Probiotic Lactobacillus johnsonii BS15 Prevents Memory Dysfunction Induced by Chronic High-Fluorine Intake through Modulating Intestinal Environment and Improving Gut Development.

In recent years, the influence of chronic fluorosis on the brain has been widely reported. Our study aimed to demonstrate the potential mechanism underlying the impairment of memory function by excessive fluorine intake. We also evaluated whether improvement of intestinal microflora could be a potential therapy to prevent the negative influences from the perspective of gut-brain axis. Male ICR mice were randomly divided into three groups and administered with either phosphate buffered saline (PBS) (Control and F groups) or Lactobacillus johnsonii BS15 (FP group; daily amounts of 1 × 109 CFU/mL), a probiotic strain, by oral gavage throughout a 98-day experimental period. Sodium fluoride (100 mg/L) was added to the drinking water of the F and FP groups. Animals were sacrificed for sampling with or without water avoidance stress (WAS) at two phases of the experiment and behavioral tests including T-maze test and passive avoidance test were also performed. Based on the results of behavioral tests, probiotic reversed the fluorine-induced memory dysfunction. In addition, L. johnsonii BS15 also increased the antioxidant capacities (serum and hippocampal tissue) and hippocampal synaptic plasticity-related mRNA expression after excessive fluoride ingestion. Moreover, the increased colonization of L. johnsonii BS15 also protected the small intestines from the damages of growth performance, visceral indexes, intestinal development, digestive, and secretory functions by changing the structure of the microflora and then improving intestinal permeability and integrity. L. johnsonii BS15 also improved the ability of flourosis mice against psychological stress indicated by the changes in behavioral tasks, hippocampal antioxidant levels, and synaptic plasticity-related mRNA expressions. Lactobacillus johnsonii BS15 intake appears as a promising way to ameliorate fluorine-induced memory dysfunction, especially under psychological stress.

Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort.

OBJECTIVE: (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide. Recently, several animal studies indicated that the 'gut-brain' axis might contribute to the amyloid deposition of AD. However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD. In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC). Additionally, the potential association between IM and clinical characteristics of AD was evaluated. METHODS: A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study. The composition of gut bacterial communities was determined by 16S ribosomal RNA Miseq sequencing. In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients. RESULTS: The fecal microbial diversity was decreased in AD patients compared with aMCI patients and HC. And the microbial composition was distinct among aMCI, AD and healthy control groups. Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC. In addition, similar alterations were observed at the order, class and family levels of these two phyla. And Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae showed a progressive enriched prevalence from HC to aMCI and AD patients. Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes. Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients. Importantly, the discriminating models based on predominant microbiota could effectively distinguish aMCI and AD from HC (AUC = 0.890, 0.940, respectively), and also AD from aMCI (AUC = 0.925). Notably, the models based on the abundance of family Enterobacteriaceae could distinguish AD from both aMCI (AUC = 0.688) and HC (AUC = 0.698). CONCLUSIONS: Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects. These novel findings will give new clues to understand the disease and provide new therapeutic target for intervention or a marker for this disease.