Have Some Guts

Is there more benefit to probiotics than we thought?
by Jeannie Wraight

Probiotics are live microorganisms that help to preserve the good bacteria and balance of organisms (microflora) in the gut. Probiotics have been utilized for their health benefits for nearly a century. An essential question now being asked is how much benefit can be obtained through the use of probiotics in HIV disease? Can probiotics help change the course of disease progression? Three important studies examine whether probiotics can positively affect HIV disease progression by helping to reduce the destruction of GALT tissue through the reestablishment of healthy flora in the gut, reducing inflammation, and restoring GALT tissue to a healthier state.

HIV progression is closely associated with chronic immune activation. Upon initial HIV infection, massive damage is done to the gut mucosal CD4+ 17 cells that sets the course of disease progression. Recent data indicates that preservation of Th17 cells in the gut-associated lymphoid tissue (GALT) tissue may help preserve viral host restrictive factors that assist cells in fighting HIV. Normal gut flora has been shown to induce the maturation of CD4+ 17 cells in the small intestine.

Although presently a debatable topic, several studies have shown that microbial translocation—the leaking of normally friendly bacteria from the gut into the systemic circulation—and an increase in lipopolysaccharide (LPS) levels correlate with HIV disease progression. There is ongoing deliberation to determine whether these factors are a cause or a consequence of HIV disease progression. Bacterial LPS in the circulation activate immune cells, which results in the acceleration of HIV replication and progression.

The AIDS Healthcare Foundation (AHF) sponsored a double blind, randomized, placebo-controlled Phase II clinical trial to measure the safety and efficacy of GanedenBC30 probiotics on the immune system.

The study measured the effects of GanedenBC30 on CD4 cells and gastrointestinal symptoms such as diarrhea, nausea, and bloating, on twenty-four HIV-positive participants over twenty-four days.

GBI-30 contains a probiotic strain called Bacillus coagulans. A stark benefit of this probiotic is that it can withstand extreme heat, cold, and stomach acid. This allows it to reach the gut where it can successfully colonize the intestines with beneficial bacteria.

GBI-30 has been shown to significantly increase the T-cell production of TNF-alpha, a key immune marker, in a study of its effects on immune responses to common viral respiratory tract infections such as influenza and colds. GBI-30 also was shown to reduce abdominal pain and bloating in irritable bowel syndrome.

The AHF GanedenBC30 study is complete and results will be released at the 19th International AIDS Conference in Washington, D.C., in July of this year.

Oslo University Hospital is currently recruiting participants for a randomized, double-blind Phase II study of Progut, a multi-strain of probiotics, previously used in farm animals.

The 100-participant, two-month study will measure safety as well as efficacy of Progut in participants not receiving ART as well as those on ART without normalized CD4 counts (below 500).

This study will measure the changes in microbial translocation, specifically LPS and soluble CD14 levels. Changes in immune activation, expressly CD38 cells, HLA-DR and PD-1 on CD4 T-cells will also be evaluated.

Secondary outcomes include disease progression in untreated participants (viral load, CD4 cells, clinical events and indication for ART initiation), immune reconstitution in ART treated patients (changes in CD4 count) and changes in gut microbiotia in both groups.

A pending trial sponsored by The National Institute of Drug Abuse (NICHD) and the National Institute on Mental Health (NIMH) will measure LPS levels and immune activation in HIV-positive adolescents when treated with Lactobacillus plantarum probiotics. Lactobacillus plantarum has been shown to have a benefit effect on gastrointestinal effects in patients with irritable bowel syndrome.

This randomized, double blind, placebo-controlled, multicenter trial will measure if once-daily probiotics therapy (Lactobacillus plantarum) will decrease LPS levels, levels of plasma pro-inflammatory cytokines, macrophage activation, and T-cell activation markers, and also affect viral load levels, CD4 count, and stool microbial composition.

This thirty-two week, eighty-patient trial will be conducted in sites through out the United States.

The results of these studies may be highly pertinent to our knowledge of HIV pathogenesis as well as affect and improve the course of treatment of HIV disease. If probiotics are shown to adequately lower LPS levels and microbial translocation to effect disease progression, probiotics could be used to slow disease, prolong the need for initiation of ART, and better the degree of immune reconstitution with ART.

Additionally, the effect of such research on HIV treatment could be immense and especially beneficial to the care of HIV-positive individuals in developing nations, where access to HIV antiretrovirals is sparse. The advantage to PEPFAR alone in terms of decreasing individual cost by pre-empting the need for ARVs, allowing larger numbers of people to be treated, warrants greater attention than is being granted. Curious is why a study such as the one being conducted by NICHD and NIMH would not be designated instead to a more appropriate branch of the NIH, in particularly the AIDS Clinical Trials Groups, where the results would garner significantly more attention.

Jeannie Wraight has been an AIDS treatment activist and HIV writer for over fifteen years. She lives in New York City.

May 2012