Intestinal epithelial cell toll-like receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice
Open accessAbstract
Background & aims Mice lacking the receptor Toll-like receptor 5 (TLR5-null mice), which recognizes flagellin, have an altered intestinal microbiota composition compared with wild-type mice; they develop low-grade inflammation and metabolic syndrome and are prone to colitis. The relative roles of intestinal epithelial cell (IEC) vs dendritic cell (DC) TLR5 in mediating these phenotypes are not clear; modification of intestinal microbiota composition has been reported to reflect animal husbandry practices rather than loss of TLR5. We generated mice with specific disruption of Tlr5 in IECs or DCs by using a breeding scheme that allows comparison with cohoused siblings as controls.Methods We generated C57BL/6 mice with LoxP sites flanking Tlr5. These mice were crossed with mice expressing Cre recombinase, regulated by the villin or CD11c promoters, to generate mice that lacked expression of TLR5 by IECs (TLR5(ΔIEC)) or DCs (TLR5(ΔDC)), respectively. Tlr5(fl/fl) siblings were used as controls. On weaning, mice were housed by sex and genotype or by sex only (genotypes cohoused). Mice were examined for basal phenotypes, including microbiota composition; we also analyzed responses to pathobiont challenge, administration of dextran sodium sulfate, and high-fat diets.Results Similar to previous findings from TLR5-null mice, TLR5(ΔIEC) mice had low-grade inflammation (mild splenomegaly, shortened colons, and increased fecal levels of lipocalin 2), metabolic syndrome, and an inability to clear pathobionts and were prone to developing colitis compared with their sibling controls under both housing conditions. Development of this inflammation in the TLR5(ΔIEC) mice was eliminated by administration of antibiotics and associated with alterations in localization of microbiota and levels of fecal lipopolysaccharide and flagellin. The composition of the microbiota clustered more closely according to genotype than housing. Loss of TLR5 from DCs did not associate with development of inflammation-associated phenotypes or alterations in the composition of the microbiota but resulted in complete loss of flagellin-induced production of interleukin-22.Conclusions In mice, flagellin activation of TLR5 on DCs leads to production of interleukin-22. Expression of TLR5 on IECs regulates the composition and localization of the intestinal microbiota, preventing diseases associated with intestinal inflammation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Expression and activation of TLR5 on IECs regulates the composition and localization of microbiota and prevents disease associated intestinal inflammation.
“It was demonstrated in numerous reports from Dr Gewirtz’s group that expression and activation of TLR5 on IECs regulates the composition and localization of microbiota and prevents disease associated intestinal inflammation.165, 166, 167, 168”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [165]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Gut Microbiota Is a Key Modulator of Insulin Resistance in TLR 2 Knockout Mice
Caricilli, A. M., Picardi, P. K., de Abreu, L. L., Ueno, M., Prada, P. O., Ropelle, E. R., Hirabara, S. M., Castoldi, Â., Moraes‐Vieira, P. M., Câmara, N. O. S., et al. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001212 · Cited by 281 · see citing works
RetractedQIIME allows analysis of high-throughput community sequencing data
Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Peña, A. G., Goodrich, J. K., Gordon, J. I., et al. (2010) · Nature Methods · doi:10.1038/nmeth.f.303 · Cited by 34,887 · see citing works
Search and clustering orders of magnitude faster than BLAST
Edgar, R. C. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq461 · Cited by 20,617 · see citing works
Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms
Caporaso, J. G., Lauber, C. L., Walters, W. A., Berg-Lyons, D., Huntley, J., Fierer, N., Owens, S. M., Betley, J., Fraser, L., Bauer, M., et al. (2012) · The ISME Journal · doi:10.1038/ismej.2012.8 · Cited by 8,839 · see citing works
UniFrac: a New Phylogenetic Method for Comparing Microbial Communities
Lozupone, C., & Knight, R. (2005) · Applied and Environmental Microbiology · doi:10.1128/aem.71.12.8228-8235.2005 · Cited by 8,227 · see citing works
FastTree: Computing Large Minimum Evolution Trees with Profiles instead of a Distance Matrix
Price, M. N., Dehal, P. S., & Arkin, A. P. (2009) · Molecular Biology and Evolution · doi:10.1093/molbev/msp077 · Cited by 5,602 · see citing works
McDonald, D. T., Price, M. N., Goodrich, J. K., Nawrocki, E. P., DeSantis, T. Z., Probst, A. J., Andersen, G. L., Knight, R. D., & Hugenholtz, P. (2011) · The ISME Journal · doi:10.1038/ismej.2011.139 · Cited by 5,010 · see citing works
