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Alzheimer's disease, marked by amyloid-β accumulation, is a leading cause of dementia. Gut microbiota may influence its development by affecting inflammation or amyloid-β metabolism. However, this association is not well studied in older adults in Japan, whose characteristic diet may uniquely impact gut bacteria. To determine the association between the gut microbiota and positron emission tomography (PET)-determined brain amyloid-β positivity in community-dwelling older adults in Japan. This cross-sectional study investigated 136 participants aged 68-86 years from Tokyo. Brain amyloid-β was assessed using PET imaging, and gut microbiota were analyzed from fecal samples using 16S rRNA gene sequencing processed with the QIIME2 pipeline. Taxonomic composition was evaluated at both the phylum and genus levels; participants were classified into above- and below-median groups based on the relative abundance of each taxon. Binomial logistic regression adjusted for age, sex, and antibiotic use was conducted to examine the association between bacterial abundance and PET positivity. For genus-level analyses, p-values were further corrected for multiple comparisons. In addition, α diversity (Shannon, Simpson, Observed OTUs) and β diversity (PCoA based on unweighted UniFrac distances, PERMANOVA) were compared between PET-positive and PET-negative groups. Of the 136 participants, 34.6% were PET-positive for amyloid-β. Firmicutes showed a significant difference: 26.4% PET-positive in the above-median group vs. 42.6% in the below-median group (p for χ² = 0.047). The binomial logistic regression analysis showed that lower Firmicutes abundance was significantly associated with an increased odds of PET positivity (odds ratio and confidence interval: 2.15 [1.03, 4.52]). At the genus level, no taxon remained significant after correction for multiple comparisons. No significant differences were observed in α or β diversity indices between groups. A lower abundance of Firmicutes may be associated with amyloid-β accumulation in the brain, linking the gut microbiota to Alzheimer's disease.

Lactic acid bacteria are well known to possess immune-modulating effects, but the mechanisms underlying their modulation of the gut immune system are not fully understood. Here, we examined the localization of heat-killed Lactobacillus pentosus strain b240 (b240) in intestinal tissues and the effect of b240 on adaptive immune cascades in the gut. Histological analysis showed that b240 co-localized with dendritic cells (DCs) in the subepithelial dome region of Peyer's patches (PPs). In a PP cell culture system, b240 promoted the production of immunoglobulin A (IgA), interleukin (IL)-6, IL-10, interferon (IFN)-γ, and tumor necrosis factor, but not IL-4, IL-5, B-cell activating factors, IFN-α, IFN-β, and transforming growth factor-β1. The enhanced IgA production by b240 was attenuated by neutralizing IL-6, a potent IgA-enhancing cytokine. b240 stimulated DCs to produce an elevated amount of IL-6 in a Toll-like receptor (TLR) 2-, but not TLR4- or TLR9-dependent manner. Finally, we demonstrated that TLR2-mediated IL-6 production from PP DCs in response to b240 activated B cells to produce a large amount of IgA in a DC-B cell co-culture system. Our findings open up the possibility that the heat-killed form of Lactobacillus pentosus strain b240 can be used as a TLR2-mediated DC-activating biologic for enhancing IgA production in the intestine.

Neurodegenerative changes in the preclinical stage of Alzheimer's disease (AD) have recently been the focus of attention because they may present a range of treatment opportunities. A total of 134 elderly volunteers who lived in a local community were investigated and grouped into preclinical and mild cognitive impairment stages according to the Clinical Dementia Rating test; we also estimated amyloid deposition in the brain using positron emission tomography (PET). A significant interaction between clinical stage and amyloid PET positivity on cerebral atrophy was observed in the bilateral parietal lobe, parahippocampal gyri, hippocampus, fusiform gyrus, and right superior and middle temporal gyri, as previously reported. Early AD-specific voxel of interest (VOI) analysis was also applied and averaged Z-scores in the right, left, bilateral, and right minus left medial temporal early AD specific area were computed. We defined these averaged Z-scores in the right, left, bilateral, and right minus left early AD specific VOI in medial temporal area as R-MedT-Atrophy-score, L-MedT-Atrophy-score, Bil-MedT-Atrophy-score, and R_L-MedT-Atrophy-score, respectively. It revealed that the R_L-MedT-Atrophy-scores were significantly larger in the amyloid-positive than in the amyloid-negative cognitively normal (CN) elderly group, that is, the right medial temporal areas were smaller than left in amyloid positive CN group and these left-right differences were significantly larger in amyloid positive than amyloid negative CN elderly group. The L-MedT-Atrophy-score was slightly larger (p=0.073), that is, the left medial temporal area was smaller in the amyloid-negative CN group than in the amyloid-positive CN group. Conclusively, the left medial temporal area could be larger in CN participants with amyloid deposition than in those without amyloid deposition. The area under the receiver operating characteristic curve for differentiating amyloid positivity among CN participants using the R_L-MedT-Atrophy-scores was 0.73; the sensitivity and specificity were 0.828 and 0.606, respectively. Although not significant, a negative correlation was observed between the composite cerebral standardized uptake value ratio in amyloid PET images and L-MedT-Atrophy-score in CN group. The left medial temporal volume might become enlarged because of compensatory effects against AD pathology occurring at the beginning of the amyloid deposition.

