Interplay between the microbiota and treatments
The gut microbiota can be modulated by our diet, and particularly by dietary fiber. We have shown that a carbohydrate-restricted diet can restructure the human gut microbiota within a few days. The Segal (https://genie.weizmann.ac.il/) /Elinav teams have shown that the gut microbiota can be used to guide recommendations for personalized nutrition. However, future studies are required to determine how specific bacteria can be targeted by dietary interventions.
The interaction between the gut microbiota and commonly prescribed drugs is complex and bidirectional: the gut microbiota composition can be modified by drugs, but, vice versa, microbial metabolism can contribute to the efficacy and/or adverse effects of drugs. Such bidirectional microbiota-drug interactions have been observed for metformin, which is known to have a profound effect on the gut microbiota. These interactions are exemplified in the following studies from our group. (1) We colonized mice with feces taken before and after treatment with metformin from individuals with type 2 diabetes, and observed improved glucose tolerance in mice that received the metformin-altered microbiota. (2) We showed that metformin signaling is inhibited by the microbial metabolite imidazole propionate. Thus, the gut microbiota appears to both mediate and inhibit metformin’s antidiabetic effects. Within the MetaCardis project, the study lead by the Raes lab has also shown that treatment with statins (commonly prescribed cholesterol-lowering drugs) reduced the prevalence of a microbiota configuration that has been associated with obesity and inflammatory bowel disease. Thus, statins potentially modulate the disrupted gut microbiota observed in these disease states.
Bariatric surgery is the only long-term treatment for obesity, and it also has beneficial effects on the metabolic syndrome. We recently showed that the gut microbiota is altered by Roux-en-Y gastric bypass, the most common type of bariatric surgery, and that the changes in microbial composition may contribute to the beneficial metabolic outcomes following surgery. We have also identified post-surgery alterations in bile acid metabolism. Bile acids signal through farnesoid X receptor (FXR), and we have shown that the beneficial metabolic effects following bariatric surgery in mice require functional FXR signaling. Further exploration is required to clarify how different types of bariatric surgery affect the gut microbiota and whether the pre-surgery microbiota composition can affect metabolic outcomes after bariatric surgery.
The worldwide increase in type 2 diabetes is a major health issue with considerable medical and societal implications. We are now performing clinical trials with novel probiotics containing important bacteria. The potential products stemming from this project may be able to change how many diseases are treated today reducing health care costs and suffering for individuals.
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- Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella, Cell Metabolism (2015)
- Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR Signaling, Cell Metabolism (2015)
- An integrated understanding of the rapid metabolic benefits of a carbohydrate-restricted diet on hepatic steatosis in humans, Cell Metabolism (2018)
- Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug, Nature Medicine (2017)
- Microbial imidazole propionate affects responses to metformin through p38γ-dependent inhibitory AMPK phosphorylation, Cell Metabolism (2020)
- Statin therapy is associated with lower prevalence of gut microbiota dysbiosism, Nature (2020)
- Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation, Cell Metabolism (2015)
- FXR is a molecular target for the effects of vertical sleeve gastrectomy, Nature (2014)