HIV in the gut research

[Almost2late]

With many of us who experience bouts with diarrhea, think this sort of research is so important to plwh.. My understanding of this is that the gut is where HIV makes it self at home first and causes havoc.. I think..

How Gut Microbiota Impacts HIV Disease
A new understanding of the role gut microbiota plays in HIV disease is beginning to emerge, suggesting potential new strategies to manage the infection
By Bob Roehr on March 1, 2016

HIV is a disease of the gut, a concept that’s easy to lose sight of with all the attention paid to sexual transmission and blood measurements of the virus and the CD4+ T cells it infects and kills. But the bottom line is that about two thirds of all T cells reside in the lymphoid tissue of the gut, where the virus spreads after exposure, even before it shows up in blood.
Blood, however, has been the focus of research and care because it is easy to sample and broadly represents what is going on throughout the entire body. The gut is a lot harder to access, which is why much of it remains a crudely delineated terrain that can only be examined with blunt and invasive tools. But a better understanding of the gut environment will be necessary to achieve the next level of advances in comprehending the disease and fashioning better interventions, researchers said last Wednesday at the annual Conference on Retroviruses and Opportunistic Infections in Boston. “Why do we care about the microbiome?” asked Nichole Klatt, a University of Washington (U.W.) pathobiologist, whose lab focuses on mucosal immunology. Klatt, who organized and chaired the conference session, answered her own rhetorical question, summarizing that HIV infection decreases the number and diversity of beneficial bacteria and increases those that have negative effects on the gut. “There are health consequences to dysbiosis,” she said.
One main area of investigation, dysbiosis, is a perturbation of the microbiome that allows organisms inside the gut to escape through the gut barrier wall into surrounding space and eventually enter the bloodstream. Dysbiosis is a general process where various forms of disruption involving different microbes, at locations along the roughly nine meters of the intestinal tract are likely to cause different medical problems.
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. These and other findings suggested that it is possible to enhance the immune response in the gut and could work as a way to increase immune responses to vaccination that typically are weaker in people infected with HIV, the elderly and other persons at risk. But Manuzak cautions against expecting commercially available probiotics to deliver the same results; there is simply no data to support that belief.
Just how does HIV infection affect the human gut microbiome? The answer may depend on where you look. Jesus Luevano, a medical student at Harvard Medical School and a researcher the Ragon Institute examined bacterial communities from the gut of 145 people in Boston and 120 subjects in Uganda. He found very little difference between samples from the gut of HIV- positive and negative persons in Uganda, but a significant difference in Boston. Interestingly, the healthy HIV-negative Bostonians were the outliers, the guts of the other three groups was relatively similar; that was particularly true of untreated persons on both continents. “HIV-uninfected patients had much greater richness in their samples as well as a unique population that was primarily composed of bacteria from the phylum Fermicutes,” Luevano says. Viral load and treatment also had effects on community composition, but the number of persons in each subgroup of the study was too small to say anything more.
Fecal microbial transplantation (FMT) has gained acceptance for treating Clostridium difficile infection, a life threatening and difficult to treat dysbiosis that often is caused by heavy use of antibiotics. The procedure, which has a 90 percent success rate, transplants the fecal microbial ecosystem from a healthy person into a sick one, often using a colonoscope for inserting the material, to restore a healthy equilibrium.
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.

http://www.scientificamerican.com/article/how-gut-microbiota-impacts-hiv-disease/

[Almost2late]

Research of this particular probiotic is proving beneficial to the gut of hiv+ people..

. Probiotic improves gut barrier function in patients with HIV

Probiotic supplementation improved the physical and immunological integrity of the intestinal mucosal barrier in HIV-1-positive patients being treated with antiretroviral therapy, according to new research.

These findings are significant as intestinal epithelial cells are often damaged by the virus in patients with HIV, even after treatment with antiretrovirals, and a compromised intestinal mucosal barrier “can result in a low-grade, long-term, systemic immune activation and inflammation which is commonly associated with a variety of HIV-related comorbidities, such as cardiovascular disease, kidney disease, diabetes, and bone fracture,” according to a press release.

The researchers sought to evaluate the effects of a high potency multistrain probiotic — marketed in the U.S. as Visbiome (ExeGi Pharma) and Vivomixx in Europe — on intestinal immunity in HIV-1 patients on antiretroviral therapy. They performed a sub-study of a pilot longitudinal, non-randomized, single arm trial of 10 patients who received the supplement twice daily for 6 months between May 2014 and February 2015. All patients were white men with a median age of 42 years, and were all on antiretroviral therapy for a median of 6 years.

Histological and immunohistochemical analyses of intestinal biopsies revealed a number of clinical and biochemical markers demonstrating improved integrity of the gastrointestinal epithelial cell wall and reduced systemic inflammation.

“We believe this is the first time a probiotic has been shown to clearly improve the integrity of the GI epithelial cell wall in HIV patients,” Giancarlo Ceccarelli, MD, PhD, clinical researcher and HIV treatment specialist at Sapienza University in Rome, said in the press release. “There appear to be multiple therapeutic mechanisms at work, but the improvement in Th17 immune cells in the GI tissue was of particular interest. In the HIV population, a depletion of Th17 in the gastrointestinal tract is common and is a significant driver of the loss of intestinal barrier function.”

Patients reported their adherence was excellent, and the supplement appeared to be safe with no related adverse reactions.

The investigators concluded that these findings demonstrate the potential benefits of probiotic supplementation for restoring mucosal intestinal barrier integrity in HIV-1 patients treated with antiretroviral therapy, but emphasized that the results should not be generalized to all probiotics, as “it is the probiotic strain itself which determines the efficacy of the product and hence the associated findings.” This is especially important in immunocompromised patients, they added.

Two large studies of Visbiome in HIV patients are ongoing in the U.S. and Canada, according to the press release. One, a multicenter study being led by the NIH-funded AIDS Clinical Trials Group, is evaluating whether the supplement can reduce systemic inflammation in these patients, with results expected early next year.

http://www.healio.com/gastroenterology/therapeutics-diagnostics/news/online/%7B08d3f230-1668-446b-8a0b-61db609e422f%7D/probiotic-improves-gut-barrier-function-in-patients-with-hiv

[tryingtostay]

I've noticed my bowel movements go from the point of decent to chronically loose and unhealthy.  Almost went to see a GI doctor after my ID doc told me it could be from anything... almost cost me heavy


Thanks for sharing.

[Jim Allen]

Thanks for sharing.