{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T08:17:41Z","timestamp":1776154661929,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cystic Fibrosis Trust SRC 011","award":["Se460\/19-1"],"award-info":[{"award-number":["Se460\/19-1"]}]},{"name":"Cystic Fibrosis Trust SRC 011","award":["For5046 Se460\/22-1"],"award-info":[{"award-number":["For5046 Se460\/22-1"]}]},{"DOI":"10.13039\/501100001659","name":"the Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Se460\/19-1"],"award-info":[{"award-number":["Se460\/19-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"the Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["For5046 Se460\/22-1"],"award-info":[{"award-number":["For5046 Se460\/22-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mutations in the CFTR chloride channel result in intestinal obstructive episodes in cystic fibrosis (CF) patients and in CF animal models. In this study, we explored the possibility of reducing the frequency of obstructive episodes in cftr\u2212\/\u2212 mice through the oral application of a gut-selective NHE3 inhibitor tenapanor and searched for the underlying mechanisms involved. Sex- and age-matched cftr+\/+ and cftr\u2212\/\u2212 mice were orally gavaged twice daily with 30 mg kg\u22121 tenapanor or vehicle for a period of 21 days. Body weight and stool water content was assessed daily and gastrointestinal transit time (GTT) once weekly. The mice were sacrificed when an intestinal obstruction was suspected or after 21 days, and stool and tissues were collected for further analysis. Twenty-one day tenapanor application resulted in a significant increase in stool water content and stool alkalinity and a significant decrease in GTT in cftr+\/+ and cftr\u2212\/\u2212 mice. Tenapanor significantly reduced obstructive episodes to 8% compared to 46% in vehicle-treated cftr\u2212\/\u2212 mice and prevented mucosal inflammation. A decrease in cryptal hyperproliferation, mucus accumulation, and mucosal mast cell number was also observed in tenapanor- compared to vehicle-treated, unobstructed cftr\u2212\/\u2212 mice. Overall, oral tenapanor application prevented obstructive episodes in CFTR-deficient mice and was safe in cftr+\/+ and cftr\u2212\/\u2212 mice. These results suggest that tenapanor may be a safe and affordable adjunctive therapy in cystic fibrosis patients to alleviate constipation and prevent recurrent DIOS.<\/jats:p>","DOI":"10.3390\/ijms23179993","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T21:27:17Z","timestamp":1662067637000},"page":"9993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The NHE3 Inhibitor Tenapanor Prevents Intestinal Obstructions in CFTR-Deleted Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Xinjie","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3392-642X","authenticated-orcid":false,"given":"Archana","family":"Kini","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothee","family":"R\u00f6mermann","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9600-2769","authenticated-orcid":false,"given":"Ursula","family":"Seidler","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/MPG.0b013e3181a6e01d","article-title":"Defining DIOS and Constipation in Cystic Fibrosis with a Multicentre Study on the Incidence, Characteristics, and Treatment of DIOS","volume":"50","author":"Houwen","year":"2010","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1136\/flgastro-2012-100184","article-title":"Gastrointestinal surgery in adult patients with cystic fibrosis","volume":"3","author":"Sharma","year":"2012","journal-title":"Front. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e805","DOI":"10.1097\/DCR.0000000000002162","article-title":"Abdominal Surgical Procedures in Adult Patients with Cystic Fibrosis: What Are the Risks?","volume":"65","author":"Hite","year":"2022","journal-title":"Dis. Colon Rectum"},{"key":"ref_4","first-page":"Cd012798","article-title":"Interventions for treating distal intestinal obstruction syndrome (DIOS) in cystic fibrosis","volume":"12","author":"Gilchrist","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","first-page":"Cd012619","article-title":"Interventions for preventing distal intestinal obstruction syndrome (DIOS) in cystic fibrosis","volume":"12","author":"Carroll","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1177\/2050640619841545","article-title":"A high prevalence of chronic gastrointestinal symptoms in adults with cystic fibrosis is detected using tools already validated in other GI disorders","volume":"7","author":"Hayee","year":"2019","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Beaufils, F., Mas, E., Mittaine, M., Addra, M., Fayon, M., Delhaes, L., Clouzeau, H., Galode, F., Lamireau, T., and