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Title: The impact of South Asian ethnicity on inflammatory bowel disease epidemiology and insights into pathogenesis through microbial and metabolic profiling
Author: Misra, Ravi
ISNI:       0000 0005 0287 3152
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2020
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The inflammatory bowel diseases are chronic autoimmune diseases associated with significant co-morbidity. Previous epidemiological studies have shown differences in incidence and phenotype of IBD between South Asian (SA) migrants and Caucasians however the reasons for this observation remain unclear. This thesis aimed to re-examine the incidence, phenotype and disease behaviour of IBD and describe the microbial and metabolic profile of SA and Caucasians with Ulcerative colitis (UC). A systematic review and meta-analysis demonstrated a higher incidence of UC and pan-colonic phenotype in SAs compared to Caucasians. A comparison between ethnic groups of colectomy rates for refractory UC demonstrated the Indian ethnic group had a significantly higher colectomy rate versus the White European and Pakistani groups (9.8%, 6.9% and 6.3% respectively). A multicentre prospective cohort identified 339 incident cases. The age adjusted incidence of IBD and UC were significantly higher in the Indian group (25.2.100,000 and 20.5/100,000) compared to White European (14.9/100,000, p=0.009 and 8.2/100,000, p<0.001) and Pakistani groups (14.9/100,000, p=0.001 and 11.2/100,000, p=0.007). A pilot study of newly diagnosed patients with UC was performed. 16S rRNA, urinary 1HNMR and mass spectroscopy (hydrophobic liquid chromatography and bile acid assays) techniques were employed to create microbial and metabolic profiles for comparison between SA and Caucasians with UC. Dietary assessment revealed no significant differences in macronutrient or micronutrient dietary intake. Significant metataxonomic differences at the phylum [higher relative abundance of Firmicutes (p=3.0x10-3) and Bacteroidetes (p=7.9x10-3) in Caucasians], family [higher relative abundance Bifidobacteriaceae (p=0.018), Streptococcaceae (p=0.03) and Veillonellaceae (p=0.035) in SA] and genus level [higher relative abundance of Ruminococcus (p=0.025) and Lachnospiraceae p=0.043) in Caucasians] were demonstrated. The relative concentration of urinary metabolites associated with gut microbial activity were significantly lower in SAs (hippurate and 4-cresol sulfate, p<0.001). Untargeted liquid chromatography analysis of faecal samples showed significant overall differences in metabolite profile HILIC (R2X 0.129, R2Y 0.8, Q2Y 0.596, p=6.47x10-5) between SA and Caucasians but no discriminatory metabolites could be identified. Targeted bile acids assay showed conjugated and primary conjugated bile acids concentrations in faeces were significantly higher in the SA group (p=0.02 and p=0.03 respectively). Conclusions The Indian population appears to be more susceptible to UC with pan-colonic disease and higher colectomy rates. SA ethnicity may alter microbial and metabolic profiles in UC patients. Further studies targeting the Indian population may provide reasons behind differences in disease behaviour.
Supervisor: Marchesi, Julian ; Faiz, Omar ; Arebi, Naila Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral