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People’s sexual partners could impact both their gut microbiome and their immune system, according to a new study from the University of Colorado, Denver, done in mice.

Mice that received stool transfers from men who had anal intercourse had different microbiomes than mice whose stool donors only had vaginal intercourse, the study found. When researchers checked the mice’s immune systems, the mice whose stool donors had anal intercourse also showed signs that, were they human, they might have a higher risk of HIV infection.


The new mouse study — published Thursday in PLoS Pathogens — is very preliminary, but it underscores just how little we know about the microbiome and its connections to the immune system, as well as its impact on susceptibility to infections like HIV.

“I think it’s really interesting to the HIV-microbiome field overall,” said Sam Li, a postdoctoral fellow at UCD and the first author on the paper.

Li and his colleagues gathered stool samples from 35 healthy men, then transferred those samples to mice that had been specifically bred to lack a gut microbiome. Then, they analyzed the T cells they found in the mice’s blood and guts. (The team used stool samples from men with HIV as a control group, since immune activation can be associated with HIV infection.)


Specifically, they found an increased number of activated T cells with a particular receptor called CD4 in the mice that received a stool transfer from men who only had anal intercourse. Higher numbers of activated T cells with CD4 have been associated with an increased risk of becoming infected with HIV.

Li and his colleagues also looked for a relatively high number of activated T cells carrying CD8 receptors in those same mice; a higher number of these cells are often found in people already infected with HIV who have a higher “viral load,” which can be a sign that the disease is progressing.

“HIV is still a problem worldwide, and the more we learn about what makes certain populations more susceptible to HIV, the more we can help,” said Laurel Lagenaur, the director of research at Osel. “Understanding that biological component, whether it’s in women or in men, helps us define ways that we can help modulate that.”

Lagenaur was not involved in Li’s research, but she is well-versed in the connection between a human microbiome and HIV. Osel, a California-based company, is modifying a particular type of bacteria that’s often found in the vaginal microbiome so the bacteria will produce a protein that decreases the risk of contracting HIV. In theory, the company’s website says, this kind of modified bacteria could be useful to women who want to control their HIV transmission risk without relying on condoms.

Li’s study comes with some limitations. The type of sequencing done in the paper can’t show what exactly the bacteria are doing to cause this effect. Only 35 human donors were involved and all of them were men, which means this study can’t tell us anything about what link exists or doesn’t exist for women. (Other papers have done that, Lagenaur noted.) It is also unclear whether the same findings would be replicable in the human microbiome; one bacterial species that’s known to be more prevalent among men who only have anal intercourse doesn’t transplant well to mice, Lagenaur noted.

“I want to be clear that our study does not show a link between the microbiome and HIV transmission in humans,” Li said. “The data strongly suggests that there could be a link, and provides a strong rationale for doing those studies in humans.”

And the study doesn’t answer one burning question: Why does a person’s choice of sexual partners impact their microbiome? “The cause of these microbiome differences is still not clear,” Li said. “There could be other behaviors that we may have missed in our survey that may be linked to these microbiome differences.”

Still, there are reasons to be interested in papers like this one, Li said. Microorganisms make up a significant part of the human body, and figuring out how they work will be crucial to understanding how drug developers could harness them — especially as an increasing number of companies are interested in the immune system.

Some of the leaders in the field have begun clinical trials for microbiome-based drugs that will work together with checkpoint inhibitors, which are immunotherapy drugs that override a tumor’s ability to hide itself from a person’s immune system.

Especially in this part of the field, it’s clear there’s still plenty to learn. The Parker Institute announced Tuesday that over-the-counter probiotics may decrease the efficacy of immunotherapies for melanoma for some people, according to a study it conducted with researchers at the MD Anderson Cancer Center. That same day, Seres presented preclinical data indicating that some microbes may be necessary for immunotherapies to work — also done with MD Anderson partners.

Ultimately, understanding how exactly microbes can impact the immune system will be important as people try to exploit that relationship, Langenaur said. “That may not be as easy at all, but without understanding it, you can never get there. This is certainly a first step in understanding how that might come about.”

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