The Iwaki Health Promotion Project, in the Iwaki region of Hirosaki City, Aomori Prefecture, has conducted comprehensive health checkups for over two decades, encompassing 3000 examination items among a cohort of approximately 1,000 participants. In this project, research on the gut microbiota has unveiled significant findings. Investigations into the impact of Helicobacter pylori infection have revealed that gastric mucosal atrophy resulting from H. pylori infection leads to a reduction in gastric acid secretion, exerting a substantial influence on the gut microbiota. Additionally, by exploring the association between the pathophysiology of non-alcoholic fatty liver disease (NAFLD) and the gut microbiota, it was found that NAFLD decreases the abundance of Faecalibacterium, a butyrate-producing bacterium, which was attributed to the disruption of the Gut-Liver-axis. Furthermore, a heightened affinity between equol producers and Slackia isoflavoniconvertens was discovered by examining the relationship between equol and its metabolism within the gut microbiota. Despite remaining uncertainties in the understanding of the gut microbiota, the data derived from the Iwaki Project, involving a cohort of 1,000 cases, is deemed highly valuable.

The National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN) conducts large-cohort studies of the Japanese gut microbiome to understand the functions and roles of microorganisms in our health and lifestyles. Also, aiming to contribute to the development of this research field, we are working to support other research institutions by providing standardized protocols and developing analytical tools. In this regard, we promote gut microbiome research that combines human cohorts and basic experiments. For example, we found an intestinal bacterium that can prevent and/or improve obesity and diabetes and its underlying mechanisms, and have examined postbiotics produced by intestinal bacteria and their functions. We also promote precision research focusing on individual differences in the gut microbiome. Here, we introduce an overview of gut microbiome studies at NIBIOHN and our recent findings.

Interactions between the gut microbiome and humans have drawn significant attention in recent years and this relationship is now recognized as a critical factor in human pathophysiology. However traditional studies of the human gut microbiome have primarily focused on which bacterial species are associated with the host’s pathophysiology, while knowledge of how these bacteria exert their influence has been limited. Metabolites produced by gut bacteria are thought to serve as messengers that transmit signals from the bacteria. Here we introduce our recent study focusing on the relationship between the gut microbiome and host metabolism in an attempt to elucidate the functional aspects of the human gut microbiome. This study comprehensively searched for small molecules in feces in addition to performing metagenomic analysis. We identified an increase in carbohydrates, particularly monosaccharides, that are accessible to the host in the feces of insulin-resistant subjects. Although these compounds are not direct metabolites of gut bacteria our metagenomic findings suggest that changes in gut bacteria may contribute to an increase in intestinal monosaccharides through functional changes such as polysaccharide degradation and monosaccharide utilization. This study provides functional insights into how gut bacteria and their metabolites influence human metabolic functions opening the door to novel therapeutic interventions targeting gut bacterial metabolic functions and compounds produced by them.