Biotics are a significant category of interest in the dietary supplement industry, with postbiotics being the most recent inductee to join the ranks of pre- and probiotics. Although their introduction to the industry was only about a decade or so ago, the postbiotic supplements market was valued at $1.6 billion in 2021,1 and estimated to reach $3 billion by 2031 with a compound annual growth rate of 6.8 percent. Postbiotics are trending, and Akkermansia muciniphila (AKK) is one of those postbiotics. Before jumping into a discussion of AKK, however, let’s first define postbiotics.

Defining Postbiotics

But what exactly are postbiotics? According to International Scientific Association for Probiotics and Prebiotics (ISAPP), postbiotics are defined as “a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host.”2 Essentially, a postbiotic could be any virtually any probiotic that has been pasteurized or heat-treated, and yet still provides health benefits—a sort of zombie probiotic if you will. Now, if you are wondering how a probiotic that has been pasteurized or heat-treated can still have benefits, consider the following.

Scientific evidence suggests that the beneficial health benefits of probiotics are not necessarily directly related to viable bacteria in all instances. Rather, the beneficial effects of probiotics are often based on bacteria metabolites, such as butyric acid. Postbiotic components are diverse and perform well when compared to live probiotics in terms of technology, safety and cost. Postbiotics have been shown to have bioactivities such as antimicrobial, antioxidant, anti-inflammatory, anti-proliferative and immunomodulation. Moreover, numerous studies have revealed the significant potential of postbiotics for disease treatment. Inactivation is a key step in the production of postbiotics. The most classic is thermal inactivation or pasteurization which has been used for centuries to inactivate microorganisms. Pasteurization and sterilization are used almost every day for food preservation.3

What is AKK?

AKK is a human intestinal microorganism (aka a probiotic). It colonizes the gastrointestinal tract of humans and other animals and can be found within the intestinal mucosal layer of intestinal epithelial cells as well as in the caecum (an area at the beginning of the large intestine).4 It is found in about 90 percent of healthy humans, making up about 1 percent to 3 percent of the fecal microbiota and colonizing the gut during the first year of life. As a nutraceutical, AKK is available in both probiotic and postbiotic forms.

AKK Functions

AKK’s primary function revolves around the degradation of mucin proteins (i.e., heavily glycosylated proteins that form the structural components of mucus), serving as a gatekeeper of intestinal permeability, and thus, influencing the integrity of the gut-brain axis.5 Its prevalence can decrease with age or in the presence of disease states.6 The abundance of AKK is associated with less metabolic disease, including obesity, type 2 diabetes and hypertension. This has been demonstrated in human research.7-9

AKK Functions in Weight Loss

A significant factor linked to the presence of AKK is longer food transit time, meaning digestion takes longer in the intestines.10,11 This results in heightened nutrient absorption and an extended feeling of satiation after eating. Extended food transit time, leading to decreased appetite, is also a noteworthy effect observed in one of the world’s most widely used pharmaceuticals for diabetes management and weight loss—semaglutide, available under brand names Ozempic, Wegovy and Rybelsus.12 This phenomenon appears to be attributed to the natural activation of a glucagon-like peptide-1 (GLP-1) inducing protein by AKK.13

Furthermore, during a six-week period of caloric restriction in a human study14 followed by a six-week weight stabilization diet in overweight and obese adults (N=49, including 41 women), fecal AKK abundance was measured. The results were that, at baseline, AKK was inversely related to fasting glucose, waist-to-hip ratio and subcutaneous adipocyte diameter. Subjects with higher gene richness and AKK abundance exhibited the healthiest metabolic status, particularly in fasting plasma glucose, plasma triglycerides and body fat distribution. Individuals with higher baseline AKK displayed greater improvement in insulin sensitivity markers and other clinical parameters after caloric restriction.

So, what happens when AKK is given as a supplement, especially when it is given as a postbiotic? Let’s start with a mouse study.

Mouse Study on AKK for Weight Loss

A study15 was conducted to investigate the effects of pasteurized (postbiotic) AKK on whole-body energy metabolism during high-fat diet feeding of mice. The results were that daily oral administration of pasteurized AKK alleviated diet-induced obesity. This effect was associated with an increase in energy expenditure and spontaneous physical activity. It was observed that treatment with pasteurized AKK increased energy (i.e., calorie) excretion in the feces. In conclusion, these data further support the impact of targeting the gut microbiota by using specific bacteria to control whole-body energy metabolism.

