Gut microbiota differences in elderly subjects between rural city Kyotango and urban city Kyoto: an age-gender-matched study.

Several outcomes have been reported on the role of gut microbiota in health promotion and disease prevention. Kyotango, one of the longevity areas with various centenarians, is a provincial city located in the northern part of Kyoto Prefecture in Japan. To understand the relationship between gut microbiota and urbanization, we compared the diversity, abundance, and function of gut microbiota in older healthy subjects between Kyotango and Kyoto cities; Kyoto is an urban city located in the southern part of Kyoto Prefecture. In total, 51 subjects at Kyotango and 51 subjects at Kyoto matched by age and gender were recruited, and their fecal samples were obtained to analyze the gut microbiota using 16S rRNA gene sequencing. Principal coordinate analysis for ß-diversity revealed significant differences in the gut microbiota between two cities. In contrast, the analysis of α-diversity revealed no significant differences between the groups. On comparison at the phylum levels, the abundance of Firmicutes was decreased with the urbanization, whereas that of Proteobacteria and Bacteroidetes increased. On comparison at the genus levels, with urbanization, a significant decrease was observed in Lachnospiraceae families including genus Roseburia and Coprococcus, and significant increases was observed in Bacteroides, Oscillospira, Parabacteroides, and Ruminococcus. The most markedly increased functional pathway with urbanization was lipopolysaccharide biosynthesis proteins and lipopolysaccharide biosynthesis, and decreased pathway was transporters and ABC transporters. In conclusion, the present findings indicate significant differences in the gut microbiota between the provincial city and urban cities at Kyoto Prefecture. These alterations in the microbiota may provide new insights to consider the relationship between longevity and gut microbiota.

The influence of long-term use of proton pump inhibitors on the gut microbiota: an age-sex-matched case-control study.

Proton pump inhibitors (PPIs) are widely used to treat gastro-esophageal reflux and prevent gastric ulcers, and have been considered as low risk. However, recent studies have identified possible associations between PPI use and gut microbiota, suggesting that PPIs use increases the risk of enteric infections, including Clostridium difficile infection. To investigate gut microbiota in Japanese PPIs users, we conducted 16S metagenomics analysis of fecal samples collected from PPI users and healthy adults. In total, 36 PPI users and 36 PPI non-users (as control subjects) matched by age and sex were recruited and fecal samples were obtained to analyze the gut microbiome using 16S rRNA gene sequencing. There were significant differences in the microbial structure between PPI non-users and PPI users. In contrast, the analysis of α-diversity revealed no significant differences between PPI non-users and PPI users. When comparing in genus level between these two groups, the genera Streptococcus was significantly abundant and the genera Faecalibacterium was significantly decreased in PPI users. Our findings indicate a probable association between PPI use and the alternation of microbiota. These alterations might provide a mechanism by which PPIs predispose enteric infection such as Clostridium difficile infection.

Transcriptional Analysis of Hair Follicle-Derived Keratinocytes from Donors with Atopic Dermatitis Reveals Enhanced Induction of IL32 Gene by IFN-γ.

We cultured human hair follicle-derived keratinocytes (FDKs) from plucked hairs. To gain insight into gene expression signatures that can distinguish atopic dermatitis from non-atopic controls without skin biopsies, we undertook a comparative study of gene expression in FDKs from adult donors with atopic dermatitis and non-atopic donors. FDK primary cultures (atopic dermatitis, n = 11; non-atopic controls, n = 7) before and after interferon gamma (IFN-γ) treatment were used for microarray analysis and quantitative RT-PCR. Comparison of FDKs from atopic and non-atopic donors indicated that the former showed activated pathways with innate immunity and decreased pathways of cell growth, as indicated by increased NLRP2 expression and decreased DKK1 expression, respectively. Treatment with IFN-γ induced the enhanced expression of IL32, IL1B, IL8, and CXCL1 in the cells from atopic donors compared to that in cells from non-atopic donors at 24 h after treatment. IL1B expression in FDKs after IFN-γ treatment correlated with IL32 expression. We hypothesized that overexpression of IL32 in hair follicle keratinocytes of patients with atopic dermatitis would lead to the excessive production of pro-IL1ß and that the activation of IL1ß from pro-IL1ß by inflammasome complex, in which NLRP2 protein might be involved, would be augmented. This is the first report to show enhanced induction of cytokine/chemokine genes by IFN-γ in atopic dermatitis using cultured FDKs.

Changes in the Gut Microbiota are Associated with Hypertension, Hyperlipidemia, and Type 2 Diabetes Mellitus in Japanese Subjects.

The human gut microbiota is involved in host health and disease development. Therefore, lifestyle-related diseases such as hypertension (HT), hyperlipidemia (HL), and type 2 diabetes mellitus (T2D) may alter the composition of gut microbiota. Here, we investigated gut microbiota changes related to these diseases and their coexistence. This study involved 239 Japanese subjects, including healthy controls (HC). The fecal microbiota was analyzed through the isolation of bacterial genomic DNA obtained from fecal samples. Although there were no significant differences in the microbial structure between groups, there was a significant difference in the α-diversity between HC and the patients in whom two diseases coexisted. Moreover, Actinobacteria levels were significantly increased, whereas Bacteroidetes levels were significantly decreased in all disease groups. At the genus level, Bifidobacterium levels were significantly increased in the HL and T2D groups, as were those of Collinsella in all disease groups. In contrast, Alistipes levels were significantly lower in the HL group. Furthermore, metabolic enzyme families were significantly increased in all disease groups. Interestingly, the structure and function of the gut microbiota showed similar profiles in all the studied diseases. In conclusion, several changes in the structure of the gut microbiota are associated with T2D, HT, and HL in Japanese subjects.

Differences in gut microbiota associated with age, sex, and stool consistency in healthy Japanese subjects.

BACKGROUND: Human gut microbiota is involved in host health and disease development. Investigations of age-related and sex-related alterations in gut microbiota are limited, and the association between stool consistency and gut microbiota has not been fully investigated. We investigated gut microbiota differences related to age, sex, and stool consistency in healthy Japanese subjects. METHODS: Two-hundred and seventy-seven healthy Japanese subjects aged 20-89 years were enrolled. Fecal samples were obtained to analyze the gut microbiome. We evaluated the association between stool consistency [Bristol stool scale (BSS)] and gut microbiota. RESULTS: Although there were significant differences in the microbial structure between males and females, the α-diversity of gut microbiota showed no difference between males and females or among age groups. There were significant increases in genera Prevotella, Megamonas, Fusobacterium, and Megasphaera and Bifidobacterium, Ruminococcus, and Akkermansia in males and females, respectively. The ratio of hard stools (BSS types 1 and 2) was higher in females; the ratio of loose stools (BSS type 6) was higher in males. No younger male had BSS type 1 or type 2. Fusobacterium in males was significantly higher in the loose consistency group, and Oscillospira was significantly higher in the hard consistency group in males; Campylobacter, SMB53, and Turicibacter were significantly higher in the hard consistency group in females. CONCLUSIONS: Several changes in gut microbiota were associated with age and sex. Stool consistency and gut microbiota associations emphasized the importance of stool consistency assessments to understand intestinal function.

Correction to: Differences in gut microbiota associated with age, sex, and stool consistency in healthy Japanese subjects.

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