Effect of Clostridium butyricum against Microglia‐Mediated Neuroinflammation in Alzheimer's Disease via Regulating Gut Microbiota and Metabolites Butyrate

Abstract

Scope: Recent evidences demonstrate that abnormal gut microbiota (GM) might be involved in the pathogenesis of Alzheimer's disease (AD). However, the role of probiotics in preventing AD by regulating GM-gut-brain axis remains unclear. Here, the anti-neuroinflammatory effect and its mechanism of probiotic Clostridium butyricum (CB) against AD is investigated by regulating GM-gut-brain axis. Methods and results: APPswe/PS1dE9 (APP/PS1) transgenic are treated intragastrically with CB for 4 weeks then cognitively tested. Amyloid-(A ) burden, microglial activation, proinflammatory cytokines production, GM, and metabolites butyrate are analyzed. Moreover, A -induced BV2 microglia are pretreated with butyrate, and the levels of cluster of differentiation 11b (CD11b), cyclooxygenase-2 (COX-2), and NF-B p65 phosphorylation are determined. The results show that CB treatment prevents cognitive impairment, A deposits, microglia activation, and production of tumor necrosis factor (TNF)-and interleukin (IL)-1 in the brain of APP/PS1 mice. Meanwhile, abnormal GM and butyrate are reversed after CB treatment. Notably, butyrate treatment reduces the levels of CD11b and COX-2, and suppresses phosphorylation of NF-B p65 in the A -induced BV2 microglia. Conclusions: These findings indicate that CB treatment could attenuate microglia-mediated neuroinflammation via regulating the GM-gut-brain axis, which is mediated by the metabolite butyrate.

Volatilomes of Bacterial Infections in Humans

“…Furthermore, butyrate-producing microbiota were diminished in elder patients with Alzheimer's disease (Haran et al, 2019). Recently, the butyrate-producing probiotic, Clostridium butyricum, was found to have an anti-neuroinflammatory effect in Alzheimer's disease (Sun et al, 2020). This effect was mediated via butyrate by regulating the gut-brain axis (Sun et al, 2020).…”

“…Recently, the butyrate-producing probiotic, Clostridium butyricum, was found to have an anti-neuroinflammatory effect in Alzheimer's disease (Sun et al, 2020). This effect was mediated via butyrate by regulating the gut-brain axis (Sun et al, 2020). Therefore, butyrate and other volatile short-chain fatty acids are promising preventive and therapeutic interventions in Alzheimer's disease.…”

Therapeutic, Prophylactic, and Functional Use of Probiotics: A Current Perspective

“…Type 2 diabetes mellitus (T2DM) is the fourth most common non-transmissible disease. Frequent weight loss, high urination, thirst, and poor foot lesions healing power are the most common symptoms, which may later lead to complications, such as coronary heart diseases, obesity, retinopathy, sexual weakness, kidney failures, and atherosclerosis ( Sun J. et al, 2020 ). T2DM has multifactor roots, including physiological, psychological, genetic, and environmental factors ( Ardeshirlarijani et al, 2019 ).…”

Gut microbiota regulate cognitive deficits and amyloid deposition in a model of Alzheimer’s disease

“…Additionally, several studies have reported that there is a relationship between AD and specific gut microbiota, such as Helicobacter pylori , Porphyromonas gingivalis, and Actinomycetes (Dominy, Lynch, & Ermini, 2019; Emery et al., 2017; Franceschi, Ojetti, & Candelli, 2019). Some studies have shown that probiotics, such as Lactobacillus, Bifidobacterium, and Clostridium, reduce amyloid β (Aβ) deposition, neurofibrillary tangles, and neuroinflammation, and improve cognitive dysfunction (Lee, Lee, Kim, & Kim, 2019; Nimgampalle & Kuna, 2017; Sun, Xu, & Yang, 2020). In one study, a germ‐free (GF) mouse model of AD showed a reduction in cerebral Aβ amyloid pathology, yet did not evaluate cognitive function (Harach et al., 2017).…”