Human Study on AKK for Weight Loss

A three-month, randomized, double-blind, placebo-controlled trial16 divided 32 overweight/obese people with insulin resistance into three groups, with two intervention groups receiving 10 billion CFU of live (probiotic) or pasteurized (postbiotic) AKK daily for three months. The primary endpoints were on safety, tolerability and metabolic parameters (i.e., insulin resistance, circulating lipids, visceral adiposity, body mass). The secondary outcomes were the gut barrier function (i.e., plasma lipopolysacharrides (LPS) and gut microbiota composition. The results were that AKK was safe and well tolerated, and pasteurized AKK was more effective than live AKK. Compared to the placebo, pasteurized AKK improved insulin sensitivity (+28.62 percent, P=0.002), reduced insulinemia (-34.08 percent, P=0.006) and plasma total cholesterol (-8.68 percent, P=0.02). Although it fell short of reaching statistical significance, pasteurized AKK supplementation decreased body weight (-2.27 kg [~5 lbs], P=0.091) as compared to the placebo group, and fat mass (-1.37 kg [~3 lbs], P=0.092) and hip circumference (-2.63 cm, P= 0.091) as compared to baseline. AKK reduced the levels of relevant blood markers of liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study showed that the intervention was safe and well-tolerated and that the supplementation with AKK improves several metabolic parameters.

A Human Study on AKK Related to Metabolic Signatures

Reduced levels of AKK in the gut microbiota is a widely accepted signature associated with obesity-related metabolic disorders. Using untargeted metabolomics profiling of fasting plasma, a study17 aimed at identifying metabolic signatures associated with beneficial properties of live (probiotic) and pasteurized (postbiotic) AKK (10 billion CFU) when administrated to a cohort of insulin-resistant individuals with metabolic syndrome. Results showed that there was an induction in ketogenesis through enhanced β-oxidation (i.e., fat burning). The data showed that two different ketone bodies tended to increase in the group given the pasteurized AKK, although both live and pasteurized AKK groups experienced increased ketogenesis.

AKK Safety

Pasteurized AKK studies have been conducted in vitro and as a toxicity study18 in rats. Pasteurized AKK was administered at doses of 75, 375 or 1500 mg/kg body weight/day (equivalent to 480 million, 2.4 billion, or 9.6 billion CFU/kg body weight/day) for 90 consecutive days. The study assessed potential effects on clinical observations, body weight, food and water consumption, clinical pathology, organ weights, and macroscopic and microscopic pathology. The results of both in-vitro genotoxicity studies were negative. No test item-related adverse effects were observed in the 90-day study; therefore, 1,500 mg/kg body weight/day (the highest dose tested, was established as the no-observed-adverse-effect-level. These results support that pasteurized AKK is safe for use as a food ingredient. Likewise, the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) also found pasteurized AKK to be safe for consumption.19

The AKK001 Strain

As with any pro- or postbiotic, specific strains may offer benefits beyond the genus and species. Such is the case with the strain AKK001 (distributed in the U.S. by Nutraland USA) which was cultivated using samples from 30 centenarians in Rugao, a town in China known for the longevity of its residents.20 For this reason, it is often referred to as “the longevity postbiotic”.

Additional AKK studies

In 2020, five probiotics, including AKK, were used in a 12-week parallel, double-blind, placebo-controlled, proof-of-concept study21 for the treatment of type 2 diabetes. Results were that, compared with the placebo group, subjects receiving AKK and the other probiotics experienced significant improvements in the primary outcome of glucose total area under the curve (AUC, -36.1 mg/dL/180 min, p=0.0500) and improvements in the secondary outcomes of glycated hemoglobin (A1c, -0.6, glucose) and incremental-AUC (-28.6 mg/dL/180 min).

In 2019, clinical research22 was completed in which AKK was found to yield better results in metabolic health, when compared to research with NMN. AKK increased insulin sensitivity were increased by 42.42 percent after 12 weeks. Blood cholesterol, blood triglycerides and blood glucose was also improved. Likewise body weight, body fat, waist circumference, and hip circumference all decreased. Compared with the human clinical data on NMN,23 metabolic improvement with AKK was 70 percent higher than that of NMN.