Influenza A(H1N1)pdm virus caused the first human pandemic of the 21st century. Although various probiotic Lactobacillus species have been shown to have anti-microbial effects against pneumonia-inducing pathogens, the prophylactic efficacy and mechanisms behind their protection remain largely unknown. Here, we evaluated the prophylactic efficacy of heat-killed Lactobacillus pentosus b240 against lethal influenza A(H1N1)pdm virus infection in a mouse model. To further define the protective responses induced by b240, we performed virologic, histopathologic and transcriptomic analyses on the mouse lungs. Although we did not observe an appreciable effect of b240 on virus growth, cytokine production, or histopathology, gene expressional analysis revealed that oral administration of b240 differentially regulates antiviral gene expression in mouse lungs. Our results unveil the possible mechanisms behind the protection mediated by b240 against influenza virus infection and provide new insights into probiotic therapy.

Background Immunoglobulin A (IgA) secretion in saliva decreases with age and may be the cause of increased vulnerability of the elderly to respiratory infections. The effect of oral intake of lactic acid bacteria on salivary secretory IgA (SIgA) in the elderly has not been reported. The objective of this study was to demonstrate the acceleration of salivary SIgA secretion by oral intake of Lactobacillus pentosus strain b240 (b240) in the elderly. Results A total of 80 healthy elderly individuals were randomly allocated to either an intervention (i.e., b240) or a control (i.e., placebo) group. The elderly individuals in the b240 group were given a sterile water beverage (125 mL) containing heat-killed b240 (4 × 10 9 cells), while those in the placebo group were given only a sterile water beverage (125 mL); both groups received their respective beverages once daily for 12 weeks. Saliva was collected before initiation of the study and every 2 weeks thereafter. Saliva flow rate and SIgA concentration were determined, and the SIgA secretion rate was calculated. The mean salivary SIgA secretion rate in the b240 group steadily increased until week 4 (exhibiting a 20% elevation relative to that at week 0), and then remained stable until week 12. Changes in SIgA secretion rate over the intervention period were significantly greater in the b240 group than in the placebo group. The treatment groups exhibited no significant differences in adverse events. Conclusions Oral intake of L. pentosus strain b240 for 12 weeks significantly accelerated salivary SIgA secretion, thereby indicating its potential utility in the improvement of mucosal immunity and resistance against infection in the elderly.

Alzheimer's disease, marked by amyloid-[beta] accumulation, is a leading cause of dementia. Gut microbiota may influence its development by affecting inflammation or amyloid-[beta] metabolism. However, this association is not well studied in older adults in Japan, whose characteristic diet may uniquely impact gut bacteria. To determine the association between the gut microbiota and positron emission tomography (PET)-determined brain amyloid-[beta] positivity in community-dwelling older adults in Japan. This cross-sectional study investigated 136 participants aged 68-86 years from Tokyo. Brain amyloid-[beta] was assessed using PET imaging, and gut microbiota were analyzed from fecal samples using 16S rRNA gene sequencing processed with the QIIME2 pipeline. Taxonomic composition was evaluated at both the phylum and genus levels; participants were classified into above- and below-median groups based on the relative abundance of each taxon. Binomial logistic regression adjusted for age, sex, and antibiotic use was conducted to examine the association between bacterial abundance and PET positivity. For genus-level analyses, p-values were further corrected for multiple comparisons. In addition, [alpha] diversity (Shannon, Simpson, Observed OTUs) and [beta] diversity (PCoA based on unweighted UniFrac distances, PERMANOVA) were compared between PET-positive and PET-negative groups. Of the 136 participants, 34.6% were PET-positive for amyloid-[beta]. Firmicutes showed a significant difference: 26.4% PET-positive in the above-median group vs. 42.6% in the below-median group (p for X² = 0.047). The binomial logistic regression analysis showed that lower Firmicutes abundance was significantly associated with an increased odds of PET positivity (odds ratio and confidence interval: 2.15 [1.03, 4.52]). At the genus level, no taxon remained significant after correction for multiple comparisons. No significant differences were observed in [alpha] or [beta] diversity indices between groups. A lower abundance of Firmicutes may be associated with amyloid-[beta] accumulation in the brain, linking the gut microbiota to Alzheimer's disease.

