Defining cooperative roles for colonic microbiota and Muc2 mucin in mediating innate host defense against Entamoeba histolytica.
Leon-Coria A, Kumar M, Moreau F, Chadee K
PLoS Pathog. 11 2018. doi: 10.1371/journal.ppat.1007466
Comment: Recent studies have linked microbiota with the outcome of Entamoeba histolytica (Eh) infection, however the relationship is poorly understood. MUC2 is the major secretory mucin in the gastrointestinal tract, it has previously found that Eh cysteine proteases cleave MUC2 facilitating Eh contact with epithelial cells. This study demostrates critical roles for microbiota and the mucus layer in the innate host defense against Eh invasion.
In this study, we explored the distinct contributions of microbiota and the Muc2 mucus barrier in Eh-induced innate and pro-inflammatory responses critical in disease pathogenesis.
Our findings show that indigenous commensal microbiota that colonizes the outer Muc2 mucus layer plays an important role in fortifying innate host defense against Eh and that dysbiosis (antibiotic and/or alterations in the mucus layer) renders the colonic epithelium susceptible to Eh-induced pro-inflammatory responses and tissue injury.
These studies clearly show a requirement for colonic microbiota in forming the first line of innate host defense against Eh, independent of the Muc2 mucus layer.
Disruption of microbiota with antibiotics, sensitized animals for exacerbated pro-inflammatory responses and high output water and mucus secretion toward Eh that was normalized with fecal microbial transplants.
In the absence of microbiota, Eh failed to induce pro-inflammatory responses that together with a dysfunctional mucus layer allowed Eh to contact and disrupt the epithelium.