Akkermansia muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer

Abstract

e Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals. A. muciniphila has been linked with intestinal health and improved metabolic status in obese and type 2 diabetic subjects. Specifically, A. muciniphila has been shown to reduce high-fat-diet-induced endotoxemia, which develops as a result of an impaired gut barrier. Despite the accumulating evidence of the health-promoting effects of A. muciniphila, the mechanisms of interaction of the bacterium with the host have received little attention. In this study, we used several in vitro models to investigate the adhesion of A. muciniphila to the intestinal epithelium and its interaction with the host mucosa. We found that A. muciniphila adheres strongly to the Caco-2 and HT-29 human colonic cell lines but not to human colonic mucus. In addition, A. muciniphila showed binding to the extracellular matrix protein laminin but not to collagen I or IV, fibronectin, or fetuin. Importantly, A. muciniphila improved enterocyte monolayer integrity, as shown by a significant increase in the transepithelial electrical resistance (TER) of cocultures of Caco-2 cells with the bacterium. Further, A. muciniphila induced interleukin 8 (IL-8) production by enterocytes at cell concentrations 100-fold higher than those for Escherichia coli, suggesting a very low level of proinflammatory activity in the epithelium. In conclusion, our results demonstrate that A. muciniphila adheres to the intestinal epithelium and strengthens enterocyte monolayer integrity in vitro, suggesting an ability to fortify an impaired gut barrier. These results support earlier associative in vivo studies and provide insights into the interaction of A. muciniphila with the host.

A Commensal Bifidobacterium longum Strain Prevents Gluten-Related Immunopathology in Mice through Expression of a Serine Protease Inhibitor

“…were exclusively increased in B. longum srp(Con)-treated mice compared to all other groups. The commensal Akkermansia muciniphila is considered to be antiinflammatory and beneficial for the intestinal mucus layer and barrier integrity in some models of inflammatory disorders (41,42), and decreased levels of A. muciniphila have been observed in patients with IBD and metabolic disorders (43,44). This suggests the hypothesis that a significant level of Srp delivery, such as that provided by B. longum srp(Con), may improve the overall performance of the mucosal barrier and immune function of the gut, in part through increases in the levels of Akkermansia species.…”

A place for host–microbe symbiosis in the comparative physiologist's toolbox

“…Mechanisms of host selection of bacterial taxa include the secretion of nutrients, such as mucin glycans from epithelial cells, that are used as primary or alternative energy sources by certain bacteria (Derrien et al, 2010). Some of these 'dedicated' mucindegraders have intimate relationships with host cells and promote processes associated with host health, such as the maintenance of gut barrier function (Reunanen et al, 2015). Retention of beneficial microbes that can degrade host-derived nutrients also promotes ecological stability within the gut community during nutritional deprivation, such as acute or predictable fasts, when metabolic activity of some bacteria is compromised because of an inadequate supply of diet-derived nutrients (Costello et al, 2010;DillMcFarland et al, 2014;Kohl et al, 2015).…”

Metabolic characterization and viable delivery of Akkermansia muciniphila for its future application

“…Since GEMs stochiometrically represent all metabolic reactions in a microbe or microbial community, such models enable to estimate the production of these transient metabolites, estimate their distributions within the global metabolic network and provide hypotheses for the metabolic interactions among gut microbes and of those with their host. Moreover, GEMs are instrumental in optimizing growth of GIT microbes in laboratory conditions and hence are relevant for the production of biomolecules that are involved in host signalling, such as TLR ligands or specific functional proteins (Ottman, 2015. First, we briefly describe the process of genome-scale metabolic reconstruction and its implications for network modelling.…”

“…This layer forms a barrier between the colonic content and the host and thereby prevents infections (Hansson, 2012). However, the presence of A. muciniphila was found to be associated with an increased thickness of the mucus layer (Everard, et al, 2013), and possibly increase the gut barrier function (Reunanen, et al, 2015, Schneeberger, et al, 2015. This could be caused by the increase of mucin-producing goblet cells upon administration of A. muciniphila (Shin, et al, 2014).…”

“…muciniphila was initially described as a strict anaerobe . However more recently, it was reported that A. muciniphila can tolerate low amounts of oxygen (Reunanen, et al, 2015). The oxygen that diffuses from the gastrointestinal epithelial cells is thought to be one of the factors that keep strictly anaerobic commensal microbiota at a distance (Van den Abbeele, et al, 2011, Khan, et al, 2012).…”