About this item:

192 Views | 171 Downloads

Author Notes:

Address correspondence to: Mansour Mohamadzadeh, Department of Infectious Diseases & Immunology, University of Florida, 2015 SW 16th Avenue, Building 1017, Gainesville, Florida 32608, USA. Phone: 352.294.4117; Email: m.zadeh@ufl.edu

MM directed and designed the cellular and molecular experiments, which were executed by NC, YG, BS, MG, MZ, JLO, and FA.

NC, MZ, YG, and BS performed the mouse work.

YG, MG, and FA performed the molecular studies, gene deletion and complementation, transcriptomic studies, and generation of ΔactA L. m and ΔactA L. m3pep

SL and DJ performed, analyzed, and directed metabolomic studies.

SL, KL, and MG conducted all bioinformatic work for metabolic data analyses.

WGF analyzed the genome of P.UF1.

MG and YG performed experiments involving microbiota, transcriptomic analyses, and P. UF1 genome-wide analyses.

JN collected and provided the fecal samples. NC, YG, MG, BS, JLO, JN, FA, SL, DPJ, and MM analyzed and interpreted the data.

MM wrote the manuscript.

We thank Melissa N. Valletti and Max R. Van Belkum for excellent technical assistance.

Conflict of interest: M. Mohamadzadeh and B. Sahay are the inventors of P. UF1 (US provisional application no. US2016/032096).

Subjects:

Research Funding:

This work was supported by NIH R01 DK109560 (to MM), the NIH/NCRR Clinical and Translational Science Award (to MM), and Gatorade Trust Funds Florida (to MM).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • INNATE LYMPHOID-CELLS
  • NEONATAL NECROTIZING ENTEROCOLITIS
  • SEGMENTED FILAMENTOUS BACTERIA
  • HUMAN-MILK OLIGOSACCHARIDES
  • T-CELLS
  • IMMUNE-RESPONSE
  • DENDRITIC CELLS
  • GUT MICROBIOTA
  • TGF-BETA
  • GASTROINTESTINAL MICROBIOTA

Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation

Show all authors Show less authors

Tools:

Journal Title:

Journal of Clinical Investigation

Volume:

Volume 127, Number 11

Publisher:

, Pages 3970-3986

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2017, American Society for Clinical Investigation

Export to EndNote