Faecal microbiota transplantation for recurrent Clostridioides difficile infection: An updated systematic review and meta-analysis

Background Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (CDI), but inconsistent effect rates and uncertain evidence levels have warranted caution. To clarify, we aimed to establish the evidence of FMT for recurrent CDI, updated across different delivery methods, treatment regimens, and in comparison with standard antibiotics. Methods In this updated systematic review and meta-analysis, we searched PubMed, Scopus, Embase, Web of Science, Clinical Key, and Svemed+ for FMT literature published in English until November 11, 2019. We included observational and clinical trials with or without antibiotic comparators and excluded studies with below 8 weeks follow-up and fewer than 15 patients. The primary outcome was clinical outcome by week 8. We comprehensively extracted patient and procedural data. In a random-effects meta-analysis, we estimated the clinical effect for repeat or single FMT, different delivery methods, and versus antibiotics. We rated the evidence according to the Cochrane and GRADE methods. The PROSPERO preregistration number is CRD42020158112. Findings Of 1816 studies assessed, 45 studies were included. The overall clinical effect week 8 following repeat FMT (24 studies, 1855 patients) was 91% (95% CI: 89–94%, I2=53%) and 84% (80–88%, I2=86%) following single FMT (43 studies, 2937 patients). Delivery by lower gastrointestinal endoscopy was superior to all other delivery methods, and repeat FMT significantly increased the treatment effect week 8 (P<0·001). Compared with vancomycin, the number needed to treat (NNT) for repeat FMT was 1·5 (1·3–1·9, P<0·001) and 2.9 (1·5–37·1, P=0·03) for single FMT. Repeat FMT had high quality of evidence. Interpretation High-quality evidence supports FMT is effective for recurrent CDI, but its effect varies with the delivery method and the number of administrations. The superior NNT for FMT compared with antibiotics suggests that patients may benefit from advancing FMT to all instances of recurrent CDI

SARS-CoV-2 vaccines and donor recruitment for FMT

Non peer reviewe

The Monitoring Efficacy of Neurogenic Bowel Dysfunction Treatment on Response (MENTOR) in a Non-Hospital Setting

Background: Most patients with a spinal cord injury (SCI) suffer from neurogenic bowel dysfunction (NBD). In spite of well-established treatment algorithms, NBD is often insufficiently managed. The Monitoring Efficacy of Neurogenic bowel dysfunction Treatment On Response (MENTOR) has been validated in a hospital setting as a tool to support clinical decision making in individual patients. The objective of the present study was to describe clinical decisions recommended by the MENTOR (either &ldquo;monitor&rdquo;, &ldquo;discuss&rdquo; or &ldquo;act&rdquo;) and the use of the tool to monitor NBD in a non-hospital setting. Methods: A questionnaire describing background data, the MENTOR, ability to work and participation in various social activities was sent by mail to all members of The Danish Paraplegic Association. Results: Among 1316 members, 716 (54%) responded, 429 men (61%) and 278 women (39%), aged 18 to 92 (median 61) years. Based on MENTOR, the recommended clinical decision is to monitor treatment of NBD in 281 (44%), discuss change in treatment in 175 (27%) and act/change treatment in 181 (28%). A recommendation to discuss or change treatment was associated with increasing age of the respondent (p = 0.016) and with impaired ability to work or participate in social activities (p &lt; 0.0001). Conclusion: A surprisingly high proportion of persons with SCI have an unmet need for improved bowel care. The MENTOR holds promise as a tool for evaluation of treatment of NBD in a non-hospital setting

Determining Gut Microbial Dysbiosis - A review of applied indexes for assessment of intestinal microbiota imbalances

