie restriction were useful among the nomadic human population where food resources were scarce, but many generations passed before their expression decreased in today’s society, with the rise in obesity-related disorders, as an adjustment of the human genome to the current obesogenic environment.

Although some caveats arise when trying to characterize the human microbiota of our pre-industrialized ancestors, key differences allow us to differentiate the traditional gut microbiota from the microbiota found in industrialized populations. These differences include:

  • An enrichment of bacterial taxa in the traditional microbiota that are rare in industrialized populations, such as Prevotellaceae, Spirochaetaceae and Succinivibrionaceae Although their role in the gut is currently unknown, these taxa (named VANISH for volatile and/or associated negatively with industrialized societies of humans) represent one-third of the gut microbiota from traditional populations, whereas they are almost absent in industrialized populations.
  • An absence or low presence of mucus-degrading enzymes and mucus-consuming species (e.g. Akkermansia muciniphila) and low Bacteroides abundance in traditional populations.
  • High bacterial phylogenetic and carbohydrate-active enzyme diversity in traditional populations. Immigrants to the United States from Thailand have shown a loss of enzymes involved in degrading certain types of plants.
  • The presence of different patterns of microbial community composition (compared with their absence in industrialized populations) reflecting the seasonal availability of food in the wild environment, as studied in the Hadza hunter-gatherers of Tanzania.

The authors hypothesize that in the long-term future the human genome might adapt to the microbiome present in industrialized populations. As a result, these new host-microbiota interactions may contribute to a susceptibility to immune, metabolic and even central nervous system-related diseases across Western populations, probably by selecting genes that predispose the host to chronic diseases.

In order to improve health by targeting the gut microbiota, two mainstream strategies are proposed. First, population-wide interventions, including dietary changes and reducing the inappropriate use of antibiotics, followed by personalized strategies for individuals suffering from non-communicable chronic diseases who do not respond to general interventions. The second strategy consists of supporting the personalized assembly of a healthy gut microbiota in early life. Strategies for doing so may include plant-based high-MAC diets, engineered MAC-rich foods, the reintroduction of beneficial ancestral taxa, and prebiotics.

Although further research is needed to better explore the functional impact of industrialization on the gut microbiota, current findings show that the gut microbiota is an important lever that might help prevent or treat the current rise in chronic diseases. In this regard, studying the gut microbiota of traditional populations is helping us build an overall picture of what the composition of a healthy gut microbiota looks like.



Sonnenburg ED, Sonnenburg JL. The ancestral and industrialized gut microbiota and implications for human health. Nat Rev Microbiol. 2019; 17(6):383-90. doi: 10.1038/s41579-019-0191-8.