Pasteurized bacteria supplement could “reduce the risk of heart disease in half of the West’s population”

04 Jul 2019 --- Supplementation with the pasteurized form of gut-bacteria Akkermansia muciniphila (A. muciniphila) has been found to reduce cardiovascular risk factors, moderate pre-diabetes progression, as well as lower cholesterol levels in obese participants. Looking forward, researchers at the University of Louvain (UCLouvain), Belgium, are planning larger-scale tests and commercialization of the bacteria in the form of food supplements, expected for 2021. They hope that it proves helpful for the Western population where one in two people are overweight and have increased cardiovascular risks, according to the World Health Organization (WHO) data.

The commercial form of A. muciniphila as a dietary supplement will be developed by the University of Louvain and the University of Wageningen’s spinoff company – A-Mansia Biotech. Last year, the company raised €13 million at the close of Series A financing, which allowed them to push forward with their A. muciniphila bacterium research.

“Supplementation with A. muciniphila prevented the deterioration of the subjects’ health by targeting several cardiovascular risk factors. This included reduced insulinemia, improved insulin sensitivity – that is a limitation of the pre-diabetes – as well as lower cholesterol,” Patrice Cani, Head Researcher at the Louvain Drug Research Institute of the UCLouvain and study leader, tells NutritionInsight.

Subjects with an increased cardio-metabolic risk (insulin resistance, hyperglycemia, high blood cholesterol and visceral fat accumulation) are characterized by lower A. muciniphila in the gut, notes A-Mansia.Subjects with an increased cardio-metabolic risk are characterized by lower A. muciniphila in the gut.

The study
The UCLouvain researchers administered A. muciniphila to overweight or obese volunteers, all of who displayed insulin resistance (pre-diabetes Type 2) and metabolic syndrome. The volunteers were randomly divided into three groups – placebo, live bacteria and pasteurized bacteria – and were asked not to change their dietary habits or their physical activity. A. muciniphila was provided as a nutritional supplement.

Published in Nature Medicine, the primary goal of the study was to demonstrate the feasibility of daily A. muciniphila ingestion for three months, without risk. Clara Depommier and Amandine Everard, UCLouvain researchers, observed “excellent compliance,” noting that the supplements were easy to ingest and tolerate, meaning there were no side effects in the groups taking live or pasteurized bacteria.

Why are the pasteurized bacteria more efficient?
Significantly, Cani explains that the tests in humans confirm what had already been observed in mice; that the pasteurized form was more efficient than the live bacteria in terms of several parameters. “This also means that although the bacteria is dead and therefore absolutely not touching the mucus, its activity is robust. This may also increase the safety profile for future approaches,” he notes.

When it comes to A. muciniphila, Cani notes that the greater efficacy that pasteurization brought may be because the numerous proteins on the outer membrane of A. muciniphila became more accessible after the process. Another possibility, he says, is that the exopolysaccharides (a kind of slime) which are surrounding the bacteria are removed by the pasteurization, leading to more outer membrane molecules accessibility and probably better contact with the host cells.

“The most interesting thing for me is the fact that the markers of inflammation, such as the blood endotoxins levels, were decreased. This suggests a reinforcement of the gut barrier, which was also supported by lower liver inflammatory markers and better insulin resistance. In fact, we were not really expecting effects on the body weight and waist/hip, but still, we observed interesting trends.”

“We are really surprised to see that as observed in mice, the pasteurized bacteria was more efficient than the live bacteria,” he adds.

Moving forward, the team plans to confirm the results of this smaller pilot study in a larger cohort, alongside examining the effects of dietary restriction. A-Mansia Biotech will now push forward with research on the bacteria. 

“VIP access” to A. muciniphila
A-Mansia Biotech will now push forward with research on the bacteria. The two founders – Professor Willem M. de Vos from Wageningen University and Professor Cani – isolated the Akkermansia in 2004 at Wageningen University, and went on to begin A-Mansia in 2016.

Speaking to NutritionInsight, Jean-Christophe Malrieu, CEO of A-Mansia, says that the Akkermansia strand is “new,” as it was discovered ten years ago by the founders of the company, but is not on the market yet.

A. muciniphila is one of the most abundant species found in the gut microbiota, the population of microorganisms housed in the gastrointestinal tract. The species is located in a particular niche: the mucus layer covering the intestinal epithelium. This location allows the bacterium to establish a “close cross-talk with the host.” Due to these interactions with the host’s immune and metabolic functions, it is said that Akkermansia can act as the gatekeeper of the intestinal barrier.

In this way, A-Mansia has a “VIP access for using it, in whatever form, and in as well as growing it.”

As the microbiome platform continues to expand in terms of clinical research, the efficacy of particular strands for specific health outcomes can be expected to grow - and attract further investment. In this vein, microbiome start-up Vedanta Biosciences – developers of a new category of therapies for immune-mediated diseases using live human microbiome-derived bacteria – raised an additional US$18.5 million in its third round of financing this week, bringing the total funding to US$45.5 million. 

By Laxmi Haigh