3 Key Takeaways
Plain English Summary- 01Core Finding
Here, using fecal shotgun metagenomics from 6,803 adults in the Japanese 4D cohort, we identified two opposing microbiome-mediated axes linking lifestyle to health and 15 diseases.
- 02Study Evidence
Tested in a observational cohort study (6,803 adults) at the real-world cohort stage.
- 03Practical Meaning
Observational cohort findings reveal real-world links, though lifestyle or unmeasured factors cannot be fully ruled out without an RCT.
What This Means for You
Microbiome-defined health- and disease-oriented mediator axes were supported by fecal short-chain fatty acids and plasma cytokines from >1,700 individuals, revealing butyrate-associated anti-inflammatory and pro-inflammatory host profiles, respectively. Microbiome-based prediction (MADE) scores captured lifestyle-microbiome-disease mediation patterns and distinguished individual diseases across 13 independent external cohorts from the United States, China, Sweden, Russia and Australia. We identify the gut microbiome as a key mediator linking lifestyle to health and disease, providing a framework for microbiome-based assessment to guide lifestyle interventions for health promotion and disease prevention.
The Discovery
Analyses disentangling the role of the gut microbiome in linking lifestyle factors to health outcomes remain limited. Here, using fecal shotgun metagenomics from 6,803 adults in the Japanese 4D cohort, we identified two opposing microbiome-mediated axes linking lifestyle to health and 15 diseases. A health-associated axis enriched in microbial metabolism of dietary components was linked to plant-based, soy and dairy intake. In contrast, a disease-associated axis, enriched in oral-derived bacteria and pathobionts, was linked to refined carbohydrates and sedentary behavior. Starter culture microorganisms used to ferment foods did not show statistically significant mediation of the observed health effects. Alcohol was associated with both health- and disease-oriented mediation patterns involving microbial host-glycan utilization.
How It Works, Simply
This endocrinology research focuses on gut bacteria · Inflammation. Researchers evaluated it using an observational cohort study (6,803 adults) at the real-world cohort stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Here, using fecal shotgun metagenomics from 6,803 adults in the Japanese 4D cohort, we identified two opposing microbiome-mediated axes linking lifestyle to health and 15 diseases.
- 02Study Evidence
Tested in a observational cohort study (6,803 adults) at the real-world cohort stage.
- 03Practical Meaning
Observational cohort findings reveal real-world links, though lifestyle or unmeasured factors cannot be fully ruled out without an RCT.
Biological Mechanism & Study Design
Study Design & Cohort
Observational cohort study
Observational cohort study (6,803 adults) · Real-World Cohort
Biological Pathway & Modality
Gut bacteria · Inflammation
Intervention: Opposing microbiome-mediated axes link modifiable lifestyles to health and chronic
Experimental Findings & Endpoints
Analyses disentangling the role of the gut microbiome in linking lifestyle factors to health outcomes remain limited.
Here, using fecal shotgun metagenomics from 6,803 adults in the Japanese 4D cohort, we identified two opposing microbiome-mediated axes linking lifestyle to health and 15 diseases. A health-associated axis enriched in microbial metabolism of dietary components was linked to plant-based, soy and dairy intake.
In contrast, a disease-associated axis, enriched in oral-derived bacteria and pathobionts, was linked to refined carbohydrates and sedentary behavior. Starter culture microorganisms used to ferment foods did not show statistically significant mediation of the observed health effects.
Alcohol was associated with both health- and disease-oriented mediation patterns involving microbial host-glycan utilization.
Clinical Translation & Practice Context
Microbiome-defined health- and disease-oriented mediator axes were supported by fecal short-chain fatty acids and plasma cytokines from >1,700 individuals, revealing butyrate-associated anti-inflammatory and pro-inflammatory host profiles, respectively.
Microbiome-based prediction (MADE) scores captured lifestyle-microbiome-disease mediation patterns and distinguished individual diseases across 13 independent external cohorts from the United States, China, Sweden, Russia and Australia. We identify the gut microbiome as a key mediator linking lifestyle to health and disease, providing a framework for microbiome-based assessment to guide lifestyle interventions for health promotion and disease prevention.
The Bottom Line · Clinical Pearl
“We identify the gut microbiome as a key mediator linking lifestyle to health and disease, providing a framework for microbiome-based assessment to guide lifestyle interventions for health promotion and disease prevention.”
Published in Nature Medicine · Current Stage: Real-World Cohort