Through the month of September, the microbiome scientific literature had some particularly interesting contributions related to human health. First up is a pair of papers on the significance of serotonin that’s made in the gut, linking it to host metabolic regulation; this is followed by a large study looking at the gut microbiota of infants born by Caesarean section (C-section); then, a study on the extent to which gut microbiota affects host gene regulation; and finally, the curious case of a man who regularly became drunk without consuming any alcohol – all because certain gut bacteria in his gut, which were linked to non-alcoholic fatty liver disease (NAFLD), produced alcohol from the carbohydrates he consumed.
Previous work from Hsiao lab has found that certain bacterial species from the gut microbiome stimulate the hosts’s gut endocrine cells to produce serotonin.(And to clarify: this ‘peripheral serotonin’ is the same molecule as the serotonin produced in the brain, but it’s produced very differently.) In turn, more serotonin in the gut shapes the bacteria that thrive there. This new work from the lab singles out a particular species, Turicibacter sanguinis (linked to host metabolism),that uses serotonin to increase its own fitness in the gut environment.
To date, we only have a basic idea of how microbiota perturbations affect host metabolism. In mice, scientists manipulated the gut microbiota and levels of gut serotonin to observe how the animals fared metabolically. The group found that the glucose homeostasis of the mice dramatically improved with these manipulations—ultimately implicating intestinal serotonin in the mechanism by which the gut microbiome influences host glucose metabolism.
Scientists have amply demonstrated the microbiome differences between infants born by C-section and those born vaginally, yet the significance of these differences for health remain unclear. In particular, we are lacking mechanistic connections between the early-life microbiome and health. This large study took a close look at the microbiomes of babies born by C-section, describing them in unprecedented detail after both sequencing and culturing the microbes. The researchers identified some potentially worrying signs—virulence factors and the presence of antimicrobial resistance (probably typical of a hospital environment) in the microbiota—but it should be noted that the effects on infant health were not tracked in this study.
The authors of this paper set out to demonstrate how microbes might change gene regulation in the host epithelial cells, which are in close proximity to intestinal microbes. They took colonic epithelial cells and added live microbial communities from healthy people to observe what happened with transcriptional regulation and chromatin accessibility in the host cells. Over 5000 host genes ended up changing their expression. Furthermore, the researchers used a manipulated microbial community as a proof-of-concept for how targeting a certain microbiota composition yields a particular gene expression profile.
Non-alcoholic fatty liver disease (NAFLD) has been linked with gut microbiota changes—but this paper finally gets us closer to finding a causal link. After investigating a person with liver disease who would become alcohol-impaired without drinking (because his gut microbes fermented carbohydrates into alcohol), the scientists discovered that a large proportion of people with NAFLD have strains of ethanol-producing Klebsiella pneumoniae in their guts. Perhaps surprisingly, these alcohol-producing bacteria were able to induce NAFLD when transferred into mice. It’s possible that the identified strains of bacteria (or others) that produce ‘endogenous alcohol’ could turn out to be a risk factor for NAFLD.