The effect of pyridostigmine on small intestinal bacterial overgrowth (SIBO) and plasma inflammatory biomarkers in HIV-associated autonomic neuropathies

Abstract

Small intestinal bacterial overgrowth (SIBO) is common among patients with HIV-associated autonomic neuropathies (HIV-AN) and may be associated with increased bacterial translocation and elevated plasma inflammatory biomarkers. Pyridostigmine is an acetylcholinesterase inhibitor which has been used to augment autonomic signaling. We sought preliminary evidence as to whether pyridostigmine could improve proximal gastrointestinal motility, reduce SIBO, reduce plasma sCD14 (a marker of macrophage activation and indirect measure of translocation), and reduce the inflammatory cytokines IL-6 and TNFα in patients with HIV-AN. Fifteen participants with well-controlled HIV, HIV-AN, and SIBO were treated with 8 weeks of pyridostigmine (30 mg PO TID). Glucose breath testing for SIBO, gastric emptying studies (GES) to assess motility, plasma sCD14, IL-6, and TNFα, and gastrointestinal autonomic symptoms were compared before and after treatment. Thirteen participants (87%) experienced an improvement in SIBO following pyridostigmine treatment; with an average improvement of 50% (p = 0.016). There was no change in gastrointestinal motility; however, only two participants met GES criteria for gastroparesis at baseline. TNFα and sCD14 levels declined by 12% (p = 0.004) and 19% (p = 0.015), respectively; there was no significant change in IL-6 or gastrointestinal symptoms. Pyridostigmine may ameliorate SIBO and reduce levels of sCD14 and TNFα in patients with HIV-AN. Larger placebo-controlled studies are needed to definitively delineate how HIV-AN affects gastrointestinal motility, SIBO, and systemic inflammation in HIV, and whether treatment improves clinical outcomes.

Keywords: Autonomic neuropathy; Dysmotility; HIV; Inflammation; Pyridostigmine; SIBO.

Figures

Figure 1.

Flow of participants through the study Abbreviations: COPD= chronic obstructive pulmonary disease, GI=gastrointestinal

Figure 2.

Dark gray bars represent baseline and light gray bars follow-up after 8-weeks of pyridostigmine treatment for each of the fifteen participants who completed the study. Units for the breath test results are parts per million; units for sCD14, TNFα and IL-6 are mean florescence intensity.

Figure 3.

Median percent retention of gastric contents as a function of time (minutes) pre- (dark gray) and post-pyridostigmine (light gray) treatment among the fifteen participants who completed the study.