Human Gut Microbiome Diverged from Industrialization

As early humans began their migration out of Africa tens of thousands of years ago, they were accompanied by an invisible entourage - trillions of microorganisms that inhabit our gut and play a vital role in keeping us healthy.

These tiny passengers in our intestines are responsible for various essential functions, including breaking down fibrous foods, producing vitamins, and fine-tuning our immune systems. They have long been recognized as crucial components of human health, with evidence suggesting their composition can be influenced by lifestyle factors.

Research has revealed a stark contrast between the gut microbiomes of people living in industrialized countries and those from non-industrialized communities. The former often exhibit a significant loss of microbial diversity, which is associated with higher rates of chronic diseases such as autoimmune disorders, type 2 diabetes, and obesity.

In contrast, populations living traditional lifestyles tend to have more diverse and resilient gut microbiomes, raising questions about the potential link between industrialization and human health outcomes. This disparity has sparked intense interest in understanding the impact of lifestyle on the human microbiome.

A new study led by researchers at Stanford University aims to shed light on the historical relationship between humans and their gut microbiomes, with a focus on identifying long-term residents that co-evolved with our species over millennia.

The researchers conducting this study selected two distinct groups for comparison: the Hadza in Tanzania and the Tsimane in Bolivia's Amazon region. The Hadza are one of the last remaining hunter-gatherer populations worldwide, while the Tsimane have had relatively limited exposure to industrialization.

Although their ancestral populations separated tens of thousands of years ago, these two groups share a significant number of bacterial species - over 1,200. A substantial portion of these shared species were found in the diverse microbiomes of the Tsimane, with nearly 90% identified.

Further analysis revealed that about 60% of these shared species are rare or absent in industrialized populations' microbiomes. This finding highlights a significant difference between modern and ancient human microbiomes.

Using various population genetics techniques, researchers estimated when microbial strains diverged from one another. The results suggest that many species separated during prehistoric human migrations out of Africa into the Americas.

The study's findings indicate that several hundred bacterial species in these contemporary populations have deep evolutionary roots dating back to ancient human migrations.

These long-term associations between humans and their gut microbiomes have significant implications for understanding how recent biodiversity loss may impact our biology and health.

The method used by researchers to analyze microbial DNA, known as deep metagenomic sequencing, involves characterizing the microbes present in a sample by reading all the letters representing the building blocks of DNA. This process generates millions of short sequences that are then matched up into longer sequences for identification against microbial genome databases.

The researchers at Stanford University built upon previous metagenomic sequencing efforts by conducting a comprehensive analysis of the Tsimane microbiome.

Their study focused on stool samples provided voluntarily by the Tsimane, which had been previously sequenced at low resolution in a 2020 Nature Communications study.

In contrast to the Hadza, whose average individual has around 750 species in their microbiome, the researchers found that the sampled Tsimane individuals hosted approximately 1,400 different species.

The comparison between the two groups' microbiomes revealed an unexpected similarity: about 90% of the species present in the Tsimane's microbiome were also found among the Hadza.

This finding is notable given the distinct diets of the two populations. The Hadza are hunter-gatherers who consume a diverse range of meats, fruits, and vegetables.

The Tsimane, on the other hand, primarily grow their own food and rely heavily on plant-based staples such as plantains, rice, manioc root, and corn.

The two groups, the Hadza and Tsimane, have been geographically separated for tens of thousands of years, yet their gut microbiomes show a high level of overlap at the species level.

This unexpected similarity has led researchers to question whether there is a core set of bacterial and other species that accompanied the ancestors of these groups as they migrated across continents.

The senior co-author of the study, Benjamin Good, Ph.D., notes that this finding suggests the possibility of a long-standing relationship between certain microorganisms and humans.

To investigate further, researchers turned to analyzing genomic signatures that could distinguish deep shared ancestry from more recent microbial exchange. This is crucial because bacteria not only inherit DNA from their direct ancestors but also frequently exchange DNA with other strains through horizontal gene transfer.

The team used several independent methods to estimate when species diverged from a common ancestor, including looking at mutation rates in vertically inherited DNA. Mutations accumulate over time at a steady pace, making it possible to track evolutionary history.

The genetic analysis revealed that many of the bacterial species shared between the microbiomes of nonindustrialized groups have evolutionary histories spanning thousands of years.

These ancient ties are consistent with major human migrations, as evidenced by the detailed analyses of genetic isolation of strains. The results suggest that these bacteria were present in the ancestors of both the Tsimane and the Hadza populations.

The findings raise an important question about the impact of industrialization on our resident microbial populations. If humans have coexisted with many of these organisms for tens of thousands of years, what happens when they are suddenly eliminated over just a few generations?

Previous research has linked changes in microbiomes to various disease states, and the current study suggests that the loss of biodiversity could be incompatible with human biology. Dramatic changes to our resident microbial populations may have significant biological consequences.

The researchers plan to continue investigating the history of our microbiome and its links to health and well-being, including exploring the long-standing relationships between humans and their gut microbes.

The study of human gut microbiomes has revealed a fascinating link to ancient migrations across continents. By analyzing genetic data, researchers have found that certain species of bacteria present in modern humans are identical to those found in ancient human remains.

This suggests that these microorganisms accompanied early humans as they migrated from Africa to other parts of the world, adapting to new environments and ecosystems along the way. The discovery has significant implications for our understanding of the complex relationships between humans and their gut microbes, which play a crucial role in maintaining overall health and well-being.