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Ulcerative colitis （UC）， a chronic inflammatory bowel disease affecting the colorectum with high morbidity and prevalence， has become a global burden. However， the causes and pathogenesis are still unclear. Available studies have verified that the imbalance of intestinal microenvironment is crucial in the occurrence and development of UC. Intestinal microenvironment is mainly composed of intestinal microbiota and intestinal mucosal cells， which are involved in the physiological and pathological activities of the body through the intestinal microbial barrier， chemical barrier， mechanical barrier， and immune barrier. Thus， probiotic agents， 5-aminosalicylic acid preparations， corticosteroids， immunosuppressants， biological preparations and other drugs are commonly used in western medicine for the treatment of UC， which， however， have limitations. Therefore， it is the key task for the prevention and treatment of UC to find new therapies. In recent years， it has been found that traditional Chinese medicine （TCM） has unique advantages in the prevention and treatment of UC. Chinese medicine compounds and Chinese medicine monomers can regulate the intestinal microenvironment through multiple pathways and targets， thereby intervening the occurrence and development of UC. It has gradually become a hot spot in the prevention and treatment of UC and attracted extensive attention. Therefore， this study first discussed the correlation between intestinal microenvironment imbalance and UC and then summarized the mechanisms of TCM against UC from the aspects of regulating intestinal flora， improving chemical barrier， protecting mechanical barrier， and inhibiting immune inflammatory response， in order to provide new ideas for the research on TCM in the treatment of UC.
ABSTRACT
Objective To study the change and characterization of metabolic profile of intestinal contents of the neonatal rats with necrotizing enterocolitis (NEC) using metabolomics approach,in order to figure out potential biomarkers of NEC.Method Twenty rats with three-postnatal day-old fed with special formula were assigned to control group (n =8) and NEC group (n =12) randomly.Experimental NEC of rats in NEC group were induced by exposing to cold stimulation at 4 degrees Celsius for 10 minutes and to hypoxia at 95％ nitrogen for 10 minutes,three times a day for three consecutive days.All the rats were sacrificed after model preparation.Segments of the ileum of all the rats were collected for hematoxylin-eosin staining and subsequent pathological damage evaluation.The intestinal contents of the ileum and colon were collected by perfusion,followed by lyophilization and analyzed by UHPLC-QE-MS in order to conduct the non-target metabolomic determination.The information of the metabolites determined was calculated by multivariable analysis using SIMCA software.Result The pathological damage scores of NEC group were higher than those of the control group [(3.13 ± 0.83) vs.(0.25 ± 0.46),P ＜ 0.001].The results of orthogonal partial least squares discriminant analysis (OPLS-DA) model showed that in the ESI + mode,R2(x) =0.604,R2(y) =0.583,Q2 =0.960,while in the ESI-mode,the OPLS-DA model R2(x) =0.828,R2(y) =0.999,and Q2 =0.713,indicating that there is a significant difference in the intestinal content metabolic profile between the control group and the NEC group.Forty-eight differential metabolites related to NEC were identified.In ESI-mode,there were 22 differential metabolites,including L-isoisoleucine (+ 221％) and D-phenylalanine (+ 230％),L-histidine (+ 284％),xanthine (+ 207％),glutamyl leucine (+ 246％),allose (-70％),myristic acid (-57％) and pentadecanoic acid (-35％).What is more,in the ESI + mode,26 other differential metabolites were identified,including ornithine (+ 268％),D-leucine (+ 176％),L-iso Leucine (+ 213％),acetylcholine (+ 195％),nicotinamide adenine dinucleotide (+ 199％),citrulline (+ 158％),cytosine (-58％),xanthoic acid (-64％).These metabolites were reflected to 33 different metabolic pathways in KEGG databases.The pathway enrichment analysis and pathway topology analysis with MetaboAnalyst indicated that the arginine and proline metabolic pathways,histidine metabolic pathways,and glutathione metabolic pathways were the top altered pathways in the condition of NEC.Conclusion The metabolic profile of intestinal contents in NEC rats was significantly different from that in normal rats,which was characterized by amino acid accumulation,mainly involving the metabolic pathways of arginine,proline,histidine and glutathione.The detection of intestinal contents metabolic profile,especially amino acid metabolize group may be of great significance for the diagnosis of NEC,and improving intestinal microenvironment may be the key strategy for the prevention and treatment of NEC.
