Diet and drugs are known drivers of the gut microbiome, but the role of host genetics has been more challenging to determine. A study in Nature Communications reports that, in rats, the genetic influence on gut microbes extends to social partners through microbial exchange.
The work, led by teams at the University of California, San Diego and the Centre for Genomic Regulation, analyzed genetic and microbiome data from 4,000 genetically distinct rats raised under standardized conditions. The animals were distributed across four cohorts housed at different U.S. facilities, allowing the researchers to test whether gene-associated microbial patterns were consistent across environments.
“The things that live in their gut are similar but not identical,” said Abraham Palmer of UC San Diego, after introducing him as a co-author. The controlled setting helped isolate genetic effects. “This was a nice opportunity because the animals are all eating the same food, so we don't have to worry about genes influencing their microbiome via their food choices, for example. It's a much simpler system.”
Three genomic regions showed consistent associations with specific bacterial groups. The strongest signal linked St6galnac1, which modifies sugars in gut mucus, with the abundance of Paraprevotella. Another region containing mucus-related genes correlated with Firmicutes. A third region containing Pip, which encodes an antimicrobial peptide, was associated with Muribaculaceae.
The study also quantified indirect genetic effects arising through social contact. “This is the result of genetic influences spilling over to others through social contact,” said senior author Amelie Baud. “Genes shape the gut microbiome, and we found that it is not just our own genes that matter.”
Using a computational model that separated direct genetic effects from socially mediated ones, the researchers found that accounting for social transmission increased the estimated genetic influence four to eightfold for the identified gene-microbe links. The abundance of several Muribaculaceae species showed strong socially propagated genetic effects.
The findings were derived from controlled animal cohorts and genome-wide microbiome profiling, providing a framework for dissecting host genetic contributions to gut microbial composition under defined social conditions.
Publication Details
Tonnelé, H., Chen, D., Morillo, F. et al. Genetic architecture and mechanisms of host-microbiome interactions from a multi-cohort analysis of outbred laboratory rats. Nat Commun 16, 10126 (2025). https://doi.org/10.1038/s41467-025-66105-z
The work, led by teams at the University of California, San Diego and the Centre for Genomic Regulation, analyzed genetic and microbiome data from 4,000 genetically distinct rats raised under standardized conditions. The animals were distributed across four cohorts housed at different U.S. facilities, allowing the researchers to test whether gene-associated microbial patterns were consistent across environments.
“The things that live in their gut are similar but not identical,” said Abraham Palmer of UC San Diego, after introducing him as a co-author. The controlled setting helped isolate genetic effects. “This was a nice opportunity because the animals are all eating the same food, so we don't have to worry about genes influencing their microbiome via their food choices, for example. It's a much simpler system.”
Three genomic regions showed consistent associations with specific bacterial groups. The strongest signal linked St6galnac1, which modifies sugars in gut mucus, with the abundance of Paraprevotella. Another region containing mucus-related genes correlated with Firmicutes. A third region containing Pip, which encodes an antimicrobial peptide, was associated with Muribaculaceae.
The study also quantified indirect genetic effects arising through social contact. “This is the result of genetic influences spilling over to others through social contact,” said senior author Amelie Baud. “Genes shape the gut microbiome, and we found that it is not just our own genes that matter.”
Using a computational model that separated direct genetic effects from socially mediated ones, the researchers found that accounting for social transmission increased the estimated genetic influence four to eightfold for the identified gene-microbe links. The abundance of several Muribaculaceae species showed strong socially propagated genetic effects.
The findings were derived from controlled animal cohorts and genome-wide microbiome profiling, providing a framework for dissecting host genetic contributions to gut microbial composition under defined social conditions.
Publication Details
Tonnelé, H., Chen, D., Morillo, F. et al. Genetic architecture and mechanisms of host-microbiome interactions from a multi-cohort analysis of outbred laboratory rats. Nat Commun 16, 10126 (2025). https://doi.org/10.1038/s41467-025-66105-z