Interestingly, in a mouse enteritis model, pasteurized AKK (postbiotic) performed better compared with multiple market AKK strains in the Disease Activity Index (DAI), intestinal knot length ratio and other scores. Specifically, the AKK postbiotic reduced the DAI score by 46 percent, while the score for other market AKK strains showed a decrease of 36 percent and 40 percent.24

Conclusion

AKK is a postbiotic shown in research to offer meaningful benefits for improving insulin sensitivity, reducing insulinemia and plasma total cholesterol, as well as decreasing body weight fat mass and hip circumference. The postbiotic AKK001 strain (distributed in the U.S. by Nutraland USA) may offer greater benefits for metabolic health than other AKK strains.VR

References

1 Postbiotic Market Expected to Reach $3 Billion by 2031. Allied Market Research. Retrieved March 24, 2025 from www.alliedmarketresearch.com/press-release/postbiotic-market.html.

2 Postbiotics: debate continues and the ISAPP definition gains support. ISAPP. Retrieved June 19, 2024 from https://isappscience.org/postbiotics-debate-continues-and-the-isapp-definition-gains-support/.

3 Liang B, Xing D. The Current and Future Perspectives of Postbiotics. Probiotics Antimicrob Proteins. 2023;15(6):1626-1643.

4 Aggarwal V, Sunder S, Verma SR. Disease-associated dysbiosis and potential therapeutic role of Akkermansia muciniphila, a mucus degrading bacteria of gut microbiome. Folia Microbiol (Praha). 2022;67(6):811-824. doi:10.1007/s12223-022-00973-6.

5 Cani PD, Depommier C, Derrien M, Everard A, de Vos WM. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms. Nature Reviews Gastroenterology & Hepatology 2022 19:10. 2022;19(10):625-637.

6 Iwaza R, Wasfy RM, Dubourg G, Raoult D and Lagier J-C (2022) Akkermansia muciniphila: The state of the art, 18 years after its first discovery. Front. Gastroenterol. 1:1024393.

7 Brahe LK, et al. Specific gut microbiota features and metabolic markers in postmenopausal women with obesity. Nutrition & Diabetes. 2015;5:e159.

8 Zhang X, et al. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One. 2013;8:e71108.

9 Yassour M, et al. Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes. Genome Med. 2016;8:17.

10 Yoon, H.S., Cho, C.H., Yun, M.S. et al. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat Microbiol. 2021; 6: 563–573.

11 Asnicar F, Leeming ER, Dimidi E, et al. Blue poo: impact of gut transit time on the gut microbiome using a novel marker. Gut. 2021;70(9):1665-1674.

12 Jensterle M, Ferjan S, Ležaič L, et al. Semaglutide delays 4-hour gastric emptying in women with polycystic ovary syndrome and obesity. Diabetes Obes Metab. 2023;25(4):975-984.

13 Yoon HS, Cho CH, Yun MS. et al. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat Microbiol. 2021; 6: 563–573.

14 Dao MC, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016;65:426–436.

15 Depommier C, Van Hul M, Everard A, Delzenne NM, De Vos WM, Cani PD. Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice. Gut Microbes. 2020;11(5):1231-1245.

16 Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S et al (2019) Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med 25(7):1096–1103.

17 Depommier C, Everard A, Druart C, et al. Serum metabolite profiling yields insights into health promoting effect of A. muciniphila in human volunteers with a metabolic syndrome. Gut Microbes. 2021;13(1):1994270.

18 Druart C, Plovier H, Van Hul M, et al. Toxicological safety evaluation of pasteurized Akkermansia muciniphila. J Appl Toxicol. 2021;41(2):276-290.

19 EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Dominique Turck, Torsten Bohn, Jacqueline Castenmiller, et al. Safety of pasteurised Akkermansia muciniphila as a novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 01 September 2021; https://doi.org/10.2903/j.efsa.2021.6780.

20 Next-generation probiotic AKK001. Unpublished.

21 Perraudeau F, McMurdie P, Bullard J, et al. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Res Care. 2020;8(1):e001319. doi:10.1136/bmjdrc-2020-001319.

22 Next-generation probiotic AKK001. Unpublished.

23 Yoshino M, Yoshino J, Kayser BD, Patti G, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021 Apr 22: eabe9985.

24 Next-generation probiotic AKK001. Unpublished.

Gene Bruno, DBM, MHS, Professor Emeritus of Nutraceutical Science, is a writer, educator and a nutraceutical scientist with more than 45 years of experience educating natural product retailers and health care professionals and formulating natural products for dozens of dietary supplement companies. He has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. Dr. Bruno also hosts “The Vitamin Professor Podcast” brought to you by VRM Media. He can be reached at [email protected].