PMID- 33917155 OWN - NLM STAT- MEDLINE DCOM- 20210526 LR - 20240226 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 13 IP - 4 DP - 2021 Apr 7 TI - Probiotics Supplements Reduce ER Stress and Gut Inflammation Associated with Gliadin Intake in a Mouse Model of Gluten Sensitivity. LID - 10.3390/nu13041221 [doi] LID - 1221 AB - Exposure to gluten, a protein present in wheat rye and barley, is the major inducer for human Celiac Disease (CD), a chronic autoimmune enteropathy. CD occurs in about 1% worldwide population, in genetically predisposed individuals bearing human leukocyte antigen (HLA) DQ2/DQ8. Gut epithelial cell stress and the innate immune activation are responsible for the breaking oral tolerance to gliadin, a gluten component. To date, the only treatment available for CD is a long-term gluten-free diet. Several studies have shown that an altered composition of the intestinal microbiota (dysbiosis) could play a key role in the pathogenesis of CD through the modulation of intestinal permeability and the regulation of the immune system. Here, we show that gliadin induces a chronic endoplasmic reticulum (ER) stress condition in the small intestine of a gluten-sensitive mouse model and that the coadministration of probiotics efficiently attenuates both the unfolded protein response (UPR) and gut inflammation. Moreover, the composition of probiotics formulations might differ in their activity at molecular level, especially toward the three axes of the UPR. Therefore, probiotics administration might potentially represent a new valuable strategy to treat gluten-sensitive patients, such as those affected by CD. FAU - Ferrari, Eleonora AU - Ferrari E AD - Department of Health Science, University of Piemonte Orientale, 28100 Novara, Italy. AD - Center for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, 28100 Novara, Italy. FAU - Monzani, Romina AU - Monzani R AD - Department of Health Science, University of Piemonte Orientale, 28100 Novara, Italy. AD - Center for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, 28100 Novara, Italy. FAU - Saverio, Valentina AU - Saverio V AUID- ORCID: 0000-0002-1770-2661 AD - Department of Health Science, University of Piemonte Orientale, 28100 Novara, Italy. AD - Center for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, 28100 Novara, Italy. FAU - Gagliardi, Mara AU - Gagliardi M AD - Department of Health Science, University of Piemonte Orientale, 28100 Novara, Italy. AD - Center for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, 28100 Novara, Italy. FAU - Panczyszyn, Elzbieta AU - Panczyszyn E AD - Department of Health Science, University of Piemonte Orientale, 28100 Novara, Italy. AD - Center for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, 28100 Novara, Italy. FAU - Raia, Valeria AU - Raia V AD - Regional Cystic Fibrosis Center, Pediatric Unit, Department of Translational Medical Sciences, Federico II University Naples, 80134 Naples, Italy. AD - European Institute for Research in Cystic Fibrosis (IERFC-Onlus), San Raffaele Scientific Institute, 20132 Milan, Italy. FAU - Villella, Valeria Rachela AU - Villella VR AUID- ORCID: 0000-0003-4858-4853 AD - European Institute for Research in Cystic Fibrosis (IERFC-Onlus), San Raffaele Scientific Institute, 20132 Milan, Italy. FAU - Bona, Gianni AU - Bona G AUID- ORCID: 0000-0003-0611-7341 AD - Division of Pediatrics, Department of Health Science, University of Piemonte Orientale, 28100 Novara, Italy. FAU - Pane, Marco AU - Pane M AD - Probiotical Research Srl, 28100 Novara, Italy. FAU - Amoruso, Angela AU - Amoruso A AD - Probiotical Research Srl, 28100 Novara, Italy. FAU - Corazzari, Marco AU - Corazzari M AUID- ORCID: 0000-0002-6246-5968 AD - Department of Health Science, University of Piemonte Orientale, 28100 Novara, Italy. AD - Center for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, 28100 Novara, Italy. AD - Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, 28100 Novara, Italy. LA - eng PT - Journal Article DEP - 20210407 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Anti-Inflammatory Agents) RN - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator) RN - 8002-80-0 (Glutens) RN - 9007-90-3 (Gliadin) RN - EC 2.3.2.13 (Protein Glutamine gamma Glutamyltransferase 2) RN - EC 2.3.2.13 (Transglutaminases) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology/therapeutic use MH - Caco-2 Cells MH - Cystic Fibrosis Transmembrane Conductance Regulator/metabolism MH - *Dietary Supplements MH - Disease Models, Animal MH - *Endoplasmic Reticulum Stress/drug effects MH - Food Intolerance/*therapy MH - GTP-Binding Proteins/metabolism MH - Gastrointestinal Tract/drug effects/*pathology MH - Gliadin/*adverse effects MH - Glutens/*adverse effects MH - Humans MH - Inflammation/*pathology MH - Mice, Inbred BALB C MH - Permeability MH - Probiotics/administration & dosage/*therapeutic use MH - Protein Glutamine gamma Glutamyltransferase 2 MH - Transglutaminases/metabolism MH - Up-Regulation MH - Mice PMC - PMC8067866 OTO - NOTNLM OT - CD OT - CFTR OT - TG2 OT - UPR OT - probiotics COIS- A.A. and M.P. are employees of Probiotical Research srl and have the following competing interests: probiotics production. They have no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. EDAT- 2021/05/01 06:00 MHDA- 2021/05/27 06:00 PMCR- 2021/04/07 CRDT- 2021/04/30 01:05 PHST- 2020/12/22 00:00 [received] PHST- 2021/01/20 00:00 [revised] PHST- 2021/04/06 00:00 [accepted] PHST- 2021/04/30 01:05 [entrez] PHST- 2021/05/01 06:00 [pubmed] PHST- 2021/05/27 06:00 [medline] PHST- 2021/04/07 00:00 [pmc-release] AID - nu13041221 [pii] AID - nutrients-13-01221 [pii] AID - 10.3390/nu13041221 [doi] PST - epublish SO - Nutrients. 2021 Apr 7;13(4):1221. doi: 10.3390/nu13041221.