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Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized
Noel T Mueller1,2, Moira K Differding3,2, Mingyu Zhang3,2
1Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD noeltmueller@jhu.edu.
Diabetes Care
|May 19, 2021
Summary
Metformin significantly altered gut microbiota composition and increased short-chain fatty acids (SCFAs) like acetate, which correlated with lower fasting insulin. Behavioral weight loss had minimal impact on gut microbiota but also increased acetate.
Area of Science:
- Microbiome research
- Metabolic health
- Oncology survivorship
Background:
- Overweight/obesity is common in cancer survivors.
- Gut microbiota and short-chain fatty acids (SCFAs) play roles in metabolic health.
- Metformin and behavioral weight loss are potential interventions.
Purpose of the Study:
- To investigate the long-term effects of metformin and behavioral weight loss on gut microbiota and SCFAs in overweight/obese cancer survivors.
- To compare the impact of metformin, behavioral weight loss, and self-directed care on these parameters.
Main Methods:
- A 12-month randomized trial with 121 overweight/obese adults (no active cancer treatment).
- Interventions included metformin, coach-directed behavioral weight loss, or self-directed care.
- Stool and serum samples were analyzed for microbial DNA, metagenomic sequencing, and SCFAs at baseline, 6, and 12 months.
Main Results:
- Metformin significantly altered gut microbiota composition, increasing *Escherichia coli* and *Ruminococcus torques*, and decreasing *Intestinibacter bartlettii* and *Roseburia* species.
- Metformin increased serum butyrate and acetate at 6 months, while behavioral weight loss increased acetate at 6 months.
- Increased acetate levels were associated with decreased fasting insulin.
- Metformin altered 62 metagenomic functional pathways, including acetate production and glucose metabolism.
Conclusions:
- Metformin, unlike behavioral weight loss, significantly impacted gut microbiota composition and SCFA levels.
- Both interventions increased acetate at 6 months, linking to improved insulin sensitivity.
- Further research is needed to understand the role of the gut microbiome in mediating metformin's health effects.
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