{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T18:06:08Z","timestamp":1765994768301,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T00:00:00Z","timestamp":1606348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005851","name":"Shahid Beheshti University of Medical Sciences","doi-asserted-by":"publisher","award":["RIGLD 851"],"award-info":[{"award-number":["RIGLD 851"]}],"id":[{"id":"10.13039\/501100005851","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Abnormal activation of Toll-like receptor (TLRs) signaling can result in colon cancer development. The aim of this study was to investigate the expression of important TLRs in different histological types of colorectal polyps and evaluate their relationship with intestinal microbiota. The expression levels of TLR2, 3, 4, and 5 were analyzed in intestinal biopsy specimens of 21 hyperplastic polyp (HP), 16 sessile serrated adenoma (SSA), 29 tubular adenoma (TA), 21 villous\/tubulovillous (VP\/TVP) cases, and 31 normal controls. In addition, selected gut bacteria including Streptococcus bovis, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum, Porphyromonas spp., Lactobacillus spp., Roseburia spp., and Bifidobacterium spp. were quantified in fecal samples using absolute qRT PCR, and, finally, the association between TLRs and these gut microbiota- was evaluated by Spearman\u2019s correlation coefficient. Higher expression of TLR2 and TLR4 in VP\/TVP and TA, and lower expression levels of TLR3 and TLR5 in all type of polyps were observed. The differences in TLR expression patterns was not only dependent on the histology, location, size, and dysplasia grade of polyps but also related to the intestinal microbiota patterns. TLR2 and TLR4 expression was directly associated with the F. nucleatum, E. faecalis, S. bovis, Porphyromonas, and inversely to Bifidobacterium, Lactobacillus, and Roseburia quantity. Furthermore, TLR3 and TLR5 expression was directly associated with Bifidobacterium, Roseburia, and Lactobacillus quantity. Our results suggest a possible critical role of TLRs during colorectal polyp progression. An abnormal regulation of TLRs in relation to gut microbial quantity may contribute to carcinogenesis.<\/jats:p>","DOI":"10.3390\/ijms21238968","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T09:04:15Z","timestamp":1606381455000},"page":"8968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Expression of Main Toll-Like Receptors in Patients with Different Types of Colorectal Polyps and Their Relationship with Gut Microbiota"],"prefix":"10.3390","volume":"21","author":[{"given":"Sama","family":"Rezasoltani","sequence":"first","affiliation":[{"name":"Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reza","family":"Ghanbari","sequence":"additional","affiliation":[{"name":"Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran 1411713135, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0700-1431","authenticated-orcid":false,"given":"Mehdi Azizmohammad","family":"Looha","sequence":"additional","affiliation":[{"name":"Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehsan Nazemalhosseini","family":"Mojarad","sequence":"additional","affiliation":[{"name":"Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2135-7581","authenticated-orcid":false,"given":"Abbas","family":"Yadegar","sequence":"additional","affiliation":[{"name":"Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7516-2790","authenticated-orcid":false,"given":"Delisha","family":"Stewart","sequence":"additional","affiliation":[{"name":"Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5589-8856","authenticated-orcid":false,"given":"Hamid Asadzadeh","family":"Aghdaei","sequence":"additional","affiliation":[{"name":"Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Reza","family":"Zali","sequence":"additional","affiliation":[{"name":"Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.5217\/ir.2019.00021","article-title":"Prevalence and risk factors of colorectal cancer in Asia","volume":"17","author":"Wong","year":"2019","journal-title":"Intest. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.5114\/pg.2018.81072","article-title":"Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors","volume":"14","author":"Rawla","year":"2019","journal-title":"Gastroenterol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1158\/1055-9965.EPI-16-0337","article-title":"Shifts in the Fecal Microbiota Associated with Adenomatous Polyps","volume":"26","author":"Hale","year":"2017","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40168-016-0218-6","article-title":"The gut microbiota in conventional and serrated precursors of colorectal cancer","volume":"4","author":"Peters","year":"2016","journal-title":"Microbiome"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1365-2559.2006.02549.x","article-title":"Classification of colorectal cancer based on correlation of clinical, morphological and molecular features","volume":"50","author":"Jass","year":"2007","journal-title":"Histopathology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1159\/000366032","article-title":"Serrated and Non-Serrated Precursor Lesions of Colorectal Cancer","volume":"33","author":"Langner","year":"2015","journal-title":"Dig. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1056\/NEJMra1513581","article-title":"Colorectal Adenomas","volume":"374","author":"Strum","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"G351","DOI":"10.1152\/ajpgi.00360.2012","article-title":"The gastrointestinal microbiota and colorectal cancer","volume":"308","author":"Keku","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.3389\/fimmu.2018.02223","article-title":"Receptors and Signaling Pathways for Recognition of Bacteria in Livestock and Crops: Prospects for Beneficial Microbes in Healthy Growth Strategies","volume":"9","author":"Villena","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_10","first-page":"55","article-title":"Gut microbiota, epigenetic modification and colorectal cancer","volume":"9","author":"Rezasoltani","year":"2017","journal-title":"Iran. J. