11 November 2026, Tokyo, JP: Researchers in Japan have found two opposing groups of gut bacteria that appear to link everyday habits to chronic disease. One group is associated with plant foods, fermented foods, coffee and exercise. The other is associated with refined carbohydrates, sugary soft drinks, smoking and long hours of sitting. The findings come from a study of 6,803 Japanese people, published on 5 November in Nature Medicine.
The work was carried out jointly by Tokyo Medical University, the Japan Institute for Health Security (JIHS), the University of Tokyo’s Graduate School of Frontier Sciences and RIKEN, Japan’s national research institute. The corresponding author is Associate Professor Naoyoshi Nagata of Tokyo Medical University’s centre for health screening and preventive medicine. Collaborators include Hiroshi Ohno, team director at RIKEN’s Center for Integrative Medical Sciences, and Suguru Nishijima, project associate professor at the University of Tokyo.
Participants came from the Japanese 4D cohort, a large national gut microbiome study group. The team used shotgun metagenomics, which sequences all the genetic material in a stool sample to identify which microbes are present and what they can do. They added stool metabolite measurements and, for about 1,700 people, blood tests for cytokines, the signalling proteins that drive inflammation. A statistical technique called mediation analysis was then used to estimate how much of the link between a habit and a health outcome runs through specific bacteria. The analysis covered overall health status and 15 chronic diseases, including inflammatory bowel disease and type 2 diabetes.
On the health-oriented side, the main bacteria were butyrate producers such as Faecalibacterium prausnitzii and Anaerostipes hadrus. Butyrate is a short-chain fatty acid that gut microbes make when they ferment dietary fibre, and it helps maintain the gut lining. These bacteria tracked closely with higher butyrate levels and lower inflammation. Vegetables, fruit and mushrooms were linked to microbial genes for breaking down plant fibres such as pectin, hemicellulose and cellulose. Fermented soy foods were linked to bacteria of the genus Adlercreutzia, which are involved in producing equol, a compound made from soy isoflavones.
The disease-oriented side looked quite different. More than a quarter (26.3%) of the bacteria mediating disease links normally live in the mouth, such as Streptococcus species and Bifidobacterium dentium. None of the health-side mediators came from the mouth. Pathogen-related bacteria made up 14.3% of the disease-side mediators and none of the health-side ones. Refined carbohydrates such as white rice, bread and noodles, along with soft drinks, were associated with Escherichia coli and Klebsiella pneumoniae. They were also tied to microbial genes for sugar uptake, lactate production, biofilm formation and lipopolysaccharide, a bacterial molecule known to trigger inflammation. Alcohol pointed both ways: it was linked to the health-side bacterium Bacteroides uniformis and to Ruminococcus gnavus, a species that degrades the gut’s protective mucus layer.
Fermented foods, not their live microbes
The study also touches on the probiotic market. Participants ate fermented foods such as natto (fermented soybeans), miso, pickles, kimchi and yoghurt, and the live microbes from those foods were detected in their guts. Those food-borne microbes did not mediate any of the health links, though. The benefit flowed instead through the gut’s own butyrate producers and equol-related bacteria. The study therefore suggests that fermented foods may help by feeding or supporting resident microbes, rather than by colonising the gut themselves.
The team turned the results into a classification tool called the MADE score, which uses a person’s gut bacteria to estimate their health status and disease risk. It distinguished inflammatory bowel disease with an AUC of 0.87, a statistical measure where 1.0 is perfect separation and 0.5 is chance. The pattern was tested in 13 independent cohorts totalling 3,095 people in the United States, China, Sweden, Russia and Australia, and it held in 11 of them. The health score rose with higher intake of vegetables, fruit and natto. The disease score rose with soft-drink consumption, smoking and prolonged sitting.
The study is observational. Mediation analysis can show that a link between a habit and a disease runs statistically through certain bacteria, but it cannot prove that those bacteria cause the outcome. The researchers present their findings as possible pathways. They plan to use the MADE score to track how the microbiome changes when people change their lifestyle, as a step toward evidence-based guidance on gut health.
Funding came from the Japan Agency for Medical Research and Development (AMED), JSPS KAKENHI research grants, the National Center for Global Health and Medicine and several foundations. The research also received grants from food companies Ezaki Glico and Danone and from J-Milk, Japan’s dairy industry association. The institutions state that the funders had no role in the study’s design, analysis or publication.
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