Relationship between clinical features and intestinal microbiota in Chinese patients with ulcerative colitis

BACKGROUNDDysbacteriosis may be a crucial environmental factor for ulcerative colitis (UC). Further study is required on microbiota alterations in the gastrointestinal tract of patients with UC for better clinical management and treatment.AIMTo analyze the relationship between different clinical features and the intestinal microbiota, including bacteria and fungi, in Chinese patients with UC. METHODSEligible inpatients were enrolled from January 1, 2018 to June 30, 2019, and stool and mucosa samples were collected. UC was diagnosed by endoscopy, pathology, Mayo Score, and Montreal classification. Gene amplicon sequencing of 16S rRNA gene and fungal internal transcribed spacer gene was used to detect the intestinal microbiota composition. Alpha diversity, principal component analysis, similarity analysis, and Metastats analysis were employed to evaluate differences among groups. RESULTSA total of 89 patients with UC and 33 non-inflammatory bowel disease (IBD) controls were enrolled. For bacterial analysis, 72 stool and 48 mucosa samples were obtained from patients with UC and 21 stool and 12 mucosa samples were obtained from the controls. For fungal analysis, stool samples were obtained from 43 patients with UC and 15 controls. A significant difference existed between the fecal and mucosal bacteria of patients with UC. The α-diversity of intestinal bacteria and the relative abundance of some families, such as Lachnospiraceae and Ruminococcaceae, decreased with the increasing severity of bowel inflammation, while Escherichia-Shigella showed the opposite trend. More intermicrobial correlations in UC in remission than in active patients were observed. The bacteria-fungi correlations became single and uneven in patients with UC.CONCLUSIONThe intestinal bacteria flora of patients with UC differs significantly in terms of various sample types and disease activities. The intermicrobial correlations change in patients with UC compared with non-IBD controls.     

Enteric microbiota leads to new therapeutic strategies for ulcerative colitis

Ulcerative colitis(UC) is a leading form of inflammatory bowel disease that involves chronic relapsing or progressive inflammation. As a significant proportion of UC patients treated with conventional therapies do not achieve remission, there is a pressing need for the development of more effective therapies. The human gut contains a large, diverse, and dynamic population of microorganisms, collectively referred to as the enteric microbiota. There is a symbiotic relationship between the human host and the enteric microbiota, which provides nutrition, protection against pathogenic organisms, and promotes immune homeostasis. An imbalance of the normal enteric microbiota composition(termed dysbiosis) underlies the pathogenesis of UC. A reduction of enteric microbiota diversity has been observed in UC patients, mainly affecting the butyrateproducing bacteria, such as Faecalibacterium prausnitzii, which can repress pro-inflammatory cytokines. Many studies have shown that enteric microbiota plays an important role in anti-inflammatory and immunoregulatory activities, which can benefit UC patients. Therefore, manipulation of the dysbiosis is an attractiveapproach for UC therapy.Various therapies targeting a restoration of the enteric microbiota have shown efficacy in treating patients with active and chronic forms of UC.Such therapies include fecal microbiota transplantation,probiotics,prebiotics,antibiotics,helminth therapy,and dietary polyphenols,all of which can alter the abundance and composition of the enteric microbiota.Although there have been many large,randomized controlled clinical trials assessing these treatments,the effectiveness and safety of these bacteria-driven therapies need further evaluation.This review focuses on the important role that the enteric microbiota plays in maintaining intestinal homeostasis and discusses new therapeutic strategies targeting the enteric microbiota for UC.     

Fecal microbiota transplantation broadening its application beyond intestinal disorders

Intestinal dysbiosis is now known to be a complication in a myriad of diseases.Fecal microbiota transplantation(FMT),as a microbiota-target therapy,is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases.New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota.This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas,including metabolic diseases,neuropsychiatric disorders,autoimmune diseases,allergic disorders,and tumors.A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces,with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity,along with increased levels of butyrate-producing intestinal microbiota.Case reports of FMT have also shown favorable outcomes in Parkinson's disease,multiple sclerosis,myoclonus dystonia,chronic fatigue syndrome,and idiopathic thrombocytopenic purpura.FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.     

Immunological mechanisms of fecal microbiota transplantation in recurrent Clostridioides difficile infection

Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT.     

