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Authors: Klopp, Jonas
Title: Study of eu- and dysbiosis in the intestinal microbiome of very preterm infants in the PRIMAL study cohort
Online publication date: 5-Aug-2022
Language: english
Abstract: Dysbiosis, generally defined as a reduction of diversity and beneficial bacteria and a bloom of pathobionts in a given microbiome, has been proposed as a concept to explain why changes in the (gut) microbiome composition can lead to negative health outcomes, especially in the vulnerable population of preterm infants. This microbiome state is in contrast to an implicit state of balanced eubiosis. The main aims of this thesis were to analyze and comprehensively describe the gut microbiome composition of preterm neonates and mothers enrolled in the PRIMAL study cohort and to evaluate the overall utility of the dysbiosis concept in the context of the preterm infant gut microbiome and the use of probiotics. For 1353 infant fecal samples comprised of three visits (day 0, day 28 and day 365 of life) and 290 associated mother samples, taxonomic profiles were compiled through 16S rRNA gene sequencing to establish a baseline characterization of their microbiome composition. Right after birth, infant gut microbiomes were dominated by the genera Staphylococcus and Bifidobacterium. During the further development over the course of the first month of life, Bifidobacterium gained dominance in the microbiomes. Bifidobacterium remained the most abundant genus after one year of life during which the infant microbiome slowly matured to more closely resemble the adult mother microbiome which was primarily dominated by the genera Bacterioides, Blautia and Faecalibacterium. To evaluate the usefulness and validity of the dysbiosis concept, results from conventional, culture based microbiological analyses and next-generation sequencing were compared with a focus on taxonomic classifications and antibiotic resistance capacity. Further, possible interactions in the microbiomes from the PRIMAL study cohort were analyzed through co-occurrence network analyses and the PRIMAL microbiomes were set into the context of publicly available preterm and full term reference microbiome datasets. Conceptual challenges with the generic term dysbiosis were resolved by proposing that dysbiosis should be used as a description of a dysfunctional state with defined genetic deficits within the microbiome. A distinction can be made between dysbiosis as an umbrella term for a general deviation from the genetic capabilities of a normal reference microbiome on the one hand and a two-part actionable concept on the other hand that can drive hypothesis driven research. This two-part concept differentiates between a short-term (acute) dysbiosis characterized by the presence of a concrete pathogen and a long-term (chronic) dysbiosis characterized by complex microecological interactions with the host that cause chronic diseases. Overall, this study demonstrates the complexity within the human gut microbiome even at the earliest stages of life and stresses the importance of a deep mechanistic understanding of host-microbe interactions to develop rationally designed therapeutic interventions.
DDC: 570 Biowissenschaften
570 Life sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 10 Biologie
Place: Mainz
URN: urn:nbn:de:hebis:77-openscience-d8d0bb4b-8775-48e9-ad3b-faf6818cc5d87
Version: Original work
Publication type: Dissertation
License: CC BY
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Extent: Getrennte Zählung, Illustrationen, Diagramme
Appears in collections:JGU-Publikationen

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