There is more to us humans than our 30-odd trillion eukaryotic cells. The things that make us us – our metabolism, our mental health, our athletic ability, etc. – are dictated not only by our eukaryotic cells but also by the chemical signatures of trillions of prokaryotic cells that inhabit the nooks, crannies and crevices of our bodies. These cells, which are mostly bacterial, congregate at their highest density in the large intestine, and their diversity and composition are heavily influenced by our diet. Samuel Smits and his colleagues at Stanford University were curious about how dietary changes throughout human evolution correspondingly changed the gut microbiome. Because ancestral humans were hunter–gatherers, the team turned to one the few remaining hunter–gatherer tribes – the Hadza of Tanzania – to approximate an ancestral human diet and, subsequently, the ancestral gut microbiome.
Before the team could compare the Hadza microbiome with that of other modern populations, they needed to characterize the seasonality of the Hadza microbiome because the Hadza diet fluctuates over the year: meat in the dry season, berries and honey in the wet season, and fiber-rich tubers the whole year through. The group explored this seasonality by collecting fecal samples from 188 Hadza individuals at five points over a 12 month period, and then used 16S ribosomal RNA to identify the bacterial composition. True to the team's predictions, the bacterial composition cycled over the course of the year, changing as the season progressed from dry to wet and then back again. The dry season saw greater bacterial diversity than the wet season and, looking at the two major gut bacterial groups, the abundance of Firmicutes remained stable throughout the seasons while that of Bacteroidetes declined significantly in the wet season.
The group next hypothesized that these seasonal bacterial changes would manifest in changes at the functional level, specifically a seasonal cycling of bacterial enzymes to complement the Hadza's seasonal cycling of diet. Shotgun metagenomic sequencing and untargeted metabolomics revealed this to be true. The Hadza's dry season microbiomes were rich in enzymes specialized for metabolizing animal-derived carbohydrates, and their wet season microbiomes were rich in enzymes specialized for plant-derived carbohydrates, perfectly complementing the seasonal dietary changes.
With this understanding of how an ancestral-like hunter–gatherer lifestyle influenced the gut microbiome, the group then employed the comparative approach to understand how it differed from that of a modern Western lifestyle. They compared the Hadza with 18 communities from 16 countries of varying lifestyles and found the bacterial families that typified the Hadza microbiome varied significantly from those of the Western microbiome, but were strikingly similar to those of other ‘traditional’ populations across Asia, Africa and South America, some of which were also hunter–gatherers. These differences were also present at the enzyme level; Hadza guts had more plant carbohydrate-digesting enzymes than Western guts, and Western guts had more animal carbohydrate-digesting enzymes than Hadza guts. Interestingly, the bacterial families that varied most across the seasons in the Hadza's digestive systems were altogether absent from the Western microbiomes.
To put this evolutionarily, the modern Western microbiome lacks some of the dynamic bacterial species humans co-evolved with – bacteria still possessed by the Hadza. The consequences of this are unknown, but might be understood by identifying the unique metabolites these bacteria produce. While the seasonal cycling of the Hadza microbiome is impressive, it is less than that seen in some non-human animals such as the hibernators, whose diets see even more extreme seasonal fluctuations. How this cycling impacts the host to make a Hadza human different from a Western human, or a hibernating ground squirrel different from an active ground squirrel, is yet to be discovered.