Bui, S. (2020). Increased Fecal Calprotectin is Associated with Worse Gastrointestinal Symptoms and Quality of Life Scores in Children with Cystic Fibrosis. J. Clin. Med., 9.","DOI":"10.3390\/jcm9124080"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1097\/MPG.0000000000003357","article-title":"Abdominal Symptoms Assessed With the CFAbd-Score are Associated with Intestinal Inflammation in Patients with Cystic Fibrosis","volume":"74","author":"Jaudszus","year":"2022","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"G104","DOI":"10.1152\/ajpgi.00548.2006","article-title":"Altered transit and bacterial overgrowth in the cystic fibrosis mouse small intestine","volume":"293","year":"2007","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1016\/j.jcf.2017.07.014","article-title":"Bacterial overgrowth, dysbiosis, inflammation, and dysmotility in the Cystic Fibrosis intestine","volume":"16","author":"Dorsey","year":"2017","journal-title":"J. Cyst. Fibros."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5223\/pghn.2022.25.1.1","article-title":"Fecal Calprotectin and Phenotype Severity in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis","volume":"25","author":"Talebi","year":"2022","journal-title":"Pediatr. Gastroenterol. Hepatol. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1097\/MPG.0000000000002864","article-title":"Reduced Intestinal Inflammation with Lumacaftor\/Ivacaftor in Adolescents with Cystic Fibrosis","volume":"71","author":"Mittaine","year":"2020","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1097\/MCP.0b013e3283659ef2","article-title":"Intestinal complications of cystic fibrosis","volume":"19","author":"Borowitz","year":"2013","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_14","first-page":"612","article-title":"Increased survival of CFTR knockout mice with an oral osmotic laxative","volume":"46","author":"Clarke","year":"1996","journal-title":"Lab. Anim. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1126\/science.1163600","article-title":"Disruption of the CFTR Gene Produces a Model of Cystic Fibrosis in Newborn Pigs","volume":"321","author":"Rogers","year":"2008","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1172\/JCI68867","article-title":"Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs","volume":"123","author":"Stoltz","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1111\/bph.15323","article-title":"Inhibition of Na +\/H + exchanger isoform 3 improves gut fluidity and alkalinity in cystic fibrosis transmembrane conductance regulator-deficient and F508del mutant mice","volume":"178","author":"Tan","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.jcf.2021.12.007","article-title":"Magnetic resonance imaging of the gastrointestinal tract shows reduced small bowel motility and altered chyme in cystic fibrosis compared to controls","volume":"21","author":"Dellschaft","year":"2021","journal-title":"J. Cyst. Fibros."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e13883","DOI":"10.1111\/nmo.13883","article-title":"Motor dysfunction of the gut in cystic fibrosis","volume":"32","author":"Malagelada","year":"2020","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.jcf.2016.06.005","article-title":"A novel guluronate oligomer improves intestinal transit and survival in cystic fibrosis mice","volume":"15","author":"Vitko","year":"2016","journal-title":"J. Cyst. Fibros."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e13498","DOI":"10.1111\/apha.13498","article-title":"Slc26a3 deletion alters pH-microclimate, mucin biosynthesis, microbiome composition and increases the TNF\u03b1 expression in murine colon","volume":"230","author":"Kini","year":"2020","journal-title":"Acta Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"G1032","DOI":"10.1152\/ajpgi.00473.2003","article-title":"Inflammation of the cystic fibrosis mouse small intestine","volume":"286","author":"Norkina","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9320","DOI":"10.1038\/s41598-018-27465-3","article-title":"Kcnn4 is a modifier gene of intestinal cystic fibrosis preventing lethality in the Cftr-F508del mouse","volume":"8","author":"Philp","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5056","DOI":"10.1074\/jbc.M808128200","article-title":"Slc2a5 (Glut5) Is Essential for the Absorption of Fructose in the Intestine and Generation of Fructose-induced Hypertension","volume":"284","author":"Barone","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/969","article-title":"Renal and intestinal absorptive defects in mice lacking the NHE3 Na+\/H+ exchanger","volume":"19","author":"Schultheis","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1042\/CS20200065","article-title":"An inducible intestinal epithelial cell-specific NHE3 knockout mouse model mimicking congenital sodium diarrhea","volume":"134","author":"Xue","year":"2020","journal-title":"Clin. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1113\/expphysiol.2005.029959","article-title":"H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine","volume":"92","author":"Thwaites","year":"2007","journal-title":"Exp. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1111\/bcp.13313","article-title":"Tenapanor administration and the activity of the H+ -coupled transporter PepT1 in healthy volunteers","volume":"83","author":"Johansson","year":"2017","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1002\/jcp.20337","article-title":"Indirect regulation of the intestinal H+-coupled amino acid transporter hPAT1 (SLC36A1)","volume":"204","author":"Anderson","year":"2005","journal-title":"J. Cell. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"G423","DOI":"10.1152\/ajpgi.00167.2016","article-title":"Intestinal brush-border Na+\/H+ exchanger-3 drives H+-coupled iron absorption in the mouse","volume":"311","author":"Shawki","year":"2016","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1126\/science.257.5073.1083","article-title":"An Animal Model for Cystic Fibrosis Made by Gene Targeting","volume":"257","author":"Snouwaert","year":"1992","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1124\/jpet.105.094847","article-title":"Talniflumate Increases Survival in a Cystic Fibrosis Mouse Model of Distal Intestinal Obstructive Syndrome","volume":"317","author":"Walker","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lord, R., Fairbourn, N., Mylavarapu, C., Dbeis, A., Bowman, T., Chandrashekar, A., Banayat, T., Hodges, C.A., and Al-Nakkash, L. (2018). Consuming Genistein Improves Survival Rates in the Absence of Laxative in \u0394F508-CF Female Mice. Nutrients, 10.","DOI":"10.20944\/preprints201808.0084.v1"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"G681","DOI":"10.1152\/ajpgi.2001.281.3.G681","article-title":"Proliferation, not apoptosis, alters epithelial cell migration in small intestine of CFTR null mice","volume":"281","author":"Gallagher","year":"2001","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"G1241","DOI":"10.1152\/ajpgi.00493.2004","article-title":"Chloride conductance of CFTR facilitates basal Cl\u2212\/HCO3\u2212exchange in the villous epithelium of intact murine duodenum","volume":"288","author":"Simpson","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"C1492","DOI":"10.1152\/ajpcell.00392.2011","article-title":"Functional Cftr in crypt epithelium of organotypic enteroid cultures from murine small intestine","volume":"302","author":"Liu","year":"2012","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.jcmgh.2017.11.013","article-title":"Cftr Modulates Wnt\/\u03b2-Catenin Signaling and Stem Cell Proliferation in Murine Intestine","volume":"5","author":"Strubberg","year":"2018","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1053\/j.gastro.2015.11.047","article-title":"Human Enteroids as a Model of Upper Small Intestinal Ion Transport Physiology and Pathophysiology","volume":"150","author":"In","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"G82","DOI":"10.1152\/ajpgi.00245.2010","article-title":"Physiological relevance of cell-specific distribution patterns of CFTR, NKCC1, NBCe1, and NHE3 along the crypt-villus axis in the intestine","volume":"300","author":"Jakab","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"G886","DOI":"10.1152\/ajpgi.90520.2008","article-title":"Reduced NHE3-mediated Na+ absorption increases survival and decreases the incidence of intestinal obstructions in cystic fibrosis mice","volume":"296","author":"Bradford","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"G203","DOI":"10.1152\/ajpgi.00491.2005","article-title":"Increased levels of mucins in the cystic fibrosis mouse small intestine, and modulator effects of the Muc1 mucin expression","volume":"291","author":"Malmberg","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1172\/JCI3820","article-title":"Cystic fibrosis mice lacking Muc1 have reduced amounts of intestinal mucus","volume":"102","author":"Parmley","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1203\/00006450-200003000-00010","article-title":"Evidence of Chronic Inflammation in Morphologically Normal Small Intestine of Cystic Fibrosis Patients","volume":"47","author":"Raia","year":"2000","journal-title":"Pediatr. