On April 9th, 2024, Fullscript and Pendulum hosted an educational webinar titled “GLP-1-gut connection: Hacking the popular satiety hormone through the microbiome.
Fullscript and Pendulum
Over the past few years, Fullscript and Pendulum have collaborated closely to provide healthcare practitioners with comprehensive education and actionable strategies aimed at enhancing patient outcomes. The following information is provided as a summary of a recent webinar led by Fullscript and Pendulum on the subject of the GLP-1-gut connection.
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About the webinar speakers
Dr. Colleen Cutcliffe, PhD, Chief Executive Officer
Colleen Cutcliffe is the chief executive officer and co-founder of Pendulum. Colleen completed her postdoctoral studies at Northwestern’s Children’s Memorial Hospital. Colleen received her PhD in biochemistry and molecular biology from Johns Hopkins University and her BA in biochemistry from Wellesley College.
Dr. Jeff Gladd, MD, Chief Medical Officer
Dr. Gladd is the chief medical officer at Fullscript. Dr. Gladd graduated from the Indiana University School of Medicine and, after successfully opening a family practice, shifted focus toward health-promoting care by completing the University of Arizona Integrative Medicine fellowship program.
Dr. Alex Keller, ND, Medical Director
Dr. Keller is the medical director at Fullscript. Dr. Keller is a graduate of the University of Ottawa with an HBSc in Health Sciences and Psychology. Although originally planning to attend conventional medical school, Dr. Keller shifted direction and completed a degree in naturopathic medicine at the Canadian College of Naturopathic Medicine.
What is GLP-1?
Glucagon-like peptide-1 (GLP-1) is a hormone produced in the human gut in response to food intake that plays an important role in regulating blood glucose levels and appetite.
GLP-1 has numerous metabolic effects, including:
- Decreasing gastric emptying speed
- Supporting satiety
- Inhibiting glucagon secretion
- Supporting appetite regulation
- Stimulating insulin secretion
- Supporting blood glucose control (Müller 2019)
The GLP-1-gut connection
Studies have demonstrated that increased butyrate production by fermentation of dietary fiber within the gut microbiome leads to increased secretion of GLP-1 by L-cells within the intestine’s mucosal lining. Additionally, specific naturally occurring gut bacteria important to glucose and insulin homeostasis may exist in lower concentrations in individuals with type 2 diabetes compared to healthy individuals. New research is emerging to explore these different relationships and subjects.
Did you know? GLP-1, a satiety hormone, is stimulated when we eat. Consequently, when fasting for prolonged periods of time, GLP-1 isn’t secreted. Dr. Cutcliffe explains that it’s especially important to eat foods rich in fiber and polyphenolic compounds when breaking the fast in order to feed the microbes that stimulate GLP-1 production.
The research
In a multicenter, double-blind, randomized, placebo-controlled trial study, researchers aimed to investigate whether introducing specific microbes with supportive metabolic functions (gut barrier stability, butyrate production, and glucose and insulin homeostasis) could safely enhance glycemic control measures, thus contributing to the dietary management of early-stage type 2 diabetes. (Perraudeau 2020)
The trial design
Seventy-six subjects across six study sites were assigned to one of three groups (arms) of the study for 12 weeks:
- Placebo (containing excipients only)
- WBF-010 containing inulin fiber and three live microbial strains:
- Clostridium beijerinckii (C. beijerinckii)
- Clostridium butyricum (C. butyricum)
- Bifidobacterium infantis (B. infantis)
- WBF-011 containing inulin fiber and five live microbial strains:
- Akkermansia muciniphila (A. muciniphila)
- Anaerobutyricum hallii (A. hallii)
- C. beijerinckii
- C. butyricum
- B. infantis (Perraudeau 2020)
The key primary and secondary outcomes that were measured at week 12 included:
- Safety and tolerability
- Area under three-hour glucose curves (∆AUC) after meal tolerance test (MTT)
- Hemoglobin A1c (HbA1c)
- C-reactive protein (CRP) (Perraudeau 2020)
The results
During the 12-week intervention, increased circulating butyrate was observed, as well as other short-chain fatty acids (SCFAs) correlated with stool butyrate and HbA1c response, in both the WBF-010 and WBF-011 groups. (Perraudeau 2020)
The A. muciniphila-containing WBF-0011 probiotic combination was safe and well tolerated and provided beneficial metabolic effects and improved postprandial glucose control. The WBF-0011 probiotic combination significantly improved:
- Glucose total area under the curve (AUC): -36.1 mg/dL/180 min
- Glycated hemoglobin (A1c): -0.6%
- Glucose incremental-AUC: -28.6 mg/dL/180 min (Perraudeau 2020)
CalloutThe administration of disease-relevant microbial species may be a promising new dietary management tool for improving glucose control in type 2 diabetes. (Perraudeau 2020)
Microbial strains that influence GLP-1
Microbial strains Akkermansia muciniphila, Clostridium butyricum, and Bifidobacterium infantis may influence metabolic health and GLP-1.
