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.

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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).

Introduction:Noninvasive ventilation (NIV) has emerged as an important tool for the management of acute hypoxic respiratory failure (AHRF) and has been the area of research in the last two decades. In this study, we have tried to find out the outcome of NIV in patients with AHRF.Materials and Methods:In this prospective, observational study, all the patients of AHRF requiring NIV were enrolled, and heart rate (HR), respiratory rate (RR), arterial blood gas parameters, and NIV settings at baseline, 1 h, and 4 h were collected. The patients were classified as AHRF with acute respiratory distress syndrome (ARDS) and AHRF without ARDS, which were further classified according to the outcome.Results:Among 200 patients admitted in medical intensive care unit (ICU), 50 patients (27 with ARDS and 23 without ARDS) were put on NIV. There was a significant improvement in HR, RR, PaO 2, and inspiratory positive airway pressure after 1 and 4 h and significant improvement at 4 h in expiratory positive airway pressure in all the groups on NIV. Length of ICU stay and hospital stay was less in the nonintubated group. Mortality rate was 25.92% in the intubated group, while it was nil in the nonintubated group.Conclusion:NIV found to reduce the endotracheal intubation and mortality, by improving the outcome of the patient.

Background Crohn’s disease (CD) and intestinal tuberculosis (ITB) are chronic granulomatous inflammatory disorders characterized by a compromised mucosal immunity. Even with diverging etiologies, CD and ITB presents an uncanny resemblance in clinical manifestation resulting in diagnostic dilemma. The gut microbiota regulates myriad of gut mucosal immunological processes. Present study aims to decipher gut microbial dysbiosis in the two disorders and utilize the CD and ITB-specific gut dysbiosis to construct a machine learning (ML)-based predictive model, which can aid in their differential diagnosis. Methods Fecal samples from healthy controls (n=12) and from patients with CD (n=23) and ITB (n=25) were subjected to 16S (V3-V4) amplicon sequencing. Processing of raw reads, construction of ASV feature tables, diversity, core microbiome analysis and ML classifier construction was done using QIIME2-2021.4. Differential abundance analysis (DAA) between the groups was carried out using Deseq2, after adjusting for the subject-specific confounders. Results The α and β diversity indices in CD and ITB groups were significantly reduced than HC group (p = 0.011 and 0.012 resp.), with no significant differences between the two diseases (Fig.1A, 1B). On comparison with HC, CD and ITB groups showed reduction in members of Firmicutes and Bacteroidetes, with enhancement of Actinobacteria and Proteobacteria (Fig.1C and 1D). DAA (FDR q &lt;0.1, FC &gt;2.5) between CD and ITB groups revealed expansion of Succinivibrio dextrinisolvens, Odoribacter splanchnicus, Megasphaera massiliensis, Bacteroides uniformis and B.xylanisolvens in CD group, while Clostridium sp., Haemophilus parainfluenzae and Bifidobacterium sp. were elevated in ITB (Fig.2A). Random Forest-based ML model constructed on the basis of raw microbiome reads and using 80% of the samples to train the model, showed predictive accuracy of 0.78 (AUC=93%). (Fig.2B) Conclusion Our study shows that CD and ITB witnesses significant changes in gut microbial structure. With no significant differences in microbial diversity between two diseases, the signature of gut dysbiosis is distinct between CD and ITB. Exploitation of these differences to construct ML models can potentiate differential diagnosis of CD and ITB.

Background and objectives Crohn’s disease (CD) and Intestinal tuberculosis (ITB) are chronic inflammatory ulcero-constrictive intestinal diseases with similar phenotype. Although both are disease models of chronic inflammation and their clinical presentations, imaging, histological and endoscopic findings are very similar, yet their etiologies are diverse. Hence, we aimed to look at differences in the prevalence of pathobionts like adherent-invasive Escherichia coli (AIEC), Listeria monocytogenes, Campylobacter jejuni and Yersinia enterocolitica in CD and ITB as well as their associations with host-associated genetic polymorphisms in genes majorly involved in pathways of microbial handling and immune responses. Methods The study cohort included 142 subjects (69 patients with CD, 32 with ITB and 41 controls). RT- PCR amplification was used to detect the presence of AIEC, L. monocytogenes, C. jejuni, and Y. enterocolitica DNA in colonic mucosal biopsies. Additionally, we tested three SNPs in IRGM (rs13361189, rs10065172, and rs4958847), one SNP in ATG16L1 (rs2241880) and one SNP in TNFRSF1A (rs4149570) by real-time PCR with SYBR green from peripheral blood samples in this cohort. Results In patients with CD, AIEC was most frequently present (16/ 69, 23.19%) followed by L. monocytogenes (14/69, 20.29%), C. jejuni (9/69, 13.04%), and Y. enterocolitica (7/69, 10.14%). Among them, L. monocytogenes and Y. enterocolitica were significantly associated with CD (p = 0.02). In addition, we identified all the three SNPs in IRGM (rs13361189, rs10065172, and rs4958847), one SNP in ATG16L1 (rs2241880) and TNFRSF1A (rs4149570) with a significant difference in frequency in patients with CD compared with ITB and controls (p<0.05). Conclusion Higher prevalence of host gene polymorphisms, as well as the presence of pathobionts, was seen in the colonic mucosa of patients with CD as compared to ITB, although both are disease models of chronic inflammation.

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Diet is an important determinant of health and consequently is often implicated in the development of disease, particularly gastrointestinal (GI) diseases, given the high prevalence of meal-related symptoms. The mechanisms underlying diet-driven pathophysiology are not well understood, but recent studies suggest that gut microbiota may mediate the effect of diet on GI physiology. In this review, we focus primarily on two distinct GI diseases where the role of diet has been best studied: irritable bowel syndrome and inflammatory bowel disease. We discuss how the concurrent and sequential utilization of dietary nutrients by the host and gut microbiota determines the eventual bioactive metabolite profiles in the gut and the biological effect of these metabolites on GI physiology. We highlight several concepts that can be gleaned from these findings, such as how distinct effects of an individual metabolite can influence diverse GI diseases, the effect of similar dietary interventions on multiple disease states, and the need for extensive phenotyping and data collection to help make personalized diet recommendations. Expected final online publication date for the Annual Review of Nutrition, Volume 43 is August 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.