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Preventing dysbiosis of the neonatal mouse intestinal microbiome protects against late-onset sepsis

Singer, Jeffrey R ; Blosser, Emily G ; Zindl, Carlene L ; Silberger, Daniel J ; Conlan, Sean ; Laufer, Vincent A ; DiToro, Daniel ; Deming, Clay ; Kumar, Ranjit ; Morrow, Casey D ; Segre, Julia A ; Gray, Michael J ; Randolph, David A ; Weaver, Casey T

Nature medicine, 2019-11, Vol.25 (11), p.1772-1782 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
Preventing dysbiosis of the neonatal mouse intestinal microbiome protects against late-onset sepsis
Autor: Singer, Jeffrey R ; Blosser, Emily G ; Zindl, Carlene L ; Silberger, Daniel J ; Conlan, Sean ; Laufer, Vincent A ; DiToro, Daniel ; Deming, Clay ; Kumar, Ranjit ; Morrow, Casey D ; Segre, Julia A ; Gray, Michael J ; Randolph, David A ; Weaver, Casey T
Assuntos: Age of Onset ; Animals ; Animals, Newborn ; Antibiotics ; Colonization ; Disease Models, Animal ; Dysbacteriosis ; Dysbiosis ; Dysbiosis - drug therapy ; Dysbiosis - microbiology ; Dysbiosis - prevention & control ; E coli ; Ecological succession ; Gastrointestinal Microbiome - drug effects ; Health aspects ; Humans ; Infant, Premature ; Infants ; Infection ; Intestine ; Lactobacillus ; Mice ; Microbiomes ; Mother and infant ; Neonates ; Patient outcomes ; Prevention ; Probiotics ; Probiotics - therapeutic use ; Prophylaxis ; Protective Agents - therapeutic use ; Risk factors ; Sepsis ; Sepsis - drug therapy ; Sepsis - microbiology ; Sepsis - prevention & control
É parte de: Nature medicine, 2019-11, Vol.25 (11), p.1772-1782
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G.B. and D.A.R. conceived of the original model. E.G.B. generated Kp-43816lux. J.R.S. generated Kp-39gfp. J.R.S. and E.G.B. designed and performed all experiments with guidance from C.T.W., D.A.R. and M.J.G. J.A.S., C.D. and S.C. helped to perform and analyze metagenomics sequencing and strain-tracking experiments. Some immunofluorescence experiments were performed by C.L.Z. Some bioluminescence experiments were performed by D.J.S. D.D. helped prepare figures for the initial submission. V.A.L. fit the statistical models for the analysis of bioluminescence data. 16S rRNA microbiome sequencing and initial analysis were performed by C.D.M. and R.K. J.R.S. analyzed all the data, wrote the original manuscript and prepared the final figures. C.T.W., D.A.R. and J.A.S. secured funding for this project. J.R.S. and C.T.W. authored the final manuscript.
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Descrição: Late-onset sepsis (LOS) is thought to result from systemic spread of commensal microbes from the intestines of premature infants. Clinical use of probiotics for LOS prophylaxis has varied owing to limited efficacy, reflecting an incomplete understanding of relationships between development of the intestinal microbiome, neonatal dysbiosis and LOS. Using a model of LOS, we found that components of the developing microbiome were both necessary and sufficient to prevent LOS. Maternal antibiotic exposure that eradicated or enriched transmission of Lactobacillus murinus exacerbated and prevented disease, respectively. Prophylactic administration of some, but not all Lactobacillus spp. was protective, as was administration of Escherichia coli. Intestinal oxygen level was a major driver of colonization dynamics, albeit via mechanisms distinct from those in adults. These results establish a link between neonatal dysbiosis and LOS, and provide a basis for rational selection of probiotics that modulate primary succession of the microbiome to prevent disease.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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Preventing dysbiosis of the neonatal mouse intestinal microbiome protects against late-onset sepsis

Singer, Jeffrey R ; Blosser, Emily G ; Zindl, Carlene L ; Silberger, Daniel J ; Conlan, Sean ; Laufer, Vincent A ; DiToro, Daniel ; Deming, Clay ; Kumar, Ranjit ; Morrow, Casey D ; Segre, Julia A ; Gray, Michael J ; Randolph, David A ; Weaver, Casey T

United States: Nature Publishing Group

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