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

Vagal dysfunction and small intestinal bacterial overgrowth: novel pathways to chronic inflammation in HIV.
Author Information (click to view)

Robinson-Papp J, Nmashie-Osei A, Pedowitz E, Benn EKT, George MC, Sharma S, Murray J, Machac J, Heiba S, Mehandru S, Kim-Schulze S, Navis A, Elicer I, Morgello S,


Robinson-Papp J, Nmashie-Osei A, Pedowitz E, Benn EKT, George MC, Sharma S, Murray J, Machac J, Heiba S, Mehandru S, Kim-Schulze S, Navis A, Elicer I, Morgello S, (click to view)

Robinson-Papp J, Nmashie-Osei A, Pedowitz E, Benn EKT, George MC, Sharma S, Murray J, Machac J, Heiba S, Mehandru S, Kim-Schulze S, Navis A, Elicer I, Morgello S,

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AIDS (London, England) 2018 03 28() doi 10.1097/QAD.0000000000001802

Abstract
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 which 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.

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