Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation

• Type of Material: Article
• Authors: Natacha Colliou, University of Florida; Yong Ge, University of Florida; Bikash Sahay, University of Florida; Minghao Gong, University of Florida; Mojgan Zadeh, University of Florida; Jennifer L. Owen, University of Florida; Josef Neu, University of Florida; William G. Farmerie, University of Florida; Francis Alonzo, Loyola University Chicago; Ken Liu, Emory University; Dean P Jones, Emory University; Shuzhao Li, Emory University; Mansour Mohamadzadeh, University of Florida
• Language: English
• Date: 2017-11-01
• Publisher: American Society for Clinical Investigation
• Publication Version: Final Published Version
• Copyright Statement: © 2017, American Society for Clinical Investigation
• Final Published Version (URL): http://dx.doi.org/10.1172/JCI95376
• Title of Journal or Parent Work: Journal of Clinical Investigation
• ISSN: 0021-9738
• Volume: 127
• Issue: 11
• Start Page: 3970
• End Page: 3986
• Grant/Funding Information: 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: TGF-BETA; Medicine, Research & Experimental; DENDRITIC CELLS; SEGMENTED FILAMENTOUS BACTERIA; Science & Technology; T-CELLS; GASTROINTESTINAL MICROBIOTA; IMMUNE-RESPONSE; Research & Experimental Medicine; INNATE LYMPHOID-CELLS; NEONATAL NECROTIZING ENTEROCOLITIS; GUT MICROBIOTA; HUMAN-MILK OLIGOSACCHARIDES; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology

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.