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

Abstract

The response of patients with inflammatory bowel disease (IBD) to fecal microbial transplantation (FMT) has been inconsistent possibly due to variable engraftment of donor microbiota. This failure to engraft has resulted in the use of several different strategies to attempt optimization of the recipient microbiota following FMT. The purpose of our study was to evaluate the effects of two distinct microbial strategies—antibiotic pre-treatment and repeated FMT dosing—on IBD outcomes. A systematic literature review was designed and implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A medical librarian conducted comprehensive searches in MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library on 25 November 2019 and updated on 29 January 2021. Primary outcomes of interest included comparing relapse and remission rates in patients with IBD for a single FMT dose, repeated FMT dosages, and antibiotic pre-treatment groups. Twenty-eight articles (six randomized trials, 20 cohort trials, two case series) containing 976 patients were identified. Meta-analysis revealed that both repeated FMT and antibiotic pre-treatment strategies demonstrated improvements in pooled response and remission rates. These clinical improvements were associated with increases in fecal microbiota richness and α-diversity, as well as the enrichment of several short-chain fatty acid (SCFA)-producing anaerobes including Bifidobacterium, Roseburia, Lachnospiraceae, Prevotella, Ruminococcus, and Clostridium related species.

Strain-resolved analysis in a randomized trial of antibiotic pretreatment and maintenance dose delivery mode with fecal microbiota transplant for ulcerative colitis

“…According to meta-analyses, half of the UC patients receiving FMT display a response to treatment, and one third achieve clinical remission of their symptoms. (3)(4)(5)(6) after FMT. Across four randomized, placebo-controlled studies (RCTs) (7-10), 28% of FMT and only 9% of placebo recipients achieved remission (4).…”

“…Most include an initial dose via colonoscopy, and many follow up with a maintenance dose regimen ranging from just once three weeks after the initial dose (7) to five times a week for two months (9). Maintenance doses may improve efficacy (6), but their cost and tolerability are substantial challenges. The recent development of FMT capsule formulations may make maintenance dosing logistically easier and more acceptable to patients (15)(16)(17).…”

Alteration of Gut Microbiota Relates to Metabolic Disorders in Primary Aldosteronism Patients

“…We found that the relative abundances of Prevotella, Blautia, Coprococcus, Anaerostipes, and Ruminococcus were lower in the gut microbiota of PA patients than in healthy controls and primary hypertension patients. All these bacteria could produce SCFAs (18)(19)(20)(21). SCFAs, the energy sources of enterocytes, could maintain the intestinal epithelial barrier and decrease the permeability of the gut, circulating lipopolysaccharides, and systemic inflammation.…”

Mucosa-Associated Microbial Profile Is Altered in Small Intestinal Bacterial Overgrowth

“…A prior study also found that the relative abundance of Dialister in children with autism spectrum disorder was decreased ( Andreo-Martínez et al, 2020 ). Additionally, Prevotella, which is a short-chain fatty acid producing anaerobes ( Mocanu et al, 2021 ), was found to be implicated in the development of severe gastrointestinal symptoms ( Tan et al, 2021 ). These bacteria with the same changing trend in different intestine sites may guide future research on understanding the pathophysiology behind SIBO or provide insight into potential therapeutic targets.…”