A risk estimation method for depression based on the dysbiosis of intestinal microbiota in Japanese patients.

Introduction: Early detection of depression is important for preventing depression-related suicides and reducing the risk of recurrence. This study explored the association between depression and intestinal microbiota and developed a depression risk-estimation method based on this. Methods: The intestinal microbiota of Japanese patients with depression (33 males and 35 females) and disease-free controls (246 males and 384 females) in their 20's to 60's were compared by sex using 16S rRNA gene amplicon sequencing. A depression-risk estimation method was developed using structural equation modeling. Results: Intestinal bacteria taxa that differed between depression and control groups were identified based on effect size (absolute value greater than 0.2). Neglecta was more abundant, while Coprobacter, Butyricimonas, Clostridium_XlVb, and Romboutsia were less abundant in the male depression group compared to the male control group. In the female depression group, Massilimicrobiota, Merdimonas, and Sellimonas were more abundant, whereas Dorea and Agathobacter were less abundant compared to the female control group. Several of the intestinal bacterial taxa that were less abundant in depression were associated with butyrate or hydrogen production. Using these depression-associated intestinal bacteria as indicators, risk-estimation models using structural equation modeling for depression were developed. In the risk-estimation models for males and females, the areas under the receiver operating characteristic curve were 0.72 and 0.70, respectively, indicating that these models can distinguish between individuals with and without depression. Conclusions: This study provides insights into depression etiology and aids in its early detection and treatment.

Characteristics of the Gut Microbiota in Japanese Patients with Premenstrual Syndrome.

Purpose: The present study aimed to characterize the gut microbiota of individuals with premenstrual syndrome. Patients and Methods: The gut microbiota of 24 Japanese women with PMS (PMS group) and 144 healthy Japanese women (control group) were compared. Analysis of the α- and ß-diversities and the gut microbial composition at the genus level were performed using 16S rRNA gene sequence data obtained from stool samples. Results: A significant difference in age was observed between the PMS and control groups; however, no significant difference was observed in BMI. The α-diversity measured using the Simpson index was significantly higher in the PMS group than the control group. Visualization of the ß-diversity using non-metric multidimensional scaling and permutational multivariate analysis of variance (PERMANOVA) showed that the distance of the gut microbiota between the PMS and control groups is significantly different. Furthermore, a significant difference in the composition of the gut microbiota was observed between the PMS and control groups. At the genus level, the abundances of Collinsella, Bifidobacterium, and Blautia were significantly higher in the PMS group than in the control group. In particular, the abundance of Collinsella in the PMS group was approximately 4.5 times higher than that in the control group. To rule out the confounding effect of age in the abundances of Bifidobacterium, Blautia, and Collinsella, the gut microbiota of the PMS and control groups were compared by age group. Results showed that Collinsella had the highest effect size in participants of 30-40 years of age (mean age: 36.39 ± 4.68 years). Conclusion: These results suggest that the PMS group possesses a characteristic gut microbiota. In particular, Collinsella was strongly associated with PMS. Since Collinsella has been reported to be associated with diet, dietary interventions such as prebiotics targeting Collinsella may be effective in preventing, improving, and alleviating PMS.

Fluctuations in Intestinal Microbiota Following Ingestion of Natto Powder Containing Bacillus subtilis var. natto SONOMONO Spores: Considerations Using a Large-Scale Intestinal Microflora Database.

Improving the intestinal microbiota using probiotics, prebiotics, and synbiotics has attracted attention as a method of disease prevention and treatment. This is the first study to discuss the effects of food intake on the intestinal microbiota using a large Japanese intestinal microbiota database. Here, as a case study, we determined changes in the intestinal microbiota caused by ingestion of a processed natto food containing B. subtilisvar. natto SONOMONO spores, SONOMONO NATTO POWDER CAPSULESTM, by analyzing 16S rRNA sequence data generated using next-generation sequencing techniques. The results showed that the relative abundance of Bifidobacterium and Blautia as well as the relative abundance of Bifidobacterium were increased in males and females in the ingesting group, respectively. Additionally, the effects of SONOMONO NATTO POWDER CAPSULESTM intake on Bifidobacterium and Blautia abundance depended on the relative abundance of Bifidobacterium at baseline. Finally, analysis of a large Japanese intestinal microbiota database suggested that the bacterial genera that fluctuated with the ingestion of SONOMONO NATTO POWDER CAPSULESTM may be associated with lifestyle-related diseases such as diabetes.

Tumor suppression effects of bilberry extracts and enzymatically modified isoquercitrin in early preneoplastic liver cell lesions induced by piperonyl butoxide promotion in a two-stage rat hepatocarcinogenesis model.

To investigate the protective effect of bilberry extracts (BBE) and enzymatically modified isoquercitrin (EMIQ) on the hepatocarcinogenic process involving oxidative stress responses, we used a two-stage hepatocarcinogenesis model in N-diethylnitrosamine-initiated and piperonyl butoxide (PBO)-promoted rats. We examined the modifying effect of co-administration with BBE or EMIQ on the liver tissue environment including oxidative stress responses, cell proliferation and apoptosis, and phosphatase and tensin homolog (PTEN)/Akt and transforming growth factor (TGF)-ß/Smad signalings on the induction mechanism of preneoplastic lesions during early stages of hepatocellular tumor promotion. PBO increased the numbers and area of glutathione S-transferase placental form (GST-P)(+) liver cell foci and the numbers of Ki-67(+) proliferating cells within GST-P(+) foci. Co-administration of BBE or EMIQ suppressed these effects with the reductions of GST-P(+) foci (area) to 48.9-49.4% and Ki-67(+) cells to 55.5-61.4% of the PBO-promoted cases. Neither BBE nor EMIQ decreased microsomal reactive oxygen species induced by PBO. However, only EMIQ suppressed the level of thiobarbituric acid-reactive substances to 78.4% of the PBO-promoted cases. PBO increased the incidences of phospho-PTEN(-) foci, phospho-Akt substrate(+) foci, phospho-Smad3(-) foci and Smad4(-) foci in GST-P(+) foci. Both BBE and EMIQ decreased the incidences of phospho-PTEN(-) foci in GST-P(+) foci to 59.8-72.2% and Smad4(-) foci to 62.4-71.5% of the PBO-promoted cases, and BBE also suppressed the incidence of phospho-Akt substrate(+) foci in GST-P(+) foci to 75.2-75.7% of the PBO-promoted cases. These results suggest that PBO-induced tumor promotion involves facilitation of PTEN/Akt and disruptive TGF-ß/Smad signalings without relation to oxidative stress responses, but this promotion was suppressed by co-treatment with BBE or EMIQ through suppression of cell proliferation activity of preneoplastic liver cells.