Small intestinal bacterial overgrowth in Alzheimer\u2019s disease

Karol Kowalski,Agata Mulak

doi:10.1007/s00702-021-02440-x

Abstract

The results of animal studies and clinical data support the gut microbiota contribution to the pathogenesis of Alzheimer’s disease (AD). The aim of this pilot study was to evaluate the prevalence of small intestinal bacterial overgrowth (SIBO) and fecal markers of intestinal inflammation and permeability in AD patients. The study was conducted in 45 AD patients and 27 controls. Data on comorbidities, pharmacotherapy, and gastrointestinal symptoms were acquired from medical records and a questionnaire. SIBO was evaluated using lactulose hydrogen breath test. Fecal calprotectin and zonulin levels were assessed by ELISA assays. The positive result of SIBO breath test was found in 49% of the AD patients and 22% of the controls (p = 0.025). The comparative analysis between SIBO-positive and SIBO-negative AD patients with respect to the degree of cognitive impairment, comorbidities and used medications did not reveal any statistically significant difference, except for less common heartburn in SIBO-positive AD patients than in SIBO-negative ones (9 vs 35%, p = 0.038). The median fecal calprotectin and zonulin levels in the AD group compared to the control group amounted to 43.1 vs 64.2 µg/g (p = 0.846) and 73.5 vs 49.0 ng/ml (p = 0.177), respectively. In the AD patients there was no association between the presence of SIBO and fecal calprotectin level. Patients with AD are characterized by higher prevalence of SIBO not associated with increased fecal calprotectin level that may be related to anti-inflammatory effect of cholinergic drugs used in the treatment of AD.

Highlights

Alzheimer’s disease (AD) is the most common cause of dementia characterized by a progressive decline in cognitive function (Reitz and Mayeux 2014)
Given the growing understanding of the role of gut microbiota alterations, the gut immune system activation and increased intestinal permeability in AD, the main aim of the study was to evaluate the prevalence of small intestinal bacterial overgrowth (SIBO) in the course of AD and its potential association with fecal calprotectin and zonulin levels
Recently numerous studies have been published on the alterations in the gut microbiota composition in AD (Kowalski and Mulak 2019; He et al 2020; Liu et al 2020; Sochocka et al 2019), to the best of our knowledge, this is the first report on SIBO in AD patients, not including our own preliminary study presented in the abstract form (Kowalski et al 2017)

Summary

Introduction

Alzheimer’s disease (AD) is the most common cause of dementia characterized by a progressive decline in cognitive function (Reitz and Mayeux 2014). The main features of the disease are aggregation, oligomerization, and deposition of amyloid beta (Aβ) in the form of plaques as well as formation of neurofibrillary tangles composed of hyperphosphorylated tau protein (Jouanne et al 2017). Those deposits induce neuroinflammation leading to the synapse loss and neuronal cell death (Köhler et al 2016). Since acetylcholine is involved in cognitive processes, the so-called cholinergic hypothesis has been proposed according to which an increase in acetylcholine level could restore cognitive deficits (Hampel et al 2018). The current symptomatic treatment does not cure the disease, there is a need for new therapeutic strategies targeted at the mechanisms involved in the pathogenesis of AD (Zhu et al.2020)

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