Washed microbiota transplantation for Crohn’s disease:A metagenomic,metatranscriptomic,and metabolomic-based study

BACKGROUND Fecal microbiota transplantation(FMT)is a promising therapeutic approach for treating Crohn’s disease(CD).The new method of FMT,based on the automatic washing process,was named as washed microbiota transplantation(WMT).Most existing studies have focused on observing the clinical phenomena.However,the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome,metatranscriptome,and metabolome-has not yet been reported.AIM To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT.METHODS We conducted a prospective,open-label,single-center clinical study.Eleven CD patients underwent WMT.Their clinical responses(defined as a decrease in their CD Activity Index score of>100 points)and their microbiome(metagenome,metatranscriptome)and metabolome profiles were evaluated three months after the procedure.RESULTS Seven of the 11 patients(63.6%)showed an optimal clinical response three months post-WMT.Gut microbiome diversity significantly increased after WMT,consistent with improved clinical symptoms.Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains,such as Faecalibac-terium prausnitzii,Roseburia intestinalis,and Escherichia coli.In addition,metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors.However,levels of vital amino acids that may be associated with disease progression(e.g.,L-glutamic acid,gamma-glutamyl-leucine,and prolyl-glutamine)were reduced after WMT.CONCLUSION WMT demonstrated therapeutic efficacy in CD treatment,likely due to the effective reconstruction of the patient’s microbiome.Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

侧卧斜仰截石位经皮肾镜碎石取石术中标准通道“四步法”扩张的临床体会

目的探讨"四步法"建立标准通道在侧卧斜仰截石位经皮肾镜碎石取石术(PCNL)中应用的安全性和可行性。方法该科2017年5月-2017年12月应用"四步法"建立标准通道行侧卧斜仰截石位PCNL患者共30例,对其通道建立过程及结果进行回顾性分析。结果目标肾盏成功建立标准通道,结石最大径线0.8~6.7 cm,手术时间(88.19±7.08)min,术前术后血色素变化(-0.06±1.83)g/L,包膜下血肿1例;无输血者,无周围邻近脏器损伤。结论 PCNL"四步法"建立标准通道是安全有效的,值得推广。

输尿管镜直视下球囊扩张治疗输尿管狭窄(附9例初步报告)

目的探讨内镜下定位输尿管狭窄球囊扩张术应用的安全性和可行性。方法该科2017年2月-2017年12月应用内镜下定位输尿管狭窄球囊扩张术的患者共9例,对其手术过程及结果进行回顾性分析。9例患者均为单侧狭窄,右侧5例,左侧4例,狭窄长度约0.50~1.00 cm,狭窄部位:上段6例,中段2例,下段1例;泌尿系超声、静脉肾盂造影(IVP)、逆行造影或CTU检查确诊。结果全部手术顺利行顺行球囊扩张8例,逆行球囊扩张1例,手术时间(81.44±8.96) min,术后第3个月拔除双J管,随访时间4~10个月,行泌尿系B超和IVP检查,全部患者腰痛消失,7例积水减轻,2例未加重。结论内镜下定位行输尿管狭窄球囊扩张术安全、有效,值得推广。

Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn's disease

The concept of fecal microbiota transplantation(FMT)has been used in traditional Chinese medicine at least since the 4thcentury.Evidence from recent human studies strongly supports the link between intestinal bacteria and inflammatory bowel disease.We proposed that standardized FMT might be a promising rescue therapy for refractory inflammatory bowel disease.However,there were no reports of FMT used in patients with severe Crohn’s disease(CD).Here,we report the successful treatment of standardized FMT as a rescue therapy for a case of refractory CD complicated with fistula,residual Barium sulfate and formation of intraperitoneal large inflammatory mass.As far as we know,this is the first case of severe CD treated using FMT through mid-gut.

Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: The first report

Fecal microbiota transplantation(FMT)is a promising strategy that involves reconstruction of gut microbiota.Recently,it has been considered as a treatment of Crohn’s disease(CD)and certain neurological diseases.Here,to the best of our knowledge,we report the first case that used FMT to achieve remission of intestinal and neurological symptoms in a girl with CD and a 17-year history of epilepsy.During the 20 mo of follow-up,FMT has proved its efficacy in preventing relapse of seizures after withdrawing the antiepileptic drugs.Furthermore,this finding highlights the role of microbiota-gut-brain axis and inspires a novel treatment for epilepsy through remodeling gut microbiota.

