Across our bodies -- on our skin, in our mouth and nose, inside our intestines, on our genitalia, and in other places -- colonies of microorganisms flourish. We call these colonies of bacteria, viruses and fungi that live in and on our bodies the microbiota, or the microbiome. The largest microbiome colony lives in our gastrointestinal tract -- our gut -- and in healthy people, helps us do things like digest carbohydrates, produce vitamins and prevent harmful pathogens from flourishing. When there's a disruption to our gut microbiome, problems can arise.
Now, researchers are investigating how HIV and the microbiome are linked. At CROI 2016, and at a recent San Francisco General Hospital HIV Grand Rounds presentation, research was presented about how HIV and other things change the gut microbiome -- and if things like fecal microbial transplantation and probiotics can make it healthy again.
A Bit of Background About the Microorganisms in Our Gut
A huge variety of bacteria, viruses and fungi take up residence in the mucous linings of our gastrointestinal tract starting from the time we're born. Our diet, lifestyle and environment play a huge role in the type and diversity of microorganisms that a find a home in our gut. For instance, infants who are breastfed develop different gut microbiomes than those fed on formula. In general, people develop a gut microbiome "steady-state" that's normal, healthy and functions without issue. That's why we don't notice the estimated three extra pounds of microorganisms that we carry around with us every day.
Things that disrupt a healthy microorganism balance can cause problems. Antibiotics -- used to kill off disease-causing pathogens -- also kill off healthy gut bacteria. When this happens, disease-causing bacteria have the opportunity and real estate to set up shop in our gut. The bacteria C. difficile, which is sometimes spread in hospitals and other healthcare settings, can cause life-threatening illness in people whose gut microbiomes are destroyed by antibiotics.
A change in diet, lifestyle factors, and infection -- including HIV -- can also change the composition of your microbiome.
How HIV Changes the Gut Microbiome
"We know that HIV-positive people not on antiretroviral therapy have different gut microbiomes than people who are HIV-negative," said Ma Somsouk, M.D., M.A.S., an associate professor at the University of California San Francisco during a San Francisco General HIV grand rounds presentation. Here's why.
CD4 cells in the gut are more susceptible to the HIV virus than CD4 cells circulating in the blood because a larger percentage of gut CD4 cells have a protein on their surface, called CCR5, that the virus can use to bind and enter the cell. One type of CD4 cell in the gut that HIV enters and kills off, called Th17 cells, normally work to maintain the intestinal barrier and control intestinal bacteria. Destruction of these Th17 CD4 cells by HIV leads to something referred to as "microbial translocation" -- the leaking of harmful bacterial products into the blood stream.
While the total number of gut bacteria doesn't differ between HIV-negative and HIV-positive people, the composition of the microorganisms changes with HIV infection.
At CROI, Jesus Leuvano, from Ragon Institute of MGH, MIT and Harvard shared results from a study of the microbial communities analyzed from fecal samples in 137 participants. His team found samples taken from people with HIV tended to have higher proportions of a type of bacteria called Prevotella and lower proportions of a type of bacteria called Firmicutes. In addition, Leuvano shared that samples taken from HIV-negative participants had greater bacteria "richness" (or greater diversity in the types of bacteria that were detected).
Differences in Men Who Have Sex With Men
Muntsa Rocafort, from IrsiCaixa Institute for AIDS Research, presented an unexpected finding at the CROI microbiome session. In her study, men who have sex with men (MSM) had distinct microbiomes from other men. Fecal samples from the MSM in her team's study had higher proportions of Prevotella, while other men had higher proportions of Bacteroides. This was true for both HIV-negative and HIV-positive men in the study.
"We didn't expect these results," said Rocafort. "So it was quite surprising for us to find this difference between MSM and non-MSM. We did not have a specific variable that measured sexual practices, so we don't know the mechanism [that was responsible for this effect]."
What Are the Consequences?
Some people with HIV on antiretrovirals regain a normal gut microbiome, but many do not. Leuvano reported that among his study participants, the microbiomes of people with HIV changed, even if they were on antiretroviral therapy.
Some scientists think that an altered gut microbiome may contribute to the inflammation that people living with HIV experience, since studies have found that people with HIV who have altered gut microbiomes are more likely to have higher levels of inflammatory markers such as IL-6 in the blood. While these findings suggest a relationship, more research is needed to determine if the gut microbiome is responsible for the increased inflammation seen.
Stephanie Dillon, Ph.D., of University of Colorado Anschutz Medical Campus, presented research at CROI showing a possible link between the gut microbiome and a worsening of HIV disease. She found that some gut bacteria -- notably, the type of bacteria found in higher proportions in people living with HIV -- can impact the infectiousness of immune system cells.
She found that gram-negative bacteria enhanced CCR5 expression (a protein on the surface of CD4 cells) which can increase the ability of HIV to actively infect immune system cells. "It suggests that this might be a novel mechanism which potentially links the intestinal microbiome to HIV associated mucosal pathogenesis."
"Really, we don't know [if the altered microbiome of people with HIV causes health consequences]," said Somsouk. "But there are some observations that suggest increased inflammation depending on the microbial community that you harbor."
This excerpt was cross-posted with the permission of BETAblog.org. Read the full article.