Akkermansia muciniphila
A. muciniphila is an anaerobic species of bacteria present in the mucus layer of the human gut and accounts for 1 to 3% of a healthy microbiome. (Naito 2018)
When A. muciniphila consumes mucin, it produces acetic acid and SCFAs that supply energy to goblet cells, promoting mucus secretion and playing an important role in maintaining the integrity of the intestinal barrier. (Yoon 2021)(Cani 2021)
A. muciniphila may help:
- Increase GLP-1 levels
- Produce beneficial metabolites such as acetic acid
- Promote mucus secretion in the mucus layer of the gut
- Support glucose and lipid metabolism
- Support the integrity of the intestinal barrier (Cani 2021)(Yoon 2021)(Naito 2018)
Did you know?
A. muciniphila is associated with a reduced risk of obesity. (Zhou 2020)
Clostridium butyricum
C. butyricum is an anaerobic species of bacteria found in the intestines of humans and animals as well as in soil and water. C. butyricum supports metabolic health by producing SCFAs such as butyrate through the fermentation of carbohydrates, providing energy to gut-lining cells and supporting immune and intestinal mucosa health. C. butyricum may also increase GLP-1 levels in the body. (Ishikawa 2023)
C. butyricum may help:
- Increase GLP-1 levels
- Increases the abundance of butyrate-producing bacteria in the gut
- Improve insulin sensitivity
- Support immune function
- Support the health of the gut mucosa layer
Did you know?
Low butyrate production has been associated with metabolic syndrome. (Chen 2021)
Bifidobacterium infantis
B. infantis is a species of bacteria passed down from the birthing person to their infant and is especially abundant in breastfed infants. Through the metabolism of human milk oligosaccharides (HMOs) and the production of beneficial metabolites such as acetate, butyrate, and lactate, B. infantis may support the maturation of the immune system, suppress inflammation, improve intestinal barrier function, and affect appetite regulation. (Underwood 2021)(Frost 2014)(Chichlowski 2012)(Bergmann 2013)
B. infantis may:
- Improve intestinal barrier function
- Positively affect appetite regulation
- Produce beneficial metabolites such as SCFAs
- Provide anti-inflammatory effects
- Support the immune system
Did you know?
Consuming polyphenolic-rich foods like artichoke, dark chocolate, pomegranate, grape seed, green tea, and wine may help boost Akkermansia muciniphila and GLP-1 levels.
Consumer survey data: Probiotics and food cravings
Pendulum conducted a three-month consumer study that measured the food cravings of 274 participants taking A. muciniphila, C. butyricum, and B. infantis. Participants scored how often they experience food cravings for 28 different foods in various categories (i.e., sweets, carbohydrates, fast foods, high fats).
After six weeks of supplementation, participants experienced improvements in food cravings in all four categories, including:
- Carbohydrates and starches: 87% improvement
- Fast food fats: 85% improvement
- High fats: 82% improvement
- Sweets: 88% improvement
These results suggest that A. muciniphila, C. butyricum, and B. infantis support GLP-1 production and satiety.
Did you know?
A poll conducted in 2015 by Harris Poll/Nielsen Group found that nearly 80% of women and almost 70% of men experience food guilt. (HuffPost 2015)
Learn more: Healthy weight and metabolic health with Fullscript
Explore the following Fullscript educational resources on GLP-1 and metabolic health in partnership with Pendulum.
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