Mansia - Akkermansia Muciniphila
Akkermansia muciniphila is a species of microbe found in the human gut microbiota. Akkermansia muciniphila MucT was first isolated from human feces in 2004, in the laboratory of Prof. Willem M. de Vos (Wageningen University – The Netherlands) by Dr. Muriel Derrien. The identified strain was then deposited in the American Type Culture Collection (ATCC) under the reference ATCC® BAA-835™.
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Akkermansia muciniphila is found in the human gut from infancy. Its abundance then increases significantly up to adulthood. Akkermansia muciniphila cells have even been detected in human breast milk. The capacity of the bacterium to use human milk oligosaccharides (complex sugar molecules) as the only source of energy, carbon and nitrogen could explain its presence in breast milk and the breast tissue of lactating women. In fact, human milk may act as a carrier for Akkermansia muciniphila and transfer it from mother to infant. This explains why it can already be found in the infant intestine very early in life.
Two facts firmly strongly suggest that a symbiotic relationship exists between the bacterium and its hosts:
- The bacterium can be found in many different species.
- It has a close physical proximity to the intestinal wall.
Over the last decade, a large and important body of scientific literature (Reviewed in Derrien 2016) has emerged to confirm the following assumption:
(Derrien 2016, Akkermansia muciniphila and its role in regulating host functions).
Indeed, numerous studies have found that Akkermansia muciniphila was positively associated with:
- a healthy gut lining;
- reduced metabolic disorders;
- decreased low-grade inflammation.
Akkermansia muciniphila is highly abundant in lean and non-diabetic individuals. In contrast, it has been found to be lower in several conditions such as obesity, diabetes, intestinal inflammation, liver diseases, or chronic alcohol consumption. This is associated with an altered gut barrier function which eventually triggers low-grade inflammation and metabolic disorders.
Moreover, in the context of obesity-associated disorders, Akkermansia muciniphila is systematically found to be inversely correlated with cardiometabolic risk factors. These factors include insulin resistance, serum lipids, BMI and adiposity. In contrast, it is positively correlated with protective markers such as high-density lipoprotein (HDL, or “good” cholesterol). Furthermore, the baseline intestinal levels of the bacterium in overweight or obese subjects could be a potential prognostic marker for predicting the success of dietary interventions. Indeed, after a 6-week low-calorie diet, obese individuals with higher baseline Akkermansia muciniphila all displayed an improvement of parameters related to glucose tolerance and to other cardiometabolic risk factors. (Derrien, 2016)
The role of Akkermansia muciniphila in the mucus layer- short-chain fatty acids (SCFA) such as propionate and acetate
- amino acids
- important factors, and
- vitamins as by-products of this fermentation.
This makes them accessible to the host and other gut bacteria. Because it supplies nutrients to other gut bacteria, Akkermansia muciniphila can be considered a keystone species. This bacterium is often associated with a good gut barrier function, even though it feeds on mucin. Moreover, supplementation with Akkermansia muciniphila has been associated with a restoration of the gut barrier function in mouse models of obesity. Indeed, optimal Akkermansia muciniphilalevels:
- maintain the normal permeability of the gut;
- prevent pro-inflammatory toxins from entering the bloodstream;
- prevent chronic tissue inflammation (e.g. in liver and fat tissues) involved in metabolic disorders.
To move from preclinical to clinical studies, Akkermansia muciniphila needed to be cultured in large amounts. A stable form was needed, at a quality level suitable for human use. However, the first culture medium used to grow Akkermansia muciniphila contained an animal-derived compound which was not compatible with human use. To overcome this issue, a synthetic medium was developed. This medium was devoid of incompatible compounds and enabled the culture of Akkermansia muciniphila in a high yield. A preclinical model has confirmed that Akkermansia muciniphila keeps its efficacy when grown on this synthetic medium.
Stability of the bacteria was a secondary issue that needed to be overcome in order to move from preclinical to clinical studies. Indeed, as Akkermansia muciniphila is an anaerobic bacterium, it is extremely sensitive to oxygen in its live form. By looking for a way to stabilize the bacteria, our researchers wondered if pasteurization, a milder heat inactivation method (30 minutes at 70°C) than autoclaving, could preserve the beneficial effect of Akkermansia muciniphila. To that end, they tested the impact of pasteurization and compared the effects of the live and the pasteurized bacteria after their administration in a mouse obesity model.
Much to everyone’s surprise, pasteurization of Akkermansia muciniphila not only preserved the beneficial effects of the bacteria but it even enhanced its capacity to reduce body weight gain, fat mass development, insulin resistance and dyslipidaemia in mice.
As it turns out, daily supplementation of the pasteurized form of Akkermansia muciniphila can completely block the development of obesity and metabolic disorders induced by a high-fat diet in mice models. Pasteurized Akkermansia muciniphila administration reduced body weight and fat mass gain through several complementary mechanisms. It improved gut barrier function, increased energy expenditure and excretion of energy in the faeces.
To conclude, pasteurization of Akkermansia muciniphila not only increases its stability and potential shelf life but its beneficial effects as well. This finding represents a new and innovative approach to the usually accepted definition of probiotics. Indeed, according to the definition used by the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO), probiotics are “live microorganisms which when administered in adequate amounts confer a health benefit on the host”. Our research has clearly demonstrated that the pasteurized form of Akkermansia muciniphila is more efficient than its live form for the prevention of obesity and associated disorders. This is a very strong differentiation compared to most other classic probiotics and products on the market.
Characteristics
Akkermansia muciniphila is a gram-negative anaerobic bacterium belonging to the phylum Verrucomicrobia. It is a ‘commensal’ bacterium, meaning that it is naturally found in the gastrointestinal tract of humans and animals in relatively important quantities. In fact, it represents between 0.5 and 5% of all the bacteria colonizing the intestine. Far from being restricted to mammals, Akkermansia muciniphila is universally distributed in the animal kingdom. Indeed, it has been detected in birds, amphibians, fish and reptiles.
One key characteristic of Akkermansia muciniphila is its capacity to live in the mucus and use it. Indeed, it expresses a large panel of specific mucus-degrading enzymes. Thanks to these enzymes, it does not rely on dietary substances to feed itself. This ability provides Akkermansia muciniphila with a competitive advantage compared to other bacteria that do rely on fibers and other food particles as their main nutrient source. The specificity of Akkermansia muciniphila explains its distinctive niche: it lives in the mucus layer covering our intestinal epithelial cells. This means that the bacterium is located very close to the cells of our body and is able to communicate with them. (Cani & de Vos, 2017)
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