Fecal microbiota transplantation and prednisone for severe eosinophilic gastroenteritis

Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by patchy or diffuse eosinophilic infiltration of the bowel wall to a variable depth and various gastrointestinal manifestations. We describe a case of severe eosinophilic gastroenteritis presenting as frequent bowel obstruction and diarrhea in a 35-year-old man. The patient was misdiagnosed and underwent surgery because of intestinal obstruction when he was first admitted to a local hospital. Then he was misdiagnosed as having Crohn’s disease in another university teaching hospital. Finally, the patient asked for further treatment from our hospital because of the on-going clinical trial for treating refractory Crohn’s disease by fecal microbiota transplantation. Physical examination revealed a slight distended abdomen with diffuse tenderness. Laboratory investigation showed the total number of normal leukocytes with neutrophilia as 90.5%, as well as eosinopenia, monocytopenia and lymphocytopenia. Barium radiography and sigmoidoscopy confirmed inflammatory stenosis of the sigmoid colon. We diagnosed the patient as having eosinophilic gastroenteritis by multi-examinations. The patient was treated by fecal microbiota transplantation combined with oral prednisone, and was free from gastrointestinal symptoms at the time when we reported his disease. This case highlights the importance of awareness of manifestations of a rare disease like eosinophilic gastroenteritis.

Cap-assisted endoscopic sclerotherapy for hemorrhoids: Methods, feasibility and efficacy

AIM: To evaluate the methodology, feasibility, safety and efficacy of a novel method called cap-assisted endoscopic sclerotherapy(CAES) for internal hemorrhoids.METHODS: A pilot study on CAES for grade Ⅰ to Ⅲ internal hemorrhoids was performed. Colon and terminal ileum examination by colonoscopy was performed for all patients before starting CAES. Polypectomy and excision of anal papilla fibroma were performed if polyps or anal papilla fibroma were found and assessed to be suitable for resection under endoscopy. CAES was performed based on the requirement of the cap, endoscope, disposable endoscopic long injection needle, enough insufflated air and sclerosing agent.RESULTS: A total of 30 patients with grade Ⅰ to Ⅲ internal hemorrhoids was included. The follow-up was more than four weeks. No bleeding was observed after CAES. One(3.33%) patient claimed mild tenesmus within four days after CAES in that an endoscopist performed this procedure for the first time. One hundred percent of patients were satisfied with this novel procedure, especially for those patients who underwent CAES in conjunction with polypectomy or excision of anal papilla fibroma.CONCLUSION: CAES as a novel endoscopic sclerotherapy should be a convenient, safe and effective flexible endoscopic therapy for internal hemorrhoids.

Role of transforming growth factor-beta1-smad signal transduction pathway in patients with hepatocellular carcinoma

AIM： To explore the role of transforming growth factorbeta1 （TGF-β1）-smad signal transduction pathway in patients with hepatocellular carcinoma. METHODS： Thirty-six hepatocellular carcinoma specimens were obtained from Qidong Liver Cancer Institute and Department of Pathology of the Second Affiliated Hospital of Nanjing Medical University. All primary antibodies （polyclonal antibodies） to TGF-β1, type H Transforming growth factor-beta receptor （TβR-Ⅱ）, nuclear factor-kappaB （NF-KB）, CD34, smad4 and smad7, secondary antibodies and immunohistochemical kit were purchased from Zhongshan Biotechnology Limited Company （Beijing, China）. The expressions of TGF-β1, TβR-Ⅱ, NF- KB, smad4 and smad7 proteins in 36 specimens of hepatocellular carcinoma （HCC） and its adjacent tissue were separately detected by immunohistochemistry to observe the relationship between TGF-β1 and TβR-Ⅱ, between NF-KB and TGF-β1, between smad4 and smad7 and between TGF-β1 or TβR-Ⅱ and microvessel density （MVD）. MVD was determined by labelling the vessel endothelial cells with CD34. RESULTS： The expression of TGF-β1, smad7 and MVD was higher in HCC tissue than in adjacent HCC tissue （P〈0.01, P〈0.05,P〈0.01 respectively）. The expression of TβR-Ⅱ and smad4 was lower in HCC tissue than in its adjacent tissue （P〈0.01, P〈0.05 respectively）. The expression of TGF-β1 protein and NF-KB protein was consistent in HCC tissue. The expression of TGF-β1 and MVD was also consistent in HCC tissue. The expression of TIER- Ⅱ was negatively correlated with that of MVD in HCC tissue. CONCLUSION： The expressions of TGF-IB1, TβR- Ⅱ, NF-KB, smad4 and smad7 in HCC tissue, which are major up and down stream factors of TGF-β1-smad signal transduction pathway, are abnormal. These factors are closely related with NVD and may play an important role in HCC angiogenesis. The inhibitory action of TGF-β1 is weakened in hepatic carcinoma cells because of abnormality of TGF-β1 receptors （such as TIBR- Ⅱ） and postreceptors （such as smad4 and smad7）. NF-KB may cause activation and production of TGF-β1.

