You’re likely familiar with semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) used in commercially available prescription medicines for treatment of type 2 diabetes and obesity. Are you aware that GLP-1 — the hormone semaglutide is designed to induce — is naturally produced by the body to help promote healthy blood sugar levels, curb cravings and maintain a healthy weight? Or aware of the bacterium in the gut microbiota that induces natural production of GLP-1?

GLP-1: Key to Blood Glucose Homeostasis

GLP-1 is part of a group of metabolic hormones — called incretin hormones — that help decrease blood glucose levels. The majority of GLP-1s are produced by L-cells lining the small intestine and colon; smaller quantities are secreted by the pancreas and the central nervous system.

In the pancreas, GLP-1 stimulates the release of insulin, increases the amount of insulin-producing pancreatic cells (beta cells) and reduces the release of glucagon — a hormone that raises blood sugar levels. GLP-1 also signals appetite centers in the brain, indicating a sense of fullness during and between meals by slowing gastric emptying.

Primarily triggered by food consumption, GLP-1 release occurs 10 – 15 minutes after eating. Although it remains in the blood system for several hours, nerve activity and other hormones can affect GLP-1 production and levels. For example, somatostatin, a hormone principally produced in the nervous and digestive systems, reduces GLP-1 production; dipeptidyl peptidase-4, an enzyme expressed on the surface of cells, terminates the blood glucose lowering action of GLP-1.^1,2

Remarkably, GLP-1 is glucose-dependent — it reduces blood glucose levels only after a person eats; it does not reduce glucose levels on its own. In clinical studies, GLP-1 administered intravenously to fasting patients failed to reduce blood sugar levels compared with patients who consumed a meal. This inability to induce hypoglycemia, or low blood sugar levels, in IV-administered GLP-1 led to the development of GLP-1 receptor agonists.²

Gut Microbiota Affects GLP-1

The human gut, commonly known as the gastrointestinal (GI) tract, possesses more than 1,000 microbial species that form a complex ecological community known as the gut microbiota. Composed of bacteria, viruses, yeast, fungi and other microorganisms, the gut microbiota plays a pivotal role in health and disease. It serves several functions, including fermentation of food, protection against pathogens, immune response stimulation and vitamin production. Composition, proportion and diversity of an individual’s gut microbiota are affected by genetics, lifestyle (diet), drugs (frequency/use of antibiotics), aging and other factors.^3-5

Microbial metabolites, such as secondary bile acids, short-chain fatty acids, lipopolysaccharide and others within the gut microbiota, trigger GLP-1 secretion. Eating certain foods — eggs, nuts (almonds, pistachios and peanuts), high-fiber grains (oats, barley and whole wheat), avocados, olive oil and vegetables (Brussels sprouts, broccoli and carrots) — has shown to support GLP-1 levels.^5-7

Multiple studies have linked gut dysbiosis — a change or imbalance in the diversity, composition and functions of the microbiota — to reduced GLP-1 levels. Reduced GLP-1 levels are directly associated with development of metabolic disorders, including type 2 diabetes and obesity.^3-8

Probiotics Support Gut Health

In addition to eating GLP-1-supportive foods, specific strains of probiotics can significantly alter the gut microbiome and increase GLP-1 production. For example, the probiotic Akkermansia muciniphila (A. municiphila) secretes a protein that induces natural production of GLP-1. A unique strain of A. municiphila, AH39, targets the mucosal layer of the gut, which is critical for retaining gut barrier integrity and promoting healthy inflammatory markers. It also promotes healthy systemic metabolic outcomes within the gut lining.^9,10

The Bifidobacterium animalis HN019 strain promotes the production of short-chain fatty acids in the gut microbiota. It also supports the intestinal barrier function and promotes healthy inflammatory markers.

The Bifidobacterium animalis B420 strain aids in weight management and supports metabolic health by influencing gut microbiota composition and promoting the production of short-chain fatty acids that support energy metabolism and contribute to GLP-1 secretion.

Lactobacillus rhamnosus GG is believed to support gastrointestinal health and immune balance. It may help promote the structural and functional integrity of the gut barrier. It also supports the composition and activity of the gut microbiome, promoting an increase in beneficial bacteria and the production of short-chain fatty acids. These actions may help maintain a healthy intestinal environment, promote healthy inflammatory markers and support metabolic functions.

Clostridium butyricum nourishes the gut lining, promotes healthy inflammatory markers and supports healthy barrier function. Clostridium butyricum 10 is known for its butyrate-producing capabilities. Butyrate is a primary energy source for colonocytes, supporting their health and promoting a robust intestinal barrier. It also supports the healthy expression of tight junction proteins, further enhancing barrier integrity.¹⁰

Many misrepresent the naturally occurring GLP-1 hormone with GLP-1 RA. It’s important, however, to recognize the distinctions. For individuals who cannot tolerate or afford GLP-1 RAs, options, including dietary food choices and probiotic nutritional supplements, are available.

References

1. Society for Endocrinology. Your Hormones: Glucagon-like peptide 1. Last reviewed July 2021. Accessed August 2024 at https://www.yourhormones.info/hormones/glucagon-like-peptide-1/
2. Nadkarni P, Chepurny OG, Holz GG. Regulation of glucose homeostasis by GLP-1. Prog Mol Biol Transl Sci. 2014;121:23-65. https://doi:10.1016/B978-0-12-800101-1.00002-8
3. Tomaro-Duchesneau C, LeValley SL, Roeth D, et al. Discovery of a bacterial peptide as a modulator of GLP-1 and metabolic disease. Sci Rep. 2020; 10:4922. https://doi.org/10.1038/s41598-020-61112-0
4. Zeng Y, Wu Y, Zhang Q, et al. Crosstalk between glucagon-like peptide 1 and gut microbiota in metabolic diseases. mBio 15:e02032-23. https://journals.asm.org/doi/10.1128/mbio.02032-23
5. Afzaal M, Saeed F, Shah YA, et al. Human gut microbiota in health and disease: Unveiling the relationship. Front Microbiol. 2022; 13:999001. https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.999001
6. Wang Q, Lin H, Shen C, et al. Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling. Gut Microbes. 2023; 15(2). https://doi.org/10.1080/19490976.2023.2274124
7. Pederson T. What Foods Increase GLP-1 Levels? Healthline. 2024. Medically reviewed by Adam Bernstein, MD, ScD. Accessed August 2024 at https://www.healthline.com/health/foods-that-increase-glp-1
8. Li HY, Zhou DD, Gan RY, et al. Effects and Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics on Metabolic Diseases Targeting Gut Microbiota: A Narrative Review. Nutrients. 2021;13(9):3211. https://doi:10.3390/nu13093211
9. Rodrigues VF, Elias-Oliveira J, Pereira ÍS, et al. Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes. Front Immunol. 2022;13:934695. https://doi:10.3389/fimmu.2022.934695
10. Wellness Works. Metabolic Probiotic with Akkermansia Product Data Sheet. 2024. Accessed August 2024 at https://beta.pccarx.com/prod_data/10444-Metabolic-Probiotic-with-Akkermansia.pdf

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.