Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1 Hormone Secretion*

By H. Yadav, Jihyeon Lee, J. Lloyd, P. Walter, S. Rane. Journal of Biological Chemistry, 2013

627 citations recorded by the source corpus.

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. 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.

Subfields: Food Science, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/6c0312f21a084004fff01f08dfc5fa7c23209b7b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Food Science

1. Ted G. Dinan
2. G. Clarke
3. J. Cryan

In Molecular Biology

1. J. Cryan
2. Ted G. Dinan
3. G. Clarke
4. C. Stanton
5. R. Stilling
6. M. van de Wouw
7. J. F. Mota
8. Guolong Zhang

In Physiology

1. J. Cryan
2. Ted G. Dinan
3. G. Clarke
4. Christian Hoffmann
5. C. Stanton

Citations in the corpus

• Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. (2016, background): “Probiotics may result in reduced depressive symptoms, as well as improved metabolic status, biomarkers of inflammation, and oxidative stress, through their effect on neuronal circuits and the central nervous system mediated by the microbiota-gutbrain axis [18] and through affecting gene expression [”
• The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? (2016, background): “, 2015), stimulate secretion of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and other peptide hormones to regulate appetite and energy homeostasis (Byrne et al., 2015; Nøhr et al., 2013; Sleeth et al., 2010; Yadav et al., 2013) and to potentially improve type 2 diabetes features (Puddu et al.”
• The human gut microbiota: Metabolism and perspective in obesity (2018, background): “At least in mice, modulation of the gut microbiota by probiotics increased the production of butyrate by commensal bacteria, inducing the production of GLP-1 by intestinal L cells and thus reducing adiposity.(65) In addition, the gut microbiota may favor the formation of specific bile acids that act”
• Gut Microbiota and Immune System Interactions (2020, background): “protection from body weight gain, decreased insulin resistance, and increased GLP-1 secretion [107].”
• Butyrate: A Double-Edged Sword for Health? (2018, background): “Steinert RE, Feinle-Bisset C, Asarian L, Horowitz M, Beglinger C, Geary N. Ghrelin, CCK, GLP-1, and PYY (3–36): secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB.”
• Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial (2016, background): “…intake may improve markers of insulin metabolism and lipid profiles by reducing cytokines and suppressing the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway (Shi et al., 2006) and gut microbiotashort chain fatty acids (SCFA)-hormone axis (Yadav et al., 2013).”