PMID- 29912589 OWN - NLM STAT- Publisher LR - 20240227 IS - 1530-6860 (Electronic) IS - 0892-6638 (Print) IS - 0892-6638 (Linking) VI - 32 IP - 11 DP - 2018 Jun 18 TI - Lactobacillus plantarum prevents and mitigates alcohol-induced disruption of colonic epithelial tight junctions, endotoxemia, and liver damage by an EGF receptor-dependent mechanism. PG - fj201800351R LID - 10.1096/fj.201800351R [doi] AB - Pathogenesis of alcohol-related diseases such as alcoholic hepatitis involves gut barrier dysfunction, endotoxemia, and toxin-mediated cellular injury. Here we show that Lactobacillus plantarum not only blocks but also mitigates ethanol (EtOH)-induced gut and liver damage in mice. L. plantarum blocks EtOH-induced protein thiol oxidation, and down-regulation of antioxidant gene expression in colon L. plantarum also blocks EtOH-induced expression of TNF-alpha, IL-1beta, IL-6, monocyte chemotactic protein 1 ( MCP1), C-X-C motif chemokine ligand ( CXCL)1, and CXCL2 genes in colon. Epidermal growth factor receptor (EGFR) signaling mediates the L. plantarum-mediated protection of tight junctions (TJs) and barrier function from acetaldehyde, the EtOH metabolite, in Caco-2 cell monolayers. In mice, doxycycline-mediated expression of dominant negative EGFR blocks L. plantarum-mediated prevention of EtOH-induced TJ disruption, mucosal barrier dysfunction, oxidative stress, and inflammatory response in colon. L. plantarum blocks EtOH-induced endotoxemia as well as EtOH-induced pathologic lesions, triglyceride deposition, oxidative stress, and inflammatory responses in the liver by an EGFR-dependent mechanism. L. plantarum treatment after injury accelerated recovery from EtOH-induced TJ, barrier dysfunction, oxidative stress, and inflammatory response in colon, endotoxemia, and liver damage. Results demonstrate that L. plantarum has both preventive and therapeutic values in treatment of alcohol-induced tissue injury, particularly in alcoholic hepatitis.-Shukla, P. K., Meena, A. S., Manda, B., Gomes-Solecki, M., Dietrich, P., Dragatsis, I., Rao, R. Lactobacillus plantarum prevents and mitigates alcohol-induced disruption of colonic epithelial tight junctions, endotoxemia, and liver damage by an EGF receptor-dependent mechanism. FAU - Shukla, Pradeep K AU - Shukla PK AD - Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA. FAU - Meena, Avtar S AU - Meena AS AD - Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA. FAU - Manda, Bhargavi AU - Manda B AD - Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA. FAU - Gomes-Solecki, Maria AU - Gomes-Solecki M AD - Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA. FAU - Dietrich, Paula AU - Dietrich P AD - Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA. FAU - Dragatsis, Ioannis AU - Dragatsis I AD - Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA. FAU - Rao, RadhaKrishna AU - Rao R AD - Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA. LA - eng GR - R01 DK055532/DK/NIDDK NIH HHS/United States GR - R43 AI136551/AI/NIAID NIH HHS/United States GR - R56 DK055532/DK/NIDDK NIH HHS/United States GR - R43 AI096551/AI/NIAID NIH HHS/United States GR - R01 AA012307/AA/NIAAA NIH HHS/United States PT - Journal Article DEP - 20180618 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 PMC - PMC6181630 OTO - NOTNLM OT - alcoholic hepatitis OT - barrier function OT - colon OT - cytokines OT - probiotics COIS- This study was supported by U.S. National Institutes of Health Grants AA12307 (National Institute on Alcohol Abuse and Alcoholism) and DK55532 (National Institute of Diabetes and Digestive and Kidney Diseases) to R.R. The authors declare no conflicts of interest. EDAT- 2018/06/19 06:00 MHDA- 2018/06/19 06:00 PMCR- 2019/11/01 CRDT- 2018/06/19 06:00 PHST- 2018/06/19 06:00 [entrez] PHST- 2018/06/19 06:00 [pubmed] PHST- 2018/06/19 06:00 [medline] PHST- 2019/11/01 00:00 [pmc-release] AID - FJ_201800351R [pii] AID - 10.1096/fj.201800351R [doi] PST - aheadofprint SO - FASEB J. 2018 Jun 18;32(11):fj201800351R. doi: 10.1096/fj.201800351R.