益生菌增强急性严重肝损伤粪菌移植效果

目的观察小鼠肠道菌群的变化,探讨粪菌结合益生菌移植干预急性严重肝损伤的结局。方法选雄性BALB/c小鼠40只,随机分为空白对照组10只,模型组10只,普通粪菌移植组10只,粪菌+益生菌移植组10只,除空白对照组外,其余各组给予D-氨基半乳糖(3.0 g/kg)腹腔注射制备急性严重肝损伤模型,普通粪菌移植组和粪菌+益生菌移植组在造模同时分别给予普通粪菌液和益生菌+粪菌液灌肠(1次/d),48 h后取血清用于检测丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素,取肝组织用于病理学检测。取结肠内容物用于提取DNA进行16S V3-V4区高通量测序,用生物信息学分析技术对测序结果进行可操作分类单元聚类分析,α多样性分析,β多样性分析,线性判别分析找到不同分组小鼠的结肠内容物特征性差异细菌。临床生物化学指标组间差异比较采用t检验,16S V3-V4区测序结果组间差异采用Wilcoxon检验。结果模型组小鼠血清肝脏生物化学指标高于其他3组,差异有统计学意义(P<0.05),模型组肝脏HE染色结果显示肝组织镜下呈严重炎性改变;普通粪菌移植组和粪菌+益生菌移植组较模型组明显减轻,炎症减轻。16S rRNA高通量测序分析结果显示,空白对照组小鼠群菌结构与其他3组的Shannon差异无统计学意义,Observed Species差异有统计学意义,菌群构成差异大,粪菌移植增加小鼠肠道内物种数量。β-多样性分析结果显示,空白对照组与其他3组的组间差异大于疾病组之间的组间差异,粪菌+益生菌移植组改变疾病小鼠肠道菌群结构的差异细菌多为产丁酸盐细菌。结论粪菌+益生菌增强粪菌移植治疗效果,改善肝脏炎症,增加肠道内产丁酸盐细菌数量。     

肠上皮下肌成纤维细胞与溃疡性结肠炎关系的初步探讨

目的　肠上皮下肌成纤维细胞 (ISEMF)是位于胃肠道黏膜上皮下的肌成纤维细胞 ,可分泌细胞因子、前列腺素、生长因子及细胞外基质蛋白 ,目前认为在炎症、组织修复、纤维化、肿瘤形成等方面起重要作用。通过建立肠镜活检组织标本检测ISEMF的方法 ,对ISEMF与溃疡性结肠炎 (溃结 )的关系进行初步探讨。方法　 1 5例溃结患者和 2 0例对照者肠镜活检标本 ,应用免疫组化方法 ,采用鼠抗人α 平滑肌肌动蛋白单克隆抗体检测肠黏膜中ISEMF。结果　ISEMF位于结肠黏膜上皮细胞基底部 ,为椭圆形或舟状 ,正常对照组每高倍视野ISEMF为 56 .3± 6 .9,溃结组为 71 .3± 9.1 ,溃结组ISEMF增多 ,差异有显著性 (P <0 .0 0 1 )。结论　溃结组ISEMF有增多的趋势 ,在一定程度上调节ISEMF的功能有可能改善溃结的预后     

An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis

Background:Fecal microbiota transplantation (FMT) as a promising therapy for ulcerative colitis (UC) remains controversial. We conducted a systematic review and meta-analysis to assess the efficiency and safety of FMT as a treatment for UC.Methods:The target studies were identified by searching PubMed, EMBASE, the Cochrane Library, Web of Science, and ClinicalTrials and by manual supplementary retrieval. We conducted a general review and quantitative synthesis of included studies. We used the RevMan and Stata programs in the meta-analysis. The outcomes were total remission, clinical remission, steroid-free remission, and serious adverse events. We also performed subgroup analyses based on different populations.Results:A total of 34 articles were included in the general review. Only 16 articles, including 4 randomized controlled trials, 2 controlled clinical trials, and 10 cohort studies, were selected for the meta-analysis. We found that donor FMT might be more effective than placebo for attaining total remission (risk ratio [RR]: 2.77, 95% confidence interval [CI]: 1.54–4.98; P = .0007), clinical remission (RR: 0.33, 95% CI: 0.24–0.41; P < .05), and steroid-free remission (RR: 3.63, 95% CI: 1.57–8.42; P = .003), but found no statistically significant difference in the incidence of serious adverse events (RR: 0.88, 95% CI: 0.34–2.31, P = .8). The subgroup analyses revealed significant differences between the pooled clinical remission rates for different regions, degrees of severity of the disease, and patients with steroid- or nonsteroid-dependent UC.Conclusions:FMT can achieve clinical remission and clinical response in patients with UC.     

