Mucosal healing progression after acute colitis in mice

BACKGROUND Mucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as migration, proliferation, and differentiation, are required. These events are longitudinally and tightly controlled by numerous factors including a wide range of distinct regulatory proteins. However, the sequence of events associated with colon mucosal repair after colitis and the evolution of the luminal content characteristics during this process have been little studied.AIM To document the evolution of colon mucosal characteristics during mucosal healing using a mouse model with chemically-induced colitis.METHODS C57 BL/6 male mice were given 3.5% dextran sodium sulfate(DSS) in drinking water for 5 d. They were euthanized 2(day 7), 5(day 10), 8(day 13), and 23(day28) d after DSS removal. The colonic luminal environment and epithelial repair processes during the inflammatory flare and colitis resolution were analyzed with reference to a non-DSS treated control group, euthanized at day 0. Epithelial repair events were assessed histo-morphologically in combination with functional permeability tests, expression of key inflammatory and repairing factors, and evaluation of colon mucosa-adherent microbiota composition by 16 S rRNA sequencing.RESULTS The maximal intensity of colitis was concomitant with maximal alterations of intestinal barrier function and histological damage associated with goblet cell depletion in colon mucosa. It was recorded 2 d after termination of the DSStreatment, followed by a progressive return to values similar to those of control mice. Although signs of colitis were severe(inflammatory cell infiltrate, crypt disarray, increased permeability) and associated with colonic luminal alterations(hyperosmolarity, dysbiosis, decrease in short-chain fatty acid content), epithelial healing processes were launched early during the inflammatory flare with increased gene expression of certain key epithelial repair modulators, including transforming growth factor-β, interleukin(Il)-15, Il-22, Il-33, and serum amyloid A. Whereas signs of inflammation progressively diminished, luminal colonic environment alterations and microscopic abnormalities of colon mucosa persisted long after colitis induction.CONCLUSION This study shows that colon repair can be initiated in the context of inflamed mucosa associated with alterations of the luminal environment and highlights the longitudinal involvement of key modulators.

Fate of undigested proteins in the pig large intestine:What impact on the colon epithelium?

Apart from its obvious agronomic interest in feeding billions of people worldwide,the porcine species represents an irreplaceable experimental model for intestinal physiologists and nutritionists.In this review,we give an overview on the fate of proteins that are not fully digested in the pig small intestine,and thus are transferred into the large intestine.In the large intestine,dietary and endogenous proteins are converted to peptides and amino acids(AA)by the action of bacterial proteases and peptidases.AA,which cannot,except in the neonatal period,be absorbed to any significant level by the colonocytes,are used by the intestinal microbes for protein synthesis and for the production of numerous metabolites.Of note,the production of the AA-derived metabolites greatly depends on the amount of undigested polysaccharides in the pig's diet.The effects of these AA-derived bacterial metabolites on the pig colonic epithelium have not yet been largely studied.However,the available data,performed on colonic mucosa,isolated colonic crypts and colonocytes,indicate that some of them,like ammonia,butyrate,acetate,hydrogen sulfide(H_(2)S),and p-cresol are active either directly or indirectly on energy metabolism in colonic epithelial cells.Further studies in that area will certainly gain from the utilization of the pig colonic organoid model,which allows for disposal of functional epithelial unities.Such studies will contribute to a better understanding of the potential causal links between diet-induced changes in the luminal concentrations of these AA-derived bacterial metabolites and effects on the colon epithelial barrier function and water/electrolyte absorption.