The gut microbiome, resistome, and mycobiome in preterm newborn infants and mouse pups: lack of lasting effects by antimicrobial therapy or probiotic prophylaxis
Elizabeth Y. Yuu,
Christoph Bührer,
Tim Eckmanns,
Marcus Fulde,
Michaela Herz,
Oliver Kurzai,
Christin Lindstedt,
Gianni Panagiotou,
Vitor C. Piro,
Aleksandar Radonic,
Bernhard Y. Renard,
Annicka Reuss,
Sara Leal Siliceo,
Nadja Thielemann,
Andrea Thürmer,
Kira van Vorst,
Lothar H. Wieler,
Sebastian Haller
Affiliations
Elizabeth Y. Yuu
Data Analytics & Computational Statistics, Hasso Plattner Institute, University of Potsdam
Christoph Bührer
Charité - Universitätsmedizin
Tim Eckmanns
Robert Koch Institute
Marcus Fulde
Department of Mathematics and Computer Science, Freie Universität Berlin
Michaela Herz
Institute for Hygiene and Microbiology, University of Würzburg
Oliver Kurzai
Institute for Hygiene and Microbiology, University of Würzburg
Christin Lindstedt
Charité - Universitätsmedizin
Gianni Panagiotou
Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute
Vitor C. Piro
Data Analytics & Computational Statistics, Hasso Plattner Institute, University of Potsdam
Aleksandar Radonic
Robert Koch Institute
Bernhard Y. Renard
Data Analytics & Computational Statistics, Hasso Plattner Institute, University of Potsdam
Annicka Reuss
Robert Koch Institute
Sara Leal Siliceo
Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute
Nadja Thielemann
Institute for Hygiene and Microbiology, University of Würzburg
Andrea Thürmer
Robert Koch Institute
Kira van Vorst
Department of Mathematics and Computer Science, Freie Universität Berlin
Lothar H. Wieler
Data Analytics & Computational Statistics, Hasso Plattner Institute, University of Potsdam
Abstract Background Enhancing our understanding of the underlying influences of medical interventions on the microbiome, resistome and mycobiome of preterm born infants holds significant potential for advancing infection prevention and treatment strategies. We conducted a prospective quasi-intervention study to better understand how antibiotics, and probiotics, and other medical factors influence the gut development of preterm infants. A controlled neonatal mice model was conducted in parallel, designed to closely reflect and predict exposures. Preterm infants and neonatal mice were stratified into four groups: antibiotics only, probiotics only, antibiotics followed by probiotics, and none of these interventions. Stool samples from both preterm infants and neonatal mice were collected at varying time points and analyzed by 16 S rRNA amplicon sequencing, ITS amplicon sequencing and whole genome shotgun sequencing. Results The human infant microbiomes showed an unexpectedly high degree of heterogeneity. Little impact from medical exposure (antibiotics/probiotics) was observed on the strain patterns, however, Bifidobacterium bifidum was found more abundant after exposure to probiotics, regardless of prior antibiotic administration. Twenty-seven antibiotic resistant genes were identified in the resistome. High intra-variability was evident within the different treatment groups. Lastly, we found significant effects of antibiotics and probiotics on the mycobiome but not on the microbiome and resistome of preterm infants. Conclusions Although our analyses showed transient effects, these results provide positive motivation to continue the research on the effects of medical interventions on the microbiome, resistome and mycobiome of preterm infants.