Comparison between washed microbiota transplantation and infliximab: Medical cost during long-term management in patients with inflammatory bowel disease.

BACKGROUND: Both infliximab (IFX) and fecal microbiota transplantation (FMT) have shown the efficacy for inflammatory bowel disease (IBD). However, there has no head-to-head study on the cost-value of the such treatments on IBD. This study aimed to compare the medical costs using IFX and the new method of FMT (washed microbiota transplantation [WMT]) in the long-term management for IBD under the current health economic condition in China. METHODS: Patients with IBD who underwent initial WMT via upper gastrointestinal endoscopy, mid-gut tube, or colonic transendoscopic enteral tubing at a university hospital between April 2013 and August 2021 and achieved the long-term sustainment with WMT or WMT combined with mesalazine until August 2022 were recruited in the real-world. The costs and hospitalizations were analyzed among two therapies mentioned above and IFX standard therapy. The charge of WMT was stable in the long term at our center, and the charge of IFX came from virtual statistics publicized by China Healthcare Security. RESULTS: Sixty eligible patients with IBD were included in the study. The long-term costs of patients using WMT monotherapy annually or per hospitalization were lower than those on WMT combined with mesalazine, respectively ( p < 0.001, respectively). The cumulative costs of IFX at the time of 0.52 and 0.85 years exceeded that of the above WMT, respectively ( p < 0.001, respectively). Besides, patients on WMT monotherapy paid 51.1 k CNY annually in the nonsustain phase but cut down the costs by 7.2 k CNY and duration of hospitalization by 5.1 days per hospitalization when reaching the goal of sustainment. CONCLUSION: This study demonstrated that WMT could dramatically reduce the cost and duration of hospitalizations in the long-term sustainment in the current Chinese IBD cohort. Compared with IFX, WMT could be a good way for the patients with IBD achieving long-term sustainment and saving medical costs.

Global Trends in Research of Pain-Gut-Microbiota Relationship and How Nutrition Can Modulate This Link.

INTRODUCTION: The link between gut microbiota and chronic painful conditions has recently gained attention. Nutrition, as a common intervention in daily life and medical practice, is closely related to microbiota and pain. However, no published bibliometric reports have analyzed the scientific literature concerning the link. METHODS AND RESULTS: We used bibliometrics to identify the characteristics of the global scientific output over the past 20 years. We also aimed to capture and describe how nutrition can modulate the abovementioned link. Relevant papers were searched in the Web of Science database. All necessary publication and citation data were acquired and exported to Bibliometrix for further analyses. The keywords mentioned were illustrated using visualization maps. In total, 1551 papers shed light on the relationship from 2003 to 2022. However, only 122 papers discussed how nutritional interventions can modulate this link. The citations and attention were concentrated on the gut microbiota, pain, and probiotics in terms of the pain-gut relationship. Nutritional status has gained attention in motor themes of a thematic map. CONCLUSIONS: This bibliometric analysis was applied to identify the scientific literature linking gut microbiota, chronic painful conditions, and nutrition, revealing the popular research topics and authors, scientific institutions, countries, and journals in this field. This study enriches the evidence moving boundaries of microbiota medicine as a clinical medicine.

Washed microbiota transplantation targeting both gastrointestinal and extraintestinal symptoms in patients with irritable bowel syndrome.

OBJECTIVE: Fecal microbiota transplantation (FMT) has been reported with the treatment potential for irritable bowel syndrome (IBS). However, the knowledge of its effect on extraintestinal symptoms of IBS is limited. This study aimed to evaluate the efficacy of the improved methodology of FMT, washed microbiota transplantation (WMT), on sleep disturbances, and psychological and gastrointestinal symptoms among patients with IBS. METHODS: This was a prospective observational study involving patients with IBS who underwent WMT. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The Gastrointestinal Symptom Rating Scale (GSRS) and IBS Severity Scoring System (IBS-SSS) were used to evaluate gastrointestinal symptoms and IBS severity, respectively. The Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) were used to evaluate depression and anxiety, respectively. All the symptoms were evaluated at baseline and one month after WMT. A multiple logistic regression model was used to determine the predictive factors of sleep improvement one month after WMT. RESULTS: Seventy-three patients with IBS were included in the study. Sleep quality (Z = -4.211, P < 0.001), anxiety (Z = -4.775, P < 0.001), depression (Z = -4.610, P < 0.001), gastrointestinal symptoms (Z = -5.364, P < 0.001), and IBS severity (Z = -6.468, P < 0.001) significantly improved one month after WMT in all patients. The scores of the five components of PSQI including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, and sleep disturbances decreased in 52 patients with poor sleep quality (all P < 0.05). Baseline sleep duration scores were identified as an independent predictive factor of sleep improvement one month after WMT in patients with poor sleep quality (OR 2.180 [95% CI = 1.017-4.673]; P = 0.045). Patients that experienced sleep improvement demonstrated greater alleviation in depression (Z = -1.990, P = 0.047) and IBS severity (Z = -2.486, P = 0.013) compared with patients without sleep improvement. CONCLUSION: This study suggested that WMT might be a promising therapy for patients with IBS, especially those with comorbid sleep and psychological disorders.

Root causes of long-term complications of gestational diabetes mellitus: Metabolic disturbances of the host and gut microbiota.

BACKGROUND: Gestational diabetes mellitus (GDM) poses a risk of short-term and long-term complications for both mother and fetus. However, there is a lack of consensus on the screening approach and pathophysiology of GDM. METHODS: Women were screened at 24 to 28 weeks gestation using the one-step screening approach and serum samples were collected for metabolomics based on 1H NMR spectroscopy. A random forest classifier was developed to evaluate its diagnostic efficacy on GDM. RESULTS: Serum metabolic fingerprints of women with GDM differed significantly from those with normoglycemic. Of the 59 differential metabolites identified, 25 were well-known risk metabolites associated with type 2 diabetes or cardiovascular diseases, such as branched-chain amino acids and trimethylamine N-oxide. In addition, most of the differential metabolites were microbial metabolites or could be metabolized by gut microbes. The correlation between serum metabolites and maternal 75 g OGTT glucose values supported the establishment of a random forest classifier, which selected 21 metabolites to predict GDM with an AUC of 0.988. CONCLUSIONS: Metabolic disturbances in the host and gut microbiota may be a persistent contributor to the risk of developing type 2 diabetes or cardiovascular diseases in GDM. Targeting microbiota is one intervention that needs to be considered.

Colonic Transendoscopic Enteral Tubing Is a New Pathway to Microbial Therapy, Colonic Drainage, and Host-Microbiota Interaction Research.

The limitation of traditional delivery methods for fecal microbiota transplantation (FMT) gave birth to colonic transendoscopic enteral tubing (TET) to address the requirement of frequent FMTs. Colonic TET as a novel endoscopic intervention has received increasing attention in practice since 2015 in China. Emerging studies from multiple centers indicate that colonic TET is a promising, safe, and practical delivery method for microbial therapy and administering medication with high patient satisfaction. Intriguingly, colonic TET has been used to rescue endoscopy-related perforations by draining colonic air and fluid through the TET tube. Recent research based on collecting ileocecal samples through a TET tube has contributed to demonstrating community dynamics in the intestine, and it is expected to be a novel delivery of proof-of-concept in host-microbiota interactions and pharmacological research. The present article aims to review the concept and techniques of TET and to explore microbial therapy, colonic drainage, and microbial research based on colonic TET.

Washed microbiota transplantation stopped the deterioration of amyotrophic lateral sclerosis: The first case report and narrative review.

Amyotrophic lateral sclerosis (ALS) is known as a progressive paralysis disorder characterized by degeneration of upper and lower motor neurons, and has an average survival time of three to five years. Growing evidence has suggested a bidirectional link between gut microbiota and neurodegeneration. Here we aimed to report one female case with ALS, who benefited from washed microbiota transplantation (WMT), an improved fecal microbiota transplantation (FMT), through a transendoscopic enteral tube during a 12-month follow-up. Notedly, the accidental scalp trauma the patient suffered later was treated with prescribed antibiotics that caused ALS deterioration. The subsequent rescue WMTs successfully stopped the progression of the disease with a quick improvement. The plateaus and reversals occurred during the whole course of WMT. The stool and blood samples from the first WMT to the last were collected for dynamic microbial and metabolomic analysis. We observed the microbial and metabolomic changing trend consistent with the disease status. This case report for the first time shows the direct clinical evidence on using WMT for treating ALS, indicating that WMT may be the novel treatment strategy for controlling this so-called incurable disease.

Washed preparation of faecal microbiota changes the transplantation related safety, quantitative method and delivery.

