Journal of Biological Chemistry
Volume 288, Issue 35, 30 August 2013, Pages 25088-25097
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Metabolism
Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1 Hormone Secretion*

https://doi.org/10.1074/jbc.M113.452516Get rights and content
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Obesity and diabetes are associated with excess caloric intake and reduced energy expenditure resulting in a negative energy balance. The incidence of diabetes has reached epidemic proportions, and childhood diabetes and obesity are increasing alarmingly. Therefore, it is important to develop safe, easily deliverable, and economically viable treatment alternatives for these diseases. Here, we provide data supporting the candidacy of probiotics as such a therapeutic modality against obesity and diabetes. Probiotics are live bacteria that colonize the gastrointestinal tract and impart beneficial effects for health. However, their widespread prescription as medical therapies is limited primarily because of the paucity of our understanding of their mechanism of action. Here, we demonstrate that the administration of a probiotic, VSL#3, prevented and treated obesity and diabetes in several mouse models. VSL#3 suppressed body weight gain and insulin resistance via modulation of the gut flora composition. VSL#3 promoted the release of the hormone GLP-1, resulting in reduced food intake and improved glucose tolerance. The VSL#3-induced changes were associated with an increase in the levels of a short chain fatty acid (SCFA), butyrate. Using a cell culture system, we demonstrate that butyrate stimulated the release of GLP-1 from intestinal L-cells, thereby providing a plausible mechanism for VSL#3 action. These findings suggest that probiotics such as VSL#3 can modulate the gut microbiota-SCFA-hormone axis. Moreover, our results indicate that probiotics are of potential therapeutic utility to counter obesity and diabetes.

Background: The prescription of probiotics as obesity and diabetes therapy is limited because of insufficient efficacy data and lack of understanding of their mechanism of action.

Results: The probiotic VSL#3 prevents obesity and diabetes in mice via induction of butyrate and GLP-1.

Conclusion: Probiotics modulate the gut flora to elicit beneficial metabolic effects.

Significance: Administration of probiotics represents a viable treatment option for obesity and diabetes.

Diabetes
Leptin
Metabolism
Obesity
Probiotics
GLP-1
Gut Flora

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*

This work was supported, in whole or in part, by the National Institutes of Health from the Intramural Program of NIDDK.

This article contains supplemental Figs. S1–S15 and Tables S1–S4.

1

Present address: Natl. Agri-Food Biotechnology Inst., Mohali, Punjab, India.