Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis: a randomised controlled trial

Abstract

ObjectiveMicrobiome and dietary manipulation therapies are being explored for treating ulcerative colitis (UC). We aimed to examine the efficacy of multidonor faecal microbiota transplantation (FMT) and anti-inflammatory diet in inducing remission followed by long-term maintenance with anti-inflammatory diet in patients with mild-moderate UC.DesignThis open-labelled randomised controlled trial (RCT) randomised patients with mild-moderate (Simple Clinical Colitis Activity Index (SCCAI) 3–9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)>1) on stable baseline medications in 1:1 ratio to FMT and anti-inflammatory diet (FMT-AID) versus optimised standard medical therapy (SMT). The FMT-AID arm received seven weekly colonoscopic infusions of freshly prepared FMT from multiple rural donors(weeks 0–6) with anti-inflammatory diet. Baseline medications were optimised in the SMT arm. Clinical responders (decline in SCCAI>3) at 8 weeks in both arms were followed until 48 weeks on baseline medications (with anti-inflammatory diet in the FMT-AID arm). Primary outcome measures were clinical response and deep remission (clinical—SCCAI <2; and endoscopic—UCEIS <1) at 8 weeks, and deep remission and steroid-free clinical remission at 48 weeks.ResultsOf the 113 patients screened, 73 were randomised, and 66 were included in (35—FMT-AID; 31—SMT) modified intention-to-treat analysis (age—35.7±11.1 years; male—60.1%; disease duration—48 (IQR 24–84) months; pancolitis—34.8%; SCCAI—6 (IQR 5–7); UCEIS—4 (IQR 3–5)). Baseline characteristics were comparable. FMT-AID was superior to SMT in inducing clinical response (23/35 (65.7%) vs 11/31 (35.5%), p=0.01, OR 3.5 (95% CI 1.3 to 9.6)), remission (21/35 (60%) vs 10/31 (32.3%), p=0.02, OR 3.2 (95% CI 1.1 to 8.7)) and deep remission (12/33 (36.4%) vs 2/23 (8.7%), p=0.03, OR 6.0 (95% CI 1.2 to 30.2)) at 8 weeks. Anti-inflammatory diet was superior to SMT in maintaining deep remission until 48 weeks (6/24 (25%) vs 0/27, p=0.007).ConclusionMultidonor FMT with anti-inflammatory diet effectively induced deep remission in mild-moderate UC which was sustained with anti-inflammatory diet over 1 year.Trial registration numberISRCTN15475780.

Holistic healthcare in inflammatory bowel disease: time for patient-centric approaches?

“…Unfortunately, the study was stopped early due to futility, but the UCED appeared to achieve higher clinical remission and mucosal healing, warranting trial dedicated solely to this diet. Most recently, Kedia et al also combined FMTs with dietary therapy for UC in the FMT-anti-inflammatory diet (AID) study 73. In this open-label RCT in 66 patients with mild-to-moderate UC on stable medications, seven multi-donor FMT infusions in addition to an AID was compared with standard medical therapy (increase or addition of 5-ASA (5-aminosalicylic acid) or corticosteroids).…”

The biodiversity dose-response curve translates theory and practice from ecological restoration into research and clinical priorities for fecal microbiota transplantation

“…Moreover, UCED commenced at the same time as FMT, which may not be early enough to induce meaningful taxonomic shifts (24) or physiological responses, such as recovery of the intestinal mucus layer or intestinal epithelial cells (25), to prepare recipient guts for engraftment. Finally, the study's low rate of patient responses is contradicted by a longer-term study in which FMT plus an anti-inflammatory diet that prohibited dairy was more effective than standard medical treatment in inducing both a clinical response and remission to UC (26). Much more needs to be done to better resolve effects of diet.…”

“…In summary, the biodiversity dose-response curve identifies factors likely to influence FMT success, beginning with diet as a form of passive restoration, followed by antibiotics or lavage for site prep, and finishing with high diversity donors to ensure sufficient engraftment above the threshold for system failure. These theoretical priorities are supported by early research into the beneficial effects of donor gut microbiome diversity (16) and recipient "site prep" [lavage, antibiotics (12,19)], with little and contradictory evidence for diet (22,26). Additional research is needed to better understand the extent to which these factors improve clinical success in FMT, which until now has been higher for CDI, in which the priority is pathogen removal, than it has for non-CDI diseases requiring the sustained establishment and restoration of beneficial biota (1).…”

Dietary Exposures and Interventions in Inflammatory Bowel Disease: Current Evidence and Emerging Concepts

“…Subsequent studies have explored the use of AID in conjunction with medical treatment [ 73 , 77 , 78 , 79 ]. A small case study of 11 IBD patients (8 CD, 3 UC) who followed an anti-inflammatory diet (IBD-AID) for at least 4 weeks demonstrated the potential of this type of diet to influence clinical outcomes by reducing symptoms, disease severity, and the pharmaceutical burden [ 73 ].…”

“…Further evidence of direct microbiome manipulation in following an anti-inflammatory diet was found when an anti-inflammatory diet was combined with multi-donor FMT [ 79 ]. Patients with mild to moderately active UC following this protocol went into deep, sustained remission for a year following.…”