Faecal metabolome and its determinants in inflammatory bowel disease

Arnau Vich Vila; Shixian Hu; Sergio Andreu-Sánchez; Valerie Collij; Bernadien H Jansen; Hannah E Augustijn; Laura A Bolte; Renate A A A Ruigrok; Galeb Abu-Ali; Cosmas Giallourakis; Jessica Schneider; John Parkinson; Amal Al-Garawi; Alexandra Zhernakova; Ranko Gacesa; Jingyuan Fu; Rinse K Weersma

doi:10.1136/gutjnl-2022-328048

Faecal metabolome and its determinants in inflammatory bowel disease

Arnau Vich Vila^*, Shixian Hu, Sergio Andreu-Sánchez, Valerie Collij, Bernadien H Jansen, Hannah E Augustijn, Laura A Bolte, Renate A A A Ruigrok, Galeb Abu-Ali, Cosmas Giallourakis, Jessica Schneider, John Parkinson, Amal Al-Garawi, Alexandra Zhernakova, Ranko Gacesa, Jingyuan Fu, Rinse K Weersma^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

OBJECTIVE: Inflammatory bowel disease (IBD) is a multifactorial immune-mediated inflammatory disease of the intestine, comprising Crohn's disease and ulcerative colitis. By characterising metabolites in faeces, combined with faecal metagenomics, host genetics and clinical characteristics, we aimed to unravel metabolic alterations in IBD.

DESIGN: We measured 1684 different faecal metabolites and 8 short-chain and branched-chain fatty acids in stool samples of 424 patients with IBD and 255 non-IBD controls. Regression analyses were used to compare concentrations of metabolites between cases and controls and determine the relationship between metabolites and each participant's lifestyle, clinical characteristics and gut microbiota composition. Moreover, genome-wide association analysis was conducted on faecal metabolite levels.

RESULTS: We identified over 300 molecules that were differentially abundant in the faeces of patients with IBD. The ratio between a sphingolipid and L-urobilin could discriminate between IBD and non-IBD samples (AUC=0.85). We found changes in the bile acid pool in patients with dysbiotic microbial communities and a strong association between faecal metabolome and gut microbiota. For example, the abundance of Ruminococcus gnavus was positively associated with tryptamine levels. In addition, we found 158 associations between metabolites and dietary patterns, and polymorphisms near NAT2 strongly associated with coffee metabolism.

CONCLUSION: In this large-scale analysis, we identified alterations in the metabolome of patients with IBD that are independent of commonly overlooked confounders such as diet and surgical history. Considering the influence of the microbiome on faecal metabolites, our results pave the way for future interventions targeting intestinal inflammation.

Original language	English
Pages (from-to)	1472-1485
Number of pages	14
Journal	Gut
Volume	72
Issue number	8
DOIs	https://doi.org/10.1136/gutjnl-2022-328048
Publication status	Published - Aug-2023

Keywords

Humans
Genome-Wide Association Study
Inflammatory Bowel Diseases/metabolism
Colitis, Ulcerative/metabolism
Metabolome
Feces
Arylamine N-Acetyltransferase/metabolism

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Vich Vila, A., Hu, S., Andreu-Sánchez, S., Collij, V., Jansen, B. H., Augustijn, H. E., Bolte, L. A., Ruigrok, R. A. A. A., Abu-Ali, G., Giallourakis, C., Schneider, J., Parkinson, J., Al-Garawi, A., Zhernakova, A., Gacesa, R., Fu, J., & Weersma, R. K. (2023). Faecal metabolome and its determinants in inflammatory bowel disease. Gut, 72(8), 1472-1485. https://doi.org/10.1136/gutjnl-2022-328048

@article{4eb578f213db4a1faa567841c4994175,

title = "Faecal metabolome and its determinants in inflammatory bowel disease",

abstract = "OBJECTIVE: Inflammatory bowel disease (IBD) is a multifactorial immune-mediated inflammatory disease of the intestine, comprising Crohn's disease and ulcerative colitis. By characterising metabolites in faeces, combined with faecal metagenomics, host genetics and clinical characteristics, we aimed to unravel metabolic alterations in IBD.DESIGN: We measured 1684 different faecal metabolites and 8 short-chain and branched-chain fatty acids in stool samples of 424 patients with IBD and 255 non-IBD controls. Regression analyses were used to compare concentrations of metabolites between cases and controls and determine the relationship between metabolites and each participant's lifestyle, clinical characteristics and gut microbiota composition. Moreover, genome-wide association analysis was conducted on faecal metabolite levels.RESULTS: We identified over 300 molecules that were differentially abundant in the faeces of patients with IBD. The ratio between a sphingolipid and L-urobilin could discriminate between IBD and non-IBD samples (AUC=0.85). We found changes in the bile acid pool in patients with dysbiotic microbial communities and a strong association between faecal metabolome and gut microbiota. For example, the abundance of Ruminococcus gnavus was positively associated with tryptamine levels. In addition, we found 158 associations between metabolites and dietary patterns, and polymorphisms near NAT2 strongly associated with coffee metabolism.CONCLUSION: In this large-scale analysis, we identified alterations in the metabolome of patients with IBD that are independent of commonly overlooked confounders such as diet and surgical history. Considering the influence of the microbiome on faecal metabolites, our results pave the way for future interventions targeting intestinal inflammation.",

keywords = "Humans, Genome-Wide Association Study, Inflammatory Bowel Diseases/metabolism, Colitis, Ulcerative/metabolism, Metabolome, Feces, Arylamine N-Acetyltransferase/metabolism",

