Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation

The Journal of Clinical Investigation
Natacha ColliouMansour Mohamadzadeh

Abstract

Consumption of human breast milk (HBM) attenuates the incidence of necrotizing enterocolitis (NEC), which remains a leading and intractable cause of mortality in preterm infants. Here, we report that this diminution correlates with alterations in the gut microbiota, particularly enrichment of Propionibacterium species. Transfaunation of microbiota from HBM-fed preterm infants or a newly identified and cultured Propionibacterium strain, P. UF1, to germfree mice conferred protection against pathogen infection and correlated with profound increases in intestinal Th17 cells. The induction of Th17 cells was dependent on bacterial dihydrolipoamide acetyltransferase (DlaT), a major protein expressed on the P. UF1 surface layer (S-layer). Binding of P. UF1 to its cognate receptor, SIGNR1, on dendritic cells resulted in the regulation of intestinal phagocytes. Importantly, transfer of P. UF1 profoundly mitigated induced NEC-like injury in neonatal mice. Together, these results mechanistically elucidate the protective effects of HBM and P. UF1-induced immunoregulation, which safeguard against proinflammatory diseases, including NEC.

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Citations

Feb 9, 2018·Gut Microbes·Natacha ColliouMansour Mohamadzadeh
Oct 27, 2018·Mucosal Immunology·Yingzi Cong, Yanqing Li
Nov 6, 2018·FEMS Microbiology Ecology·Vanesa Natalin Rocha MartinChristophe Lacroix
Oct 23, 2019·Signal Transduction and Targeted Therapy·Ziying ZhangYongguang Tao
Jan 17, 2019·Mucosal Immunology·Yong GeMansour Mohamadzadeh
Apr 2, 2020·Frontiers in Genetics·Kyle M CarterLingling An
Nov 7, 2019·Nature Methods·James T MortonRob Knight
Jul 10, 2020·Science Translational Medicine·Seung-Chul ChoiLaurence Morel
Dec 15, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jing LiMansour Mohamadzadeh
Nov 16, 2020·Gastroenterology·Anoop KumarPradeep K Dudeja
Oct 11, 2020·Signal Transduction and Targeted Therapy·Ziying ZhangYongguang Tao
Apr 4, 2021·International Journal of Molecular Sciences·William RothMansour Mohamadzadeh
Sep 16, 2018·Gastroenterology·Christopher G HurtadoCynthia L Sears
Apr 23, 2021·Applied Microbiology and Biotechnology·Romain Jeantet, Gwénaël Jan
Jul 30, 2021·Critical Reviews in Food Science and Nutrition·Yiqiu FeiMingfei Yao

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Software Mentioned

PHAST ( Phage Search Tool
GraphPad Prism
Rapid Annotation Server ( RAST )
KEGG Orthology And Links Annotation ( KOALA )
Blast Ring Image Generator ( BRIG )
Mummichog
Python
RAST
Rapid Prokaryotic Genome Annotation ( PROKKA )
LEfSe

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