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

Abstract

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: 89À94%, I 2 =53%) and 84% (80À88%, I 2 =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¢3À1¢9, P<0¢001) and 2.9 (1¢5À37¢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. Funding: Innovation Fund Denmark (j.no. 8056-00006B).

Repeated Fecal Microbial Transplantations and Antibiotic Pre-Treatment Are Linked to Improved Clinical Response and Remission in Inflammatory Bowel Disease: A Systematic Review and Pooled Proportion Meta-Analysis

“…Repeated FMT strategies have been employed with variable success in a number of different clinical entities thought to be associated with imbalances in host-microbial ecology [ 67 , 68 , 69 ]. Perhaps the most compelling evidence for repeated FMT is observed in the Clostridiodes difficile infection (CDI) literature.…”

“…Perhaps the most compelling evidence for repeated FMT is observed in the Clostridiodes difficile infection (CDI) literature. In a recent systematic review and meta-analysis by Baunwall et al, repeated FMT was found to be superior to single-dose FMT in management of recurrent CDI (91% vs. 84%) [ 69 ]. Similarly, El-Salhy et al demonstrated an increased clinical efficacy for repeated FMT dosing in patients with irritable bowel syndrome, albeit in a small case series of 10 patients [ 68 ].…”

The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection

“…FMT is now well-established as a safe and highly effective treatment option for patients with recurrent or refractory CDI. 44 However, whilst it is recognised that FMT acts in such patients to restore the stool microbiome to a composition comparable with the pre-morbid state, 45 – 52 the specific mechanisms underlying its efficacy have until recently remained poorly defined. The demonstration that either a defined consortium of commensal bacteria or spores derived from healthy donor stool deliver efficacy comparable with that of conventional FMT in treating rCDI support the concept that the bacterial component of FMT is a key contributor to efficacy.…”

The Role of the Microbiome in Liver Cancer

“…FMT is highly effective for treatment of Clostridium difficile infections [ 121 , 122 ], while its efficacy in the treatment of chronic liver disease is still under current investigation. In mice, FMT alleviated high fat diet-induced steatosis [ 109 ] and prevented alcohol-induced steatosis and liver inflammation in mice [ 108 ].…”