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Fused Omics Data Models Reveal Gut Microbiome Signatures Specific of Inactive Stage of Juvenile Idiopathic Arthritis
Pamela Vernocchi1, Federico Marini2, Giorgio Capuani2,3
1Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
Insights
Juvenile idiopathic arthritis (JIA) gut microbiome (GM) signatures, including specific volatile organic compounds (VOCs) and bacterial taxa, can distinguish inactive JIA from healthy controls.
Area of Science:
- Microbiome Research
- Pediatric Rheumatology
- Metabolomics
Background:
- Juvenile idiopathic arthritis (JIA) is the most prevalent rheumatic condition in children.
- Understanding the gut microbiome's role in JIA pathogenesis and phenotype is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the relationship between the gut microbiome (GM) and JIA disease phenotypes.
- To identify specific GM signatures, including microbial metabolites and taxa, that characterize JIA patients.
Main Methods:
- An integrated omics approach combining 16S rRNA targeted-metagenomics and metabolomics (volatile and non-volatile organic compounds - VOCs).
- Analysis of stool samples from Italian JIA patients (baseline, active, inactive disease) and healthy controls (CTRLs).
- Chemometric models were used to classify and fuse data from operational taxonomic units (OTUs) and VOCs.
Main Results:
- Specific VOCs (Ethanol, Methyl-isobutyl-ketone, 2,6-Dimethyl-4-heptanone, Phenol) characterized JIA patients at baseline and inactive stages.
- Bacterial taxa Ruminococcaceae, Lachnospiraceae, and Clostridiacea discriminated between JIA inactive stage and CTRLs.
- Fused omics data successfully differentiated inactive and baseline JIA stages from CTRLs, with VOCs and Ruminococcaceae being key contributors.
Conclusions:
- Gut microbiome signatures, particularly specific VOCs and Ruminococcaceae, can distinguish the inactive JIA disease stage from healthy controls.
- The study highlights the potential of GM analysis for non-invasive JIA diagnosis and monitoring.
Abstract:
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Herein, we evaluated the relationship between the gut microbiome (GM) and disease phenotype by an integrated omics fused approach. In a multicenter, observational cohort study, stools from Italian JIA patients were collected at baseline, active, and inactive disease stages, and their GM compared to healthy controls (CTRLs). The microbiota metabolome was analyzed to detect volatile- and non-volatile organic compounds (VOCs); the data were fused with operational taxonomic units (OTUs) from 16S RNA targeted-metagenomics and classified by chemometric models. Non-VOCs did not characterize JIA patients nor JIA activity stages compared to CTRLs. The core of VOCs, (Ethanol, Methyl-isobutyl-ketone, 2,6-Dimethyl-4-heptanone and Phenol) characterized patients at baseline and inactive disease stages, while the OTUs represented by Ruminococcaceae, Lachnospiraceae and Clostridiacea discriminated between JIA inactive stage and CTRLs. No differences were highlighted amongst JIA activity stages. Finally, the fused data discriminated inactive and baseline stages versus CTRLs, based on the contribution of the invariant core of VOCs while Ruminococcaceae concurred for the inactive stage versus CTRLs comparison. In conclusion, the GM signatures enabled to distinguish the inactive disease stage from CTRLs.
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