Genetic Interactions Shape Gut Microbial Communities

A new study in rats shows that the gut microbiome is influenced not only by an individual’s own genes but also by the genes of those they live with. Conducted by researchers from the University of California San Diego and the Centre for Genomic Regulation in Barcelona, the work uncovers how genetic and social factors intertwine through the exchange of gut microbes. The study, published in Nature Communications, offers new insights into how genes and the microbiome interact, potentially informing human health research.

In humans, only two genes have been reliably linked to gut microbes—the lactase gene, involved in milk digestion, and the ABO blood‑group gene, which affects bacteria through unknown mechanisms. To explore broader gene–microbe relationships, the team analyzed 4,000 genetically unique rats raised under controlled conditions across four U.S. facilities. “The things that live in their gut are similar but not identical,” explained co-author Abraham Palmer. This approach allowed researchers to isolate genetic effects because all animals consumed the same diet. 

The team identified three major genetic regions that consistently influenced gut bacteria across different environments. One region, containing the St6galnac1 gene, which adds sugars to gut mucus, was linked to higher levels of Paraprevotella, a bacterium that feeds on those sugars. Another region, involving genes that build the protective mucus layer, was associated with Firmicutes bacteria. A third, containing the antibacterial peptide–encoding gene Pip, correlated with Muribaculaceae, a family of microbes common to rodents and humans.

The study also showed that genes can have indirect effects on others through microbial transmission. “This is the result of genetic influences spilling over to others through social contact,” said senior author Amelie Baud. Using computational models, the researchers separated direct genetic effects from those exerted by cage‑mates. Some Muribaculaceae species were shaped by these indirect influences, with social genetic effects amplifying total genetic impact four to eight fold for the identified gene–microbe links.

Co-author Rob Knight noted that such mechanisms might extend to humans. “Although the details will be different in humans from what we find in rats, the study points the way towards understanding the mechanisms of how host and microbial genes work together to produce complex diseases that the microbiome is involved in, which range from cardiovascular disease to obesity to Alzheimer’s.”