Abstract
ScopeMucus 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 resultsThe 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.ConclusionIt 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.
Highlights
Lactic acid bacteria (LAB) have been shown to impact mucus production
To determine whether fibroblasts influence mucus production, we investigated the expression of goblet cell function-associated genes (MUC2, trefoil factor 3 (TFF3), RETNLB, carbohydrate sulfotransferase 5 (CHST5), and galactose-3-Osulfotransferase 2 (GAL3ST2)) in the LS174T goblet cell line in the presence and absence of CCD-18Co intestinal fibroblasts
We confirm the presence of crosstalk between intestinal subepithelial fibroblasts and goblet cells and its impact on the expression of mucus barrier-associated genes (MUC2, TFF3, RETNLB, CHST5, and GAL3ST2) in goblet cells
Summary
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. Barrier function of mucus can be impaired by luminal insults such as by pathogens, by food-related mycotoxin deoxynivalenol, and by proinflammatory cytokines that impact the synthesis of mucus-related components in goblet cells.[5,6,12,13] This has been shown to contribute to the pathogenesis of various intestinal disorders.[5,6]. We determined whether fibroblasts influenced the modulatory effects of different LAB strains on gene expression in goblet cells with or without exposure to TNF-α, IL-13, or a mucin synthesis disruptor Tm. In addition, in order to gain more mechanistic insights in the effects of interactions between goblet cells and fibroblasts on mucus regulation, alterations of the growth factor genes (FGF7, HGF, and IGF2) in CCD-18Co fibroblasts were studied during their co-culture with LS174T goblet cells. Kefir CGMCC7317 a)CCFM, Culture Collections of Food Microbiology, Jiangnan University, Wuxi, China; b)CGMCC, China General Microbiological Culture Collection Center, Beijing, China; c)CICC, China Center of Industrial Culture Collection, Beijing, China
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