A Gut Microbiome Alternative

to Injectables for Weight Loss

Julia Malkowski, ND, DC | March 28, 2023

Medication-induced weight loss is the latest health fad. Weight loss drugs such as Ozempic and Wegovy have increased in popularity so drastically that they are currently in short supply according to the FDA. The active ingredient in these medications is the gastrointestinal glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide. GLP-1 receptor agonists exert multimodal effects; suppressing glucagon section and gluconeogenesis, while delaying gastric emptying, and stimulating satiety, lipolysis and insulin secretion. Akkermansia muciniphilia, Bifidobacterium, polyphenols, short chain fatty acids and GABA all play a role regarding GLP-1 activity. Addressing the Gut Brain Axis may be a reasonable alternative for individuals who do not meet the qualifications for GLP-1 medications.

As it’s first action, GLP-1 binds to myenteric intestinofungal neurons resulting in gut distention and feelings of satiety in the hypothalamus. Gastric volume is sensed by hypothalamic neurons via spinal afferent pathways. Myenteric intestinofungal neurons mediate gastric effects of GLP-1. Rather than a circulating hormone, endogenous GLP-1 acts on ileal enteric neurons. Semaglutide is almost identical to GLP-1, albeit one key difference. The half-life of endogenously produced GLP-1 is two minutes, while the half-life for 0.5 to 1 mg semaglutide is 7 days. This allows for the once weekly injection and increased availability for the effects of the drug.

Akkermansia muciniphila acts as a GLP-1 receptor agonist. A. muciniphila has been shown to increase thermogenesis, GLP-1 secretion and brown adipose tissue (BAT) via uncoupling of protein 1, in a murine model. BAT is metabolically active and abundant in infancy, yet decreases with age. There exists a role for A. muciniphila to not only induce GLP-1, yet BAT as well. Bifidobacterium plays a role analogous to GLP-1 receptor agonists.

Dietary polyphenols such as olive oil, pomegranates and blueberries stimulate the release of GLP-1. We know polyphenols support healthy gut microbial populations. Fecal short chain fatty acids (SCFA), largely derived from dietary soluble fiber, interact with enteroendocrine L-cells. There exists a potential mechanism for SCFA to collectively provide a lingering physical tone to stimulate L-cells to release GLP-1. Another potential mechanism involves a specific role for acetate, propionate and/or butyrate. More research is needed to elucidate the exact link between SCFA and GLP-1. Berberine, an isoquinoloine alkaloid that has been attributed to anti-inflammatory and weight-loss effects, increases GLP-1.

Gamma-aminobutyric acid (GABA) and glycine increase GLP-1, but only in a parasympathetic state. Proper eating hygiene assists in inducing a parasympathetic state during feeding. Eating hygiene includes smelling cooking food to stimulate digestive enzymes, sitting down to eat, chewing food and consuming meals with others. Monitoring and addressing fecal elastase levels may support proper digestion and therefore GLP-1 secretion. There is some evidence that supplementing elastase may support endogenous levels over time.

Medication induced weight-loss drugs have been approved for those with Diabetes Mellitus (DM) Type II, as well as those with obesity and one co-condition. For others, a gut microbial approach to GLP-1 may be warranted. Common gastrointestinal side effects of semaglutide drugs may be treated with laxatives or stool softeners, yet these GI side effects may be avoided all together with a primary gut microbiome approach. Supporting GLP-1 via the Gut Brain Axis may be a feasible, non-pharmaceutical approach for the majority of individuals.

 

References

Blum, Dani. (2023) What Is Ozempic and Why Is It Getting So Much Attention? The New York Times. What Is Ozempic and Why Is It Getting So Much Attention? - The New York Times (nytimes.com)

Gameiro, A., Reimann, F., Habib, A. M., O'Malley, D., Williams, L., Simpson, A. K., & Gribble, F. M. (2005). The neurotransmitters glycine and GABA stimulate glucagon-like peptide-1 release from the GLUTag cell line. The Journal of physiology, 569(Pt 3), 761–772. https://doi.org/10.1113/jphysiol.2005.098962

Hernández, M. A. G., Canfora, E. E., Jocken, J. W. E., & Blaak, E. E. (2019). The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity. Nutrients, 11(8), 1943. https://doi.org/10.3390/nu11081943

Kim, Y. A., Keogh, J. B., & Clifton, P. M. (2018). Probiotics, prebiotics, synbiotics and insulin sensitivity. Nutrition research reviews, 31(1), 35–51. https://doi.org/10.1017/S095442241700018X

Ray, K. GLP1-mediated gut–brain neural circuit controls appetite suppression. Nat Rev Gastroenterol Hepatol 19, 486 (2022). https://doi.org/10.1038/s41575-022-00648-0

Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., Kushner, R. F., & STEP 1 Study Group (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England journal of medicine, 384(11), 989–1002. https://doi.org/10.1056/NEJMoa2032183

Yoon, H. S., Cho, C. H., Yun, M. S., Jang, S. J., You, H. J., Kim, J. H., Han, D., Cha, K. H., Moon, S. H., Lee, K., Kim, Y. J., Lee, S. J., Nam, T. W., & Ko, G. (2021). Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nature microbiology, 6(5), 563–573. https://doi.org/10.1038/s41564-021-00880-5


 

Stress And The HPA Axis: Helping Your Patients Shift From Surviving to Thriving

Presented by Ruth Hobson, ND

April 5, 2023 at 9:30 AM and 12 PM Pacific

Each session is approximately 60 minutes with Q&A

Learning Objectives:

  1. Review healthy HPA axis regulation
  2. Discuss physiological adaptations within the HPA axis including phases of HPA axis dysfunction
  3. Discuss physiologic changes in the body due to HPA axis dysfunction
  4. Review testing options for HPA axis including diurnal cortisol, CAR and metabolites
  5. Gain tools to optimize HPA axis dysfunction once identified.
 
 

Testing Hormone Metabolites and Neurotransmitters: Considerations for Comprehensive Patient Support

Presented by Lylen Ferris, ND

April 19, 2023 at 12:30 PM Eastern

Each session is approximately 60 minutes with Q&A

Patients are complex. Similar symptoms can be the result of many different, and individualized, neurotransmitter and hormone imbalances. Mental health challenges are not isolated in the brain alone. There are many factors affecting our mental wellbeing, and by assessing neurotransmitters and reproductive and adrenal hormones, we can get a more well-rounded understanding of how nutrition, digestion, inflammation, stress, metabolism, and methylation may be contributing to the symptom picture. Proper testing can be utilized to determine which therapeutics may be considered appropriate.

Learning Objectives:

  1. Review enzyme activity and connections with hormone metabolism and neurotransmission
  2. Assess how influences on the HPA axis including chronic stress and inflammation can impact mood, sleep, cognition, weight and more
  3. Identify scenarios where considering neurotransmitter testing in conjunction with hormone metabolite testing would be appropriate, utilizing the Doctor's Data Hormone and Urinary Metabolites Assessment Profile, or HuMap™
  4. Introduce treatment options based on specific patient imbalances

Disclaimer: All information given about health conditions, treatment, products, and dosages are for educational purposes only and do not constitute medical advice.

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