Gut Microbiota and its Metabolites: Bridge of Dietary Nutrients and Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment and neuroinflammation. Recent research has revealed the crucial role of gut microbiota and microbial metabolites in modulating AD. However, the mechanisms by which the microbiome and microbial metabolites affect brain function remain poorly understood. Here, we review the literature on changes in the diversity and composition of the gut microbiome in patients with AD and in animal models of AD. We also discuss the latest progress in understanding the pathways by which the gut microbiota and microbial metabolites from the host or diet regulate AD. By understanding the effects of dietary components on brain function, microbiota composition, and microbial metabolites, we examine the potential for manipulation of the gut microbiota through dietary intervention to delay the progression of AD. Although it is challenging to translate our understanding of microbiome-based approaches to dietary guidelines or clinical therapies, these findings provide an attractive target for promoting brain function.

Bifidobacterium breve HNXY26M4 Attenuates Cognitive Deficits and Neuroinflammation by Regulating the Gut-Brain Axis in APP/PS1 Mice.

Alzheimer's disease (AD) is a neurodegenerative disease, pathological markers of which are amyloid plaques and neurofibrillary tangles. As a key node of gut-brain axis, gut microbiota is increasingly associated with changes in cognitive behaviors and brain function. Psychobiotics are known to benefit patients with neurodegenerative diseases by the production and deliberation of neuroactive substances. However, psychobiotics are strain-specific probiotics, and their neuroprotective effects on the brain and modulation effects on the gut microbiome are not generalizable. In this study, we investigated the effects of Bifidobacterium breve HNXY26M4 in APP/PS1 mice. By assessing the alterations associated with brain function, we found that B. breve HNXY26M4 attenuated cognitive deficits and suppressed neuroinflammation and synaptic dysfunction in APP/PS1 mice. Moreover, by determining the modulation effects of B. breve HNXY26M4 on gut homeostasis, we identified that B. breve HNXY26M4 supplementation restored the composition of gut microbiota and short-chain fatty acids, as well as enhanced the function of the intestinal barrier. These findings indicate that microbiome-derived acetate and butyrate modulated by B. breve HNXY26M4 administration may be transported to the brain through the blood-brain barrier, and thus confer neuroprotective effects against AD-associated brain deficits and inflammation via the gut-brain axis.

Bifidobacterium breve intervention combined with environmental enrichment alleviates cognitive impairment by regulating the gut microbiota and microbial metabolites in Alzheimer's disease mice.

Alzheimer's disease (AD) is characterized by behavioral and cognitive impairments and its increasing prevalence imposes a healthcare burden on society. To date, most intervention studies have only focused on a single AD-related factor and have yielded modest cognitive improvements. Here, we show that environmental enrichment (EE) training combined with Bifidobacterium breve CCFM1025 intervention significantly alleviated amyloid-ß (Aß)-induced cognitive impairment and inhibited neuroinflammation in mice. Moreover, we found that EE combined with B. breve CCFM1025 treatment restored AD-associated gut microbiota dysbiosis and reversed microbial metabolites changes. By integrating behavioral and neurological data with metabolomic profiles, we corroborated the microbiota-metabolite-brain interactions, with acetate and tryptophan metabolism as potential drivers. Taken together, our results provide a promising multidomain intervention strategy to prevent cognitive decline and delay the progression of AD through a combination of dietary microbiome-based approaches and lifestyle interventions.

Integrative Metabolomic Characterization Reveals the Mediating Effect of Bifidobacterium breve on Amino Acid Metabolism in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is commonly accompanied by global alterations in metabolic profiles, resulting in cognitive impairment and neuroinflammation in the brain. Using ultraperformance liquid chromatography-mass spectrometry, we performed integrative untargeted metabolomic analysis of metabolite alterations in the serum and hippocampal tissues of amyloid-ß (Aß)-injected AD model mice and sham controls. Multivariate analysis revealed that a Bifidobacterium breve CCFM1025 intervention significantly restored the differential metabolites induced by Aß-injection, resulting in B. breve CCFM1025 serum and hippocampal metabolomes clustering between control and model mice. Furthermore, pathway and metabolite set enrichment analysis found that these altered metabolites were predominantly linked to amino acid metabolism. Overall, the integrative metabolome analysis indicated that B. breve CCFM1025 supplementation could modulate serum and hippocampal metabolomes in the early stage of AD, with amino acids as a potential driver.

