{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T09:04:32Z","timestamp":1779786272860,"version":"3.53.1"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to delineate the alterations in the gut microbiome and host amino acid metabolism in children with comorbid allergic rhinitis and functional constipation (ARFC), and to explore their links with clinical allergy markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed shotgun metagenomic sequencing and amino acid-targeted metabolomics on fecal samples from 19 children with ARFC and 16 age-matched healthy controls (HC). Microbial community structure, differentially abundant taxa, and metabolic profiles were analyzed. Integrative analyzes, including correlation networks and machine learning modeling, were employed to investigate microbiota-metabolite-host interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Significant beta-diversity distinction was found between ARFC and HC gut microbiota (PCoA R\n                      <jats:sup>2<\/jats:sup>\n                      =0.228, P\u00a0=\u00a00.001). ARFC children exhibited enrichment of mucin-degrading Bacteroidota (e.g., Bacteroides, Phocaeicola) and depletion of beneficial Bacillota (e.g., Bifidobacterium, Blautia). Metabolomics identified 50 differentially abundant metabolites, with widespread downregulation of immunomodulatory amino acids including L-glutamine and \u03b3-aminobutyric acid (GABA). Enriched pathways involved mTOR and FoxO signaling, and neurotransmitter synapses. Integration revealed significant correlations between specific microbial genera (e.g., Bacteroides, Proteus) and metabolites (e.g., kynurenine), and between gut species (e.g., Bacteroides thetaiotaomicron) and serum IgE levels. A machine learning model integrating key microbial and metabolic features, evaluated under a rigorous leave-one-out cross-validation framework, demonstrated robust discriminative performance in this cohort (AUC\u00a0=\u00a00.946).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This multi-omics study unveils a distinct \u201cgut dysbiosis-metabolite dysregulation-immune dysfunction\u201d axis in ARFC children. The synergistic shift towards a mucolytic, pro-inflammatory microbiota alongside deficient immunomodulatory metabolite production, which correlates with clinical allergy markers, provides a novel mechanistic framework for this comorbidity and highlights potential diagnostic biomarkers for future validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1779298","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:25:42Z","timestamp":1779783942000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative metagenomic and metabolomic analysis reveals a gut microbiota-metabolite-immune axis in pediatric allergic rhinitis with functional constipation"],"prefix":"10.3389","volume":"16","author":[{"given":"Hui","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Child Health and Rehabilitation, Maternal and Child Health Hospital of PanYu District","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Affiliated Longgang Central Hospital of Shantou University Medical College","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shenzhen Fourth People\u2019s Hospital, Shenzhen Sami Medical Center","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Child Health and Rehabilitation, Maternal and Child Health Hospital of PanYu District","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congfu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Longgang Maternity and Child Institute of Shantou University Medical College, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.immuni.2023.12.009","article-title":"Nutritional regulation of microbiota-derived metabolites: implications for immunity and inflammation","volume":"57","author":"Arifuzzaman","year":"2024","journal-title":"Immunity"},{"key":"B2","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nature12726","article-title":"Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation","volume":"504","author":"Arpaia","year":"2013","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature12331","article-title":"Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota","volume":"500","author":"Atarashi","year":"2013","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1111\/all.70100","article-title":"Methodology for the development of the allergic rhinitis and its impact on asthma (ARIA)-EAACI 2024\u20132025 guidelines: From evidence-to-decision frameworks to digitalised shared decision-making algorithms","volume":"81","author":"Bousquet","year":"2026","journal-title":"Allergy"},{"key":"B5","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1007\/s00203-025-04496-9","article-title":"Pediococcus pentosaceus strain SPARC2 as a potential probiotic food supplement: genomic insight, probiotic potential, and biosafety profiling in BALB\/c mice","volume":"207","author":"Butt","year":"2025","journal-title":"Arch. 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