@article{fc4a7e0a44ee45eba40d1b657dbb62e3,
title = "Host miRNA-21 promotes liver dysfunction by targeting small intestinal Lactobacillus in mice",
abstract = "New evidence shows that host-microbiota crosstalk can be modulated via endogenous miRNAs. We have previously reported that miR-21 ablation protects against liver injury in cholestasis. In this study, we investigated the role of miR-21 in modulating the gut microbiota during cholestasis and its effects in liver dysfunction. Mice lacking miR-21 had reduced liver damage and were protected against small intestinal injury as well as from gut microbiota dysbiosis when subjected to bile duct ligation surgery. The unique microbiota profile of miR-21KO mice was characterized by an increase in Lactobacillus, a key microbiome genus for gut homeostasis. Interestingly, in vitro incubation of synthetic miR-21 directly reduced Lactobacillus load. Moreover, supplementation with Lactobacillus reuteri revealed reduced liver fibrosis in acute bile duct-ligated mice, mimicking the protective effects in miR-21 knockout mice. D-lactate, a main product of Lactobacillus, regulates gut homeostasis that may link with reduced liver fibrosis. Altogether, our results demonstrate that miR-21 promotes liver dysfunction through direct modulation of the gut microbiota and highlight the potential therapeutic effects of Lactobacillus supplementation in gut and liver homeostasis.",
keywords = "Cholestasis, D-lactate, Gut microbiota, miRNAs, Small intestinal homeostasis",
author = "Santos, {Andr{\'e} A.} and Afonso, {Marta B.} and Ramiro, {Ricardo S.} and David Pires and Madalena Pimentel and Castro, {Rui E.} and Rodrigues, {Cec{\'i}lia M. P.}",
note = "Funding Information: This study was supported t by Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia [PTDC/MED-FAR/29097/2017]. AAS was supported by young researcher contract from Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (CEECIND/04663/2017). RSR was supported by post-doctoral fellowship from Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia (SFRH/BPD/119110/2016) and from the ONEIDA Project (LISBOA-01-0145-FEDER-016417) co-funded by FEEI - “Fundos Europeus Estruturais e de Investimento” - from “Programa Operacional Regional Lisboa 2020” and by national funds from Funda{\c c}{\~a}o para a Ci{\^e}ncia e aTecnologia. The authors thank Eric Olson (Southwestern Medical Center, University of Texas, USA) for kindly providing miR-21KO mice, Jo{\~a}o Sobral (Genomics Unit, Instituto Gulbenkian de Ci{\^e}ncia, Portugal) for the analysis of the bacterial DNA, and Stefan Roos (Biogaia, USA) for kindly providing Lactobacillus strains. We also thank Manuela Gaspar (iMed.ULisboa, Universidade de Lisboa) for help in the animal facility, T{\^a}nia Carvalho and Pedro Ruivo (iMM, Universidade de Lisboa) for support with histology analysis, and Elisa Micaelo (Faculty of Pharmacy, Universidade de Lisboa) for serum biochemistries. Finally, we thank all members of the laboratory for insightful discussions; particular thanks to Pedro Rodrigues. Publisher Copyright: {\textcopyright} 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.",
year = "2020",
doi = "10.1080/19490976.2020.1840766",
language = "English",
volume = "12",
pages = "1--18",
journal = "Gut Microbes",
issn = "1949-0976",
publisher = "Landes Bioscience",
number = "1",
}