Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants
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Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants. / Graspeuntner, S; Waschina, S; Künzel, S; Twisselmann, N; Rausch, T K; Cloppenborg-Schmidt, K; Zimmermann, J; Viemann, D; Herting, E; Göpel, W; Baines, J F; Kaleta, C; Rupp, J; Härtel, C; Pagel, J.
In: CLIN INFECT DIS, Vol. 69, No. 2, 02.07.2019, p. 268-277.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants
AU - Graspeuntner, S
AU - Waschina, S
AU - Künzel, S
AU - Twisselmann, N
AU - Rausch, T K
AU - Cloppenborg-Schmidt, K
AU - Zimmermann, J
AU - Viemann, D
AU - Herting, E
AU - Göpel, W
AU - Baines, J F
AU - Kaleta, C
AU - Rupp, J
AU - Härtel, C
AU - Pagel, J
N1 - © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
PY - 2019/7/2
Y1 - 2019/7/2
N2 - BACKGROUND: Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS.METHODS: In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics.RESULTS: We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease.CONCLUSIONS: Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.
AB - BACKGROUND: Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS.METHODS: In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics.RESULTS: We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease.CONCLUSIONS: Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.
KW - Anaerobiosis
KW - Cluster Analysis
KW - DNA, Bacterial/chemistry
KW - DNA, Ribosomal/chemistry
KW - Dysbiosis/complications
KW - Feces/chemistry
KW - Gastrointestinal Microbiome
KW - Humans
KW - Infant
KW - Infant, Newborn
KW - Infant, Premature
KW - Male
KW - Metabolome
KW - Metabolomics
KW - Metagenomics
KW - Neonatal Sepsis/pathology
KW - Phylogeny
KW - Prospective Studies
KW - RNA, Ribosomal, 16S/genetics
KW - Sequence Analysis, DNA
U2 - 10.1093/cid/ciy882
DO - 10.1093/cid/ciy882
M3 - SCORING: Journal article
C2 - 30329017
VL - 69
SP - 268
EP - 277
JO - CLIN INFECT DIS
JF - CLIN INFECT DIS
SN - 1058-4838
IS - 2
ER -