Dataset Information

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives.

ABSTRACT:

BACKGROUND & AIMS: The cause of Crohn's disease (CD) is unknown, but the current hypothesis is that microbial or environmental factors induce gut inflammation in genetically susceptible individuals, leading to chronic intestinal inflammation. Case-control studies of patients with CD have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether the altered gut microbiome composition is associated with initiation of CD or is the result of inflammation or drug treatment.

METHODS: In this prospective cohort study, 3483 healthy first-degree relatives (FDRs) of patients with CD were recruited to identify the gut microbiome composition that precedes the onset of CD and to what extent this composition predicts the risk of developing CD. We applied a machine learning approach to the analysis of the gut microbiome composition (based on 16S ribosomal RNA sequencing) to define a microbial signature that associates with future development of CD. The performance of the model was assessed in an independent validation cohort.

RESULTS: In the validation cohort, the microbiome risk score (MRS) model yielded a hazard ratio of 2.24 (95% confidence interval, 1.03-4.84; P = .04), using the median of the MRS from the discovery cohort as the threshold. The MRS demonstrated a temporal validity by capturing individuals that developed CD up to 5 years before disease onset (area under the curve > 0.65). The 5 most important taxa contributing to the MRS included Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceae, and Roseburia.

CONCLUSION: This study is the first to demonstrate that gut microbiome composition is associated with future onset of CD and suggests that gut microbiome is a contributor in the pathogenesis of CD.

INSTRUMENT(S): Q Exactive

SUBMITTER: Williams Turpin Richard Robinson

PROVIDER: MTBLS300 | MetaboLights | 2023-11-16

REPOSITORIES: MetaboLights

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Publications

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives.

Raygoza Garay Juan Antonio JA Turpin Williams W Lee Sun-Ho SH Smith Michelle I MI Goethel Ashleigh A Griffiths Anne M AM Moayyedi Paul P Espin-Garcia Osvaldo O Abreu Maria M Aumais Guy L GL Bernstein Charles N CN Biron Irit A IA Cino Maria M Deslandres Colette C Dotan Iris I El-Matary Wael W Feagan Brian B Guttman David S DS Huynh Hien H Dieleman Levinus A LA Hyams Jeffrey S JS Jacobson Kevan K Mack David D Marshall John K JK Otley Anthony A Panaccione Remo R Ropeleski Mark M Silverberg Mark S MS Steinhart A Hillary AH Turner Dan D Yerushalmi Baruch B Paterson Andrew D AD Xu Wei W Croitoru Kenneth K

Gastroenterology 20230530 3

<h4>Background & aims</h4>The cause of Crohn's disease (CD) is unknown, but the current hypothesis is that microbial or environmental factors induce gut inflammation in genetically susceptible individuals, leading to chronic intestinal inflammation. Case-control studies of patients with CD have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether the altered gut microbiome composition is associated with initiation of CD or is the result of i ...[more]

PMID: 37263307

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Project description:Aims Gut microbiota-mediated inflammation promotes obesity-associated low-grade inflammation, which represents a hallmark of the metabolic syndrome (MetS). Lifestyle-induced weight loss (WL) is regarded as an efficient therapy to reverse MetS and to prevent disease progression. The objective of this study was to investigate if lifestyle-induced WL modulates the gut microbiome and its interaction with the host. Methods We analyzed and compared the fecal metaproteome of 33 individuals with MetS in a longitudinal study before and after lifestyle-induced WL in a well-defined cohort (ICTRP Trial Number: U1111-1158-3672). Results The 6-month WL intervention resulted in reduced BMI (-13.9%), increased insulin sensitivity (HOMA-IR; -53.70%) and reduced levels of circulating CRP (-66.86%), indicating MetS reversal. The metaprotein spectra of the host revealed a decrease of human proteins associated with gut inflammation and reduced abundance of human pancreatic alpha-amylase. Surprisingly, taxonomic analysis of the fecal metaproteome revealed only minor changes in the bacterial composition with an increase of low-abundant families (Desulfovibrionaceae, Leptospiraceae, Syntrophomonadaceae, Thermotogaceae, Verrucomicrobiaceae). Yet, we detected increased abundance of microbial metaprotein spectra that correspond to enhanced hydrolysis of complex carbohydrates (endoglucanase A, β-1,4-mannooligosaccharide phosphorylase, galactokinase, 5-keto-D-gluconate 5-reductase), indicating functional changes of the gut microbiome. Conclusions Our results indicate that lifestyle induced WL may improve interaction between the gut microbiome and the host in individuals with MetS, while bacterial composition remained almost stable. Metaproteome analysis of host proteins reveals reduced gut inflammation whereas microbial metaprotein spectra indicate functional changes towards degradation of complex carbohydrates. The filenames correspond to the ID of the patient (1-33), whereas “C” corresponds to baseline and “ABC” to weight loss.

Dataset Information

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives.

CONCLUSION: This study is the first to demonstrate that gut microbiome composition is associated with future onset of CD and suggests that gut microbiome is a contributor in the pathogenesis of CD.

Publications

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives.

Similar Datasets

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