缺血性结肠炎与溃疡性结肠炎临床诊断对比分析

目的对比分析缺血性结肠炎及溃疡性结肠炎临床特点与组织病理学的差异,为临床鉴别诊断提供依据。方法收集广西医科大学第一附属医院2010~2013年20例缺血性结肠炎及30例溃疡性结肠炎患者性别、病程、年龄、基础疾病史、临床表现,肠镜结果及病理特点等资料,并进行对比分析。结果缺血性结肠炎发病以60岁以上老年人为主,起病急,病程短,多伴有高血压、糖尿病等基础疾病,溃疡性结肠炎以中青年患者为主,病程长,伴随基础疾病较少见,前者临床表现以腹胀、呕吐多见,后者以黏液血便及里急后重症状较多见。缺血性结肠炎肠镜下病变较少累及直肠,多出现黏膜水肿,溃疡多呈纵行,溃疡性结肠炎常累及直肠,常合并炎性假息肉,溃疡以地图状为主,病变部位呈连续性。病理上,缺血性结肠炎以血管扩张充血、间质水肿及血管壁增厚多见,而炎性细胞浸润及隐窝脓肿较少见。结论结合年龄、既往病史、临床症状及内镜、组织病理学检查结果,有助于缺血性结肠炎与溃疡性结肠炎的鉴别诊断。     

Gut microbiota contributes to the distinction between two traditional Chinese medicine syndromes of ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun(PXSY)and Da-Chang-Shi-Re(DCSR).The relationships among gut microbiota,TCM syndromes,and UC pathogenesis have not been well investigated.AIM To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes.METHODS From May 2015 to February 2016,UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study.Fresh stool specimens of UC patients with PXSY or DCSR were collected.The feces of the control group came from the health examination population of Longhua Hospital.The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA.The high-throughput sequencing reads were processed with QIIME,and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.RESULTS The composition of gut bacterial communities in 93 stool samples(30 healthy controls,32 patients with PXSY syndrome,and 31 patients with DCSR syndrome)was determined by the pyrosequencing of 16S ribosomal RNA.Beta diversity showed that the composition of the microbiota was different among the three groups.At the family level,Porphyromonadaceae,Rikeneliaceae,and Lachnospiraceae significantly decreased while Enterococcus,Streptococcus,and other potential pathogens significantly increased in UC patients compared to healthy subjects.At the genus level,Parabacteroides,Dorea,and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls.Five differential taxa were identified between PXSY and DCSR syndromes.At the genus level,a significantly increased abundance of Streptococcus was observed in DCSR patients,while Lachnoclostridium increased in PXSY patients.The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism,immunity,and the metabolism of polypeptides.CONCLUSION Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.     

Remission induction and maintenance effect of probiotics on ulcerative colitis: A meta-analysis

AIM:To evaluate the induction of remission and main-tenance effects of probiotics for ulcerative colitis.METHODS: Information was retrieved from MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The induction of remission and promotion of mainte-nance were compared between probiotics treatment and non-probiotics treatment in ulcerative colitis.RESULTS: Thirteen randomized controlled studies met the selection criteria. Seven studies evaluated the remission rate, and eight studies estimated the re...     

Step-up fecal microbiota transplantation (FMT) strategy

Gut dysbiosis is a characteristic of inflammatory bowel disease (IBD) and is believed to play a role in the pathogenesis of IBD. Fecal microbiota transplantation (FMT) is an effective strategy to restore intestinal microbial diversity and has been reported to have a potential therapeutic value in IBD. Our recent study reported a holistic integrative therapy called “step-up FMT strategy,” which was beneficial in treating steroid-dependent IBD patients. This strategy consists of scheduled FMTs combined with steroids, anti-TNF-α antibody treatment or enteral nutrition. Herein, we will elaborate the strategy thoroughly, introducing the concept, potential indication, methodology, and safety of “step-up FMT strategy” in detail.     

Multidonor FMT capsules improve symptoms and decrease fecal calprotectin in ulcerative colitis patients while treated – an open-label pilot study

Background: Growing evidence indicates that gut dysbiosis is a factor in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) appears to be promising in inducing UC remission, but there are no reports regarding administration using capsules.

Methods: Seven patients with active UC, aged 27–50 years, were treated with 25 multidonor FMT capsules daily for 50 days as a supplement to their standard treatment in an open-label pilot study. The primary objective was to follow symptoms through the Simple Clinical Colitis Activity Index (SCCAI). Secondary objectives were to follow changes in fecal calprotectin and microbial diversity through fecal samples and quality of life through the Inflammatory Bowel Disease Questionnaire (IBDQ). Participants were followed through regular visits for six months.

