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Number and Diversity of Gut Microbes Lower With HIV and Tied to Activation
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CROI 2014, March 3-6, 2014, Boston
Mark Mascolini
Compared with healthy HIV-negative people, a group with HIV had significantly lower numbers and diversity of gut microbiota [1]. Reduced microbiota richness and diversity correlated with microbial translocation, monocyte activation, and immune dysfunction in this small comparative study.
Researchers from the Karolinska Institute and colleagues from other centers noted that the intestinal mucosal barrier endures abnormalities during progressive HIV infection, with changes including translocation of microbial products and subsequent chronic systemic inflammation. (Microbial translocation is movement of viable bacteria or bacterial products across the intestinal wall and into the lymphatic system, liver, spleen, kidney, or peripheral circulation [2].)
To determine how gut microflora are altered in people with HIV infection--and how antiretroviral therapy may affect that process--these investigators prospectively compared gut microbiota in 32 HIV-positive people and 9 healthy HIV-negative controls. They did not include people taking antibiotics or probiotics in the past 2 months or people with infectious diarrhea. Among people with HIV, including 3 elite controllers, median CD4 count stood at 355 (interquarile range 120 to 2470). (Elite controllers maintain a high CD4 count and low viral load without antiretroviral therapy.)
The researchers collected plasma and fecal samples from all participants at a baseline visit and a median of 10 months later in 19 people who had started antiretroviral therapy. The researchers used deep sequencing of the 16S rRNA gene to evaluate microbiota composition. They also evaluated soluble markers of microbial translocation and monocyte activation.
Numbers and alpha diversity of observed bacterial species were lower in HIV-positive participants than in HIV-negative controls. Reduced baseline microbiota richness and alpha diversity in people with HIV correlated with markers of microbial translocation, monocyte activation, and immune dysfunction. Baseline alpha diversity correlated significantly with CD4 percent (r = 0.42, P = 0.01) and CD8 percent (r = -0.37, P = 0.03). Twelve HIV-positive people with a detectable viral load and low microbiota diversity had significantly lower CD4 counts than 19 viremic patients with high microbiota diversity (about 250 versus 400, P = 0.01).
Microbiota of the 3 elite controls resembled microbiota of healthy controls. Compared with viremic HIV-positive people, elite controllers had an increased relative abundance of bacteroidetes. Elite controllers and HIV-negative controls had lower levels of actinobacteria than viremic HIV-positive people. In the 16 people who started antiretroviral therapy, gut flora abnormalities persisted after a median of 10 months and alpha diversity of microbiota declined significantly from baseline measures (P = 0.006).
Because starting antiretroviral therapy did not restore microbiota diversity, the researchers proposed that adjuvant therapy may be needed to reshape microbiota in people with HIV infection. Similar gut microbiota in HIV-positive elite controllers and HIV-negative controls suggested to the investigators "that a healthy state of gut microbiota may be associated with delayed disease progression."
References
1. Nowak P, Barqasho B, Avershina E, et al. Decreased diversity of gut microbiota is associated with immune status during HIV-1 infection. CROI 2014. Conference on Retroviruses and Opportunistic Infections. March 3-6, 2014. Boston. Abstract 315.
2. Berg RD. Bacterial translocation from the intestinal tract. Adv Exp Med Biol. 1999;473:11-30.
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