Community and gut health: How others’ genes help shape the microbiome

New research finds that the environment, specifically genetic interactions between social companions, is an essential factor in shaping the gut microbiome. Although the role and importance of diet have been widely studied, these findings shed light on the lesser-known impact of genetics on bacterial composition and, indirectly, on each other. 

The study suggests that the exchange of commensal gut microbes between people may reveal how genes and microbiomes interact in human disease. Certain genes create gut conditions that favor specific bacteria, which can be transmitted to others through close social interactions.

Researchers at the University of California (UC) San Diego, US, demonstrated this in controlled experiments involving more than 4,000 rats, where gut bacteria were transmitted through interactions between social partners — animals living in the same cage.

Nutrition Insight speaks to the senior corresponding author, Abraham Palmer, Ph.D., professor and vice chair of basic research in the Department of Psychiatry, to learn about the study’s implications for nutrition research and approaches to the microbiome.

“One of the main findings of this paper is that, in addition to diet, genetic differences from person to person also influence the microbiome. One of the exciting things about this paper is that we showed that it’s not only an individual’s genotype that influences the microbiome; the genotype of our social partners also matters — our microbiomes are shaped by the individuals that we interact with.”

Based on their findings, the researchers suggest a new mechanism of action in which the genetic effects of one can extend across social groups, changing the biology of others without altering their DNA.

“Although the details will be different in humans from what we find in rats, the study points the way toward 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 disease,” notes co-author Rob Knight, Ph.D., professor at UC San Diego and director of the Center for Microbiome Innovation.

Rethinking how bacteria shape illness

Palmer suggests that assumptions about diet-microbiome relationships might need some rethinking, pointing to, for instance, how certain strains of Escherichia coli and Salmonella can act as contagions, causing diarrhea that can be transmitted from person to person

Abraham Palmer (Image credit: UC San Diego Health Sciences).“An expansion of that model suggests that the people we are around (our ‘social partners’) might have specific genotypes that could affect our microbiome, even if those changes don’t necessarily make us sick.” 

“There are probably some situations where our social partners make us healthier and others where they make us less healthy,” he says.

What it means for gut health

Palmer also details how socially shared microbes might help explain why people respond differently to the same gut-health products or diets. 

“As a geneticist, I think of the world as having two important components: an individual’s genotype and everything else, which I often call ‘the environment.’ One part of the environment is the other people and animals we interact with. Other people and animals are themselves genetically unique.” 

“What we’re showing in this paper is that, at least for rats, the genotype of your social partners, as well as your own genotype, influences your microbiome. As a geneticist, what’s exciting about this idea is that some aspects of the environment (social partners) actually have a genotype, which means we know how to study them using the tools of genetics,” he explains.

Gene-bacteria links

The publication in Nature Communications identified three genetic regions linked to bacteria. 

Socially interacting rats (Image credit: Katie Holl).The strongest link was found with the St6galnac1 rat gene, functionally related to the human gene ST6GAL1, linked to the gut bacteria family Paraprevotella. By adding sugar molecules to the gut lining, this gene helps determine which bacteria can survive and thrive there.

Study senior author Dr. Amelie Baud, researcher at the Centre for Genomic Regulation, Spain, says: “I am obsessed with this bacterium now.”

“Our results are supported by data from four independent facilities, which means we can do follow-up studies in any new setting. They’re also remarkably strong compared with most host-microbiome links. It’s a unique opportunity.” 

In another region, researchers found genes involved in forming the gut’s protective mucus layer, which were linked to Firmicutes bacteria.

The third region included the Pip gene, which encodes an antibacterial molecule and is linked to Muribaculaceae bacteria. These are common in rodents and humans.

“We’ve probably only uncovered the tip of the iceberg,” says Baud. “These are the bacteria where the signal is strongest, but many more microbes could be affected once we have better microbiome profiling methods.” 

The researchers note that, in humans, only two genes have been reliably linked to gut bacteria. One is the lactase gene and milk-digesting microbes that determine whether adults can digest milk. Another is the ABO blood group gene, however, its mechanisms are yet to be discovered.

Gut microbiome composition can be influenced by social interactions, with the genetics of close companions shaping which bacteria thrive alongside diet and environment.It is difficult to know whether genes, environment, or diet singularly shape the microbiome, as nature and nurture are difficult to separate in the real world, the paper explains. This is why it was tested in genetically distinct rats, which were fed the same diet with controlled interactions with other rats.

Personalization includes social groups

According to Palmer, his study does not complicate personalized nutrition approaches but instead expands them.

“Now we can think about not just the genotype of the individual but also the genotype of social partners. They’re both important for the microbiome.”

Furthermore, he believes that his research on indirect genetic effects could help shape how microbiome and nutrition trials are designed and interpreted.

“A statistician named George Box once said, ‘All models are wrong, but some are useful.’ Our paper shows that a better model to explain an individual’s microbiome would account for both that individual’s genotype and the genotype of their social partners.” 

“That’s still not going to be a perfect model, since we know there are numerous environmental factors at play, but it’s a better model,” he suggests.