Oral intake of Lactobacillus pentosus strain b240 (b240) has been shown to enhance the secretion of salivary secretory IgA in elderly adults. However, its clinical benefits remain to be determined. We tested the hypothesis that b240 exerts a protective effect against the common cold in elderly adults. The design of the present study was a randomised, double-blind, placebo-controlled trial (RCT) with parallel three-group comparison. For this purpose, 300 eligible elderly adults were randomly allocated to one of three groups, namely a placebo, low-dose or high-dose b240 group. Participants in the low-dose and high-dose b240 groups were given tablets containing 2 × 109 or 2 × 1010 cells, respectively, of heat-killed b240, while those in the placebo group were given tablets without b240. Each group consumed their respective tablets once daily for 20 weeks. The common cold was assessed on the basis of a diary. Change in quality of life was evaluated using the SF-36®. Of the total participants, 280 completed the 20-week RCT. The accumulated incidence rate of the common cold was 47·3, 34·8 and 29·0 % for the placebo, low-dose b240 and high-dose b240 groups, respectively (P for trend = 0·012). Lower incidence rates were consistently observed throughout the experimental period in the b240 groups (log-rank test, P= 0·034). General health perception, as determined by the SF-36®, dose-dependently increased in the b240 groups (P for trend = 0·016). In conclusion, oral intake of b240 significantly reduced the incidence rate of the common cold in elderly adults, indicating that b240 might be useful in improving resistance against infection through mucosal immunity.

Background and objectives: Some triathletes often feel sick in conditioning period (peaking period) toward the race. The aim of this study is to consider the method of conditioning athletes by investigating the changes of the immunity through examining the variation of salivary IgA secretion. Methods: For the college students' triathletes of 33 males and 7 females who participate the race, the amount of salivary IgA about one month before the race were continuously measured. In addition, meal content and the amount of water intake and physical activity in the training were recorded and the relationship with salivary IgA secretion was evaluated. Results: No significant change in nutrition intake during the test period was observed. Significant high level of water intake was shown only on the race day. The average amount of physical activity a week of two to three weeks before the race was the highest as 744.7 ± 51.5 kcal/day, and that of one to two weeks before the race was 513.2 ± 28.5 kcal/day. That of last week before the race was 305.5 ± 29.9 kcal/day, and this value was significantly lower than the initial value (P <0.05). In the subjects whose average amount of physical activity of the three days in one to two weeks before the race (pre-race 12 to 14 days) was more than 1000 kcal/day, the amount of salivary IgA secretion significantly reduced at one week before the race (P <0.05), and at the day before the race further reduction was observed (P <0.1). When the daily high-intensity exercises above a certain level two weeks before the race were performed, the salivary IgA secretion from the week to the day before the race reduced. Therefore, peaking method performed during a certain period before the race which contains high-intensity exercise weakens the mucosal immune function and induces the state which is easy to break a condition. Conclusions: In the college students' triathletes, the amount of the salivary IgA secretion was decreased by the peaking carried out toward the race. This was considered to be one of the causes breaking the condition just before the race.

Lactic acid bacteria are well known to possess immune-modulating effects, but the mechanisms underlying their modulation of the gut immune system are not fully understood. Here, we examined the localization of heat-killed Lactobacillus pentosus strain b240 (b240) in intestinal tissues and the effect of b240 on adaptive immune cascades in the gut. Histological analysis showed that b240 co-localized with dendritic cells (DCs) in the subepithelial dome region of Peyer's patches (PPs). In a PP cell culture system, b240 promoted the production of immunoglobulin A (IgA), interleukin (IL)-6, IL-10, interferon (IFN)- gamma , and tumor necrosis factor, but not IL-4, IL-5, B-cell activating factors, IFN- alpha , IFN- beta , and transforming growth factor- beta 1. The enhanced IgA production by b240 was attenuated by neutralizing IL-6, a potent IgA-enhancing cytokine. b240 stimulated DCs to produce an elevated amount of IL-6 in a Toll-like receptor (TLR) 2-, but not TLR4- or TLR9-dependent manner. Finally, we demonstrated that TLR2-mediated IL-6 production from PP DCs in response to b240 activated B cells to produce a large amount of IgA in a DC-B cell co-culture system. Our findings open up the possibility that the heat-killed form of Lactobacillus pentosus strain b240 can be used as a TLR2-mediated DC-activating biologic for enhancing IgA production in the intestine.