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How Gut Microbiota Impacts HIV Disease


Senior Member

Eight days after exposing monkeys to SIV, the simian equivalent of HIV, Adam Ericsen, an immunologist at the University of Wisconsin–Madison saw “up to a 1,300-fold increase of bacteria circulating in the blood” of the animals. The temporal association—the number of bacteria increased in the blood before the SIV appeared in the blood—led him to believe that the virus first attacks CD4+ T cells that help protect the gut wall from microbial translocation. But then, as the animal's immune system began to exercise some control over the virus and gut barrier function improved, the level of bacteria in the blood declined. He suggests that modulating this activity might reduce the initial burst of inflammation that fuels HIV infection and the establishment of viral set points and the seeding of reservoirs.

Meanwhile on the Pacific Coast, Jennifer Manuzak, a U.W. immunologist, administered a probiotic called PBio to uninfected monkeys to modulate a more favorable microbial ecosystem in the gut and improve immune function. She found “an increase in IgG- [immunoglobulin-] producing B cells in both the colon and the lymph nodes” as well as an increase in T helper cells in the lymph nodes.

This upcoming study is also worth keeping an eye on:

Ma Somsouk, gastroenterologist from the University of California, San Francisco, hoped that an FMT might restore balance to the gut of HIV patients experiencing dysbiosis and immune activation that can lead to things like cardiovascular disease. After trying it in six patients Somsouk found there was little benefit. Luckily, the subjects experienced the same few side effects as other patients who have tried FMT. The main problem appeared to have been minimal engraftment—the transplanted organisms did not thrive and supplant the bugs that were already present and causing dysbiosis. Somsouk, however, was not surprised. With C. difficile a combination of antibiotics and massive diarrhea wipes out most of the bacteria in the gut, so the transplanted organisms have little competition in colonizing the gut. Somsouk was transplanting his organisms into the microbial equivalent of Manhattan and most of them got lost in the crowd.

The next phase of the study will first “condition” patients with antibiotics to knock down the local population of bacteria, as has already taken place in trying unsuccessfully to treat C. difficile patients, Somsouk says. It is similar to how radiation and chemotherapy are used to “condition” patients for a bone marrow transplant, to improve engraftment of transplanted immune cells. Somsouk thought all along that conditioning probably would be necessary to improve the changes of engraftment but he wanted to first try the less invasive approach using no antibiotics. He hopes to begin that second study in 12 patients later this year.