Vagal dysfunction and small intestinal bacterial overgrowth: novel pathways to chronic inflammation in HIV.

TitleVagal dysfunction and small intestinal bacterial overgrowth: novel pathways to chronic inflammation in HIV.
Publication TypeJournal Article
Year of Publication2018
AuthorsRobinson-Papp, J, Nmashie, A, Pedowitz, E, Benn, EKT, George, MCatherine, Sharma, S, Murray, J, Machac, J, Heiba, S, Mehandru, S, Kim-Schulze, S, Navis, A, Elicer, I, Morgello, S
Date Published2018 06 01
KeywordsAdolescent, Adult, Aged, Bacterial Translocation, Blind Loop Syndrome, Breath Tests, Cross-Sectional Studies, Cytokines, Gastric Emptying, Gastrointestinal Motility, HIV Infections, Humans, Inflammation, Macrophage Activation, Middle Aged, Prevalence, Vagus Nerve Diseases, Young Adult

OBJECTIVE: Chronic inflammation in HIV-infected individuals drives disease progression and the development of comorbidities, despite viral suppression with combined antiretroviral therapy. Here, we sought evidence that vagal dysfunction, which occurs commonly as part of HIV-associated autonomic neuropathy, could exacerbate inflammation through gastrointestinal dysmotility, small intestinal bacterial overgrowth (SIBO), and alterations in patterns of soluble immune mediators.DESIGN: This is a cross-sectional observational study.METHODS: Forty participants on stable combined antiretroviral therapy with gastrointestinal symptoms, and no causes for vagal or gastrointestinal dysfunction other than HIV, underwent autonomic testing, hydrogen/methane breath testing for SIBO, and gastric emptying scintigraphy. A panel of 41 cytokines, high-mobility group box 1, and markers of bacterial translocation (lipopolysaccharide) and monocyte/macrophage activation (sCD14 and sCD163) were tested in plasma.RESULTS: We found that participants with vagal dysfunction had delayed gastric emptying and higher prevalence of SIBO. SIBO was associated with IL-6, but not sCD14; lipopolysaccharide could not be detected in any participant. We also found alteration of cytokine networks in participants with vagal dysfunction, with stronger and more numerous positive correlations between cytokines. In the vagal dysfunction group, high mobility group box 1 was the only soluble mediator displaying strong negative correlations with other cytokines, especially those cytokines that had numerous other strong positive correlations.CONCLUSION: The current study provides evidence that the vagal component of HIV-associated autonomic neuropathy is associated with changes in immune and gastrointestinal function in individuals with well treated HIV. Further study will be needed to understand whether therapies targeted at enhancing vagal function could be of benefit in HIV.

Alternate JournalAIDS
PubMed ID29596112
PubMed Central IDPMC5945300
Grant ListR01 DK112296 / DK / NIDDK NIH HHS / United States
R21 DK105917 / DK / NIDDK NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States