Study On The Effect Of Vinegar Sediment On Ulcerative Colitis In Mice And Its Mechanism

Vinegar sediment is a precipitate formed during storage of traditional brewed vinegar.It has been proven to have various functions such as anti-inflammatory,anti-tumor,hypoglycemic and hypolipidemic.However,the research on the mechanism of anti-colitis is still insufficient.Here,we investigeted the therapeutic effects of vinegar sediment on two mice models of ulcerative colitis(UC).The main research contents and conclusions are as follows:(1)In order to study whether the vinegar sediment can improve DSS-induced UC in mice,we used tripartite doses of 0.5,1.0 and 2.0 g/kg of vinegar sediment to gavage mice continuously for 14 days.The equimolar acetic acid(0.88 mmol/kg)contained in the middle dose vinegar sediment was used as contrast.On days 8-14 of administation,mice were free to drink 2.5%DSS to induce UC.The results of the study found that the vinegar sediment alleviated the weight loss and shortened colon length,improved colonic epithelial tissue damage,maintained the intestinal immune system homeostasis and epithelial barrier function in mice with ulcerative colitis caused by DSS.We found low-dose vinegar sediment down-regulated the expression of C-C motif chemokine ligand 1(Ccl-1),interleukin 6(1l-6),Il-17 and Il-23 mRNA in colon tissue;medium-dose vinegar sediment down-regulated the expression of tumor necrosis factor-α(Tnf-α),Ccl-1,Il-6,Il-17 and Il-23 mRNA;high-dose vinegar sediment down-regulated Tnf-α,inducible nitric oxide synthesis Relative expression of enzymes(Inos),Il-6,Il-17 and Il-23 mRNA were down-regulated,while the expression of Mucin 2(Muc-2)mRNA was up-regulated.However,acetic acid did not alleviated ulcerative colitis in mice.(2)In order to study the anti-inflammatory effect of vinegar sediment on spontaneous UC in mice,we administered vinegar sediment at a dose of 1 g/kg to Il-10-/-mice for 42 days.We found that vinegar sediment inhibited the inflammatory response and oxidative stress in the colon,such as inhibiting the activity of Myeloperoxidase(MPO)and Malondialdehyde(MDA),as well as the expression of inflammatory cytokine genes such as Tnf-α,Inos and Il-23 mRNA in the colon tissue,and down-regulated levels of various pro-inflammatory cytokines such as IL-2,IL-6,IL-13,Granulocyte colony stimulating factor(G-CSF),Granulocyte-macrophage colony-stimulatingfactor(GM-CSF),Interferon y(IFN-γ)and Regulated upon activation normal T cell expressed and secreted(RANTES)in serum.Vinegar sediment also improved the intestinal epithelial barrier function in mice by reducing the crypts damage and epithelial cell loss of colon,promoting mucin secretion by intestinal epithelial cells,and up-regulating the expression of mRNA such as Muc-2,Mucin 3(Muc-3),Mucin 4(Muc-4)and Recombinant regenerating islet derived protein 3γ(Reg3γ).In addition,vinegar sediment increased the content of acetic acid and valeric acid in the intestines of Il-10-/-mice.(3)In order to study whether the vinegar sediment affects the development of UC in mice associated with modulating the composition of gut microbiota,DNA was extracted from feces of Il-10-/-mice on day 0 and day 42 and processed by 16S rRNA gene sequence analysis.Results showed that the vinegar sediment changed the structure of the intestinal microbiota of mice,promoted the abundance of Akkermansia,Alipipes and Lactobacillus,while inhibited Desulfovibrio and Clostridium sensu stricto 1 in the gut of mice.Refering to the analysis of the co-occurrence network of gut microbiota and the correlation analysis between inflammatory phenotypes and bacterial relative abundance,we found that Akkermansia may play a key role in contribution to alleviation of colitis,which resulted from adjustment of gut microbiota by vinegar sediment.In order to verify the effect of vinegar sediment on the growth of Akkermansia,we cultured A.muciniphila(ATCC(?)BAA 835TM)in vitro by adding vinegar sediment,simulated digestion of vinegar sediment and sodium acetate.The results showed vinegar sediment promoted the growth of A.muciniphila in vitro.In conclusion,our research proves that vinegar sediment may be used as an auxiliary treatment for improving UC.