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.

Salmonella Typhimurium is an intracellular pathogen that causes gastroenteritis in humans. Aided by a battery of effector proteins, S. Typhimurium resides intracellularly in a specialized vesicle, called the Salmonella-containing vacuole (SCV) that utilizes the host endocytic vesicular transport pathway (VTP). Here, we probed the possible role of SUMOylation, a post-translation modification pathway, in SCV biology. Proteome analysis by complex massspectrometry (MS/MS) revealed a dramatically altered SUMOproteome (SUMOylome) in S. Typhimurium-infected cells. RAB7, a component of VTP, was key among several crucial proteins identified in our study. Detailed MS/MS assays, in vitro SUMOylation assays and structural docking analysis revealed SUMOylation of RAB7 (RAB7A) specifically at lysine 175. A SUMOylation-deficient RAB7 mutant (RAB7 K175R) displayed longer half-life, was beneficial to SCV dynamics and functionally deficient. Collectively, the data revealed that RAB7 SUMOylation blockade by S. Typhimurium ensures availability of long-lived but functionally compromised RAB7, which was beneficial to the pathogen. Overall, this SUMOylation-dependent switch of RAB7 controlled by S. Typhimurium is an unexpected mode of VTP pathway regulation, and unveils a mechanism of broad interest well beyond Salmonella-host crosstalk. This article has an associated First Person interview with the first author of the paper.

Post-translational modification pathways such as SUMOylation are integral to all cellular processes and tissue homeostasis. We investigated the possible involvement of SUMOylation in the epithelial signalling in Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD). Initially in a murine model of IBD, induced by dextran–sulfate–sodium (DSS mice), we observed inflammation accompanied by a lowering of global SUMOylation of colonic epithelium. The observed SUMOylation alteration was due to a decrease in the sole SUMO E2 enzyme (Ubc9). Mass-spectrometric analysis revealed the existence of a distinct SUMOylome (SUMO-conjugated proteome) in DSS mice with alteration of key cellular regulators, including master kinase Akt1. Knocking-down of Ubc9 in epithelial cells resulted in dramatic activation of inflammatory gene expression, a phenomenon that acted via reduction in Akt1 and its SUMOylated form. Importantly, a strong decrease in Ubc9 and Akt1 was also seen in endoscopic biopsy samples (N = 66) of human CD and UC patients. Furthermore, patients with maximum disease indices were always accompanied by severely lowered Ubc9 or SUMOylated-Akt1. Mucosal tissues with severely compromised Ubc9 function displayed higher levels of pro-inflammatory cytokines and compromised wound-healing markers. Thus, our results reveal an important and previously undescribed role for the SUMOylation pathway involving Ubc9 and Akt1 in modulation of epithelial inflammatory signalling in IBD.

Aim: To characterize vaso-occlusive crises (VOCs) and describe healthcare costs among commerciallyinsured, Medicaid-insured, and Medicare-insured patients with sickle cell disease (SCD).

Summary Background Intravenous corticosteroids are the mainstay of therapy for acute severe ulcerative colitis (ASUC), but 30%‐40% of patients fail to respond. Aim To investigate the effectiveness of exclusive enteral nutrition (EEN) as adjunctive therapy to intravenous corticosteroids in patients with ASUC. Methods This was an open‐label randomised controlled trial, in which patients who were admitted with ASUC between August 2018 and May 2020 were randomised 1:1 to EEN or standard of care (SOC). Patients on EEN received a semi‐elemental formula for 7 days along with SOC. The primary outcome was corticosteroid failure, defined by the need for salvage medical therapy or colectomy. Faecal microbial analysis was performed on day 1 and day 7 by 16s ribosomal RNA sequencing in some patients. Results Of 62 patients (mean age 35.3 ± 12.1 years, 40% male), 32 were randomised to EEN and 30 to SOC. Corticosteroid failure was lower on EEN compared to SOC (intention‐to‐treat analysis 25% vs 43%, P = 0.051; per protocol analysis 19% vs 43%, P = 0.04), without any difference in colectomy rate (9% vs 13%; P = 0.41). Patients on EEN had a shorter hospital stay [median (range) 10 (8‐17) vs 13 (8‐24) days; P = 0.04], higher day 7 albumin level (34 ± 4 vs 29 ± 3 g/L, P < 0.01), greater reduction in serum C‐reactive protein and faecal calprotectin levels (both P = 0.04) and a lower composite outcome of colectomy/hospitalisation at 6 months (16% vs 39%; P = 0.045) compared to SOC. Patients on EEN showed increased abundance of Erysipelotrichaceae on day 7, with reduced Bifidobacterium and Veillonellaceae compared to SOC. Conclusions EEN for 7 days may augment corticosteroid responsiveness in patients with ASUC. (REF/2018/05/019844; CTRI/2020/06/025989).