Endoscopic retrieval of 28 foreign bodies in a 100-year-old female after attempted suicide

Foreign body ingestion is a common emergency situation in children with one or a few objects having been ingested. Here we report our experience using endo-scopic retrieval in a female centenarian with dyspnea and foreign bodies in the esophagus. She attempted suicide by swallowing 26 coins and two other foreign bodies. A gastroscope was used to remove all foreign bodies in the lower esophagus. In total, 26 coins, one ferrous ring and one cylindrical plastic object were retrieved. To our knowledge, this is the first clinical report on retrieval of so many foreign bodies in a single case.

Cholecystectomy does not significantly increase the risk of fatty liver disease

AIM: To investigate the relationship between cholecystectomy and fatty liver disease(FLD) in a Chinese population.METHODS: A total of 32428 subjects who had voluntarily undergone annual health checkups in the Second Affiliated Hospital of Nanjing Medical University from January 2011 to May 2013 were included in this study. Basic data collection, physical examination, laboratory examination, and abdominal ultrasound examination were performed.RESULTS: Subjects undergoing cholecystectomy were associated with greater age, female sex, higher body mass index, and higher levels of systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, and triglycerides. However, no significant differences were found in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, gammaglutamyl transpeptidase, albumin, and serum uric acid. The overall prevalence of FLD diagnosed by ultrasonography was high at 38.4%. The prevalence of FLD was significantly higher for subjects who had undergone cholecystectomy(46.9%) than those who had not undergone cholecystectomy(38.1%; χ2 test, P < 0.001). Cholecystectomy was positively associated with FLD(OR = 1.433, 95%CI: 1.259-1.631). However, after adjusting for possible factors associated withFLD, multivariate regression analysis showed that the association between cholecystectomy and FLD was not statistically significant(OR = 1.096; 95%CI: 0.939-1.279). CONCLUSION: According to our study results, cholecystectomy may not be a significant risk factor for FLD.

Impact of cap-assisted colonoscopy during transendoscopic enteral tubing:A randomized controlled trial

BACKGROUND Colonic transendoscopic enteral tubing(TET)requires double cecal intubation,raising a common concern of how to save cecal intubation time and make the tube stable.We hypothesized that cap-assisted colonoscopy(CC)might reduce the second cecal intubation time and bring potential benefits during the TET procedure.AIM To investigate if CC can decrease the second cecal intubation time compared with regular colonoscopy(RC).METHODS This prospective multicenter,randomized controlled trial was performed at four centers.Subjects≥7 years needing colonic TET were recruited from August 2018 to January 2020.All subjects were randomly assigned to two groups.The primary outcome was the second cecal intubation time.Secondary outcomes included success rate,insertion pain score,single clip fixation time,purpose and retention time of TET tube,length of TET tube inserted into the colon,and all procedurerelated(serious)adverse events.RESULTS A total of 331 subjects were randomized to the RC(n=165)or CC(n=166)group.The median time of the second cecal intubation was significantly shorter for CC than RC(2.2 min vs 2.8 min,P<0.001).In patients with constipation,the median time of second cecal intubation in the CC group(n=50)was shorter than that in the RC group(n=43)(2.6 min vs 3.8 min,P=0.004).However,no difference was observed in the CC(n=42)and RC(n=46)groups of ulcerative colitis patients(2.0 min vs 2.5 min,P=0.152).The insertion pain score during the procedure in CC(n=14)was lower than that in RC(n=19)in unsedated colonoscopy(3.8±1.7 vs 5.4±1.9;P=0.015).Multivariate analysis revealed that only CC(odds ratio[OR]:2.250,95%confidence interval[CI]:1.161-4.360;P=0.016)was an independent factor affecting the second cecal intubation time in difficult colonoscopy.CC did not affect the colonic TET tube’s retention time and length of the tube inserted into the colon.Moreover,multivariate analysis found that only endoscopic clip number(OR:2.201,95%CI:1.541-3.143;P<0.001)was an independent factor affecting the retention time.Multiple regression analysis showed that height(OR:1.144,95%CI:1.027-1.275;P=0.014)was the only independent factor influencing the length of TET tube inserted into the colon in adults.CONCLUSION CC for colonic TET procedure is a safe and less painful technique,which can reduce cecal intubation time.

