The Mechanism Of Isoflavones In Regulating Intestinal Barrier Function And Peristaltic Function

The intestine is the main place where the host exchanges substances with the outside world.Its barrier function is responsible for the bidirectional flow of water,ions and macromolecules between the lumen and the host,and its peristalsis function is responsible for the transportation and removal of the contents of the cavity,thus maintaining the steady-state of the intestinal microenvironment.The barrier and peristalsis function of intestinal tract is very important to the health of human body,and its structural damage or dysfunction will lead to serious pathological consequences.Dietary composition is an important factor affecting intestinal function.Isoflavones are a class of phenolic compounds based on phenylchromone ring,which mainly derived from soybeans and their products,and have a variety of biological effects.However,its mechanism on intestinal barrier and peristalsis is still unclear.Therefore,through establishing animal and cell models,this paper explores the beneficial effects of dietary isoflavones on intestinal barrier function and peristalsis function and the possible mechanism,including the following aspects:1.Researches on the effect of puerarin on improving the intestinal barrier damage caused by 2,4,6-trinitrobenzene sulfonic acid(TNBS).Compared with the TNBS group,dietary supplementation of puerarin significantly strengthened the thickness of the mucus layer,increased the levels of mucins(Muc2 and Muc4)and the number of goblet cells,and increased the content of indole-3-propionic acid(IPA)in feces.Secondly,dietary supplementation of puerarin changed the structure of the symbiotic flora,showing that the relative abundance of Bacteroidetes was significantly reduced,and the relative abundance of the mucin-utilizing bacterium Akkermansia was significantly increased.These results indicate that puerarin improved the intestinal barrier function by strengthening the goblet cell and mucus barrier.Food rich in puerarin can protect and repair the intestinal barrier function and promote intestinal health.2.In this study,the intestinal barrier model in vitro was established by co-culture of Caco-2/HT29 to evaluate the protective effect of IPA on LPS-induced intestinal barrier injury and its mechanism.The results showed that IPA intervention increased transepithelial resistance and decrease paracellular permeability,which was consistent with the increase of tight junction proteins(Claudin-1,Occludin and ZO-1).In addition,IPA intervention up-regulated the levels of mucins(Muc2,Muc4)and goblet cell secretion products(TFF3,RELM?),enhanced goblet cell function,and reduced m RNA levels of pro-inflammatory cytokines.The results indicated that IPA improved the intestinal barrier damage induced by LPS by enhancing the epithelial barrier and mucus layer barrier.These findings provided new insights for understanding the intestinal microbial metabolism of aromatic amino acids to improve the intestinal barrier.3.The mechanism of puerarin combined with tryptophan or its metabolite(IPA)on intestinal barrier injury induced by dextran sodium sulfate(DSS)was explored.The results showed that puerarin combined with tryptophan or IPA significantly improved the growth performance(including body weight,disease activity index,food intake and food utilization rate)of DSS rats,and decreased the levels of D-Lac,DAO and LPS in serum.Further study found that puerarin combined with tryptophan or IPA increased the length of colon,the number of goblet cell in the crypt,the thickness of mucus layer and the level of Muc2.In addition,the thickness of mucus layer in DSS+ puerarin +IPA group was significantly higher than that in DSS+ puerarin group and DSS+ puerarin+Trp group.These results indicate that the combination of puerarin and tryptophan or IPA could strengthen the intestinal barrier and ensure the health of intestinal microecology.4.The protective effects of four common isoflavones(puerarin,daidzein,genistein and formononetin)on DSS-induced intestinal peristalsis dysfunction were studied.This experiment focused on the regulation of isoflavones on intestinal tissue structure and enteric nervous system(5-HT)in DSS rats,and determined the effects of isoflavones on fecal water content and short chain fatty acids(SCFAs)content.The results showed that isoflavones intervention significantly protected the growth performance(body weight and feed utilization)of DSS rats,prevented the increase of short-chain fatty acid content in the colon,reduced the water content in the stool,and improved colon motility.In terms of tissue structure,isoflavones intervention prevented the decrease of colonic crypt depth and the thickness of colon muscle layer.In nervous system,isoflavones intervention prevented the increase of 5-HT concentration in the tissues.Compared with DSS group,puerarin +DSS,genistein+DSS,and formononetin +DSS group had significantly longer intestinal transit time,significantly higher intestinal villi height and more chromaffin cells.Therefore,isoflavones affected intestinal peristalsis by regulating intestinal tissue structure and nervous system.To sum up,the main benefits of dietary isoflavones on intestinal function are:(1)enhancing mucus barrier by up-regulating mucin expression and goblet cell function;(2)improving the relative abundance of beneficial intestinal flora and the contents of beneficial flora derivatives;(3)Enhancing intestinal epithelial barrier by up-regulating tight junction proteins;(4)Keeping the normal operation of intestinal peristalsis by protecting intestinal tissue and maintaining 5-HT level.These studies show that dietary supplementation with isoflavones is an important means to improve intestinal physiological function.