HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy.

The IFN-I response is compartmentalized during chronic untreated HIV-1 infection, with IFNβ being more predominant in the gut. Gut IFN-I responses are associated with immunopathogenesis, and viral replication is likely a major driver of this response.

The preference of the sleep/wake cycle can be grouped into categories or chronotypes. Inflammatory bowel disease (IBD) has been linked to poor sleep quality which correlates with disease severity. Social jet lag (SJL) is the difference between sleep timing on work and free days and is a marker for circadian misalignment which has been linked to increased inflammation. We investigated whether chronotype, SJL, sleep debt (SD), and food timing were associated with an IBD specific complications and a lower quality of life. Overall, 191 subjects (115 IBD subjects and 76 healthy controls (HC)) completed the Pittsburgh Sleep Quality Index (PSQI), Morningness-Eveningness Questionnaire (MEQ), Munich ChronoType Questionnaire (MCTQ), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and a structured Food Timing Questionnaire. Later chronotype (by MEQ) was associated with a worse SIBDQ (r = -0.209; P < 0.05). SJL was increased in IBD at 1.32 h ± 1.03 vs. 1.05 h ± 0.97 in HC, P < 0.05, when adjusted for age. SJL (>2 h) was present in 40% of severe/complicated Crohn's patients (fistulizing or structuring Crohn's or history of Crohn's related surgery) compared to only 16% of uncomplicated Crohn's patients (P < 0.05). Sleep debt was increased in IBD subjects compared to HC at 21.90 m ± 25.37 vs. 11.49 m ± 13.58, P < 0.05. IBD subjects with inconsistent breakfast or dinner times had lower SIBDQ scores (4.78 ± 1.28 vs. 5.49 ± 1.02, P < 0.05; 4.95 ± 0.31 vs. 5.42 ± 0.32, P < 0.05 respectively). In summary, later chronotype, and markers of circadian misalignment (social jet lag, sleep debt, and inconsistent meal timing) were associated with IBD disease specific complications and/or lower quality of life.

Background HIV-infection is associated with dramatic changes in the intestinal mucosa. The impact of other viral pathogens is unclear. Methods Eighty biopsies from left and right colon (n=63) and terminal ileum (n=17) were collected from 19 HIV-infected and 22 HIV-uninfected subjects. Levels of cytomegalovirus (CMV) and Epstein Barr Virus (EBV) DNA were measured by droplet-digital (dd)PCR. Mucosal gene expression was measured via multiplex-assay. Microbiome analysis was performed using bacterial 16S-rDNA-pyrosequencing. The effect of CMV and EBV replication on the microbiome composition and mRNA-expression of selected cytokines (IL-6, IFN-γ, IL-1β, CCL2, IL-8 IFN-β1) was evaluated. RESULTS Overall, CMV and EBV were detected in at least one intestinal site in 60.5% and 78.9% of subjects, respectively. HIV-infected individuals demonstrated less detectable CMV (p=0.04); CMV was more frequently detected in terminal ileum than colon (p=0.04). Detectable EBV was more frequent among HIV-infected (p=0.05) without differences by intestinal site. The number of operational taxonomic units did not differ by CMV or EBV detection status. Among HIV-infected subjects, higher CMV was only associated with lower relative abundance of Actinobacteria in the ileum (p=0.03). Presence of CMV was associated with up-regulated expression of all selected cytokines in the ileum (p<0.02) and higher expression of IL-8 and IFN-β1 in the colon (P<0.05) of HIV-uninfected subjects, but not among HIV-infected. EBV had no effect on cytokine expression or microbiome composition whatsoever. CONCLUSIONS These results illustrate a complex interplay between HIV-infection, intestinal CMV replication and mucosal gut environment, and highlight a possible modulatory effect of CMV on the microbial and immune homeostasis.

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