The gut metagenome harbors metabolic and antibiotic resistance signatures of moderate-to-severe asthma.

Autor:	Wilson NG; Division of Allergy and Immunology, Department of Medicine and Center for Women's Infectious Disease Research, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States., Hernandez-Leyva A; Division of Allergy and Immunology, Department of Medicine and Center for Women's Infectious Disease Research, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States., Schwartz DJ; Division of Infectious Diseases, Department of Pediatrics and Center for Women's Infectious Disease Research, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States., Bacharier LB; Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt University Medical Center, 2200 Children's Way, Nashville, TN 37232, United States., Kau AL; Division of Allergy and Immunology, Department of Medicine and Center for Women's Infectious Disease Research, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States.
Jazyk:	angličtina
Zdroj:	FEMS microbes [FEMS Microbes] 2024 Mar 07; Vol. 5, pp. xtae010. Date of Electronic Publication: 2024 Mar 07 (Print Publication: 2024).
DOI:	10.1093/femsmc/xtae010
Abstrakt:	Asthma is a common allergic airway disease that has been associated with the development of the human microbiome early in life. Both the composition and function of the infant gut microbiota have been linked to asthma risk, but functional alterations in the gut microbiota of older patients with established asthma remain an important knowledge gap. Here, we performed whole metagenomic shotgun sequencing of 95 stool samples from a cross-sectional cohort of 59 healthy and 36 subjects with moderate-to-severe asthma to characterize the metagenomes of gut microbiota in adults and children 6 years and older. Mapping of functional orthologs revealed that asthma contributes to 2.9% of the variation in metagenomic content even when accounting for other important clinical demographics. Differential abundance analysis showed an enrichment of long-chain fatty acid (LCFA) metabolism pathways, which have been previously implicated in airway smooth muscle and immune responses in asthma. We also observed increased richness of antibiotic resistance genes (ARGs) in people with asthma. Several differentially abundant ARGs in the asthma cohort encode resistance to macrolide antibiotics, which are often prescribed to patients with asthma. Lastly, we found that ARG and virulence factor (VF) richness in the microbiome were correlated in both cohorts. ARG and VF pairs co-occurred in both cohorts suggesting that virulence and antibiotic resistance traits are coselected and maintained in the fecal microbiota of people with asthma. Overall, our results show functional alterations via LCFA biosynthetic genes and increases in antibiotic resistance genes in the gut microbiota of subjects with moderate-to-severe asthma and could have implications for asthma management and treatment. Competing Interests: None declared. (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)
Databáze:	MEDLINE
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