Results: From a median of 6 at baseline, the SCCAI of all participants decreased, with median decreases of 5 (p?=?.001) and 6 (p?=?.001) after 4 and 8 weeks, respectively. Three of the seven patients had flare-up/relapse of symptoms after the active treatment period. The median F-calprotectin of ≥1800?mg/kg at baseline decreased significantly during the treatment period, but increased again in the follow-up period. The median IBDQ improved at all visits compared to baseline. The fecal microbiota α-diversity did not increase in the study period compared to baseline. All participants completed the treatment and no serious adverse events were reported.

Conclusion: Fifty days of daily multidonor FMT capsules temporarily improved symptoms and health-related life quality and decreased F-calprotectin in patients with active UC.     

益生菌干预下溃疡性结肠炎结肠组织中防御素的表达及意义

目的 研究益生菌治疗溃疡性结肠炎（UC）前后防御素（HNP1-3）在结肠组织中的表达水平,明确益生菌对UC患者的治疗作用,探讨防御素在UC发病机制中的作用以及益生菌治疗UC的作用机制。方法30例UC患者,随机分成A、B、C三组,A组口服柳氮磺胺吡啶和美常安,B组口服柳氮磺胺吡啶和丽珠肠乐,C组口服柳氮磺吡啶,疗程均为1个月。于治疗前后各取病变肠组织,用免疫组化法检测其中HNP。的表达水平。结果A、B、ci组治疗前病变肠组织中HNP。均为阳性表达,治疗后均为阴性或弱阳性表达,各组治疗前后差异有统计学意义（P〈0．01）。A、B两组肠组织中HNP。的表达在治疗前后下降幅度比C组大,其差异有统计学意义（P〈0．01）,而A、B两组服药前后下降幅度比较,其差异无统计学意义（P≥0．05）。结论HNP。参与UC的发生发展,能反映疾病的炎症程度;益生菌能有效降低UC患者的HNP1-3表达水平;HNP1-3可能与益生菌治疗UC的作用机制有关。     

肠道菌群及其代谢物与溃疡性结肠炎的关系

溃疡性结肠炎(ulcerative colitis,UC)是一种慢性非特异性结肠和直肠炎性疾病,属于炎症性肠病(inflammatory bowel disease,IBD)中的一种。病变主要局限于大肠黏膜和黏膜下层,通常涉及直肠和乙状结肠,也可延伸至整个结肠。病程漫长,常反复发作,严重影响患者的生活质量[1]。流行病学调查发现,UC见于任何年龄,但初发以20~30岁多见,男女比例为1.0:1~1.3:1。     

Fecal microbiota in pouchitis and ulcerative colitis

AIM To investigate the changes in microbiota in feces of patients with ulcerative colitis(UC) and pouchitis using genomic technology.METHODS Fecal samples were obtained from UC patients with or without an ileal pouch-anal anastomosis(IPAA) procedure, as well as healthy controls. The touchdown polymerase chain reaction technique was used to amplify the whole V3 region of the 16 S r RNA gene, which was transcribed from DNA extracted from fecal samples. Denaturing gradient gel electrophoresis was used to separate the amplicons. The band profiles and similarity indices were analyzed digitally. The predominant microbiota in different groups was confirmed by sequencing the 16 S rR NA gene. RESULTS Microbial biodiversity in the healthy controls was significantly higher compared with the UC groups(P 0.001) and IPAA groups(P 0.001). Compared with healthy controls, the UC patients in remission and those in the mildly active stage, the predominant species in patients with moderately and severely active UC changed obviously. In addition, the proportion of the dominant microbiota, which was negatively correlated with the disease activity of UC(r =-6.591, P 0.01),was decreased in pouchitis patients. The numbers of two types of bacteria, Faecalibacterium prausnitzii and Eubacterium rectale, were reduced in UC. Patients with pouchitis had an altered microbiota composition compared with UC patients. The microbiota from pouchitis patients was less diverse than that from severely active UC patients. Sequencing results showed that similar microbiota, such as Clostridium perfringens, were shared in both UC and pouchitis.CONCLUSION Less diverse fecal microbiota was present in patients with UC and pouchitis. Increased C. perfringens in feces suggest its role in the exacerbation of UC and pouchitis.