Fibroblasts Impact Goblet Cell Responses to Lactic Acid Bacteria After Exposure to Inflammatory Cytokines and Mucus Disruptors

SCOPE: Mucus produced by goblet cells contributes to gut barrier function. Lactic acid bacteria (LAB) have been shown to impact mucus production. It is not completely known whether mucus production is influenced by the abundantly present fibroblasts in the intestine. METHODS AND RESULTS: The influence of fibroblasts on mucus‐related genes including mucin‐2 (MUC2), trefoil factor 3 (TFF3), resistin‐like molecule β (RETNLB), carbohydrate sulfotransferase 5 (CHST5), and galactose‐3‐O‐sulfotransferase 2 (GAL3ST2) is examined after co‐culture of LS174T‐goblet cells and CCD‐18Co colonic fibroblasts in the presence and absence of LAB‐strains known to impact mucus function. This is also tested after exposure to TNF‐α, IL‐13, or the mucin synthesis inhibitor tunicamycin (Tm). Effects of fibroblasts are treatment duration‐ and bacterial species‐dependent under homeostatic conditions. During TNF‐α challenge, fibroblasts reverse Lactobacillus (L.) rhamnosus CCFM237‐elicited declined TFF3 expression. After IL‐13 exposure, L. rhamnosus CCFM237 and L. fermentum CCFM787 attenuate enhanced TFF3 and RETNLB expression, respectively, only in the presence of fibroblasts. LAB has no effects on Tm‐induced decreased expression of goblet cell‐related genes regardless of the presence of fibroblasts. CONCLUSION: It is demonstrated that goblet cell–fibroblast crosstalk impacts mucus synthesis and influences the effects of LAB on goblet cell‐related genes. Effects are LAB‐species and stressor dependent.