Project description:BackgroundAlthough transplantation of the fecal microbiota from normotensive donors has been shown to have an antihypertensive effect in hypertensive animal models, its effect on blood pressure in patients with hypertension is unclear. This study aimed to assess the effect of washed microbiota transplantation (WMT) from normotensive donors on blood pressure regulation in hypertensive patients.MethodsThe clinical data of consecutive patients treated with washed microbiota transplantation (WMT) were collected retrospectively. The blood pressures of hypertensive patients before and after WMT were compared. The factors influencing the antihypertensive effect of WMT in hypertensive patients and fecal microbial composition of donors and hypertensive patients were also analyzed.ResultsWMT exhibited an antihypertensive effect on blood pressure: the blood pressure at hospital discharge was significantly lower than that at hospital admission (change in systolic blood pressure: -5.09 ± 15.51, P = 0.009; change in diastolic blood pressure: -7.74 ± 10.42, P < 0.001). Hypertensive patients who underwent WMT via the lower gastrointestinal tract (β = -8.308, standard error = 3.856, P = 0.036) and those not taking antihypertensive drugs (β = -8.969, standard error = 4.256, P = 0.040) had a greater decrease in systolic blood pressure, and hypertensive patients not taking antihypertensive drugs also had a greater decrease in diastolic blood pressure (β = -8.637, standard error = 2.861, P = 0.004). After WMT, the Shannon Diversity Index was higher in six of eight hypertensive patients and the microbial composition of post-WMT samples tended to be closer to that of donor samples.ConclusionWMT had a blood pressure-lowering effect in hypertensive patients, especially in those who underwent WMT via the lower gastrointestinal tract and in those not taking antihypertensive drugs. Therefore, modulation of the gut microbiota by WMT may offer a novel approach for hypertension treatment.
Project description:Fecal microbiota transplantation (FMT) by manual preparation has been applied to treat diseases for thousands of years. However, this method still endures safety risks and challenges the psychological endurance and acceptance of doctors, patients and donors. Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events. This washing preparation makes delivering a precise dose of the enriched microbiota feasible, instead of using the weight of stool. Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration. The toxic reactions that include death, the change in the level of peripheral white blood cells, and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted. The metagenomic next-generation sequencing (NGS) indicated the increasing types and amount of viruses could be washed out during the washing process. Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4, corticosterone, and prostaglandin G2 could be removed by repeated washing. Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washing-process. In conclusion, this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation (WMT) is safer, more precise and more quality-controllable than the crude FMT by manual.
Project description:BackgroundChanges in the gut microbiota composition is a hallmark of chronic kidney disease (CKD), and interventions targeting the gut microbiota present a potent approach for CKD treatment. This study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT), a modified faecal microbiota transplantation method, on the renal activity of patients with renal dysfunction.MethodsA comparative analysis of gut microbiota profiles was conducted in patients with renal dysfunction and healthy controls. Furthermore, the efficacy of WMT on renal parameters in patients with renal dysfunction was evaluated, and the changes in gut microbiota and urinary metabolites after WMT treatment were analysed.ResultsPrincipal coordinate analysis revealed a significant difference in microbial community structure between patients with renal dysfunction and healthy controls (P = 0.01). Patients with renal dysfunction who underwent WMT exhibited significant improvement in serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen (all P < 0.05) compared with those who did not undergo WMT. The incidence of adverse events associated with WMT treatment was low (2.91%). After WMT, the Shannon index of gut microbiota and the abundance of several probiotic bacteria significantly increased in patients with renal dysfunction, aligning their gut microbiome profiles more closely with those of healthy donors (all P < 0.05). Additionally, the urine of patients after WMT demonstrated relatively higher levels of three toxic metabolites, namely hippuric acid, cinnamoylglycine, and indole (all P < 0.05).ConclusionsWMT is a safe and effective method for improving renal function in patients with renal dysfunction by modulating the gut microbiota and promoting toxic metabolite excretion.
Project description:ObjectiveWe aimed to evaluate the short-term efficacy and safety of fecal microbiota transplantation (FMT) by washed preparation for moderate to severely active UC.MethodsAn open-label prospective trial was conducted in an inflammatory bowel disease (IBD) tertiary referral center from April 2016 to March 2018. Patients with moderate to severely active UC were randomly assigned to undergo FMT thrice on day 1, 3 and 5 by nasojejunal tube (NJT) or transendoscopic enteral tubing (TET). The primary end-point was a clinical response at week 2 post-FMT. The secondary end-points were clinical and endoscopic remission at week 12 post-FMT, safety and disease progression.ResultsOf the nine patients included, 77.8% (7/9) achieved a clinical response at week 2. And 55.6% (5/9) and 33.3% (3/9), respectively, achieved clinical remission and endoscopic remission at week 12. In two patients who had no response to FMT, one switched to anti-tumor necrosis factor-? therapy, and the other underwent a colectomy. FMT was delivered through NJT in 44.4% (4/9) of the patients, while TET was used in 55.6% (5/9). The clinical outcomes did not differ significantly based on the delivery route (P?>?0.05). Adverse events, all mild and self-limiting, were observed in 33.3% (3/9) of the patients.ConclusionsFMT by washed preparation appears to be a safe and effective adjunct therapy for moderate to severely active UC during a short-term follow-up. The efficacy did not differ significantly between the NJT or TET delivery routes. Further randomized controlled studies are needed to confirm these findings.
