Diet-microbiome-metabolomic interactions in inflammatory bowel disease and comparing patients with and without a colon
File(s)
Author(s)
de Campos Braz, Lucia Maria
Type
Thesis
Abstract
The composition and function of the gut microbiome might be distorted in individuals with Inflammatory bowel disease. Diet plays a role in shaping the gut microbiome. Refractory ulcerative colitis (UC) can result in ileal anal pouch anastomosis (IPAA), however, more than half of these patients develop pouchitis.
This thesis aims to investigate differences in microbiome and metabolome composition between study cohorts, identify microbiome-metabolome interactions and explore the influence of dietary compounds on these interactions.
148 participants were recruited and categorised: pouches made for UC (PUC), pouches made for familial adenomatous polyposis (PFAP) and UC with an intact colon (UC). Dietary data, faecal samples, blood, and urine were collected. Biofluids analysis included 16S rRNA gene sequencing, nuclear magnetic resonance, and liquid chromatography-mass spectrometry for short chain fatty acid (SCFA), bile acid and tryptophan metabolites quantification.
Multivariate analysis identified a discriminatory microbiome and metabolites between UC (intact colon) and PUC (UC no colon). The PUC group ingest less fibre, fruit, and vegetables and had lower scores of adherences to the WHO dietary guidelines compared with UC group. PUC show reduced microbiome diversity, reduced abundance of Firmicutes, Ruminococcaceae, Lachnospiraceae, Faecalibacterium, Roseburia, Alistipes and lower concentrations of propionate and butyrate, and higher abundance of Escherichia coli, Enterobacteriaceae and Fusobacterium compared to UC. Elevated serum neopterin, kynurenine and cholic acid were found in PUC compared with UC.
Starch consumption positively correlated with neopterin, and Proteobacteria in PUC and protein intake positively correlated with alpha diversity, Firmicutes, Faecalibacterium and Rumminococcus. Adherence to the WHO dietary guidelines correlated with microbiome diversity and SCFA. Correlation matrix adjusted for false discovery rate showed differentiated diet-microbiome-metabolome communication links between PUC and UC.
These data suggests that pouch metabolic profile can be clearly differentiated from the colon and targeting the gut microbiome through diet may have therapeutic potential for pouch patients.
This thesis aims to investigate differences in microbiome and metabolome composition between study cohorts, identify microbiome-metabolome interactions and explore the influence of dietary compounds on these interactions.
148 participants were recruited and categorised: pouches made for UC (PUC), pouches made for familial adenomatous polyposis (PFAP) and UC with an intact colon (UC). Dietary data, faecal samples, blood, and urine were collected. Biofluids analysis included 16S rRNA gene sequencing, nuclear magnetic resonance, and liquid chromatography-mass spectrometry for short chain fatty acid (SCFA), bile acid and tryptophan metabolites quantification.
Multivariate analysis identified a discriminatory microbiome and metabolites between UC (intact colon) and PUC (UC no colon). The PUC group ingest less fibre, fruit, and vegetables and had lower scores of adherences to the WHO dietary guidelines compared with UC group. PUC show reduced microbiome diversity, reduced abundance of Firmicutes, Ruminococcaceae, Lachnospiraceae, Faecalibacterium, Roseburia, Alistipes and lower concentrations of propionate and butyrate, and higher abundance of Escherichia coli, Enterobacteriaceae and Fusobacterium compared to UC. Elevated serum neopterin, kynurenine and cholic acid were found in PUC compared with UC.
Starch consumption positively correlated with neopterin, and Proteobacteria in PUC and protein intake positively correlated with alpha diversity, Firmicutes, Faecalibacterium and Rumminococcus. Adherence to the WHO dietary guidelines correlated with microbiome diversity and SCFA. Correlation matrix adjusted for false discovery rate showed differentiated diet-microbiome-metabolome communication links between PUC and UC.
These data suggests that pouch metabolic profile can be clearly differentiated from the colon and targeting the gut microbiome through diet may have therapeutic potential for pouch patients.
Version
Open Access
Date Issued
2023-01-31
Date Awarded
2024-12-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Hart, Ailsa
Frost, Gary
Publisher Department
Department of Metabolism, Digestion and Reproduction
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)