Ethnicity Associated Microbial and Metabonomic Profiling in Newly Diagnosed Ulcerative Colitis

Abstract

Ravi Misra,1 Magali Sarafian,2 Alexandros Pechlivanis,3 Nik Ding,4 Jesus Miguens-Blanco,2 Julie McDonald,5 Elaine Holmes,2,6 Julian Marchesi,2,5,7 Naila Arebi1 1Gastroenterology, St Mark’s Academic Institute, London, UK; 2Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Imperial College, London, UK; 3Analytical Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece; 4St Vincent’s Hospital, Inflammatory Bowel Disease Unit, Melbourne, Australia; 5School of Biosciences, Cardiff University, Cardiff, UK; 6Health Futures Institute, Murdoch and Edith Cowan Universities, Murdoch, Australia; 7Centre for Gut Health, Imperial College, London, UKCorrespondence: Ravi Misra, St. Mark’s Academic Institute, Imperial College, St. Mark’s Hospital, Watford Road, London, United Kingdom, Tel [phone], Email [email protected]: Ulcerative colitis (UC) differs across geography and ethnic groups. Gut microbial diversity plays a pivotal role in disease pathogenesis and differs across ethnic groups. The functional diversity in microbial-driven metabolites may have a pathophysiologic role and offer new therapeutic avenues.Methods: Demographics and clinical data were recorded from newly diagnosed UC patients. Blood, urine and faecal samples were collected at three time points over one year. Bacterial content was analysed by 16S rRNA sequencing. Bile acid profiles and polar molecules in three biofluids were measured using liquid-chromatography mass spectrometry (HILIC) and nuclear magnetic resonance spectroscopy.Results: We studied 42 patients with a new diagnosis of UC (27 South Asians; 15 Caucasians) with 261 biosamples. There were significant differences in relative abundance of bacteria at the phylum, genus and species level. Relative concentrations of urinary metabolites in South Asians were significantly lower for hippurate (positive correlation for Ruminococcus) and 4-cresol sulfate (Clostridia) (p< 0.001) with higher concentrations of lactate (negative correlation for Bifidobacteriaceae). Faecal conjugated and primary conjugated bile acids concentrations were significantly higher in South Asians (p=0.02 and p=0.03 respectively). Results were unaffected by diet, phenotype, disease severity and ongoing therapy. Comparison of time points at diagnosis and at 1 year did not reveal changes in microbial and metabolic profile.Conclusion: Ethnic-related microbial metabolite associations were observed in South Asians with UC. This suggests a predisposition to UC may be influenced by environmental factors reflected in a distinct gene-environment interaction. The variations may serve as markers to identify risk factors for UC and modified to enhance therapeutic response.Keywords: ulcerative colitis, microbiome, metabonomics

Keywords

• ulcerative colitis
• microbiome
• metabonomics