Assessing “dysbiosis” in intestinal microbial communities is increasingly considered a routine analysis in microbiota studies, and it has added relevant information to the prediction and characterization of diseases and other adverse conditions. However, dysbiosis is not a well-defined condition. A variety of different dysbiosis indexes have been suggested and applied, but their underlying methodologies, as well as the cohorts and conditions for which they have been developed, differ considerably. To date, no comprehensive overview and comparison of all the different methodologies and applications of such indexes is available. Here, we list all types of dysbiosis indexes identified in the literature, introduce their methodology, group them into categories, and discuss their potential descriptive and clinical applications as well as their limitations. Thus, our focus is not on the implications of dysbiosis for disease but on the methodological approaches available to determine and quantify this condition

Systematic review with meta-analysis:encapsulated faecal microbiota transplantation - evidence for clinical efficacy

Background: Faecal microbiota transplantation (FMT) is an effective treatment of recurrent Clostridioides difficile infection (rCDI) and is being applied experimentally in other diseases. Encapsulated administration may be equivalent in efficacy to delivery through other routes. Methods: A systematic review was undertaken of studies using encapsulated FMT up to 26 October 2020. Data on indication, clinical outcomes, safety, treatment protocol and capsule preparation were collected and reported. Pooled rates of clinical efficacy in rCDI were calculated using random-effects meta-analysis. The impact of single variables on clinical efficacy was evaluated using univariate meta-regression. Results: A total of 35 studies reporting the treatment of 960 patients with encapsulated FMT for eight different indications met the inclusion criteria. Most studies ( n  = 18, 51%) and patients ( n  = 755, 79%) were from studies on rCDI. Cure rates after single and multiple courses of treatments with encapsulated FMT in rCDI were 85% (95% CI: 82%-88%) and 93% (95% CI: 88%-96%) respectively. The treatment outcome was not significantly affected by dose, number of delivered capsules, anaerobic/aerobic processing, single/multi-donor treatment, lyophilisation, or any other single factor in the production or delivery of encapsulated FMT. Promising but non-comparable results from the treatment of ulcerative colitis and multidrug-resistant organisms were reported. Conclusions: Encapsulated FMT is an effective and safe treatment of rCDI, with cure rates comparable to FMT delivered through other routes. The treatment is effective despite variations in donor screening, preparation and treatment protocol. For other indications, the role of FMT capsules is still not sufficiently examined, although some studies show promising results. Plain Language Summary Transfer of faecal material through capsules in the treatment of various diseases. Evidence for clinical efficacy The bacteria and other microorganisms of the gut is different in patient with various diseases in comparison with healthy subjects. Therefore, ways to change the microorganisms of the gut in a beneficial direction has been the subject of various research projects within recent years. Faecal microbiota transplantation often referred as FMT is a method of transferring microorganisms from healthy donors to patients with various diseases and is seen as one way to change the microbial community of the gut in a beneficial direction. Faecal microbiota transplantation can be performed in different ways such as through endoscopy, enemas or capsules. The transfer through capsules is preferred by the patients and has advantages since it can be administered long-term and can be delivered to the patients in their home. In this paper, we evaluated all accessible research reporting treatment with encapsulated faecal microbiota transplantation in the treatment of various diseases. We report the following major findings: -Treatment with capsules is safe when guidelines for screening donors and testing faecal material is followed. -The treatment is highly effective in the treatment of recurrent C. difficile infection, a disease with high mortality often caused by repeated antibiotic treatments. The treatment was effective in 596 of 723 patients following one course of capsule treatment. -Faecal microbiota transplantation delivered through capsules is as effective as treatment delivered through other routes in the treatment of C. difficile infection. -The treatment is effective in the treatment of C. difficile infection across studies and countries, despite great differences in the ways the capsules were prepared and delivered. -Increasing the amount of faecal material used in the production did not affect the efficacy of the treatment. -There are promising results in the treatment of other diseases such as liver disease, inflammatory bowel disease and the treatment of multi-drug resistant bacteria

Gut microbiota differs between treatment outcomes early after fecal microbiota transplantation against recurrent <i>Clostridioides difficile</i> infection

In fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (CDI), clinical outcomes are usually determined after 8 weeks. We hypothesized that the intestinal microbiota changes earlier than this timepoint, and analyzed fecal samples obtained 1 week after treatment from 64 patients diagnosed with recurrent CDI and included in a randomized clinical trial, where the infection was treated with either vancomycin-preceded FMT (N = 24), vancomycin (N = 16) or fidaxomicin (N = 24). In comparison with non-responders, patients with sustained resolution after FMT had increased microbial alpha diversity, enrichment of Ruminococcaceae and Lachnospiraceae, depletion of Enterobacteriaceae, more pronounced donor microbiota engraftment, and resolution of gut microbiota dysbiosis. We found that a constructed index, based on markers for the identified genera Escherichia and Blautia, successfully predicted clinical outcomes at Week 8, which exemplifies a way to utilize clinically feasible methods to predict treatment failure. Microbiota changes were restricted to patients who received FMT rather than antibiotic monotherapy, indicating that FMT confers treatment response in a different way than antibiotics. We suggest that early identification of microbial community structures after FMT is of clinical value to predict response to the treatment

Patient-reported outcomes and health-related quality of life in people living with ileostomies: A population-based, cross-sectional study

BACKGROUND: The impact of a stoma on long-term health-related quality of life in people living with ileostomies is not clear. OBJECTIVE: This study aimed to describe important patient-reported outcomes and health-related quality of life in people with ileostomies. DESIGN: This is a population-based, cross-sectional study. Patients were invited to answer questionnaires estimating stoma-specific and generic health-related quality of life (EQ-5D-5L and the Major Depression Inventory). Danish norms were retrieved from reference literature. SETTINGS: This study was conducted at the major stoma clinic at Aarhus University Hospital, Denmark. PATIENTS: We invited all patients with ileostomies who were in contact with the clinic between 2012 and 2017. MAIN OUTCOME MEASURES: The primary outcomes measured were patient-reported outcomes specific to people with ileostomies. RESULTS: Of 621 identified patients (50% women), 412 (67%) responded to the survey. Among the responders, 178 (43%) reported that they still had an ileostomy at the time of the survey and were included in the analysis. Fatigue was frequent; 68% (95% CI 60%–75%) reported being tired and 26% (95% CI 20%–33%) answered that they were “always tired,” whereas 43% (95% CI 36%–51%) lacked energy, 62% (95% CI 54%–69%) reported poor sleep, and 59% (95% CI 52%–66%) needed to rest during the day. Fifty-six percent (95% CI 48%–63%) needed to know the immediate location of the nearest toilet, and 58% (95% CI 51%–66%) felt sexually unattractive because of their ileostomy. Health-related quality of life measured with generic questions indicated 0.124 points lower health-related quality of life than the Danish norm (p < 0.001), and 18% (95% CI 13%–25%) scored above the threshold for depression, which is 2.6 times higher than the background population (7%, 95% CI 6%–9%; p < 0.001). LIMITATIONS: This study was limited by potential selection bias, and all participants did not answer all items. CONCLUSIONS: Fatigue and low health-related quality of life is common in people living with ileostomies. Addressing fatigue and stoma-specific challenges in patients with an ileostomy is warranted. See Video Abstract at http://links.lww.com/DCR/B803. DESENLACES INFORMADOS POR PACIENTES Y CALIDAD DE VIDA RELACIONADA CON LA SALUD EN PERSONAS QUE VIVEN CON ILEOSTOMÍAS: UN ESTUDIO TRANSVERSAL POBLACIONAL: ANTECEDENTES: El impacto de un estoma en la calidad de vida relacionada con la salud a largo plazo en personas que viven con ileostomías no está claro. OBJETIVO: Describir desenlaces importantes informados por pacientes y la calidad de vida relacionada con la salud en personas con ileostomías. DISEÑO: Estudio transversal poblacional. Se invitó a los pacientes a responder cuestionarios que estiman la calidad de vida relacionada con la salud general y específica del estoma (EQ-5D-5L y el Inventario de depresión mayor). Las normas danesas se recopilaron de la literatura de referencia. AJUSTES: El estudio se llevó a cabo en la clínica principal de estomas del Hospital Universitario de Aarhus, Dinamarca. PACIENTES: Invitamos a todos los pacientes con ileostomías que estuvieron en contacto con la clínica entre 2012 y 2017. PRINCIPALES MEDIDAS DE RESULTADO: Resultados informados por el paciente específicos para personas con ileostomías. RESULTADOS: De 621 pacientes identificados (50% mujeres), 412 (66%) respondieron la encuesta. Entre los que respondieron, 178 (43%) informaron que todavía tenían una ileostomía en el momento de la encuesta y fueron incluidos en el análisis. La fatiga era frecuente; el 68% (intervalo de confianza del 95%: 60–75%) informó estar cansado y el 26% (20–33%) respondió “siempre cansado”, mientras que el 43% (36–51%) carecía de energía, el 62% (54–69%)) refirieron dormir mal y el 59% (52–6%) necesitaba descansar durante el día. El cincuenta y seis por ciento (48–63%) necesitaba saber la ubicación inmediata del baño más cercano y el 58% (51–66%) se sentía sexualmente poco atractivo debido a su ileostomía. La calidad de vida relacionada con la salud medida con preguntas genéricas indicó una calidad de vida relacionada con la salud 0,124 puntos más baja que la norma danesa (p < 0,001), y el 18% (13–25%) puntuó con depresión, que es 2.6 veces más alta que la población de base (7%, 6–9%, p < 0,001). LIMITACIONES: Posible sesgo de selección, y no todos los participantes respondieron a todos los ítems. CONCLUSIONES: La fatiga y la baja calidad de vida relacionada con la salud es común en las personas que viven con ileostomías. Se justifica abordar la fatiga y los desafíos específicos del estoma en pacientes con una ileostomía. Consulte Video Resumen en http://links.lww.com/DCR/B803. (Traducción—Juan Carlos Reyes