The safety, quantitative method and delivery of faecal microbiota transplantation (FMT) vary a lot from different countries in practice. Recently, the improved methodology of FMT based on the automatic filtration, washing process and the related delivery was named as washed microbiota transplantation (WMT). First, this study aimed to describe the methodology development of FMT from manual to washing preparation from 2012 to 2021 in China Microbiota Transplantation System (CMTS), a centralized stool bank for providing a national non-profit service. The secondary aim is to describe donor screenings, the correlation between faecal weight and treatment doses, incidence of adverse events and delivery decision. The retrospective analysis on the prospectively recorded data was performed. Results showed that the success rate of donor screening was 3.1% (32/1036). The incidence rate of fever decreased significantly from 19.4% (6/31) in manual FMT to 2.7% (24/902) in WMT in patients with ulcerative colitis (UC), which made UC a considerable disease model to reflect the quality control of faecal microbiota preparation. We defined one treatment unit as 10 cm3 microbiota precipitation (1.0 × 1013 bacteria) based on enriched microbiota instead of rough faecal weight. For delivering microbiota, colonic transendoscopic enteral tube is a promising way especially for multiple WMTs or frequent colonic administration of drugs combined with WMT. This study should help improve the better practice of FMT for helping more patients in the future.

The potential of Akkermansia muciniphila in inflammatory bowel disease.

Akkermansia muciniphila is a next-generation probiotic with significant application prospects. The role of A. muciniphila in metabolic diseases and tumor immunotherapy has been widely recognized. Recent clinical trials further confirmed its safety and therapeutic value in human metabolic diseases. A. muciniphila also shows potential in the treatment of intestinal inflammatory diseases, especially for inflammatory bowel disease (IBD). The improvement in the efficacy of washed microbiota transplantation (WMT) in treating IBD is closely related to the increase in the abundance of A. muciniphila in patients' gut. However, there is still controversy regarding the pro-inflammatory or anti-inflammatory effect of A. muciniphila on IBD. Currently, several studies targeting the correlation between A. muciniphila and IBD have demonstrated opposite conclusions. Similarly, the interventional studies exploring causality between them also come to conflicting results. This article therefore aims to review the relationship between A. muciniphila and IBD, the effect of intervention of A. muciniphila on IBD, and the possible reasons for the contradictory role of A. muciniphila in the treatment of IBD. KEY POINTS: The effect of A. muciniphila on inflammatory bowel disease is controversy. A. muciniphila shows anti-inflammatory potential in IBD. The colitogenicity of A. muciniphila is context dependent.

Alterations of Akkermansia muciniphila in the inflammatory bowel disease patients with washed microbiota transplantation.

Akkermansia muciniphila is a promising probiotic in the gut. This study aimed to determine the presence and abundance of Akkermansia in patients with inflammatory bowel disease (IBD) who underwent washed microbiota transplantation (WMT) in order to elucidate the relationship between its level and patients' clinical data and outcomes. A cohort of Chinese volunteers including 80 healthy controls (HC), 43 patients with ulcerative colitis (UC), and 57 patients with Crohn's disease (CD) were recruited. Akkermansia presented a low colonization rate of 48.8% and a relative abundance of 0.07% in a healthy Chinese population. Compared with HC, significantly lower colonization and abundance of Akkermansia were found in UC and CD (p < 0.01, p < 0.001, respectively). The combination of Akkermansia and twelve other gut commensal bacteria significantly enriched in healthy individuals could be conductive to discriminate IBD from HC. Co-occurrence of Akkermansia-Faecalibacterium prausnitzii was at a lower level in IBD. Patients' age could affect the abundance of Akkermansia in CD. After WMT, 53.7% of patients achieved clinical response, and the colonization rate of Akkermansia increased significantly than that pre-WMT (p < 0.01). There was a positive correlation between patients and donors in the abundance of Akkermansia after WMT. Different from Europeans, the healthy Chinese population is characterized by a low presence of intestinal Akkermansia. Compared with healthy people, its colonization and abundance in IBD decreased more significantly. The efficacy of WMT for IBD was closely correlated with Akkermansia. ClinicalTrials.gov , pooled registered trials, NCT01790061, NCT01793831. Registered February 13, 2013, 18 February 2013. KEY POINTS: • Akkermansia showed a lower colonization and abundance in Chinese than Europeans. • Akkermansia could distinguish IBD from healthy people with a reduced abundance. • IBD patients achieved response from WMT through an increased Akkermansia level. Graphical abstract.

Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening.

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.