Probiotics for Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Accumulating evidence from animal studies supports the potential role of probiotics and prebiotics in alleviating neurodegenerative diseases. However, whether dietary supplementation with probiotics improves cognitive function in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) is unclear. We searched literature databases for relevant randomized control trials and compared the outcomes between control/placebo and intervention groups. The results of the included studies were meta-analyzed using a random-effects model, with standardized mean differences (SMDs) and 95% confidence intervals (CIs) calculated as summary statistics. We also performed a risk-of-bias assessment, sensitivity analysis and subgroup analysis. Among the 294 articles identified, eight articles involving 174 patients with AD and 446 with MCI were included in the qualitative synthesis and seven studies were meta-analyzed. Our analysis detected high between-group heterogeneity (SMD = 0.43, 95% CI -0.02-0.88, p < 0.0001, I2 = 86.4%) in cognitive function across the included studies. Subgroup analyses identified a significant effect of probiotics on cognitive function only in the studies involving people with MCI (I2 = 44%, p = 0.15 for heterogeneity, p = 0.0002 for overall effect). Our findings suggest that dietary supplementation with probiotics improves cognitive function, especially in people with MCI.

Administration of Bifidobacterium breve Improves the Brain Function of Aß1-42-Treated Mice via the Modulation of the Gut Microbiome.

Psychobiotics are used to treat neurological disorders, including mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the mechanisms underlying their neuroprotective effects remain unclear. Herein, we report that the administration of bifidobacteria in an AD mouse model improved behavioral abnormalities and modulated gut dysbiosis. Bifidobacterium breve CCFM1025 and WX treatment significantly improved synaptic plasticity and increased the concentrations of brain-derived neurotrophic factor (BDNF), fibronectin type III domain-containing protein 5 (FNDC5), and postsynaptic density protein 95 (PSD-95). Furthermore, the microbiome and metabolomic profiles of mice indicate that specific bacterial taxa and their metabolites correlate with AD-associated behaviors, suggesting that the gut-brain axis contributes to the pathophysiology of AD. Overall, these findings reveal that B. breve CCFM1025 and WX have beneficial effects on cognition via the modulation of the gut microbiome, and thus represent a novel probiotic dietary intervention for delaying the progression of AD.

Bifidobacteria attenuate the development of metabolic disorders, with inter- and intra-species differences.

Host gut microbiota dysbiosis occurs for multiple reasons and is often accompanied by chronic inflammation induced by a high-fat-high-sucrose (HFHS) diet and related metabolic disorders. Intervention with probiotics is a novel strategy for amelioration of metabolic syndrome, which is believed to regulate the gut microbiota composition to some extent. We investigated the relationship amongst bifidobacteria treatment, HFHS diet-induced metabolic disorders and the gut microbiota composition. Seven strains of bifidobacteria from four species were individually administered to rats fed a HFHS diet for 12 weeks. Various bifidobacteria strains showed various effects on the recovery of metabolic disorders and gut microbiota dysbiosis, and these effects seemed to be inter- or intra-species specific. Bifidobacterium longum, B. adolescentis and B. bifidum seemed to affect the blood glucose balance, whilst two strains of B. breve showed extremely different effects in this area. However, only one strain of B. longum and the B. adolescentis displayed significant regulation of blood lipid levels. The protective effects of bifidobacteria on the pancreas were strongly correlated with those on blood glucose. Furthermore, the influence of bifidobacteria on gut microbiota dysbiosis also showed a potential relationship with symptoms of metabolic disorders. Of these seven strains, B. adolescentis Z25 displayed an outstanding ability to alleviate metabolic syndrome, including glucose and lipid metabolism disorders, tissue damage and gut microbiota dysbiosis. This strain, coupled with other prebiotics and probiotics, could be used as a potential treatment approach for metabolic syndrome induced by a HFHS diet.