TBA (24S149)

Natural Compounds in Ulcerative Colitis and Irritable Bowel Syndrome: Insights from Immune-metabolic Profiles

Author(s)

McShane C1,2,3,4, O’Connell F2, Piggott M5, Obaidi I5, Kevans D1,3,4, Sheridan H5, O’Sullivan J2

Department(s)/Institutions

1. Department Gastroenterology, St. James's Hospital, Dublin, Ireland 2. Department of Surgery, Trinity St. James’s Cancer Institute and Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, Ireland 3. Wellcome – HRB Clinical Research Facility, St. James’s Hospital, James’s Street, Dublin, Ireland 4. Trinity Academic Gastroenterology Group, Trinity College Dublin, Ireland 5. NatPro Centre, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, Ireland.

Introduction

Bogland ecosystems host unique plant diversity, yielding bioactive secondary metabolites. Within the 'Unlocking Nature’s Pharmacy from Bogland Species' project, three plant extracts (NTP0226A, NTP01227B, NTP0206EA) were selected for potential IBD and IBS treatment, informed by traditional medicine and in vitro screening.

Aims/Background

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Method

Patients undergoing colonoscopy were prospectively recruited in three cohorts: healthy controls, IBS, and ulcerative colitis (UC). Recto-sigmoid biopsies were collected and cultured for 24 hours with treatments (Infliximab, NTP0226A, NTP01227B, NTP0206EA). Colonic tissue explants underwent real-time energy metabolism profiling and quantification of 10 inflammatory mediators using Seahorse Xfe24 analyser and multiplex ELISA, respectively.

Results

27 patients were recruited (6 healthy controls, 6 IBS, and 15 UC). UC patient explants exhibited elevated glycolytic metabolism and increased IL-4, IL-6, and IL-12p70 secretion compared to non-UC patients. No differences were observed between healthy controls and IBS patients. There was no change in metabolism profiles of any cohort following treatment with Infliximab or the 3 novel extracts. In the UC tissue, treatment with Infliximab reduced IL-12p70 secretion (p=0.0098), this reduction was not seen in the other 2 cohorts. NTP0206EA reduced IL-10 secretion in the UC cohort (p=0.0255). In the IBS cohort; NTP01227B reduced IL-10 secretion (p=0.0048) and NTP0226A reduced IL-4 (p=0.004) and IL-6 (p=0.0219) secretion. Principal components analysis demonstrated reduced separation between the immune-metabolic profiles of UC patients and healthy controls following treatment with NTP0226A.

Conclusions

Using an explant model, we have shown that UC patients have a distinct immune-metabolic profile modifiable by a standard IBD therapy and novel plant extracts. Blockade of IL-6 trans-signalling has recently shown promise as an effective treatment target in IBD. Our natural extract NTP0226A reduced IL-6 secretion in IBS patients and is a promising candidate for therapeutic exploration.