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A connection between gut microbiota and Parkinson's disease (PD) indicates that dysbiosis of the gut microbiota might represent a risk factor for PD. Microbiota-targeted interventions, including probiotic Clostridium butyricum (Cb), have been recently shown to have favorable effects in PD by regulating microbiota-gut-brain axis. However, the potential beneficial roles and its mechanisms of Cb on PD were still unknown. Male C57BL/6 mice were subjected to a PD model-induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and were treated intragastrically with Cb for 4 weeks. The motor functions were assessed by a series of behavioral tests including pole test, beam walking teat, forced swimming test and open field test. The dopaminergic neuron loss, synaptic plasticity and microglia activation, as well as the levels of colonic glucagon-like peptide-1 (GLP-1), colonic G protein-coupled receptors GPR41/43 and cerebral GLP-1 receptors were assessed. Gut microbial composition was assessed by 16S rRNA sequencing analysis. Our results showed that oral administration of Cb could improve motor deficits, dopaminergic neuron loss, synaptic dysfunction and microglia activation in the MPTP-induced mice. Meanwhile, Cb treatment could reverse the dysbiosis of gut microbiota and the decreased levels of colonic GLP-1, colonic GPR41/43 and cerebral GLP-1 receptor in the MPTP-induced mice. These findings indicated that the neuroprotective mechanism of Cb on PD might be related to the improvement of abnormal gut microbiota-gut-brain axis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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-β (Aβ) burden, microglial activation, proinflammatory cytokines production, GM, and metabolites butyrate are analyzed. Moreover, Aβ-induced BV2 microglia are pretreated with butyrate, and the levels of cluster of differentiation 11b (CD11b), cyclooxygenase-2 (COX-2), and NF-κB p65 phosphorylation are determined. The results show that CB treatment prevents cognitive impairment, Aβ deposits, microglia activation, and production of tumor necrosis factor (TNF)-α and interleukin (IL)-1β 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-κB p65 in the Aβ-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., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Diabetes is known to exacerbate cerebral ischemia/reperfusion (I/R) injury. Here, we investigated the effects of Clostridium butyricum on cerebral I/R injury in the diabetic mice subjected to 30min of bilateral common carotid arteries occlusion (BCCAO). The cognitive impairment, the blood glucose level, neuronal injury, apoptosis, and expressions of Akt, phospho-Akt (p-Akt), and caspase-3 level were assessed. Meanwhile, the changes of gut microbiota in composition and diversity in the colonic feces were evaluated. Our results showed that diabetic mice subjected to BCCAO exhibited worsened cognitive impairment, cell damage and apoptosis. These were all attenuated by C. butyricum. Moreover, C. butyricum reversed cerebral I/R induced decreases in p-Akt expression and increases in caspase-3 expression, leading to inhibiting neuronal apoptosis. C. butyricum partly restored cerebral I/R induced decreases of fecal microbiota diversity, changes of fecal microbiota composition. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain probiotics might prove to be useful therapeutic adjuncts in cerebral I/R injury with diabetes., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Probiotics participate actively in the neuropsychiatric disorders. However, their roles on ischemic stroke remain unclear. This study aims to determine whether Clostridium butyricum (C. butyricum) could attenuate cerebral ischemia/reperfusion (I/R) injury and its possible mechanisms. Male ICR mice were intragastrically pretreated with C. butyricum for 2 successive weeks, and then subjected to cerebral I/R injury induced by the bilateral common carotid artery occlusion (BCCAO) for 20min. After 24h of the reperfusion, neurological deficit scores were evaluated. Histopathological changes of the hippocampus neurons were observed using Hematoxylin and eosin (H&E) and TUNEL staining. Malondialdehyde (MDA) contents and superoxide dismutase (SOD) activities in the brain were detected. The expression of Caspase-3, Bax and Bcl-2 were investigated by Western blot and immunohistochemistry analysis. The butyrate contents in the brain were determined. Our results showed that cerebral I/R injury led to neurological deficit, increased levels of Caspase-3 and Bax and decreased Bcl-2/Bax ratio. C. butyricum significantly improved neurological deficit, relieved histopathologic change, decreased MDA contents and increased SOD activities in the I/R injury mice. After C. butyricum pretreatment, the expression of Caspase-3 and Bax were significantly decreased, the Bcl-2/Bax ratio was significantly increased, and butyrate contents in the brain were significantly increased. These findings suggested that C. butyricum is able to exert neuroprotective effects against I/R injury mice through anti-oxidant and anti-apoptotic mechanisms, and reversing decrease of butyrate contents in the brain might be involved in its neuroprotection., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Antibiotic-associated diarrhea (AAD) is one of the most common complications of most types of antibiotics. Our aim was to determine the efficacy of Clostridium butyricum, Bifidobacterium infantis, and their mixture for AAD treatment in mice. AAD models were administered with single probiotic strain and probiotic mixture for short term and long term to evaluate the changes of the composition and diversity of intestinal microbiota, histopathology of the colon, and the systemic inflammation. Our data indicated that long-term probiotic therapy, but not short-term course, exerted beneficial effects on the restoration of the intestinal microbiota, the recovery of the tissue architecture, and attenuation of systemic inflammation. All predominant fecal bacteria reached normal level after the long-term probiotic mixture treatment, while IL-10, IFN-γ, and TNF-α also returned to normal level. However, the efficacy for AAD was time dependent and probiotic strain specific. Short-term administration of probiotic strains or mixture showed no apparent positive effects for AAD. In addition, the beneficial effects of C. butyricum combined with B. infantis probiotic mixture were superior to their single strain. This research showed that supplementation with C. butyricum combined with B. infantis probiotic mixture may be a simple and effective method for AAD treatment.

Probiotics actively participate in neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and vascular dementia (VaD) remains unclear. We used a mouse model of VaD induced by a permanent right unilateral common carotid arteries occlusion (rUCCAO) to investigate the neuroprotective effects and possible underlying mechanisms of Clostridium butyricum. Following rUCCAO, C. butyricum was intragastrically administered for 6 successive weeks. Cognitive function was estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The BDNF-PI3K/Akt pathway-related proteins were assessed by western blot and immunohistochemistry. The diversity of gut microbiota and the levels of butyrate in the feces and the brains were determined. The results showed that C. butyricum significantly attenuated the cognitive dysfunction and histopathological changes in VaD mice. C. butyricum not only increased the levels of BDNF and Bcl-2 and decreased level of Bax but also induced Akt phosphorylation (p-Akt) and ultimately reduced neuronal apoptosis. Moreover, C. butyricum could regulate the gut microbiota and restore the butyrate content in the feces and the brains. These results suggest that C. butyricum might be effective in the treatment of VaD by regulating the gut-brain axis and that it can be considered a new therapeutic strategy against VaD.