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Associations of gut microbiota features and circulating metabolites with systemic inflammation in children.
- Source :
-
BMJ open gastroenterology [BMJ Open Gastroenterol] 2024 Aug 29; Vol. 11 (1). Date of Electronic Publication: 2024 Aug 29. - Publication Year :
- 2024
-
Abstract
- Objective: Gut microbes and microbe-dependent metabolites (eg, tryptophan-kynurenine-serotonin pathway metabolites) have been linked to systemic inflammation, but the microbiota-metabolite-inflammation axis remains uncharacterised in children. Here we investigated whether gut microbiota features and circulating metabolites (both microbe-dependent and non-microbe-dependent metabolites) associated with circulating inflammation markers in children.<br />Methods: We studied children from the prospective Gen3G birth cohort who had data on untargeted plasma metabolome (n=321 children; Metabolon platform), gut microbiota (n=147; 16S rRNA sequencing), and inflammation markers (plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1, and tumour necrosis factor-α) measured at 5-7 years. We examined associations of microbial taxa and metabolites-examining microbe-dependent and non-microbe-dependent metabolites separately-with each inflammatory marker and with an overall inflammation score (InfSc), adjusting for key confounders and correcting for multiple comparisons. We also compared the proportion of significantly associated microbe-dependent versus non-microbe-dependent metabolites, identified a priori (Human Microbial Metabolome Database), with each inflammation marker.<br />Results: Of 335 taxa tested, 149 were associated (q <subscript>FDR</subscript> <0.05) with at least one inflammatory marker; 10 of these were robust to pseudocount choice. Several bacterial taxa involved in tryptophan metabolism were associated with inflammation, including kynurenine-degrading Ruminococcus , which was inversely associated with all inflammation markers. Of 1037 metabolites tested, 315 were previously identified as microbe dependent and were more frequently associated with PAI-1 and the InfSc than non-microbe dependent metabolites. In total, 87 metabolites were associated (q <subscript>FDR</subscript> <0.05) with at least one inflammation marker, including kynurenine (positively), serotonin (positively), and tryptophan (inversely).<br />Conclusion: A distinct set of gut microbes and microbe-dependent metabolites, including those involved in the tryptophan-kynurenine-serotonin pathway, may be implicated in inflammatory pathways in childhood.<br />Competing Interests: Competing interests: NTM is on the scientific advisory board for Tiny Health; however, this organisation provided no funding for this research nor had any impact on the results or interpretation of the data.<br /> (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Subjects :
- Humans
Child
Female
Male
Prospective Studies
Child, Preschool
Tryptophan blood
Tryptophan metabolism
Kynurenine blood
Kynurenine metabolism
Tumor Necrosis Factor-alpha blood
RNA, Ribosomal, 16S genetics
Chemokine CCL2 blood
Gastrointestinal Microbiome physiology
Inflammation microbiology
Inflammation blood
Biomarkers blood
Plasminogen Activator Inhibitor 1 blood
Metabolome physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2054-4774
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMJ open gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 39209769
- Full Text :
- https://doi.org/10.1136/bmjgast-2024-001470