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Objective@#To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for intestinal disorders.@*Methods@#A retrospectively descriptive cohort study was carried out. Clinical data of 2010 patients who underwent FMT and received follow-up for more than 3 months from May 2014 to November 2018 were collected, including 1,206 cases from Tongji University Shanghai Tenth People′s Hospital and 804 cases from Nanjing Eastern Military General Hospital. Of the 2,010 patients, 797 were male and 1,213 were female, with a mean age of (49.4±16.5) years old. Inclusion criteria were those with indications for FMT and voluntary treatment of FMT. Pregnant or lactating women, patients with end-stage disease, cases who were participating or participated in other clinical trials within 3 months, and patients with previous bowel history of pathogen infection, oral antibiotics or proton pump inhibitors (PPI) for the recent2 weeks, and those at immunosuppressive state were excluded. Informed consent was obtained from the enrolled patients and their families. There were 1,356 cases of constipation, 175 cases of inflammatory bowel disease, 148 cases of chronic diarrhea, 127 cases of radiation enteritis, 119 cases of irritable bowel syndrome, and 85 cases of autism (complicating with intestinal disorders). FMT donor requirements: (1) 18 to 30 years old non-relatives, non-pregnant healthy adults with healthy lifestyle and good eating habits as volunteers to participate in fecal donation; (2) no administration of antibiotics within 3 months; (3) no chronic diseases such as constipation, irritable bowel syndrome, inflammatory bowel disease, etc., no autoimmune disease, not in immunosuppressive state, no history of malignant disease; (4) negative pathogen examination of infectious diseases (hepatitis B virus, hepatitis C virus, syphilis, HIV, etc.); (5) negative fecal examination (C.difficile, dysentery bacillus, Shigella, Campylobacter, parasites, etc.). The donor requirements after enrollment: (1) physical examination was reviewed once every two months, and the result still met the above requirements; (2) 16S rRNA sequencing was performed for every fecal donation in order to ensure that the composition and diversity of the fecal flora was stable and reliable. The preparation of the stool suspension referred to the Amsterdam criteria and the preparation process was less than 1 hour. The preparation of the FMT capsule was processed by pre-freezing the stool suspension after the preparation of the above suspension, and the frozen sample was transferred into a freeze dryer for freezing. The dried and lyophilized powder was encapsulated in capsules, and the capsule shell was made of acid-resistant hypromellose capsule (No.0) and pediatric-specific capsule (No.3), sealed and packaged in a-20℃ refrigerator. Three ways of accepting FMT treatment pathways included 6-day transplantation after the placement of the nasointestinal tube, 6-day oral FMT capsule transplantation and one-time transplantation through colonoscopy. Intestinal preparation (nasointestinal tube feeding of polyethylene glycol until watery stool) was carried out before transplantation. Other treatments were stopped during treatment and follow-up, and any medication was not recommended when necessary.@*Results@#Of the 2010 patients, 1,497 cases received nasointestinal tube transplantation (nasointestinal tube group), 452 cases oral capsule transplantation (oral capsule group) and 61 cases colonoscopy (colonoscopy group). At 3 time points of 3, 12, and 36 months after FMT, the clinical cure rates and the clinical improvement rates were 41.3% (560/1 356), 35.2% (320/909), 31.4% (69/220), and 29.0% (393/1 356), 27.8% (253/909), 29.1% (64/220), respectively in constipation patients; 33.1% (58/175), 29.9% (35/117), 24.5% (12/49), and 31.4% (55/175), 27.4% (32/117), 57.1% (28/49), respectively in inflammatory bowel disease patients; 87.8% (130/148), 81.8% (81/99), 78.3% (36/46), and 8.1% (12/148), 7.1% (7/99), 4.3% (2/46), respectively in chronic diarrhea patients; 61.4% (78/127), 56.5% (48/85), 47.6% (20/42), and 21.2% (27/127), 15.3% (13/85), 14.3% (6/42), respectively in radiation enteritis patients; 53.8% (64/119), 45.0% (36/80), 6/15, and 21.0% (25/119), 26.2% (21/80), 4/15, respectively in irritable bowel syndrome patients; 23.5% (20/85), 22.8% (13/57), 20.0%(5/25), and 55.3% (47/85), 49.1% (28/57), 40.0% (10/25), respectively in autism patients. Meanwhile the clinical cure rates and the clinical improvement rates at 3, 12, and 36 months were 47.7% (714/1 497), 42.8% (425/994), 39.1% (128/327), and 29.1% (436/1 497), 27.0% (268/994), 28.1% (92/327), respectively in the nasointestinal tube group; 38.7% (175/452), 30.2% (91/301), 33.3% (16/48), and 24.3% (110/452), 26.2% (79/301), 25.0% (12/48), respectively in the oral capsule group; 34.4% (21/61), 32.7% (17/52), 18.2% (4/22), and 21.3% (13/61), 13.5% (7/52), 45.5% (10/22), respectively in colonoscopy group. No serious adverse events occurred during treatment and follow-up period. The adverse event of nasointestinal tube group presented higher ratio of discomfort in respiratorytract accounting for 13.1% (196/1497); the oral capsule group had a higher proportion of nausea and vomiting when swallowing capsules accounting for 7.1% (32/452); the colonoscopy group was mainly diarrhea, accounting for 37.7% (23/61). The above symptoms disappeared after the nasointestinal tube was removed, or after treatment ended, or within 1 to 3 days after hospitalization.@*Conclusion@#FMT is a safe and effective method for the treatment of intestinal dysfunction.
ABSTRACT
Noninfectious diarrhea is a kind of digestive disease caused by many factors and the main clinical features are increased frequency of defecation and change of character of stool,most of the patients have intestinal microecological imbalance. Improving the intestinal microecological balance is very important in the treatment of noninfectious diarrhea. Microbial ecological agent(MEA)has definite efficacy for the treatment of noninfectious diarrhea,and gradually becomes the commonly used drug for noninfectious diarrhea in clinical practice. This article reviewed the use of MEA in the treatment of noninfectious diarrhea.