Alterations in the gut microbiome by HIV-1 infection or a high-fat diet associates with systemic immune activation and inflammation in double humanized-BLT mice

Surgery was performed on NSG mice to create humanized bone-marrow, liver, thymus mice (hu-mice). In order to create double hu-mice, the hu-mice were treated with broad spectrum antibiotics to deplete murine gut bacteria and subsequently transplanted with human fecal material from healthy human donors. We characterized 262 fecal samples from hu-mice, double hu-mice, and human fecal donors to determine the impact of HIV-1 infection or high fat diet on the gut microbiome and systemic immune activation and inflammation. We found that HIV-1 infection altered the human-like gut microbiome of double hu-mice, which was associated with decreased human CD4 T cells and increased systemic inflammation and immune activation. Further, using a high fat diet we induced gut microbial dysbiosis in double hu-mice which corresponded with increased systemic immune activation and inflammation.