The gut microbiome is vital for digestion and overall health. Diet and medication shape these microbial ecosystems, but the contribution of genetics has been more difficult to ascertain. Now, a new study of rats – a model organism for understanding the human gut – has found that the composition of the rat gut microbiome is shaped not only by a rat’s own genes but also by the genes of those it lives with. The discovery reveals a novel way in which genes and social interactions intertwine: through the exchange of commensal gut microbes that move between individuals. The findings could help shed light on how genes and the microbiome interact in human disease.
In humans, only two genes have been reliably linked to gut bacteria: the lactase gene, which influences milk-digesting microbes and determines whether adults can digest milk and the ABO blood‑group gene, which affects microbes through unknown mechanisms. More gene‑microbe associations likely exist, but have been difficult to tease apart. To better understand how genes shape the microbiome, scientists turned to rats, which share many features of mammalian biology. Combining genetic and microbiome data from 4,000 genetically unique rats, from four cohorts housed in different facilities across the US, allowed the researchers to test which genetic effects held up across distinct environments.
The team identified three genetic regions that consistently influenced gut bacteria despite differences in rearing conditions across the four cohorts. The strongest link was between the St6galnac1, a gene that codes for an enzyme that adds sugar molecules to gut mucus, and the abundance of Paraprevotella, a bacterium that feeds off these sugars. It was found in all four cohorts. A second region, containing several genes that form the protective mucus layer, correlated with Firmicutes bacteria. A third region included Pip, a gene that encodes an antibacterial peptide, and was associated with Muribaculaceae, a family of bacteria commonly found in both rodents and humans.
Though genes don’t jump between individuals, microbes can. The study found that some genes favor certain gut bacteria and these can spread through close social contact. The large size of the study allowed the researchers to estimate how much of each rat’s microbiome was explained by its own genes versus the genes of its cage‑mates. A classic example of this phenomenon, known as “indirect genetic effects”, is when a mother’s genes shape her offspring’s growth or immune system through the environment she provides. The controlled conditions of the study allowed the researchers to study these effects in a completely new way by building a computational model separating direct genetic effects on an individual’s microbes from indirect effects exerted by social partners.
The researchers discovered that the abundance of some Muribaculaceae species was shaped by genetic effects that spread socially via microbial exchange. Accounting for these indirect social effects increased the total genetic influence in the model four-to-eight fold for the three newly identified gene‑microbe links. By demonstrating that genetic influences can be coupled with gut microbe transmission, the work reveals a novel mechanism whereby the genetics of one individual can ripple through an entire social group, altering the biology of others without changing their DNA. Given increasing evidence that the gut microbiome plays an important role in health, if similar effects are found in humans, it could mean that genetic influences on disease risk may have been substantially underestimated in past studies.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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