Awareness and attitude of fecal microbiota transplantation through transendoscopic enteral tubing among inflammatory bowel disease patients

BACKGROUND Transendoscopic enteral tubing(TET)has been used in China as a novel delivery route for fecal microbiota transplantation(FMT)into the whole colon with a high degree of patient satisfaction among adults.AIM To explore the recognition and attitudes of FMT through TET in patients with inflammatory bowel disease(IBD).METHODS An anonymous questionnaire,evaluating their awareness and attitudes toward FMT and TET was distributed among IBD patients in two provinces of Eastern and Southwestern China.Question formats included single-choice questions,multiple-choice questions and sorting questions.Patients who had not undergone FMT were mainly investigated for their cognition and acceptance of FMT and TET.Patients who had experience of FMT,the way they underwent FMT and acceptance of TET were the main interest.Then all the patients were asked whether they would recommend FMT and TET.This study also analyzed the preference of FMT delivery in IBD patients and the patient-related factors associated with it.RESULTS A total of 620 eligible questionnaires were included in the analysis.The survey showed that 44.6%(228/511)of patients did not know that FMT is a therapeutic option in IBD,and 80.6%(412/511)of them did not know the concept of TET.More than half(63.2%,323/511)of the participants stated that they would agree to undergo FMT through TET.Of the patients who underwent FMT via TET[62.4%(68/109)],the majority[95.6%(65/68)]of them were satisfied with TET.Patients who had undergone FMT and TET were more likely to recommend FMT than patients who had not(94.5%vs 86.3%,P=0.018 and 98.5%vs 87.8%,P=0.017).Patients’choice for the delivery way of FMT would be affected by the type of disease and whether the patient had the experience of FMT.When compared to patients without experience of FMT,Crohn’s disease and ulcerative colitis patients who had experience of FMT preferred mid-gut TET(P<0.001)and colonic TET(P<0.001),respectively.CONCLUSION Patients’experience of FMT through TET lead them to maintain a positive attitude towards FMT.The present findings highlighted the significance of patient education on FMT and TET.

Association between body mass index and erosive esophagitis:A meta-analysis

AIM:To conduct a meta-analysis to estimate the determinants of the association between erosive esophagitis (EE)and body mass index(BMI). METHODS:We identified the studies using PubMed. Studies were selected for analysis based on certain inclusion and exclusion criteria.Data were extracted from each study on the basis of predefined items.Metaanalyses were performed to verify the risk factors,such as obesity and gender. RESULTS:Twenty-one studies were included in this systematic review.These studies demonstrated an association between increasing BMI and the presence of EE[95%confidence interval(CI):1.35-1.88,overweight,odds ratio(OR)=1.60,P value homogeneity =0.003,95%CI:1.65-2.55,obese,OR=2.05,P< 0.01].The heterogeneity disappeared by stratifying for gender.No publication bias was observed in this metaanalysis by the Egger method. CONCLUSION:This analysis demonstrates a positive association between BMI and the presence of EE,especially in males.The risk seems to progressively increase with increasing weight.

Preclinical safety,effectiveness evaluation,and screening of functional bacteria for fecal microbiota transplantation based on germ-free animals

Fecal microbiota transplantation(FMT),also known as fecal bacterial therapy,is a treatment option that can quickly reconstruct the normal composition of intestinal microbes,and it has a good therapeutic effect on Clostridium difficile infection,as well as on other microecological disorders.However,the causal mechanism of FMT efficacy remains to be clarified,its safety is a major problem,and the standardization and acceptability of FMT need to be improved.This review summarizes its current research status and potential research areas that need to be strengthened,and proposes to clarify the safety of FMT and the causal relationship between FMT and therapeutic effectiveness based on germ-free animals.Meanwhile,the research system is combined with multiomics technology to screen the effective bacteria in FMT,and develop standard,safe,effective and controllable flora of FMT.

