Commensals can become pathobionts

Abstract

Akkermansia muciniphila decreased inflammatory cell infiltration and bone destruction. Also, in bone marrow macrophages, Akkermansia increased both IL-10 expression and junctional integrity markers. These findings suggest beneficial anti-inflammatory effects of Akkermansia in these experimental models. The authors speculated that Akkermansia may be used as an adjunctive treatment for periodontal disease.We are writing this letter to caution the readers that there are no harmless commensals because under certain conditions most commensals are capable of becoming pathobionts. As we have stated in our previous review, A. muciniphila prefers euglycemia and a high-fibre diet (Janket et al., 2019b), not causing any harm most of the time.However, A. muciniphila spp. are mucin-degrading microbes (Janket et al., 2019b) and their overgrowth can erode the protective mucin layer and damage the mucosa, which will allow pathobionts for easy access causing lethal colitis in murine models (Desai et al., 2016).Moreover, in genetically susceptible hosts, or when dietary fibre is deficient, Akkermansia can become a pathobiont and express proinflammatory responses. It has been reported that enrichment of Akkermansia caused intestinal inflammation and colitis (Seregin et al., 2017). Also, excessive levels of Akkermansia were associated with endotoxin leakage and irreversible tissue damage (Wang et al., 2017). Huck et al. further experimented by addingAkkermansia to bone marrow macrophages and observed increased anti-inflammatory interleukin-10 (IL-10). Macrophages are known to be the major producers of the cytokine IL-10. Thus, it is difficult to determine whether increased IL-10 is from macrophages or from Akkermansia. This is a classic case of confounding as we have previously described as Simpson's paradox (Janket et al., 2019a). Moreover, IL-10 produced by macrophages restores epithelial integrity (Morhardt et al., 2019), Therefore, we are not certain whether the increased junctional integrity markers such as integrin-β1, E-cadherin, and ZO-1 are from Akkermansia or from IL-10 secreted by macrophages. This is another case of potential confounding. When circumstances allow, commensals can become opportunistic pathogens and cause harm to the hosts, causing endocarditis, bacteremia, and septicemia (Cone, Battista, et al., 2003;Cone, Leung, et al., 2003). We therefore hope that these potential hazards should be considered before Akkermansia can be utilized as an adjunct treatment for periodontal disease.