Henry Taylor1, Jose Ivan Serrano-Contreras2, Julie A K McDonald3, Jenny Epstein4, J M Fell4, Rocio C Seoane5, Jia V Li2, Julian R Marchesi5,6, Ailsa L Hart2,7. 1. Department of Surgery and Cancer, Imperial College London, London, UK. 2. Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. 3. MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK. 4. Paediatric Gastroenterology Department, Chelsea and Westminster Hospital, London, UK. 5. Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. 6. School of Biosciences, University of Cardiff, Cardiff, UK. 7. IBD Unit, St. Mark's Hospital, Harrow, UK.
Abstract
BACKGROUND: The gastrointestinal microbiota has an important role in mucosal immune homoeostasis and may contribute to maintaining mucosal healing in Crohn's disease (CD). AIM: To identify changes in the microbiota, metabolome and protease activity associated with mucosal healing in established paediatric CD METHODS: Twenty-five participants aged 3-18 years with CD, disease duration of over 6 months, and maintenance treatment with biological therapy were recruited. They were divided into a low calprotectin group (faecal calprotectin <100 μg/g, "mucosal healing," n = 11), and a high calprotectin group (faecal calprotectin >100 μg/g, "mucosal inflammation," n = 11). 16S gene-based metataxonomics, 1 H-NMR spectroscopy-based metabolic profiling and protease activity assays were performed on stool samples. RESULTS: Relative abundance of Dialister species was six-times greater in the low calprotectin group (q = 0.00999). Alpha and beta diversity, total protease activity and inferred metagenomic profiles did not differ between groups. Pentanoate (valerate) and lysine were principal discriminators in a machine-learning model which differentiated high and low calprotectin samples using NMR spectra (R2 0.87, Q2 0.41). Mean relative concentration of pentanoate was 1.35-times greater in the low calprotectin group (95% CI 1.03-1.68, P = 0.036) and was positively correlated with Dialister. Mean relative concentration of lysine was 1.54-times greater in the high calprotectin group (95% CI 1.05-2.03, P = 0.028). CONCLUSIONS: This multiomic study identified an increase in Dialister species and pentanoate, and a decrease in lysine, in patients with "mucosal healing." It supports further investigation of these as potential novel therapeutic targets in CD.
BACKGROUND: The gastrointestinal microbiota has an important role in mucosal immune homoeostasis and may contribute to maintaining mucosal healing in Crohn's disease (CD). AIM: To identify changes in the microbiota, metabolome and protease activity associated with mucosal healing in established paediatric CD METHODS: Twenty-five participants aged 3-18 years with CD, disease duration of over 6 months, and maintenance treatment with biological therapy were recruited. They were divided into a low calprotectin group (faecal calprotectin <100 μg/g, "mucosal healing," n = 11), and a high calprotectin group (faecal calprotectin >100 μg/g, "mucosal inflammation," n = 11). 16S gene-based metataxonomics, 1 H-NMR spectroscopy-based metabolic profiling and protease activity assays were performed on stool samples. RESULTS: Relative abundance of Dialister species was six-times greater in the low calprotectin group (q = 0.00999). Alpha and beta diversity, total protease activity and inferred metagenomic profiles did not differ between groups. Pentanoate (valerate) and lysine were principal discriminators in a machine-learning model which differentiated high and low calprotectin samples using NMR spectra (R2 0.87, Q2 0.41). Mean relative concentration of pentanoate was 1.35-times greater in the low calprotectin group (95% CI 1.03-1.68, P = 0.036) and was positively correlated with Dialister. Mean relative concentration of lysine was 1.54-times greater in the high calprotectin group (95% CI 1.05-2.03, P = 0.028). CONCLUSIONS: This multiomic study identified an increase in Dialister species and pentanoate, and a decrease in lysine, in patients with "mucosal healing." It supports further investigation of these as potential novel therapeutic targets in CD.
Authors: Hana Čipčić Paljetak; Anja Barešić; Marina Panek; Mihaela Perić; Mario Matijašić; Ivana Lojkić; Ana Barišić; Darija Vranešić Bender; Dina Ljubas Kelečić; Marko Brinar; Mirjana Kalauz; Marija Miličević; Dora Grgić; Nikša Turk; Irena Karas; Silvija Čuković-Čavka; Željko Krznarić; Donatella Verbanac Journal: Gut Microbes Date: 2022 Jan-Dec
Authors: Alessandra Frau; Umer Z Ijaz; Rachael Slater; Daisy Jonkers; John Penders; Barry J Campbell; John G Kenny; Neil Hall; Luca Lenzi; Michael D Burkitt; Marieke Pierik; Alistair C Darby; Christopher S J Probert Journal: Gut Microbes Date: 2021 Jan-Dec