Akkermansia muciniphila: Promising new human clinical trials for probiotics

The gut microbiome ​is increasingly viewed as an organ in its own right and as one that plays a vital role in overall wellness.​

Disease prevention and optimal health hinge upon a delicate equilibrium of approximately 100 trillion micro-organisms that dwell within this complex ecosystem. Imperative gut bacteria maintain immune homeostasis by balancing anti-inflammatory regulatory T cells (Tregs) and proinflammatory Th1/Th17 cells. Interestingly, research has established multiple associations between particular intestinal microbes and metabolic conditions such as obesity, type 2 diabetes, mellitus, gastrointestinal disorders, neurodegenerative diseases, and even cancers.

Amidst the gut microbiome’s diverse bacteria, Akkermansia muciniphila (A. muciniphila) has distinguished itself as a potent probiotic with promising health benefits. An anaerobic, gram-negative bacterium isolated from human feces, Akkermansia has a unique capacity to degrade mucin for use as a source of carbon and nitrogen, stimulating the growth of other beneficial bacteria in the human gastrointestinal tract.¹​

Additionally, Akkermansia regulates the immune system while improving gut barrier function and metabolism. This has been established using in vitro and in vivo models of obese and diabetic mice. 

Health benefits of Akkermansia muciniphila​

The prevalence of A. muciniphila has been connected to fewer instances of cancer, type 2 diabetes, and liver disease, and the safety and efficacy of the strain as a probiotic have been successfully established. Studies have shown that a shortfall of A. muciniphila is inversely proportional to the occurrence of acute appendicitis, ulcerative colitis, alcoholic liver disease, obesity, type 2 diabetes, and atopic dermatitis.

Some studies have revealed a link between A. muciniphila and the metabolism of glucose and its dysregulation. A 2017 study established the effect of pasteurized A. muciniphila in diminishing fat mass development, insulin resistance, and dyslipidemia in mice.²​ Another 2021 study found lower levels of Akkermansia were linked to eating disorders such as binge eating.³​

A study concentrating on the role of gut microbiota in the response to anti-programmed cell death protein 1 (Anti–PD-1) immunotherapy indicated that the presence of species, such as A. muciniphila, in the gastrointestinal tract of cancer patients was linked with a stronger immune response to the therapy and consequently contributed to an extended survival of these patients.⁴​ 

Depommier et al. conducted an exploratory study on 32 overweight and obese insulin-resistant human volunteers.⁵​ They demonstrated that daily oral supplementation with A. muciniphila was safe and well-tolerated for up to three months.

New human clinical trials and advanced encapsulation technology​

Vidya Herbs, a global leader in nutraceutical advancement, stands at the forefront of translating the therapeutic potential of A. muciniphila into tangible health benefits. In additional to designing key human clinical trials, the company has also developed a patent-pending encapsulation technology. The new stabilization process forms a continuous thin coat around the solid particles.

“Our encapsulation process protects Akkermansia from moisture, temperature, and oxygen to ensure maximum stability,” says Subhendu Nayak, Director of Formulation, Vidya Herbs.

Clinical study highlights​

The comprehensive clinical trials to validate the health benefits of A. muciniphila span across various domains:

Digestive health ​For assessing the efficacy of A. muciniphila in digestive health, 5 BCFU of A. muciniphila will be used to examine the FUT2, GCKR, MTHFR, APOA1, hsCRP, TNF-alpha, IL-6, amino acid levels, fecal microbiota composition and metabolites. The aim is to evaluate overall digestive health, protein bioavailability, and enhanced inflammatory and immune response time.

Sleep, stress, and cognition​ Due to the health benefits of A. muciniphila, 7 BCFU of the strain will be used to evaluate the reaction time measurement, cognitive control, and flexibility through questionnaires. Depression, anxiety, and stress will be evaluated through the short form (DASS-21) questionnaire and the Pittsburg sleep quality index. The objective is to reduce anxiety and depression, improve sleep and cognitive clarity, and improve accuracy and working memory.

Glucose and cholesterol reduction​ The effect of 10 BCFU of A. muciniphila will be evaluated on the fasting blood sugar level, HbA1c and lipid levels, insulin sensitivity and secretion amount, BMI and body weight, waist circumference, body vitals, and physical performance examination. The desired therapeutic effect is to improve the fasting sugar level, bring about metabolic health changes, and make positive changes to the lipid profile and total cholesterol levels.

Figure 1: Overview of Vidya Herbs’ human clinical study to evaluate the efficacy of Akkermansia muciniphila on human health​​

Dr. Rishi Trivedi, Commercial Director at Vidya Herbs highlights the company’s ambitious clinical trial program exploring the gut bacterium’s multifaceted potential: “We have designed novel clinical trials to assess the efficacy of A. muciniphila in areas impacting everyday life, from digestion to restful sleep, mental clarity, and healthy blood sugar levels. We are dedicated to unlocking the secrets of Akkermansia muciniphila and paving the way for transformative treatments.”

Akkermansia as a therapeutic probiotic​

Mounting evidence suggests a major role for Akkermansia as a therapeutic probiotic against several metabolic disorders as well as potential for reducing body weight, lowering lipid levels, and delaying the effects of aging. It also shows promising signs of improving the efficacy of immunotherapy for certain cancers. Vidya Herbs aims to finalize key human clinical trials and deliver a stabilized live culture of Akkermansis to consumers in the US market by Q1 2024.

 ​References​

1.​ Derrien, M.; Vaughan, E. E.; Plugge, C. M.; et al. (2004). Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium.​ International journal of systematic and evolutionary microbiology, 54(Pt 5), 1469–1476.
2.​ Plovier, H.; Everard, A.; Druart, C.; et al. (2017). A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice.​ Nature medicine, 23(1), 107–113.
3.​ Leyrolle, Q.; Cserjesi, R.; Mulders, M. D. G. H.; et al. (2021). Specific gut microbial, biological, and psychiatric profiling related to binge eating disorders: A cross-sectional study in obese patients.​ Clinical nutrition (Edinburgh, Scotland), 40(4), 2035–2044.
4.​ Miller, P. L.; & Carson, T. L. (2020). Mechanisms and microbial influences on CTLA-4 and PD-1-based immunotherapy in the treatment of cancer: a narrative review.​ Gut pathogens, 12, 43.
5.​ Depommier, C.; Everard, A.; Druart, C.; et al. (2019). Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study.​ Nature medicine, 25(7), 1096–1103.