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Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation
Natacha Colliou, … , Shuzhao Li, Mansour Mohamadzadeh
Natacha Colliou, … , Shuzhao Li, Mansour Mohamadzadeh
Published September 25, 2017
Citation Information: J Clin Invest. 2017;127(11):3970-3986. https://doi.org/10.1172/JCI95376.
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Research Article Immunology Inflammation

Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation

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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.

Authors

Natacha Colliou, Yong Ge, Bikash Sahay, Minghao Gong, Mojgan Zadeh, Jennifer L. Owen, Josef Neu, William G. Farmerie, Francis Alonzo III, Ken Liu, Dean P. Jones, Shuzhao Li, Mansour Mohamadzadeh

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Figure 1

Abundance of Propionibacterium in the fecal samples of HBMF preterm infants.

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Abundance of Propionibacterium in the fecal samples of HBMF preterm infa...
Fecal samples were collected from HBMF (n = 20) and FF preterm infants (n = 20), and microbiota composition was analyzed by 16S rDNA sequencing. (A) Summary box plots of Chao richness, Shannon diversity, and Pielou’s evenness indices derived from analyses of fecal samples of HBMF (blue) and FF (red) preterm infants on day 13 ± 2 to 3. (B) Linear discriminant analysis (LDA) of taxons between HBMF and FF preterm infants’ microbiota on day 13 ± 2 to 3. Taxa enriched in HBMF preterm infants’ microbiota have a negative score (blue), and taxa enriched in FF preterm infants’ microbiota have a positive score (red). Only taxa with an absolute value of LDA score of more than 2 are shown. (C) Phylum structure of the abundant bacteria in fecal samples of HBMF and FF preterm infants on days 21 ± 3. (D) Taxonomic cladogram of HBMF versus FF preterm infants’ bacterial fecal samples on day 21 ± 3 (blue, HBMF-enriched taxa; red, FF-enriched taxa). (E) Percentage of operational taxonomic units (OTUs) of Propionibacteria in the fecal samples of HBMF and FF preterm infants by day 13 ± 2 to 3 and day 21 ± 3. (F) Relative abundance of different Propionibacteria (e.g., P. freudenreichii) in fecal samples of HBMF and FF preterm infants. Error bars indicate mean ± SEM. *P < 0.05; **P < 0.01, 2-tailed unpaired t test (A, E, and F). Kruskal-Wallis test (B and D).

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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