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Targeting the gut-lung axis by synbiotic feeding to infants in a randomized controlled trial
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.ORCID iD: 0000-0002-1323-9913
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Division of CBRN Security and Defense, FOI - Swedish Defense Research Agency, Umeå, Sweden.ORCID iD: 0000-0001-5350-4219
Department of Paediatrics, Medical University of Warsaw, Warsaw, Poland.
Aarhus, Denmark.
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2023 (English)In: BMC Biology, E-ISSN 1741-7007, Vol. 21, no 1, article id 38Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Formula-fed infants are at increased risk of infections. Due to the cross-talk between the mucosal systems of the gastrointestinal and respiratory tracts, adding synbiotics (prebiotics and probiotics) to infant formula may prevent infections even at distant sites. Infants that were born full term and weaned from breast milk were randomized to prebiotic formula (fructo- and galactooligosaccharides) or the same prebiotic formula with Lactobacillus paracasei ssp. paracasei F19 (synbiotics) from 1 to 6 months of age. The objective was to examine the synbiotic effects on gut microbiota development. RESULTS: Fecal samples collected at ages 1, 4, 6, and 12 months were analyzed using 16S rRNA gene sequencing and a combination of untargeted gas chromatography-mass spectrometry/liquid chromatography-mass spectrometry. These analyses revealed that the synbiotic group had a lower abundance of Klebsiella, a higher abundance of Bifidobacterium breve compared to the prebiotic group, and increases in the anti-microbial metabolite d-3-phenyllactic acid. We also analyzed the fecal metagenome and antibiotic resistome in the 11 infants that had been diagnosed with lower respiratory tract infection (cases) and 11 matched controls using deep metagenomic sequencing. Cases with lower respiratory tract infection had a higher abundance of Klebsiella species and antimicrobial resistance genes related to Klebsiella pneumoniae, compared to controls. The results obtained using 16S rRNA gene amplicon and metagenomic sequencing were confirmed in silico by successful recovery of the metagenome-assembled genomes of the bacteria of interest. CONCLUSIONS: This study demonstrates the additional benefit of feeding specific synbiotics to formula-fed infants over prebiotics only. Synbiotic feeding led to the underrepresentation of Klebsiella, enrichment of bifidobacteria, and increases in microbial degradation metabolites implicated in immune signaling and in the gut-lung and gut-skin axes. Our findings support future clinical evaluation of synbiotic formula in the prevention of infections and associated antibiotic treatment as a primary outcome when breastfeeding is not feasible. TRIAL REGISTRATION: ClinicalTrials.gov NCT01625273. Retrospectively registered on 21 June 2012.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023. Vol. 21, no 1, article id 38
Keywords [en]
Antibiotics, Bifidobacteria, Infant gut microbiota, Klebsiella, Lower respiratory tract infection, Prebiotics, Probiotics
National Category
Nutrition and Dietetics Pediatrics
Identifiers
URN: urn:nbn:se:umu:diva-205355DOI: 10.1186/s12915-023-01531-3ISI: 000936843800002PubMedID: 36803508Scopus ID: 2-s2.0-85148399778OAI: oai:DiVA.org:umu-205355DiVA, id: diva2:1748324
Funder
Umeå UniversityRegion VästerbottenMagnus Bergvall FoundationKnut and Alice Wallenberg FoundationSwedish Research CouncilAvailable from: 2023-04-03 Created: 2023-04-03 Last updated: 2024-01-17Bibliographically approved

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Sjödin, Kotryna SimonytéSjödin, AndreasHernell, OlleWest, Christina E.

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