author = "{Vich Vila}, Arnau and Shixian Hu and Sergio Andreu-S{\'a}nchez and Valerie Collij and Jansen, {Bernadien H} and Augustijn, {Hannah E} and Bolte, {Laura A} and Ruigrok, {Renate A A A} and Galeb Abu-Ali and Cosmas Giallourakis and Jessica Schneider and John Parkinson and Amal Al-Garawi and Alexandra Zhernakova and Ranko Gacesa and Jingyuan Fu and Weersma, {Rinse K}",

note = "{\textcopyright} Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2023",

month = aug,

doi = "10.1136/gutjnl-2022-328048",

language = "English",

volume = "72",

pages = "1472--1485",

journal = "Gut",

issn = "0017-5749",

publisher = "BMJ Publishing Group",

number = "8",

}

Vich Vila, A, Hu, S, Andreu-Sánchez, S , Collij, V , Jansen, BH, Augustijn, HE, Bolte, LA, Ruigrok, RAAA, Abu-Ali, G, Giallourakis, C, Schneider, J, Parkinson, J, Al-Garawi, A, Zhernakova, A , Gacesa, R , Fu, J & Weersma, RK 2023, 'Faecal metabolome and its determinants in inflammatory bowel disease', Gut, vol. 72, no. 8, pp. 1472-1485. https://doi.org/10.1136/gutjnl-2022-328048

TY - JOUR

T1 - Faecal metabolome and its determinants in inflammatory bowel disease

AU - Vich Vila, Arnau

AU - Hu, Shixian

AU - Andreu-Sánchez, Sergio

AU - Collij, Valerie

AU - Jansen, Bernadien H

AU - Augustijn, Hannah E

AU - Bolte, Laura A

AU - Ruigrok, Renate A A A

AU - Abu-Ali, Galeb

AU - Giallourakis, Cosmas

AU - Schneider, Jessica

AU - Parkinson, John

AU - Al-Garawi, Amal

AU - Zhernakova, Alexandra

AU - Gacesa, Ranko

AU - Fu, Jingyuan

AU - Weersma, Rinse K

PY - 2023/8

Y1 - 2023/8

N2 - OBJECTIVE: Inflammatory bowel disease (IBD) is a multifactorial immune-mediated inflammatory disease of the intestine, comprising Crohn's disease and ulcerative colitis. By characterising metabolites in faeces, combined with faecal metagenomics, host genetics and clinical characteristics, we aimed to unravel metabolic alterations in IBD.DESIGN: We measured 1684 different faecal metabolites and 8 short-chain and branched-chain fatty acids in stool samples of 424 patients with IBD and 255 non-IBD controls. Regression analyses were used to compare concentrations of metabolites between cases and controls and determine the relationship between metabolites and each participant's lifestyle, clinical characteristics and gut microbiota composition. Moreover, genome-wide association analysis was conducted on faecal metabolite levels.RESULTS: We identified over 300 molecules that were differentially abundant in the faeces of patients with IBD. The ratio between a sphingolipid and L-urobilin could discriminate between IBD and non-IBD samples (AUC=0.85). We found changes in the bile acid pool in patients with dysbiotic microbial communities and a strong association between faecal metabolome and gut microbiota. For example, the abundance of Ruminococcus gnavus was positively associated with tryptamine levels. In addition, we found 158 associations between metabolites and dietary patterns, and polymorphisms near NAT2 strongly associated with coffee metabolism.CONCLUSION: In this large-scale analysis, we identified alterations in the metabolome of patients with IBD that are independent of commonly overlooked confounders such as diet and surgical history. Considering the influence of the microbiome on faecal metabolites, our results pave the way for future interventions targeting intestinal inflammation.

AB - OBJECTIVE: Inflammatory bowel disease (IBD) is a multifactorial immune-mediated inflammatory disease of the intestine, comprising Crohn's disease and ulcerative colitis. By characterising metabolites in faeces, combined with faecal metagenomics, host genetics and clinical characteristics, we aimed to unravel metabolic alterations in IBD.DESIGN: We measured 1684 different faecal metabolites and 8 short-chain and branched-chain fatty acids in stool samples of 424 patients with IBD and 255 non-IBD controls. Regression analyses were used to compare concentrations of metabolites between cases and controls and determine the relationship between metabolites and each participant's lifestyle, clinical characteristics and gut microbiota composition. Moreover, genome-wide association analysis was conducted on faecal metabolite levels.RESULTS: We identified over 300 molecules that were differentially abundant in the faeces of patients with IBD. The ratio between a sphingolipid and L-urobilin could discriminate between IBD and non-IBD samples (AUC=0.85). We found changes in the bile acid pool in patients with dysbiotic microbial communities and a strong association between faecal metabolome and gut microbiota. For example, the abundance of Ruminococcus gnavus was positively associated with tryptamine levels. In addition, we found 158 associations between metabolites and dietary patterns, and polymorphisms near NAT2 strongly associated with coffee metabolism.CONCLUSION: In this large-scale analysis, we identified alterations in the metabolome of patients with IBD that are independent of commonly overlooked confounders such as diet and surgical history. Considering the influence of the microbiome on faecal metabolites, our results pave the way for future interventions targeting intestinal inflammation.

KW - Humans

KW - Genome-Wide Association Study

KW - Inflammatory Bowel Diseases/metabolism

KW - Colitis, Ulcerative/metabolism

KW - Metabolome

KW - Feces

KW - Arylamine N-Acetyltransferase/metabolism

U2 - 10.1136/gutjnl-2022-328048

DO - 10.1136/gutjnl-2022-328048

M3 - Article

C2 - 36958817

SN - 0017-5749

VL - 72

SP - 1472

EP - 1485

JO - Gut

JF - Gut

IS - 8

ER -

Faecal metabolome and its determinants in inflammatory bowel disease

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