Nanjing consensus on methodology of washed microbiota transplantation

The methods of fecal microbiota transplantation(FMT)and the related results vary a lot among centers worldwide.Therefore,methodologic standardization can improve the clinical practice and trials about FMT.A panel of 28 experts from 22 hospitals or institutes in 15 cities has contributed to the present consensus on washed microbiota transplantation(WMT).[1]This consensus provides guidance on the methodology of WMT,which is different from that of the manually FMT in recent experts’consensus or recommendations.[2,3]All experts were assigned,according to their expertise,to the following five groups:Group 1,donor screening;Group 2,washing microbiota protocol,storing,and transport;Group 3,patient preparation;Group 4,delivery decision;Group 5,safety and management.Each statement and the following comment have passed a Delphi process and a face-to-face plenary meeting.The best available evidence was assessed according to the Grading of Recommendations Assessment,Development and Evaluation system.

Rationale,new anus positioning methods,and updated protocols:Expert recommendations on cap-assisted endoscopic sclerotherapy for hemorrhoids from China Gut Conference

Injection sclerotherapy is most effective for internal hemorrhoids,especially for patients with bleeding.Howev-er,traditional sclerotherapy via anoscope may cause iatrogenic risk and complications due to misplaced injections.[1]The flexible endoscopic sclerotherapy for internal hemorrhoids using a short needle without cap assistant was first reported in 1991 in the United States.[2]The flexible endoscopic injection using a short needle with cap assistant was reported in 2014 in Japan.[3]Cap-assisted endoscopic sclerotherapy(CAES)primarily using a long needle was reported in 2015[4]as an emerging flexible endoscopic therapy,and has been widely used for internal hemorrhoids and some prolapse in China.A panel of experts aimed to develop expert recommendations for CAES and derived guidelines on the key issues in hemorrhoidal disease,including rationale,new positioning methods for anus,indications,contraindications,techniques,post-procedure management,and core outcome set for evaluation[Figure 1].

Washed microbiota transplantation for the treatment of recurrent fungal infection in a patient with ulcerative colitis

To the Editor:Long-term use of antifungals can disrupt the balance of fungal community,making the fungal infection treatments more difficulty and aggravating colitis in patients.The exploration of fecal microbiota transplantation(FMT)in reducing Candida to contain pro-inflammatory immunity induced by gut mycobiota has gained a new appreciation.[1]The new methodology of FMT was recently coined as washed microbiota transplantation(WMT)based on the automatic purification system and washing process,released by the consensus statement from the Fecal Microbiota-standardization Study Group in 2019.[2,3]Here,we report a male patient with recurrent fungal infection who was successfully cured by serial WMTs.

Hypertension:microbiota-targeting treatment

Hypertension,as the most common cardiovascular disease(CVD),occurs with a high morbidity.The disease attacked a population of about 1.13 billion in 2015 globally,and its prevalence exceeds 27.9%in Chinese aged>18 years.[1]Unfortunately,lifestyle modifications and medical interventions fail to control the disease in a third of patients.Human gut microbiota can regulate immunity,inflammation,and metabolism.For decades,increasing evidence has shown that the activity and composition of microbiota are related to health status(like influencing blood lipid and glucose),which provides a new insight into the mechanism of hypertension.[2,3]

Risk factors for colorectal neoplasia in patients with underlying inflammatory bowel disease:a multicenter study

Background:This study sought to evaluate the risk factors for the development of colitis-associated neoplasia(CAN)in Chinese patients with inflammatory bowel disease(IBD).Methods:IBD patients who developed CAN between 1999 and 2016 were identified from eight medical centers.In addition to initial pathology evaluation,a CAN diagnosis was confirmed by two expert pathologists.Patients with CAN(n=29)were compared with non-CAN controls(n=87).Matching was performed for gender and IBD type with a ratio of three controls to one subject.Results:Of the 29 patients with CAN,8(27.6%)had colorectal cancer(CRC),20(69.0%)had a final diagnosis of low-grade dysplasia and 1(3.4%)had high-grade dysplasia.Multivariate analysis revealed that an older age at the time of IBD diagnosis and a longer IBD duration were independent risk factors for the development of CAN,with odds ratios of 1.09[95%confidence interval(CI):1.04–1.14,P<0.001]and 1.14(95%CI:1.03–1.27,P=0.013),respectively.Comparison between IBD patients with CRC and those with dysplasia indicated that the former were older at the time of IBD diagnosis(P=0.012)and had longer IBD durations(P=0.019).Conclusions:Older age at the time of IBD diagnosis and longer IBD duration were found to be associated with the development of CAN in IBD patients.