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

J Neurovirol. 2019 Aug;25(4):551-559. doi: 10.1007/s13365-019-00756-9. Epub 2019 May 16.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Autonomic Pathways / drug effects*
  • Autonomic Pathways / immunology
  • Autonomic Pathways / microbiology
  • Autonomic Pathways / pathology
  • Bacterial Translocation / drug effects
  • Bacterial Translocation / immunology
  • Cholinesterase Inhibitors / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Gastrointestinal Motility / drug effects
  • Gene Expression
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / microbiology
  • HIV Infections / pathology
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Intestine, Small / drug effects*
  • Intestine, Small / immunology
  • Intestine, Small / microbiology
  • Intestine, Small / pathology
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / immunology
  • Macrophage Activation / drug effects
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / microbiology
  • Male
  • Middle Aged
  • Neuroprotective Agents / therapeutic use*
  • Pyridostigmine Bromide / therapeutic use*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology


  • CD14 protein, human
  • Cholinesterase Inhibitors
  • IL6 protein, human
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • Pyridostigmine Bromide