Analysis of healthy reference ranges for clinically relevant gut microbial indicators: A large web-based cohort study in Japan

Background: Although several large cohort studies have focused on the human gut microbiome, large cohort study of the Japanese gut microbiome is scarce, especially that of healthy or non-diseased individuals. The purpose of this study was to establish a reference range for gut microbial indices by collecting Japanese real-world microbiome data from the web-based cohort. Methods: We collected stool samples and original survey on lifestyle from 5,843 Japanese people through web-based services. From the obtained 16S rRNA sequence data derived from the stool sample, the ratio and distribution of each taxa were analyzed. The relationship between different epidemiological attributes and gut microbial indicators were statistically tested. Results: In total, 100 taxa (genus level) of gut microbiota were shared by more than 10% of Japanese people, and 20 taxa (genus level) by 90% or more. Bacteroides-dominant type was the most popular entero-type. The qualitative and quantitative indicators of these common gut microbiota were confirmed to be strongly correlated with age, constipation / diarrhea, and a history of lifestyle-related diseases. Therefore, we set up the healthy sub-cohort that controlled for these attribute factors, and defined a reference range from the distribution of gut microbial index in that population. Conclusions: The gut microbiota of Japanese people had high beta diversity, and there was no single "typical" gut microbiota type. We believe that the reference range of the gut microbial index obtained in this study can be a new reference value for determining the balance and health of the gut microbiota of an individual. In the future, it is necessary to clarify the clinical validity of this reference value by comparing with the clinical disease cohort.