HIV Gut Microbiome
We and others have found that HIV-infected individuals in the US have profoundly altered and highly characteristic gut microbiota composition. We subsequently have found that these gut microbiome differences were evident in men who have sex with men (MSM) who exhibit behaviors that put them at high risk of HIV infection and that HIV infection and Antiretroviral therapy (ART) induce unique and relatively subtle microbiome differences. Our current work broadly focuses on how these microbiome differences affect gut and systemic inflammation states, transmission in MSM, and metabolic and lung co-morbidities.
HIV Gut Microbiome and Co-Morbidity
Metabolic disease: HIV patients, including those on long-term ART, suffer a greater incidence of diseases with a potential link to gut microbiota activity, such as metabolic and lung disease. In ongoing work, we are exploring the role of the gut microbiome in metabolic disease in HIV infected populations with and without lipodystrophy (https://www.clinicaltrials.gov/ct2/show/NCT02258685
). We are also conducting a diet intervention to assess whether a high-fiber/low-fat diet prevents systemic and gut inflammatory and metabolic disease phenotypes in HIV infected and high-risk MSM (https://www.clinicaltrials.gov/ct2/show/NCT02610374
) (Figure 1). This work, which is conducted in study participants in Colorado, is complimented by a study that we are conducting in Zimbabwe, where we are assessing the gut microbiome, inflammatory and metabolic disease phenotypes in HIV-infected and control individuals living in rural and urban centers eating a range of diets (relatively agrarian versus “Western”).
Gut:lung axis: We are also researching a link between gut microbiome composition in individuals with HIV infection and increased susceptibility to Streptococcal pneumonia both by working with human samples and with gnotobiotic mice. We hypothesize that relationships between the gut microbiome and altered susceptibility to pneumococcal infection in the lung may be mediated by translocated bacterial products/metabolites (Figure 2).
HIV and MSM Gut Microbiome as a driver of Inflammation and disease transmission
We have been using multi’omic analyses of intestinal biopsy, feces, and blood and laboratory experiments in vitro and in gnotobiotic mice to predict and test interactions between microbes and immune cell populations that influence local and systemic inflammation in HIV positive and high risk MSM and a potential role for these interactions in chronic inflammation observed in HIV-positive individuals and in disease transmission via anal intercourse in HR-MSM. We have found that fecal bacteria from HIV positive and HR-MSM induce great inflammation compared to controls both when they are used to stimulate human immune cells isolated from blood and gut tissue
, and when they are introduced until gnotobiotic mice
. We have found that CD4+ T cells that are stimulated with fecal bacteria from MSM are more readily infected by HIV in vitro than when stimulated with bacteria from controls.