But while sequencing the people’s gut bacteria, the team turned up differences in microbiome composition between men who have sex with men (MSM) and men who have sex with women (MSW). As HIV risk is known to be elevated in MSM compared to MSW, the researchers set out to investigate whether these microbiome differences might be playing a role in that risk.
The researchers compared gut microbiome samples from MSM—both HIV-positive and HIV-negative men deemed high-risk due to factors such as a history of unprotected sex—with samples from HIV-negative MSW. They found that, regardless of HIV status, MSM had consistently different microbiome compositions and higher activation of T cells in the gut (PLOS Pathog, 15:e1007611, 2019).
Elevated immune activity has previously been associated with increased risk of HIV and with disease progression. To find out if microbiome composition was responsible for the difference in immune activation, the researchers transplanted fecal matter from MSM and MSW into germ-free mice. Mice given microbes from MSM showed increased immune activation compared to animals that received fecal matter from MSW. And when the team cultured human gut lining cells in the presence of HIV and fecal microbes from the study participants, the microbiota from MSM promoted significantly higher rates of cellular HIV infection than did microbes from MSW.
The idea that the microbiome of MSM “might actually confer them a higher risk of becoming infected with HIV is certainly worth exploring further,” Roger Paredes, a microbial geneticist atIrsiCaixa AIDS Research Institute in Barcelona, Spain, who was not involved in the study, writes in an email to The Scientist.
It’s not clear why MSM’s microbiomes differ from those of MSW—the team found that lifestyle factors such as diet or frequency of anal sex didn’t explain the microbiome differences, Lozupone says, adding that the team is now looking for other factors that might play a role. The researchers will also focus on what microbial species are associated with the risk, what biological pathways they activate, and whether some microbial taxa may help keep immune system activation in check.