What is Akkermansia muciniphila?
Akkermansia muciniphila is a species of microbe found in the human gut microbiota.
It was first isolated by Dr. Muriel Derrien in 2004 in the laboratory of pre-eminent Microbiologist Prof. Willem M. de Vos.
The Chair of Microbiology at Wageningen University in the Netherlands for over 25 years, Willem de Vos has published over 600-peer-reviewed publications and been the subject of more than 170,000 citations.
Akkermansia muciniphila was deposited in the American Type Culture Collection (ATCC) under the reference ATCC® BAA-835™
A competitive advantage over other bacteria
Akkermansia muciniphila is a ‘commensal’ bacterium, meaning that it is found naturally in the gastrointestinal tract of humans and animals – representing between 0.5 and 5% of all the bacteria colonising the intestine. Far from being restricted to mammals, Akkermansia muciniphila can also be found in birds, amphibians, fish and reptiles.
One key characteristic of Akkermansia muciniphila is its ability to live in the mucus, which it does by expressing mucus-degrading enzymes. This means that Akkermansia muciniphila does not rely on dietary substances to feed itself, giving it a competitive advantage over bacteria that rely on fibres and food particles as their main source of nutrition 1.
As a result, Akkermansia muciniphila lives in the mucus layer that covers cells in the intestine. Being located so close to such cells, it is even able to communicate with them. 2
Naturally occurring from infancy
Akkermansia muciniphila can be found in the human gut during infancy, increasing in abundance as the body reaches maturity.1
Akkermansia muciniphila cells have even been detected in human breast milk, perhaps due to its ability to use the complex sugar molecules in breast milk as its sole source of energy. 1
A mutually beneficial relationship
a healthy gut lining
reduced metabolic disorders
decreased low-grade inflammation
While Akkermansia muciniphila is highly abundant in lean and non-diabetic individuals, it has been found to be lower in those with conditions such as obesity, diabetes, intestinal inflammation, liver diseases, or chronic alcohol consumption.
Low levels of Akkermansia muciniphila have been linked to altered gut barrier function, which eventually triggers low-grade inflammation and metabolic disorders. 3
High levels of Akkermansia muciniphila have also been found to decrease insulin resistance and cardiometabolic risk factors including resistance, serum lipids, BMI and adiposity, while increasing the presence of protective markers such as high-density lipoprotein (or “good” cholesterol). 4
Furthermore, the baseline intestinal levels of the bacterium in overweight or obese individuals could be a potential prognostic marker for predicting the success of dietary interventions. After a 6-week low-calorie diet, for example, obese individuals with higher baseline Akkermansia muciniphila all displayed improvements in glucose tolerance and other cardiometabolic risk factors. 1
A positive feedback loop in the mucus layer
Because of Akkermansia muciniphila’s role in the mucus layer – using mucin as its sole source of nutrients – it also acts to promote mucin production. By consuming mucin, it stimulates the body to continue mucin production, thereby renewing the mucus layer. Maintaining continual mucus production helps keep the human gut healthy by preventing the invasion of pathogenic bacteria.
As Akkermansia muciniphila produces mucin, it also produces valuable by products, including:
Short-chain fatty acids (e.g. propionate and acetate)
Amino acids
Vitamins
Optimal Akkermansia muciniphila levels have a number of positive effects:
maintaining normal gut permeability
preventing pro-inflammatory toxins from entering the bloodstream
From lab to clinic
Akkermansia muciniphila needed to be cultured in large amounts in order to move from preclinical to clinical studies. As such, a synthetic medium was developed to enable high-yield cultures, and a preclinical model confirmed that Akkermansia muciniphila retains its efficacy when grown synthetically.
It has also been vital to ensure the stability of the bacteria in its transition from preclinical to clinical studies. As an anaerobic bacterium, Akkermansia muciniphila is highly sensitive to oxygen in its live form.
Our researchers discovered that pasteurisation could stabilise Akkermansia muciniphila while also preserving its beneficial effects, and substantiated this by testing the efficacy of live and pasteurised versions of the bacterium in a mouse obesity model. 8
A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice, Plovier H. et al. , Nature Medecine, 2016
The benefits of pasteurisation
Pasteurisation of Akkermansia muciniphila not only preserved the beneficial effects of the bacteria but actually enhanced its capacity to reduce body weight gain, fat mass development, insulin resistance and dyslipidaemia in mice.
Our tests showed that daily supplementation of the pasteurised form of Akkermansia muciniphila can completely block the development of obesity and metabolic disorders induced by a high-fat diet in mice models. 9
Pasteurised Akkermansia muciniphila administration reduced body weight and fat mass gain through several complementary mechanisms. It improved gut barrier function, while also increasing energy expenditure and excretion of energy in the faeces.
The startling conclusion was that pasteurisation of Akkermansia muciniphila not only increases its stability and potential shelf life, but increases its health benefits as well. This finding represents a new and innovative approach to the usually accepted definition of probiotics.
The Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) defines probiotics as “live microorganisms which when administered in adequate amounts confer a health benefit on the host.” 10
However, our research has clearly demonstrated that the pasteurised form of Akkermansia muciniphila is more efficient than its live form for the prevention of obesity and associated disorders. This is highly unique compared to most other classic probiotics and products on the market.
REFERENCES
1 Derrien M, Belzer C, de Vos WM (2017) Akkermansia muciniphila and its role in regulating host functions. Microb Pathog 106:171-181. doi:10.1016/j.micpath.2016.02.005.
2 Cani PD, de Vos WM (2017) Next-Generation Beneficial Microbes: The Case of Akkermansia muciniphila. Front Microbiol 8:1765. doi:10.3389/fmicb.2017.01765.
3 Cani, P. D., et al. (2007). “Metabolic endotoxemia initiates obesity and insulin resistance.” Diabetes 56(7): 1761-1772.
4 Everard, A., et al. (2013). “Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity.” Proc Natl Acad Sci U S A 110(22): 9066-9071.
5 Dao, M.C., et al. (2016). “Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology.” Gut 65(3): 426-436.
6 Depommier, C., 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.
7 Cani, P. D., et al. (2022). “Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms.” Nat Rev Gastroenterol Hepatol 19(10): 625-637.
8 A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice, Plovier H. et al. , Nature Medecine, 2016
9 Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, Chilloux J, Ottman N, Duparc T, Lichtenstein L, Myridakis A, Delzenne NM, Klievink J, Bhattacharjee A, van der Ark KC, Aalvink S, Martinez LO, Dumas ME, Maiter D, Loumaye A, Hermans MP, Thissen JP, Belzer C, de Vos WM, Cani PD (2017) A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med 23 (1):107-113. doi:10.1038/nm.4236.
