TY - JOUR
T1 - Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine
AU - Neumann, Charlotte J.
AU - Mahnert, Alexander
AU - Kumpitsch, Christina
AU - Kiu, Raymond
AU - Dalby, Matthew J.
AU - Kujawska, Magdalena
AU - Madl, Tobias
AU - Kurath-Koller, Stefan
AU - Urlesberger, Berndt
AU - Resch, Bernhard
AU - Hall, Lindsay J.
AU - Moissl-Eichinger, Christine
N1 - Funding Information: We highly appreciate the contributions of Raimund Kraschl, Claudia Kanduth, and Barbara Hopfer. This research was funded in in part by the Austrian Science Fund (FWF) [DOC 31 DP-iDP and P32697, given to CME]. TM was supported by Austrian Science Fund (FWF) grants P28854, I3792 and DK-MCD W1226, the Austrian Research Promotion Agency (FFG) grants 864690 and 870454; the Integrative Metabolism Research Center Graz; Austrian Infrastructure Program 2016/2017, the Styrian Government (Zukunftsfonds) and BioTechMed-Graz (Flagship project DYNIMO). BR was supported in part by a grant of the parent association “Kleine Helden –Initiative für Früh- und Neugeborene”, Graz, Austria. LJH is supported by Wellcome Trust Investigator Awards (100974/C/13/Z and 220876/Z/20/Z); the Biotechnology and Biological Sciences Research Council (BBSRC), Institute Strategic Programme Gut Microbes and Health (BB/R012490/1), and its constituent projects BBS/E/F/000PR10353 and BBS/E/F/000PR10356. The authors acknowledge computational resources of the MedBioNode at the Medical University of Graz and the support of the ZMF Galaxy Team: Core Facility Computational Bioanalytics, Medical University of Graz, funded by the Austrian Federal Ministry of Education, Science, and Research Hochschulraum-Strukturmittel 2016 grant as part of BioTechMed Graz. The funding body had no influence on the study, collection, analysis, and interpretation of data or on the manuscript content.
Rights retention statement: For the purpose of open access, the author has applied a CC BY public copyright licence to any author-accepted manuscript version arising from this submission.
PY - 2023/3/11
Y1 - 2023/3/11
N2 - Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterize fecal samples of 55 infants (less than 1500 g, n = 383, female = 22) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses; targeted 16S rRNA gene sequencing and shotgun metagenomics), microbial function, virulence factors, antibiotic resistances and metabolic profiles, including human milk oligosaccharides (HMOs) and short-chain fatty acids (German Registry of Clinical Trials, No.: DRKS00009290). Regimens including probiotic Bifidobacterium longum subsp. infantis NCDO 2203 supplementation affect microbiome development globally, pointing toward the genomic potential to convert HMOs. Engraftment of NCDO 2203 is associated with a substantial reduction of microbiome-associated antibiotic resistance as compared to regimens using probiotic Lactobacillus rhamnosus LCR 35 or no supplementation. Crucially, the beneficial effects of Bifidobacterium longum subsp. infantis NCDO 2203 supplementation depends on simultaneous feeding with HMOs. We demonstrate that preventive regimens have the highest impact on development and maturation of the gastrointestinal microbiome, enabling the establishment of a resilient microbial ecosystem that reduces pathogenic threats in at-risk preterm infants.
AB - Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterize fecal samples of 55 infants (less than 1500 g, n = 383, female = 22) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses; targeted 16S rRNA gene sequencing and shotgun metagenomics), microbial function, virulence factors, antibiotic resistances and metabolic profiles, including human milk oligosaccharides (HMOs) and short-chain fatty acids (German Registry of Clinical Trials, No.: DRKS00009290). Regimens including probiotic Bifidobacterium longum subsp. infantis NCDO 2203 supplementation affect microbiome development globally, pointing toward the genomic potential to convert HMOs. Engraftment of NCDO 2203 is associated with a substantial reduction of microbiome-associated antibiotic resistance as compared to regimens using probiotic Lactobacillus rhamnosus LCR 35 or no supplementation. Crucially, the beneficial effects of Bifidobacterium longum subsp. infantis NCDO 2203 supplementation depends on simultaneous feeding with HMOs. We demonstrate that preventive regimens have the highest impact on development and maturation of the gastrointestinal microbiome, enabling the establishment of a resilient microbial ecosystem that reduces pathogenic threats in at-risk preterm infants.
UR - http://www.scopus.com/inward/record.url?scp=85149944476&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-36825-1
DO - 10.1038/s41467-023-36825-1
M3 - Article
VL - 14
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 1349
ER -