The composition of the human gut microbiome is determined by environmental influences. For example, diet and medication are well established factors that influence these microbial ecosystems. However, the contribution of genetics has been more difficult to ascertain.
And what is the impact of people that we interact with socially? Now, a study involving more than four thousand animals, reveals that the composition of the rat gut microbiome is shaped not only by an individual’s own genes but also by the genes of the individuals they share a living space with.
This work is published in Nature Communications in the paper, “Genetic architecture and mechanisms of host-microbiome interactions from a multicohort analysis of outbred laboratory rats.”
The work uncovers that the exchange of commensal gut microbes that move between individuals is a new path where genes and social life intertwine. Although genes don’t jump between individuals, microbes can. The study found some genes favor certain gut bacteria and these can spread through close social contact.
“This is not magic, but rather the result of genetic influences spilling over to others through social contact,” explained Amelie Baud, PhD, group leader at the Centre for Genomic Regulation (CGR) in Barcelona. “Genes shape the gut microbiome and we found that it is not just our own genes that matter.”
In this study, the rats used are genetically unique and come from one of four different cohorts, each housed in a different facility in the United States and with different care routines, allowing the researchers to test which genetic effects held up across different environments.
[Katie Holl]
By combining genetic and microbiome data from all 4,000 rats, 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 gene St6galnac1, which adds sugar molecules to the gut’s mucus, and the abundance of Paraprevotella, a bacterium the researchers hypothesize feeds off these sugars. It was found in all four cohorts. A second region contained several mucin genes, which make up the gut’s protective mucous layer and were linked to bacteria from the Firmicutes group. The third region included the Pip gene encoding an anti-bacterial molecule, and was linked to bacteria in the Muribaculaceae family, common in rodents and also found in humans.
The large size of the cohort allowed researchers, for the first time, to estimate how much of each rat’s microbiome was explained by its own genes and how much by the genes of the other rats it lives with.
The team built a computational model to separate genetic effects on a rat’s own microbes from the effects of its social partners. They found that the abundance of some Muribaculaceae was shaped by both direct and indirect genetic influences, meaning that some genetic effects spread socially through microbial exchange. Once these social, or indirect, effects were included in a statistical model, the total genetic influence increased by four to eight times for the three new gene-microbe links discovered.
“We’ve probably only uncovered the tip of the iceberg,” said Baud. “These are the bacteria where the signal is strongest, but many more microbes could be affected once we have better microbiome profiling methods.”
By demonstrating that genetic influences can be coupled with gut microbe transmission, the authors of the study paint a new mechanism of action whereby the genetic effects of one individual can ripple through entire social groups, altering the biology of others without changing their DNA. If similar effects occur in humans, and given increasing evidence that the gut microbiome plays an important role in health, it could mean that genetic influences on human health have been underestimated in large studies. Genes may shape not only an individual’s disease risk, but also the disease risk of others.
According to Baud, the microbiome has been linked to everything from immunity and metabolism to behavior, but not all the reported correlations reflect causal effects, and the exact mechanisms of action remain elusive. Genetic studies like this one, which use animal models in controlled environments, can help move from correlations to testable causal hypotheses, helping explain how genes and the gut microbiome interact in human health.
