Small Intestinal Bacterial Overgrowth as Potential Therapeutic Target in Parkinson’s Disease

Abstract

Increasing evidence suggests that the gut microbiota and the brain are closely connected via the so-called gut–brain axis. Small intestinal bacterial overgrowth (SIBO) is a gut dysbiosis in which the small intestine is abundantly colonized by bacteria that are typically found in the colon. Though not a disease, it may result in intestinal symptoms caused by the accumulation of microbial gases in the intestine. Intestinal inflammation, malabsorption and vitamin imbalances may also develop. SIBO can be eradicated by one or several courses of antibiotics but reappears if the predisposing condition persists. Parkinson’s disease (PD) is a common neurodegenerative proteinopathy for which disease modifying interventions are not available. Sporadic forms may start in the gut years before the development of clinical features. Increased gastrointestinal transit time is present in most people with PD early during the course of the disease, predisposing to gut dysbiosis, including SIBO. The role that gut dysbiosis may play in the etiopathogenesis of PD is not fully understood yet. Here, we discuss the possibility that SIBO could contribute to the progression of PD, by promoting or preventing neurodegeneration, thus being a potential target for treatments aiming at slowing down the progression of PD. The direct symptomatic impact of SIBO and its impact on symptomatic medication are also briefly discussed.

The Role of Helicobacter pylori and Small Intestinal Bacterial Overgrowth in Parkinson's Disease

“…6 Accordingly, studies in PD patients have disclosed different patterns, mainly in terms of hydrogenpredominant, methane-predominant, and mixed H2/methane bacterial overgrowth. 6,23 Animal studies have supported this model. Sampson et al reported that colonization of α-synuclein overexpressing mice with microbiota from PD patients magnified motor deficits due to microglial activation and α-synuclein pathology.…”

“…In this review, we aim to critically examine the available evidence regarding the role of Helicobacter pylori and small intestinal bacterial overgrowth (SIBO) in the onset and disease course of patients with PD. Another important role is probably played by GI microbiota-i.e., the complex of bacteria, archaea, fungi, viruses, and parasites that are part of the GI habitat, 6 which is addressed elsewhere.…”

“…5 Substantial evidence has supported the role of environmental factors associated with the onset and development of PD, in the context of complex and multifactorial interactions. 6 Among these factors, the role of the intestinal environment has received growing interest, under the assumption that the enteric nervous system (ENS) may act as a route for the transmission of pathological processes from the periphery of the body—our interface with the environment—to the central nervous system (CNS). For example, it has been hypothesized that misfolded strains of α-synuclein, the protein found to constitute the Lewy body pathology typical of PD, might spread in a prion-like fashion from the GI tract to the brainstem.…”

Mechanisms of peripheral levodopa resistance in Parkinson’s disease

“…In addition, H. pylori can cause malabsorption and motor fluctuations independently of SIBO 24 . Recently, it was hypothesized that SIBO might even be implicated in the etiological cascade of PD and that its presence may contribute to the progression of PD through inflammation-induced synucleinopathy 35 . Therefore, the authors of that article consider that eradication of SIBO might be warranted in PD patients even in the absence of GI symptoms.…”

The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

“…Rifaximin is a broad spectrum antibiotic with poor systemic absorption indicated to treat SIBO [ 210 , 220 , 221 ]. In this respect, rifaximin-mediated SIBO eradication in PD patients resulted in reduced motor fluctuations without impacting on L-dopa treatment [ 222 ].…”