Faming Zhang

Fecal microbiota transplantation through mid‐gut for refractory Crohn's disease: Safety, feasibility, and efficacy trial results

The gut microbiota plays a pivotal role in the intestinal diseases. Fecal microbiota transplantation (FMT) might be a rescue therapy for refractory inflammatory bowel disease. This study aimed to evaluate the safety, feasibility, and efficacy of FMT through mid‐gut for refractory Crohns disease (CD).

Effects of essential oil from Croton tiglium L. on intestinal transit in mice.

AIM OF THE STUDYnCroton tiglium (Croton tiglium L., Euphorbiaceae) is widely used as a herb for treatment of gastrointestinal disturbances. Previous studies established its purgative and inflammational properties. The present study aimed to investigate the effects of Croton tiglium oil (CO) on intestinal transit in mice.nnnMATERIALS AND METHODSnGastrointestinal transit in mice and contractile characteristics of isolated intestinal strips from mice were evaluated. Intestinal inflammation was confirmed by histological examination.nnnRESULTSnLow dose of CO increased the gastrointestinal transit of charcoal and barium meal as well as the production of fecal pellets in mice. In contrast, high dose exerted inhibitory effects. For normal colonic circular strips, both high and low dose of CO inhibited the contractile frequency. Low doses (0-20 microg/ml) of CO enhanced the phasic contractions, while high doses (>40 microg/ml) reduced them. Colonic longitudinal strips in CO-treated mice were less sensitive to electrical field stimulation than those in control mice. The contraction of colonic longitudinal, colonic and jejunal circular strips in CO-treated mice was more sensitive to atropine than that in control mice.nnnCONCLUSIONSnCO might modulate gastrointestinal motility and induce intestinal inflammation related to immunological milieu and motor activity. Our findings may highlight the ethno-medical uses of Croton tiglium on intestinal disorders.

Step-up fecal microbiota transplantation (FMT) strategy.

ABSTRACT 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.

Short-Term Surveillance of Cytokines and C-Reactive Protein Cannot Predict Efficacy of Fecal Microbiota Transplantation for Ulcerative Colitis

Objective There were no reports on predicting long-term efficacy of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). This study aimed to detect short-term changes of cytokines and C-reactive protein (CRP) in patients with UC undergoing FMT, and to evaluate the predictive value of CRP and cytokines for the long-term efficacy of FMT. Methods Nineteen patients with moderate to severe UC (Mayo score ≥ 6) were treated with single fresh FMT through mid-gut. Serum samples were collected before and three days post-FMT. Clinical responses were evaluated by a minimum follow-up of three months. Patients with clinical improvement and remission at the assessment point of three-month were included as response group, while patients without clinical improvement or remission were included as non-response group. Serum concentrations of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, IFN-γ, TNF, TNFR-1, TNFR-2, MCP-1, G-CSF, GM-CSF) and CRP were assayed to predict the clinical response of FMT. Results In total, 10.5% (2/19) of patients achieved clinical remission and 47.4% (9/19) achieved clinical improvement (Response group, including clinical remission and clinical improvement), 42.1% (8/19) failed to benefit from FMT (Non-response group). In both Response group and Non-response group, the level of CRP at three days after FMT didn’t show significant decrease compared with that before FMT (p>0.05). However, in Response group, CRP level at three months after FMT decreased significantly than that before FMT (p<0.05). Compared with healthy controls (n = 9), patients with UC showed a higher baseline level of serum IL-6, TNFR-2 and G-CSF, and a lower level of IL-2 and IL-4 (p<0.05). In both Response group and Non-response group, none of the eleven detectable cytokines showed a significant difference between the value at three days after FMT and that before FMT (p>0.05). Conclusions Patients with moderate to severe UC presented a complex disorder of cytokines. However, the efficacy of FMT for UC might not be predicted by the short-term surveillance of cytokines and CRP.

Colonic transendoscopic enteral tubing: A novel way of transplanting fecal microbiota

Background and study aims: Placement of a tube through the anus into the cecum has not yet been established as a method of administering whole-colonic treatment. The aim of this study was to evaluate the safety, feasibility, and value of transendoscopic enteral tubing (TET) for fecal microbiota transplantation (FMT) through the colon. Patients and methods: A prospective observational study was performed of FMT using a new colonic TET technique. Under endoscopic guidance, a TET tube was affixed to the cecum with clips. The safety, value, and satisfaction with the FMT by TET were evaluated. Results: A total of 54 patients underwent TET. The success rate of the TET procedure was 100u200a% (54/54). Duration of the TET procedures was 14.8u200a±u200a5.8u200amin. During the TET tube retention period, 98.1u200a% (53/54) of patients were satisfied with TET. The retention time for whole-colon delivery of the fecal microbiota suspension was 12.4u200a±u200a2.3 days. In 88.4u200a% (49/54) of cases, no discomfort was reported during injection through the TET tube of the microbiota suspension. No adverse events were see in patients who required tube extubation after FMT. Conclusions: Colonic TET is a novel, safe, convenient, and reliable procedure for FMT that results in a high degree of patient satisfaction.

Clinical efficacy maintains patients' positive attitudes toward fecal microbiota transplantation.

