TY - JOUR
T1 - Vagal dysfunction and small intestinal bacterial overgrowth
T2 - Novel pathways to chronic inflammation in HIV
AU - Robinson-Papp, Jessica
AU - Nmashie, Alexandra
AU - Pedowitz, Elizabeth
AU - Benn, Emma K.T.
AU - George, Mary Catherine
AU - Sharma, Sandeep
AU - Murray, Jacinta
AU - MacHac, Josef
AU - Heiba, Sherif
AU - Mehandru, Saurabh
AU - Kim-Schulze, Seunghee
AU - Navis, Allison
AU - Elicer, Isabel
AU - Morgello, Susan
N1 - Funding Information:
The current study was funded by the National Institutes of Health (PI: J.R.-P., R21DK105917:‘Autonomic neuropathy, gastrointestinal motility, and inflammation in HIV’). Additional laboratory support was provided by U24MH100931:‘The Manhattan HIV Brain Bank.’
Publisher Copyright:
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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.
AB - 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.
KW - HIV
KW - autonomic
KW - gastric emptying
KW - inflammation
KW - small intestinal bacterial overgrowth
KW - vagal
UR - http://www.scopus.com/inward/record.url?scp=85048358730&partnerID=8YFLogxK
U2 - 10.1097/QAD.0000000000001802
DO - 10.1097/QAD.0000000000001802
M3 - Article
C2 - 29596112
AN - SCOPUS:85048358730
SN - 0269-9370
VL - 32
SP - 1147
EP - 1156
JO - AIDS
JF - AIDS
IS - 9
ER -