Microbial bile salt hydrolase activity influences gene expression profiles and gastrointestinal maturation in infant mice
María A. Núñez-Sánchez,
Florence M. Herisson,
Jonathan M. Keane,
Natalia García-González,
Valerio Rossini,
Jorge Pinhiero,
Jack Daly,
Milán Bustamante-Garrido,
Cara M. Hueston,
Shriram Patel,
Nuria Canela,
Pol Herrero,
Marcus J. Claesson,
Silvia Melgar,
Ken Nally,
Noel M. Caplice,
Cormac G.M. Gahan
Affiliations
María A. Núñez-Sánchez
APC Microbiome Ireland, University College Cork, Cork, Ireland
Florence M. Herisson
APC Microbiome Ireland, University College Cork, Cork, Ireland
Jonathan M. Keane
APC Microbiome Ireland, University College Cork, Cork, Ireland
Natalia García-González
APC Microbiome Ireland, University College Cork, Cork, Ireland
Valerio Rossini
APC Microbiome Ireland, University College Cork, Cork, Ireland
Jorge Pinhiero
APC Microbiome Ireland, University College Cork, Cork, Ireland
Jack Daly
APC Microbiome Ireland, University College Cork, Cork, Ireland
Milán Bustamante-Garrido
APC Microbiome Ireland, University College Cork, Cork, Ireland
Cara M. Hueston
APC Microbiome Ireland, University College Cork, Cork, Ireland
Shriram Patel
APC Microbiome Ireland, University College Cork, Cork, Ireland
Nuria Canela
Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira I Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), Reus, Spain
Pol Herrero
Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (COS), Joint Unit Universitat Rovira I Virgili-EURECAT, Unique Scientific and Technical Infrastructures (ICTS), Reus, Spain
Marcus J. Claesson
APC Microbiome Ireland, University College Cork, Cork, Ireland
Silvia Melgar
APC Microbiome Ireland, University College Cork, Cork, Ireland
Ken Nally
APC Microbiome Ireland, University College Cork, Cork, Ireland
Noel M. Caplice
APC Microbiome Ireland, University College Cork, Cork, Ireland
Cormac G.M. Gahan
APC Microbiome Ireland, University College Cork, Cork, Ireland
The mechanisms by which early microbial colonizers of the neonate influence gut development are poorly understood. Bacterial bile salt hydrolase (BSH) acts as a putative colonization factor that influences bile acid signatures and microbe-host signaling pathways and we considered whether this activity can influence infant gut development. In silico analysis of the human neonatal gut metagenome confirmed that BSH enzyme sequences are present as early as one day postpartum. Gastrointestinal delivery of cloned BSH to immature gnotobiotic mice accelerated shortening of the colon and regularized gene expression profiles, with monocolonised mice more closely resembling conventionally raised animals. In situ expression of BSH decreased markers of cell proliferation (Ki67, Hes2 and Ascl2) and strongly increased expression of ALPI, a marker of cell differentiation and barrier function. These data suggest an evolutionary paradigm whereby microbial BSH activity potentially influences bacterial colonization and in-turn benefits host gastrointestinal maturation.