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/j.1365-2036.2004.02174.x","article-title":"Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration","volume":"20","author":"Bruzzese","year":"2004","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1097\/MPG.0b013e3181d1b013","article-title":"Evidence of Intestinal Inflammation in Patients With Cystic Fibrosis","volume":"51","author":"Werlin","year":"2010","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"322","DOI":"10.3109\/00365513.2010.486869","article-title":"Small intestine bacterial overgrowth does not correspond to intestinal inflammation in cystic fibrosis","volume":"70","author":"Lisowska","year":"2010","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.bbadis.2011.12.012","article-title":"Oxidative stress and antioxidant therapy in cystic fibrosis","volume":"1822","author":"Galli","year":"2012","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s12950-015-0107-y","article-title":"CFTR Knockdown induces proinflammatory changes in intestinal epithelial cells","volume":"12","author":"Crites","year":"2015","journal-title":"J. Inflamm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"318","DOI":"10.3748\/wjg.v21.i1.318","article-title":"Long-term follow-up of distal intestinal obstruction syndrome in cystic fibrosis","volume":"21","author":"Lavie","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jcf.2016.02.002","article-title":"International prospective study of distal intestinal obstruction syndrome in cystic fibrosis: Associated factors and outcome","volume":"15","author":"Munck","year":"2016","journal-title":"J. Cyst. Fibros."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1164\/rccm.202110-2249OC","article-title":"Effects of Elexacaftor\/Tezacaftor\/Ivacaftor Therapy on CFTR Function in Patients with Cystic Fibrosis and One or Two F508del Alleles","volume":"205","author":"Graeber","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"17834","DOI":"10.1038\/s41598-018-36364-6","article-title":"Impact of CFTR modulation with Ivacaftor on Gut Microbiota and Intestinal Inflammation","volume":"8","author":"Ooi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1080\/17512433.2020.1762570","article-title":"Tenapanor for the treatment of irritable bowel syndrome with constipation","volume":"13","author":"Sinagra","year":"2020","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.34067\/KID.0002002021","article-title":"Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM)","volume":"2","author":"Block","year":"2021","journal-title":"Kidney360"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/ng0593-35","article-title":"Production of a severe cystic fibrosis mutation in mice by gene targeting","volume":"4","author":"Ratcliff","year":"1993","journal-title":"Nat. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5317","DOI":"10.1113\/jphysiol.2012.232124","article-title":"Rescue of epithelial HCO3\u2212 secretion in murine intestine by apical membrane expression of the cystic fibrosis transmembrane conductance regulator mutant F508del","volume":"590","author":"Xiao","year":"2012","journal-title":"J. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1177\/0023677217733010","article-title":"How can we assess their suffering? German research consortium aims at defining a severity assessment framework for laboratory animals","volume":"51","author":"Bleich","year":"2017","journal-title":"Lab. Anim."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1111\/bph.15193","article-title":"The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research","volume":"177","author":"Hurst","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2041943","DOI":"10.1080\/19490976.2022.2041943","article-title":"Upregulation of antimicrobial peptide expression in slc26a3\u2212\/\u2212 mice with colonic dysbiosis and barrier defect","volume":"14","author":"Kini","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Alshamy, Z., Richardson, K.C., H\u00fcnigen, H., Hafez, H.M., Plendl, J., and Al Masri, S. (2018). Comparison of the gastrointestinal tract of a dual-purpose to a broiler chicken line: A qualitative and quantitative macroscopic and microscopic study. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0204921"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.1038\/s41598-017-04429-7","article-title":"Increasing cell density globally enhances the biogenesis of Piwi-interacting RNAs in Bombyx mori germ cells","volume":"7","author":"Honda","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/9993\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:22:05Z","timestamp":1760142125000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/9993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,1]]},"references-count":62,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms23179993"],"URL":"https:\/\/doi.org\/10.3390\/ijms23179993","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,1]]}}}