AbstractFew studies have been conducted on the attitudes of patients seeking fecal microbiota transplantation (FMT). This study aimed to investigate the reasons for patients with Crohns disease (CD) seeking FMT and their attitude changes after FMT.In this prospective study, all included patients were diagnosed with CD for at least 6 months and intended to receive FMT. A questionnaire was designed to investigate the history of medical visits and patients’ attitudes toward FMT. Only refractory patients who failed to clinically respond to previous treatment were selected for undergoing FMT. Three months after the first FMT, patients were required to complete the second questionnaire on attitudes toward the first FMT.A total of 207 patients with CD were included for questionnaire survey. In 118 refractory patients, 94.07% sought FMT because they had no other choice. In 89 nonrefractory patients, 78.65% sought FMT for the reason that they wanted to achieve better clinical results or even a cure, although the current treatment was effective for them. In all, 118 refractory patients received FMT. Three months after the first FMT, 88.98% (105/118) patients completed the questionnaire on patients’ attitudes toward FMT. Of these 105 patients, 56.19% reported to have satisfactory clinical efficacy and 74.29% were willing to receive the second FMT. Moreover, 89.52% (94/105) showed their willingness to recommend FMT to other patients.In conclusion, this study at least first time demonstrated that patients with CD were willing to accept FMT due to its efficacy.

Multiple fresh fecal microbiota transplants induces and maintains clinical remission in Crohn’s disease complicated with inflammatory mass

The ancient Chinese medical literature, as well as our prior clinical experience, suggests that fecal microbiota transplantation (FMT) could treat the inflammatory mass. We aimed to evaluate the efficacy and safety of multiple fresh FMTs for Crohn’s disease (CD) complicated with intraabdominal inflammatory mass. The one-hour FMT protocol was followed in all patients. Twenty-five patients were diagnosed with CD and related inflammatory mass by CT or MRI. All patients received the initial FMT followed by repeated FMTs every 3 months. The primary endpoint was clinical response (improvement and remission) and sustained clinical remission at 12 months. Secondary endpoints were improvement in size of phegmon/abscess based upon cross-sectional imaging and safety of FMT. 68.0% (17/25) and 52.0% (13/25) of patients achieved clinical response and clinical remission at 3 months post the initial FMT, respectively. The proportion of patients at 6 months, 12 months and 18 months achieving sustained clinical remission with sequential FMTs was 48.0% (12/25), 32.0% (8/25) and 22.7% (5/22), respectively. 9.5% (2/21) of patients achieved radiological healing and 71.4% (15/21) achieved radiological improvement. No severe adverse events related to FMT were observed. This pragmatic study suggested that sequential fresh FMTs might be a promising, safe and effective therapy to induce and maintain clinical remission in CD with intraabdominal inflammatory mass.

Microbiota transplantation: concept, methodology and strategy for its modernization

ABSTRACTFecal microbiota transplantation (FMT) has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host interactions associated with various disorders, including Clostridium difficile infection, inflammatory bowel disease, diabetes mellitus, cancer, liver cirrhosis, gut-brain disease and others. To discuss the experiences of using microbes to treat human diseases from ancient China to current era should be important in moving standardized FMT forward and achieving a better future. Here, we review the changing concept of microbiota transplantation from FMT toxa0selective microbiota transplantation, methodology development of FMT and step-up FMT strategy based on literature and state experts’ perspectives.

Cost-effectiveness analysis of fecal microbiota transplantation for inflammatory bowel disease

There is a lack of health economics evidence on the use of fecal microbiota transplantation (FMT) for inflammatory bowel disease (IBD). This study aims to evaluate the cost-effectiveness before (with conventional therapy) and after introducing FMT for treating IBD. 104 patients with IBD received FMT were recruited. Health status was evaluated by European dimension health table (ED-5Q). Incremental cost-effectiveness ratio (ICER) and net monetary benefit (NB) were calculated by different age groups, genders, smoking status, and disease subtypes. The willingness-to-pay threshold was set to the value equal to three times China’s per capita GDP (141240 CNY/QALY, 2014). From the health-care perspective, FMT strategy was 73% likely to be cost-effective compared with the conventional therapy before FMT with an ICER of -185712 CNY/QALY and a positive NB of CNY 45150. From the societal perspective, FMT strategy was 75% likely to be cost-effective with an ICER of -207417 CNY/QALY and a positive NB of CNY 48395. Moreover, younger patients (≤ 24), females, non-smokers and Crohn’s disease (CD) achieved more benefits. This study for the first time demonstrated that FMT showed its cost-effectiveness, especially on improving the life quality and decreasing the medical and societal cost, for the moderate to severe IBD in a Chinese cohort.

A novel quick transendoscopic enteral tubing in mid-gut: technique and training with video

BackgroundThis study aimed to evaluate the feasibility, safety, and value of a quick technique for transendoscopic enteral tubing (TET) through mid-gut.MethodsA prospective interventional study was performed in a single center. A TET tube was inserted into mid-gut through the nasal orifice and fixed on the pylorus wall by one tiny titanium endoscopic clip under anesthesia. The feasibility, safety, success rate, and satisfaction with TET placement were evaluated for enteral nutrition or fecal microbiota transplantation.ResultsA total of 86 patients underwent mid-gut TET. The success rate of the TET procedure was 98.8% (85/86). Mean tubing time of the TET procedure was 4.2u2009±u20091.9xa0min. 10 cases of procedure was enough for training of general endoscopist to shorten the procedure time (7.0xa0min vs 4.0xa0min, pu2009<u20090.05). 97.7% (84/86) of patients were satisfied with the TET placement. Procedure-related and tube-related adverse events were observed in 8.1% (7/86) and 7.0% (6/86) of patients respectively. There were no moderate to severe adverse events during tube extubation.ConclusionsTET through mid-gut is a novel, convenient, reliable and safe procedure for mid-gut administration with a high degree of patient satisfaction.Trial registrationThis research was retrospectively registered with clinicaltrials.gov. Trial registration date: 29th November 2017. Trial registration number: NCT03335982.