Cross-generational bacterial strain transfer to an infant after fecal microbiota transplantation to a pregnant patient:a case report

BACKGROUND: Fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (CDI). Long-term engraftment of donor-specific microbial consortia may occur in the recipient, but potential further transfer to other sites, including the vertical transmission of donor-specific strains to future generations, has not been investigated. Here, we report, for the first time, the cross-generational transmission of specific bacterial strains from an FMT donor to a pregnant patient with CDI and further to her child, born at term, 26 weeks after the FMT treatment. METHODS: A pregnant woman (gestation week 12 + 5) with CDI was treated with FMT via colonoscopy. She gave vaginal birth at term to a healthy baby. Fecal samples were collected from the feces donor, the mother (before FMT, and 1, 8, 15, 22, 26, and 50 weeks after FMT), and the infant (meconium at birth and 3 and 6 months after birth). Fecal samples were profiled by deep metagenomic sequencing for strain-level analysis. The microbial transfer was monitored using single nucleotide variants in metagenomes and further compared to a collection of metagenomic samples from 651 healthy infants and 58 healthy adults. RESULTS: The single FMT procedure led to an uneventful and sustained clinical resolution in the patient, who experienced no further CDI-related symptoms up to 50 weeks after treatment. The gut microbiota of the patient with CDI differed considerably from the healthy donor and was characterized as low in alpha diversity and enriched for several potential pathogens. The FMT successfully normalized the patient’s gut microbiota, likely by donor microbiota transfer and engraftment. Importantly, our analysis revealed that some specific strains were transferred from the donor to the patient and then further to the infant, thus demonstrating cross-generational microbial transfer. CONCLUSIONS: The evidence for cross-generational strain transfer following FMT provides novel insights into the dynamics and engraftment of bacterial strains from healthy donors. The data suggests FMT treatment of pregnant women as a potential strategy to introduce beneficial strains or even bacterial consortia to infants, i.e., neonatal seeding. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-022-01394-w

Additional file 2 of Health economic evaluations comparing faecal microbiota transplantation with antibiotics for treatment of recurrent Clostridioides difficile infection: a systematic review

Additional file 2. is a .pdf file which contains a table with the general study characteristics of the included health economic evaluations