The genes of your roommate may be shaping the bacteria in your gut, and your genes may be influencing theirs, according to a rat study published on December 18 in Nature Communications.
By examining more than four thousand rats, researchers found that the makeup of the gut microbiome is affected not only by an individual’s own genetic makeup but also by the genes of the animals they share their living space with.
The findings point to a new way genetics and social interactions are connected. Certain commensal gut microbes can move between individuals through close contact. While genes themselves stay put, microbes do not. The study showed that some genes promote the growth of specific gut bacteria, and those bacteria can spread socially.
“This is not magic, but rather the result of genetic influences spilling over to others through social contact. Genes shape the gut microbiome and we found that it is not just our own genes that matter,” says Dr. Amelie Baud, a researcher at the Centre for Genomic Regulation in Barcelona and senior author of the study.
Three new gene microbe links identified in rats
The gut microbiome consists of trillions of microorganisms living in the digestive tract, where they play important roles in digestion and overall health. Diet and medications are known to strongly influence these microbial communities, but understanding how genetics contributes has been far more challenging.
In humans, researchers have reliably linked only two genes to gut bacteria. The lactase gene determines whether adults can digest milk and affects milk digesting microbes. The ABO blood group gene also influences gut bacteria, though the exact mechanisms remain unclear.
Scientists believe additional gene microbe links likely exist, but proving them is difficult because genetic and environmental factors overlap in everyday life. Genes can shape diet and lifestyle choices, which then influence the gut microbiome. At the same time, families and friends often share food, living spaces, and microbes, making it hard to separate nature from nurture.
To overcome these challenges, researchers at the Centre for Genomic Regulation and the University of California San Diego turned to rats. Rats share many key aspects of mammalian biology and can be raised under tightly controlled conditions, including identical diets.
Each rat in the study was genetically unique and belonged to one of four separate cohorts. These cohorts were housed at different facilities across the United States and followed different care routines, allowing researchers to test whether genetic effects remained consistent across environments.
By combining genetic data with microbiome profiles from all 4,000 rats, the team identified three genetic regions that consistently influenced gut bacteria across all four cohorts.
The strongest association involved the gene St6galnac1, which adds sugar molecules to the mucus lining of the gut. This gene was linked to higher levels of Paraprevotella, a bacterium believed to feed on these sugars. This connection appeared in every cohort.
A second genetic region included several mucin genes that help form the gut’s protective mucus layer and was associated with bacteria from the Firmicutes group. A third region contained the Pip gene, which produces an antibacterial molecule, and was linked to bacteria from the Muribaculaceae family. These bacteria are common in rodents and are also found in humans.
Genes can have social effects
The large size of the study allowed researchers, for the first time, to estimate how much of a rat’s microbiome was shaped by its own genes versus the genes of the rats it lived with.
A familiar example of this concept, known as indirect genetic effects, occurs when a mother’s genes influence her offspring’s growth or immune system through the environment she provides.
In this study, controlled living conditions made it possible to examine indirect genetic effects in a new context. The researchers developed a computational model to separate the influence of a rat’s own genes on its gut microbes from the influence of its social partners.
They found that the abundance of some Muribaculaceae bacteria was shaped by both direct and indirect genetic influences. This indicates that certain genetic effects can spread socially through the exchange of microbes.
When these social effects were added to a statistical model, the overall genetic influence on the three newly identified gene microbe links increased by four to eight times. The researchers caution that this may still underestimate the true extent of genetic influence.
“We’ve probably only uncovered the tip of the iceberg,” says Dr. 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 findings describe a mechanism in which genetic effects from one individual can spread through social groups by way of gut microbes, changing the biology of others without altering their DNA.
If similar processes occur in humans, and given growing evidence that the gut microbiome plays an important role in health, genetic influences on human health may be underestimated in large population studies. Genes may shape not only an individual’s disease risk, but also the disease risk of people around them.
What the findings could mean for human health
According to Dr. Baud, the microbiome has been linked to immune function, metabolism, and behavior. However, many reported associations do not necessarily reflect cause and effect, and the biological mechanisms are often unclear. Genetic studies using animal models in controlled environments can help move beyond correlations to testable explanations of how genes and gut microbes interact in health.
The researchers note that the rat gene St6galnac1 is functionally related to the human gene ST6GAL1, which has also been linked to Paraprevotella in previous studies. This suggests that the way animals coat their gut mucus with sugars may help determine which microbes thrive in the digestive system, potentially representing a shared mechanism across species.
The team also explored how this mechanism might influence infectious diseases such as COVID-19.
Other studies have linked ST6GAL1 to breakthrough SARS-CoV-2 infections, in which vaccinated individuals still become infected. Paraprevotella has also been shown to trigger the breakdown of digestive enzymes that the virus uses to enter host cells. Based on this, the researchers hypothesize that genetic variation in ST6GAL1 could affect Paraprevotella levels and, in turn, susceptibility to viral infection.
They also suggest a possible link to IgA nephropathy, an autoimmune kidney disease. Paraprevotella may alter IgA, an antibody that normally protects the gut. When altered, IgA can leak into the bloodstream and form clumps that damage the kidneys, which is a defining feature of IgA nephropathy.
Next, the researchers plan to closely examine how St6galnac1 affects Paraprevotella in rats and what chain reactions this relationship triggers in the gut and throughout the body.
“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,” Dr. Baud concludes.
