Akkermansia muciniphila - friend or foe in colorectal cancer?

Abstract

<i>Akkermansia muciniphila</i> is a gram-negative anaerobic bacterium, which represents a part of the commensal human microbiota. Decline in the abundance of <i>A. muciniphila</i> among other microbial species in the gut correlates with severe systemic diseases such as diabetes, obesity, intestinal inflammation and colorectal cancer. Due to its mucin-reducing and immunomodulatory properties, the use of probiotics containing <i>Akkermansia</i> sp. appears as a promising approach to the treatment of metabolic and inflammatory diseases. In particular, a number of studies have focused on the role of <i>A. muciniphila</i> in colorectal cancer. Of note, the results of these studies in mice are contradictory: some reported a protective role of <i>A. muciniphila</i> in colorectal cancer, while others demonstrated that administration of <i>A. muciniphila</i> could aggravate the course of the disease resulting in increased tumor burden. More recent studies suggested the immunomodulatory effect of certain unique surface antigens of <i>A. muciniphila</i> on the intestinal immune system. In this Perspective, we attempt to explain how <i>A. muciniphila</i> contributes to protection against colorectal cancer in some models, while being pathogenic in others. We argue that differences in the experimental protocols of administration of <i>A. muciniphila</i>, as well as viability of bacteria, may significantly affect the results. In addition, we hypothesize that antigens presented by pasteurized bacteria or live <i>A. muciniphila</i> may exert distinct effects on the barrier functions of the gut. Finally, <i>A. muciniphila</i> may reduce the mucin barrier and exerts combined effects with other bacterial species in either promoting or inhibiting cancer development.