Questions & Answers

6 answers to common questions on Akkermansia

Akkermansia muciniphila is a bug that I met by chance already 2007. Here are 6 of the most common questions asked in my interviews, during my talks or even by email since more than a decade, all over the world. Any other question?
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Akkermansia muciniphila strain MucT has been isolated in 2004 in the laboratory of Prof. Willem de Vos by Muriel Derrien during her PhD research at Wageningen University. In a microbiological point of view, Akkermansia muciniphila is described as a Gram-negative, living in a strictly anaerobic condition and non-motile, non-spore-forming, with an oval shape that be or singly or in pairs. The name Akkermansia (pronounced: Ak.ker.man’si.a.) is derived from “Antoon Akkermans” a Dutch microbiologist recognized for his contribution to microbial ecology. The name “muciniphila” (pronounced mu.ci.ni’phi.la) is coming from the Latin “mucinous” for mucin and from the Greek “philos” for loving, leading to the name “muciniphila” for mucin-loving. Indeed, Akkermansia muciniphila is considered as a mucin-utilising specialist (original article describing the discovery of Akkermansia muciniphila: Derrrien et al IJSEM 2004). Akkermansia muciniphila is considered as one of the most abundant single species present in the human intestinal microbiota (0.5-5% of the total bacteria) of healthy subjects.

Akkermansia muciniphila has been isolated from the human gut, and is not present in food.
However, it is interesting to mention that the presence of Akkermansia spp. has been shown in the gastrointestinal tract of many other species that humans, such as for instance in dogs, cats, pigs, horses, fish, elephant, marine mammals and many others (Belzer and de Vos, ISME J 2012, and Ouwerkerk J, PhD thesis 2016).
In addition, since the description of the type strain Akkermansia muciniphila, another species of Akkermansia has been isolated from reticulated python feces. The bacterium has been named: Akkermansia glycaniphila PytT (Ouwerkerke et al IJSEM 2016).

Akkermansia muciniphila is not yet commercially available and not present in food. A-Mansia Biotech, the Belgian “Akkermansia company” has announced the possible launch of nutritional supplements containing Akkermansia for the end of the year 2021.
There are several products on the net mentioning that they contain Akkermansia but bear in mind that so far no products are marketed and are authorised to contain this novel bacterium.

I’m working on prebiotics1 since the beginning of the year 2000. This discovery was initiated by the notion that the original definition of prebiotics was mainly focused on the modulation of specific bacteria. Indeed, most of the first prebiotics evaluated were shown to stimulate in the human gut the expansion of Lactobacillus and Bifidobacterium specifically.

This is in 2008, that further clear indications for the function of A. muciniphila have been discovered in my lab and specifically during the use of well-characterised prebiotics such as prebiotics derived from the chicory root that is long chain inulin but also oligofructose (fructooligosaccharides (FOS)). It is true that inulin and FOS have been initially characterised as bifidogenic compounds able to increase the abundance of Bifidobacterium spp. (Gibson and Roberfroid, 1995). However, thanks to the development of different novel techniques other that the culture, we decided study the potential depth impact of inulin or FOS on the overall microbial community in mice. They have combined several techniques of molecular biology such as “phylogenetic microarray”, “high-throughput sequencing” which is the same as the one used to sequence the human genome, and also other techniques (gradient denaturation gel and quantitative PCR) that they discovered that the prebiotics were not only increasing the abundance of the Bifidobacterium but also profoundly affecting the overall microbial community. The surprise was that more than 100 different bacteria (some unknowns) were affected by the prebiotic administration (data published in Everard et al. diabetes 2011 and ISME J 2014). 

Among the different bacteria, we found that the bacterium Akkermansia muciniphila was increased by more than 100 times in the gut of the mice receiving the oligofructose treatment. The other very striking finding was that the presence of Akkermansia muciniphila was positively associated with a lower body weight, less fat mass, less insulin resistance and a stronger gut barrier. Whereas, in either diet-induced obese and diabetic mice as well as in genetically obese or diabetic mice, Akkermansia muciniphila was lower or undetectable. This finding was the beginning of a long story which is still ongoing today.
After having confirmed the lower abundance of Akkermansia muciniphila in obese subjects or in prediabetic or type 2 diabetic subjects, we decided to move to the proof of concept that Akkermansia muciniphila may play a beneficial role in this context of metabolic syndrome and cardiovascular diseases.

Obese subjects but also type 2 diabetic subjects or people suffering from inflammatory bowel diseases are characterised by a lower abundance of Akkermansia muciniphila in their gut. This has been consistently observed in the literature. However, this is an observation, the causality remains to be proven. In addition, the reason for such decrease is not yet fully understood. In animals, it has been shown that the ingestion of a diet rich in fat (mainly saturated fatty acids) induces a decrease in the presence of Akkermansia muciniphila. Whether the fatty acids are directly involved, the bile acids, the change is some other nutrients (e.g. fibres, starches, …) also contribute to this phenomenon is highly plausible. But the role of our own immunity or the competition with other microbes may also be part of the story.

Easy question… not so easy answer! Although our team and others have found in numerous animal studies that enriching the diet with either prebiotic inulin and/or oligofructose or some polyphenols (different sources) was associated with a strong change in the overall gut microbiota community including a higher abundance of Akkermansia muciniphila, these findings are poorly reproduced in humans. Indeed, Akkermansia muciniphila is highly increased in mice or rats treated with different nutrients. But in humans the story seems to be quite different. For example, a recent systematic review concluded that while the overall microbiota is changed upon different dietary interventions, more research is needed to support the assumption that Akkermansia muciniphila can be targeted with dietary intervention since the results are not consistent between studies (Verhoog et al. Nutrients 2019). This is perfectly coherent with what we observed in our laboratory in different cohorts. We established in two human studies that either the supplementation with isolated prebiotics (inulin and/or oligofructose at the dose of 16 g/day) or increasing the consumption of selected vegetables to naturally boost the intake of prebiotic fibers (15 g/day) is clearly inducing a marked shift in the gut microbiota composition with a consistent increase in Bifidobacterium spp. and another interesting bacterium called Faecalibacterium prausnitzii (Dewulf, Cani et al GUT 2013, Hiel et al American Journal of Clinical Nutrition 2019). However, besides the fact that both types of diets were enriched with vegetables and/or prebiotics none of these dietary approached induced changes in the abundance of Akkermansia muciniphila. This strongly supports the notion that generalising the effects of dietary fibers or polyphenols on Akkermansia muciniphila is not appropriate. Here again, translating mice to human data is not so simple…

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