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrc2541","article-title":"Toll-like receptors and cancer","volume":"9","author":"Medzhitov","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17699","DOI":"10.3748\/wjg.v20.i47.17699","article-title":"Toll-like receptor signaling in colorectal cancer: Carcinogenesis to cancer therapy","volume":"20","author":"Li","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.cell.2017.07.008","article-title":"Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy","volume":"170","author":"Yu","year":"2017","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"428","DOI":"10.2174\/157436211797483930","article-title":"Toll Like Receptors Signaling Pathways as a Target for Therapeutic Interventions","volume":"6","author":"Jezierka","year":"2011","journal-title":"Curr. Signal Transduct. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1177\/0394632017716048","article-title":"Profile of gene expression of TLR-signaling pathways in colorectal cancer tissues","volume":"30","author":"Bednarczyk","year":"2017","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.cyto.2016.01.021","article-title":"TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis","volume":"89","author":"Kirill","year":"2017","journal-title":"Cytokine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1007\/s10875-012-9719-7","article-title":"Toll-like receptor expression pattern: Clinical application","volume":"32","author":"Moossavi","year":"2012","journal-title":"J. Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.31557\/APJCP.2019.20.8.2299","article-title":"Investigating the TLR9 mRNA Expression Level in Different Histological Types of Colorectal Polyps","volume":"20","author":"Rezasoltani","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1007\/s10875-012-9666-3","article-title":"Study of the Expression of Toll-Like Receptors in Different Histological Types of Colorectal Polyps and Their Relationship with Colorectal Cancer","volume":"32","author":"Eiro","year":"2012","journal-title":"J. Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.molmed.2013.08.005","article-title":"Microbiota impact on the epigenetic regulation of colorectal cancer","volume":"19","author":"Yang","year":"2013","journal-title":"Trends Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1111\/j.1753-4887.2012.00498.x","article-title":"Microbiome and immunological interactions","volume":"70","author":"Kelly","year":"2012","journal-title":"Nutr. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3389\/fimmu.2015.00481","article-title":"Editorial: Pattern Recognition Receptors and Cancer","volume":"6","author":"Kutikhin","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5963","DOI":"10.2147\/OTT.S174274","article-title":"TLR9 signaling activation at different stages in colorectal cancer and NF-kappaB expression","volume":"11","author":"Gao","year":"2018","journal-title":"OncoTargets Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1080\/09168451.2016.1254534","article-title":"Expression of TLR2 and TLR4 in murine small intestine during postnatal development","volume":"81","author":"Inoue","year":"2016","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/gastro\/gox031","article-title":"Dysbiosis of gut microbiota in promoting the development of colorectal cancer","volume":"6","author":"Zou","year":"2018","journal-title":"Gastroenterol. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00109-016-1474-4","article-title":"Interaction between gut microbiota and toll-like receptor: From immunity to metabolism","volume":"95","author":"Yiu","year":"2017","journal-title":"J. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.micpath.2018.08.035","article-title":"The association between fecal microbiota and different types of colorectal polyp as precursors of colorectal cancer","volume":"124","author":"Rezasoltani","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.mimet.2018.11.007","article-title":"Applying simple linear combination, multiple logistic and factor analysis methods for candidate fecal bacteria as novel biomarkers for early detection of adenomatous polyps and colon cancer","volume":"155","author":"Rezasoltani","year":"2018","journal-title":"J. Microbiol. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.18632\/oncotarget.6549","article-title":"Epigenetic modification of TLR4 promotes activation of NF-\u03baB by regulating methyl-CpG-binding domain protein 2 and Sp1 in gastric cancer","volume":"7","author":"Kim","year":"2015","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1159\/000445659","article-title":"TLR4 Overexpression Inhibits Endothelial PAS Domain-Containing Protein 1 Expression in the Lower Respiratory Tract of Patients with Chronic COPD","volume":"39","author":"Li","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1477-7827-6-40","article-title":"TLR3 and TLR4 expression in healthy and diseased human endometrium","volume":"6","author":"Allhorn","year":"2008","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_32","first-page":"19","article-title":"Evaluating the expression level of co-stimulatory molecules CD 80 and CD 86 in different types of colon polyps","volume":"66","author":"Peyravian","year":"2018","journal-title":"Curr. Res. Transl. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/8968\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:37:33Z","timestamp":1760179053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/8968"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,26]]},"references-count":32,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21238968"],"URL":"https:\/\/doi.org\/10.3390\/ijms21238968","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2020,11,26]]}}}