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Depression is one of the most common psychiatric conditions, characterized by significant and persistent depressed mood and diminished interest, and often coexists with various comorbidities. The underlying mechanism of depression remain elusive, evidenced by the lack of an appreciate therapy. Recent abundant clinical trials and animal studies support the new notion that the gut microbiota has emerged as a novel actor in the pathophysiology of depression, which partakes in bidirectional communication between the gut and the brain through the neuroendocrine, nervous, and immune signaling pathways, collectively known as the microbiota-gut-brain (MGB) axis. Alterations in the gut microbiota can trigger the changes in neurotransmitters, neuroinflammation, and behaviors. With the transition of human microbiome research from studying associations to investigating mechanistic causality, the MGB axis has emerged as a novel therapeutic target in depression and its comorbidities. These novel insights have fueled idea that targeting on the gut microbiota may open new windows for efficient treatment of depression and its comorbidities. Probiotics, live beneficial microorganisms, can be used to modulate gut dysbiosis into a new eubiosis and modify the occurrence and development of depression and its comorbidities. In present review, we summarize recent findings regarding the MGB axis in depression and discuss the potential therapeutic effects of probiotics on depression and its comorbidities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gao, Zhao, Cheng, Lei, Wang, Liu, Zheng, Shao, Chen, Sun, Ling and Xu.)

Psychobiotics-live microorganisms with potential mental health benefits, which can modulate the microbiota-gut-brain-axis via immune, humoral, neural, and metabolic pathways-are emerging as novel therapeutic options for the effective treatment of psychiatric disorders Recently, microbiome studies have identified numerous putative psychobiotic strains, of which short-chain fatty acids (SCFAs) producing bacteria have attracted special attention from neurobiologists. Recent studies have highlighted that SCFAs-producing bacteria such as Lactobacillus , Bifidobacterium and Clostridium have a very specific function in various psychiatric disorders, suggesting that these bacteria can be potential novel psychobiotics. SCFAs, potential mediators of microbiota-gut-brain axis, might modulate function of neurological processes. While the specific roles and mechanisms of SCFAs-producing bacteria of microbiota-targeted interventions on neuropsychiatric disease are largely unknown. This Review summarizes existing knowledge on the neuroprotective effects of the SCFAs-producing bacteria in neurological disorders via modulating microbiota-gut-brain axis and illustrate their possible mechanisms by which SCFAs-producing bacteria may act on these disorders, which will shed light on the SCFAs-producing bacteria as a promising novel source of psychobiotics.

Orally administered probiotics encounter various challenges on their journey through the mouth, stomach, intestine and colon. The health benefits of probiotics are diminished mainly due to the substantial reduction of viable probiotic bacteria under the harsh conditions in the gastrointestinal tract and the colonization resistance caused by commensal bacteria. In this review, we illustrate the factors affecting probiotic viability and their mucoadhesive properties through their journey in the gastrointestinal tract, including a discussion on various mucosadhesion-related proteins on the probiotic cell surface which facilitate colonization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Han, Lu, Xie, Fei, Zheng, Wang, Liu, Lv, Ling, Berglund, Yao and Li.)

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.)

Objective This study was performed to investigate the role of probiotics ( Clostridium butyricum combined with Bifidobacterium infantis) in the treatment of minimal hepatic encephalopathy (MHE) in patients with hepatitis B virus (HBV)-induced liver cirrhosis. Methods Sixty-seven consecutive patients with HBV-induced cirrhosis without overt hepatic encephalopathy were screened using the number connection test and digit symbol test. The patients were randomized to receive probiotics (n = 30) or no probiotics (n = 37) for 3 months. At the end of the trial, changes in cognition, intestinal microbiota, venous ammonia, and intestinal mucosal barriers were analyzed using recommended systems biology techniques. Results The patients' cognition was significantly improved after probiotic treatment. The predominant bacteria ( Clostridium cluster I and Bifidobacterium) were significantly enriched in the probiotics-treated group, while Enterococcus and Enterobacteriaceae were significantly decreased. Probiotic treatment was also associated with an obvious reduction in venous ammonia. Additionally, the parameters of the intestinal mucosal barrier were obviously improved after probiotic treatment, which might have contributed to the improved cognition and the decreased ammonia levels. Conclusion Treatment with probiotics containing C. butyricum and B. infantis represents a new adjuvant therapy for the management of MHE in patients with HBV-induced cirrhosis.

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.

Whether or not treatment with antibiotics or probiotics for bacterial vaginosis (BV) is associated with a change in the diversity of vaginal microbiota in women was investigated. One hundred fifteen women, consisting of 30 healthy subjects, 30 BV-positive control subjects, 30 subjects with BV treated with a 7-day metronidazole regimen, and 25 subjects with BV treated with a 10-day probiotics regimen, were analyzed to determine the efficacy and disparity of diversity and richness of vaginal microbiota using 454 pyrosequencing. Follow-up visits at days 5 and 30 showed a greater BV cure rate in the probiotics-treated subjects (88.0 and 96 %, respectively) compared to the metronidazole-treated subjects (83.3 and 70 %, respectively [p = 0.625 at day 5 and p = 0.013 at day 30]). Treatment with metronidazole reduced the taxa diversity and eradicated most of the BV-associated phylotypes, while probiotics only suppressed the overgrowth and re-established vaginal homeostasis gradually and steadily. Despite significant interindividual variation, the microbiota of the actively treated groups or participants constituted a unique profile. Along with the decrease in pathogenic bacteria, such as Gardnerella, Atopobium, Prevotella, Megasphaera, Coriobacteriaceae, Lachnospiraceae, Mycoplasma, and Sneathia, a Lactobacillus-dominated vaginal microbiota was recovered. Acting as vaginal sentinels and biomarkers, the relative abundance of Lactobacillus and pathogenic bacteria determined the consistency of the BV clinical and microbiologic cure rates, as well as recurrent BV. Both 7-day intravaginal metronidazole and 10-day intravaginal probiotics have good efficacy against BV, while probiotics maintained normal vaginal microbiota longer due to effective and steady vaginal microbiota restoration, which provide new insights into BV treatment.

Alzheimer's disease (AD) is the most common age-related progressive neurodegenerative disease, characterized by a decline in cognitive function and neuronal loss, and is caused by several factors. Numerous clinical and experimental studies have suggested the involvement of gut microbiota dysbiosis in patients with AD. The altered gut microbiota can influence brain function and behavior through the microbiota–gut–brain axis via various pathways such as increased amyloid-β deposits and tau phosphorylation, neuroinflammation, metabolic dysfunctions, and chronic oxidative stress. With no current effective therapy to cure AD, gut microbiota modulation may be a promising therapeutic option to prevent or delay the onset of AD or counteract its progression. Our present review summarizes the alterations in the gut microbiota in patients with AD, the pathogenetic roles and mechanisms of gut microbiota in AD, and gut microbiota–targeted therapies for AD. Understanding the roles and mechanisms between gut microbiota and AD will help decipher the pathogenesis of AD from novel perspectives and shed light on novel therapeutic strategies for AD. [ABSTRACT FROM AUTHOR]