Project description:The gut and brain interact constantly in a complex fashion. Its intricacy and intrigue is progressively being revealed in the study of the "gut-brain axis". Among many factors, abnormal light exposure is a potential powerful stressor, which is becoming ever more pervasive in our modern society. However, little is known about how stress, induced by staying up late by light, affects the gut-brain axis. We addressed this question by extending the normal circadian light for four hours at night in fifteen male tree shrews to simulate the pattern of staying up late in humans. The behavior, biochemical tests, microbiota dynamics, and brain structure of tree shrews were evaluated. The simple prolongation of light in the environment resulted in substantial changes of body weight loss, behavioral differences, total sleep time reduction, and an increased level of urine cortisol. These alterations were rescued by the treatment of either ketamine or washed microbiota transplantation (WMT). Importantly, the sustainability of WMT effect was better than that of ketamine. Magnetic Resonance Imaging analysis indicated that ketamine acted on the hippocampus and thalamus, and WMT mainly affected the piriform cortex and lateral geniculate nucleus. In conclusion, long-term light stimulation could change the behaviors, composition of gut microbiota and brain structure in tree shrews. Targeting microbiota thus certainly holds promise as a treatment for neuropsychiatric disorders, including but not limited to stress-related diseases.
Project description:Gut microbiota, known as "unrecognized organs", is closely related to the occurrence and development of tumors. Cancer is thought to occur secondary to local chronic inflammation. And some bacteria, such as Helicobacter pylori, also have direct genotoxicity, changing intracellular signaling pathways and thus causing abnormal cell growth. Systemic intestinal dysbiosis may lead to cancer, and fecal microbiota transplantation (FMT) can be a new weapon in anti-cancer treatment.Washed microbiota transplantation (WMT), a new stage of FMT, is based on the automatic microfiltration machine (GenFMTer, Nanjing, China) and the following repeated centrifugation plus suspension with support from specific facilities.we conducted a prospective, one-arm, open-label study on the efficacy and safety of WMT in the treatment of oncotherapy-related complications. This study aimed to exploring the therapeutic potential of WMT in the treatment of oncotherapy-related intestinal complications and improving the quality of life of patients.
Project description:AimColonic transendoscopic enteral tubing (TET) has been used for delivering fecal microbiota transplantation by washed preparation since 2015, which was recently named as washed microbiota transplantation (WMT). However, there are few reports available regarding the feasibility and safety of these studies in low-age population. This study is aimed at evaluating the safety, feasibility, and value of colonic TET in 3-7 years old children.MethodsAll patients aged 3-7 years who underwent colonic TET in our center for WMT or medication were prospectively evaluated. The feasibility and safety of TET were evaluated. A questionnaire was completed by the children's parents to evaluate the children's response to the colonic TET as well as the parent's satisfaction.ResultsForty-seven children were included (mean age 5 years). TET was implemented into the colon of all the patients, and the success rate of the procedure was 100%. The median retention time of TET tube within the colon was 6 (IQR 5-7) days in 45 patients with tube falling out spontaneously, and the maximum retention time was up to 21 days. Multivariate analysis demonstrated that endoscopic clip number (P = 0.009) was an independent contributing factor for the retaining time of tube. With increase in the number of large clips, the retention time of TET tube was prolonged. No discomfort was reported during injection of the microbiota or medication suspension through the TET tube. During the follow-up, no severe adverse events were observed. All children's parents were satisfied with TET. Interestingly, the proportion of children's parents choosing TET as the delivery way of WMT increased from 29.79% before to 70.21% after TET (P < 0.001).ConclusionsThis study, for the first time, demonstrates that colonic TET is a novel, safe, and convenient colonic delivery way for WMT and medication in children aged 3-7 years.
Project description:Background: The potential of washed microbiota transplantation (WMT) in Crohn's disease (CD) has been reported. This study aimed to explore the suitable timing of WMT in patients with CD complicated with malnutrition. Methods: This is a randomized, open-label study. Patients with active CD complicated with malnutrition were included and 1:1 randomized to undergo WMT at day 1 (group WMT-DAY1) or day 8 (group WMT-DAY8). The observation duration was 15 days. Exclusive enteral nutrition (EEN) was administered in both groups. The primary outcome was the improvement in nutritional parameters at day 8 and day 15 in two groups. The secondary outcome was the rate of clinical remission at day 15 in two groups. Results: Totally 19 patients completed the trial. At day 8, the lymphocyte count, albumin and prealbumin increased significantly compared to those at day 1 in group WMT-DAY1 (p = 0.018, p = 0.028, p = 0.028, respectively), while no significant increase in any nutritional parameter was shown in group WMT-DAY8. At day 15, albumin increased significantly compared to that at day 1 in both groups (p < 0.05), while significant increase in prealbumin was only shown in group WMT-DAY1 (p = 0.004) compared to that at day 1. The rate of clinical remission at day 15 in group WMT-DAY1 and group WMT-DAY8 was 87.5% (7/8) and 72.7% (8/11), respectively (p = 0.603). Conclusion: EEN combined with immediate WMT intervention could rapidly improve the nutritional status and induce clinical remission in malnourished patients with CD. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02897661.