Human immunodeficiency virus-1 (HIV-1) infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T-cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T-cell activation, inflammation, and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1-infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared with uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1-infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation, and blood T-cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection.

The prevalence of obesity in the United States has increased dramatically. The aim of this study was to determine trends in carbohydrate, fat, and protein intakes in adults and their association with energy intake by using data from the National Health and Nutrition Examination Survey (NHANES)-a representative sample of the US population. Data on adults aged 20-74 y from the first NHANES (NHANES I, 1971-1975; n = 13,106) were compared with data from NHANES 2005-2006 (n = 4381). Normal weight was defined as a body mass index (BMI; in kg/m(2)) of 19 to <25, overweight as a BMI of 25 to <30, and obese as a BMI of ≥30. Carbohydrate, fat, and protein intakes were obtained by dietary recall. Regression analyses were adjusted for potential confounders. The prevalence of obesity increased from 11.9% to 33.4% in men and from 16.6% to 36.5% in women. The percentage of energy from carbohydrates increased from 44.0% to 48.7%, the percentage of energy from fat decreased from 36.6% to 33.7%, and the percentage of energy from protein decreased from 16.5% to 15.7%. Trends were identical across normal-weight, overweight, and obese groups. Energy intake increased substantially in all 3 BMI groups. In NHANES 2005-2006, a 1% increase in the percentage of energy from protein was associated with a decrease in energy intake of 32 kcal (substituted for carbohydrates) or 51 kcal (substituted for fat). Similar findings were seen across all BMI categories, in men and women, and in NHANES I. Energy intake and the prevalence of obesity have increased dramatically. Dietary interventions should focus on decreasing energy intake and potentially by substituting protein for fat or carbohydrates.

Objective: Gut microbial translocation is a major driving force behind chronic immune activation during HIV-1 infection. HIV-1-related intestinal dysbiosis, including increases in mucosa-associated pathobionts, may influence microbial translocation and contribute to mucosal and systemic inflammation. Thus, it is critical to understand the mechanisms by which gut microbes and their metabolic products, such as butyrate, influence immune cell function during HIV-1 infection. Design: A cross-sectional study was performed to compare the relative abundance of butyrate-producing bacterial (BPB) species in colonic biopsies and stool of untreated, chronic HIV-1-infected (n = 18) and HIV-1-uninfected (n = 14) study participants. The effect of exogenously added butyrate on gut T-cell activation and HIV-1 infection was evaluated using an ex-vivo human intestinal cell culture model. Methods: Species were identified in 16S ribosomal RNA sequence datasets. Ex-vivo isolated lamina propria mononuclear cells were infected with C-C chemokine receptor type 5-tropic HIV-1_Bal, cultured with enteric gram-negative bacteria and a range of butyrate doses, and lamina propria T-cell activation and HIV-1 infection levels measured. Results: Relative abundance of total BPB and specifically of Roseburia intestinalis, were lower in colonic mucosa of HIV-1-infected versus HIV-1-uninfected individuals. In HIV-1-infected study participants, R. intestinalis relative abundance inversely correlated with systemic indicators of microbial translocation, immune activation, and vascular inflammation. Exogenous butyrate suppressed enteric gram-negative bacteria-driven lamina propria T-cell activation and HIV-1 infection levels in vitro. Conclusion: Reductions in mucosal butyrate from diminished colonic BPB may exacerbate pathobiont-driven gut T-cell activation and HIV replication, thereby contributing to HIV-associated mucosal pathogenesis.