A recent study has found that the genes of an individual rat, as well as the genes of its cage-mates, influence the composition of its gut microbiome. The research was conducted by scientists at the University of California San Diego and the Centre for Genomic Regulation in Barcelona and published on December 18, 2025 in Nature Communications.
The gut microbiome consists of trillions of microbes essential for digestion and health. While it is known that diet and medication affect these microbial communities, understanding how genetics play a role has been challenging. This new study used rats as a model organism to examine genetic effects under controlled conditions.
"The things that live in their gut are similar but not identical," said Abraham Palmer, Ph.D., professor and vice chair for basic research in the Department of Psychiatry at UC San Diego School of Medicine.
Researchers analyzed genetic and microbiome data from 4,000 genetically unique rats housed across four different facilities in the United States. They identified three genetic regions that consistently influenced specific types of gut bacteria regardless of environmental differences among cohorts. One region involved the St6galnac1 gene, which affects sugar molecules in gut mucus and was linked to higher levels of Paraprevotella bacteria. Another region related to genes forming protective mucus correlated with Firmicutes bacteria. A third region included Pip, a gene producing an antibacterial peptide associated with Muribaculaceae bacteria.
The study also found evidence that while genes themselves do not transfer between individuals, microbes can move through social contact among rats sharing cages. "This is the result of genetic influences spilling over to others through social contact," said Amelie Baud, Ph.D., senior author from the Centre for Genomic Regulation. "Genes shape the gut microbiome, and we found that it is not just our own genes that matter."
By using computational models, researchers separated direct genetic effects from indirect effects caused by cage-mates' genetics. They discovered some Muribaculaceae species were influenced by these indirect genetic effects transmitted via microbial exchange.
"Because the rats in this study are assigned to random social partners, we remove all of the problems that you would have in humans, who by and large choose their own social partners," Palmer explained.
Accounting for indirect social effects increased estimates for total genetic influence on certain microbe populations by four-to-eight times compared to previous models.
"We've probably only uncovered the tip of the iceberg," Baud stated regarding future discoveries as profiling methods improve.
Rob Knight, Ph.D., co-author and director at UC San Diego's Center for Microbiome Innovation added: "Although the details will be different in humans from what we find in rats, the study points the way towards understanding 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."
Funding support came partly from a National Institutes of Health grant (#P50DA037844).
