From lab to clinic (from bench to bedside): translational development of Akkermansia muciniphila

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.

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A pasteurized bacterium with benefits

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.

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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.