Meyer, F., Paarmann, D., D'Souza, M., Olson, R., Glass, E., Kubal, M., Paczian, T., Rodriguez, A., Stevens, R. L., Wilke, A., et al. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-386 · Cited by 3,565 · see citing works
Diagnosis of multiple cancer types by shrunken centroids of gene expression
Tibshirani, R. J., Hastie, T. J., Narasimhan, B., & Chu, G. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082099299 · Cited by 2,938 · see citing works
The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria
Johansson, M. E. V., Phillipson, M., Petersson, J., Velcich, A., Holm, L., & Hansson, G. C. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803124105 · Cited by 2,200 · see citing works
Dextran Sulfate Sodium (DSS)‐Induced Colitis in Mice
Chassaing, B., Aitken, J. D., Malleshappa, M., & Vijay–Kumar, M. (2014) · Current Protocols in Immunology · doi:10.1002/0471142735.im1525s104 · Cited by 2,094 · see citing works
Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5
Vijay-Kumar, M., Aitken, J. D., Carvalho, F. A., Cullender, T. C., Mwangi, S., Srinivasan, S., Sitaraman, S. V., Knight, R., Ley, R. E., & Gewirtz, A. T. (2010) · Science · doi:10.1126/science.1179721 · Cited by 2,068 · see citing works
NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis
Elinav, E., Strowig, T., Kau, A. L., Henao-Mejia, J., Thaiss, C. A., Booth, C. J., Peaper, D. R., Bertin, J., Eisenbarth, S. C., Gordon, J. I., et al. (2011) · Cell · doi:10.1016/j.cell.2011.04.022 · Cited by 2,024 · see citing works
Kaser, A., Zeissig, S., & Blumberg, R. S. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101225 · Cited by 1,806 · see citing works
Darfeuille-Michaud, A., Boudeau, J., Bulois, P., Neut, C., Glasser, A.-L., Barnich, N., Bringer, M.-A., Swidsinski, A., Beaugerie, L., & Colombel, J.-F. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.04.061 · Cited by 1,566 · see citing works
UniFrac – An online tool for comparing microbial community diversity in a phylogenetic context
Lozupone, C., Hamady, M., & Knight, R. D. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-371 · Cited by 1,454 · see citing works
Png, C. W., Lindén, S. K., Gilshenan, K. S., Zoetendal, E. G., McSweeney, C. S., Sly, L. I., McGuckin, M. A., & Florin, T. H. J. (2010) · American Journal of Gastroenterology · doi:10.1038/ajg.2010.281 · Cited by 1,364 · see citing works
Gewirtz, A. T., Navas, T. A., Lyons, S., Godowski, P. J., & Madara, J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.4.1882 · Cited by 1,345 · see citing works
Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives
Joossens, M., Huys, G., Cnockaert, M., De Preter, V., Verbeke, K., Rutgeerts, P., Vandamme, P., & Vermeire, S. (2011) · Gut · doi:10.1136/gut.2010.223263 · Cited by 1,063 · see citing works
Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease
Darfeuille–Michaud, A., Neut, C., Barnich, N., Lederman, E., Martino, P. D., Desreumaux, P., Gambiez, L. P., Joly, B., Cortot, A., & Colombel, J.-F. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70019-8 · Cited by 859 · see citing works
Karsunky, H., Mérad, M., Cozzio, A., Weissman, I. L., & Manz, M. G. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030323 · Cited by 594 · see citing works
Chassaing, B., Srinivasan, G., Delgado, M. A., Young, A. N., Gewirtz, A. T., & Vijay–Kumar, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044328 · Cited by 555 · see citing works
Carvalho, F. A., Koren, O., Goodrich, J. K., Johansson, M. E. V., Nalbantoglu, I., Aitken, J. D., Su, Y., Chassaing, B., Walters, W. A., González, A., et al. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.07.004 · Cited by 548 · see citing works
Kinnebrew, M. A., Buffie, C. G., Diehl, G. E., Zenewicz, L. A., Leiner, I., Hohl, T. M., Flavell, R. A., Littman, D. R., & Pamer, E. G. (2012) · Immunity · doi:10.1016/j.immuni.2011.12.011 · Cited by 491 · see citing works
Uematsu, S., Jang, M. H., Chevrier, N., Guo, Z., Kumagai, Y., Yamamoto, M., Kato, H., Sougawa, N., Matsui, H., Kuwata, H., et al. (2006) · Nature Immunology · doi:10.1038/ni1362 · Cited by 450 · see citing works
The Commensal Microbiota and Enteropathogens in the Pathogenesis of Inflammatory Bowel Diseases
Chassaing, B., & Darfeuille–Michaud, A. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.01.054 · Cited by 443 · see citing works
Deletion of TLR5 results in spontaneous colitis in mice
Vijay–Kumar, M., Sanders, C. J., Taylor, R. T., Kumar, A., Aitken, J. D., Sitaraman, S. V., Neish, A. S., Uematsu, S., Akira, S., Williams, I. R., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci33084 · Cited by 420 · see citing works
Innate and Adaptive Immunity Interact to Quench Microbiome Flagellar Motility in the Gut
Cullender, T. C., Chassaing, B., Janzon, A., Kumar, K., Muller, C. E., Werner, J. J., Angenent, L. T., Bell, M. E., Hay, A. G., Peterson, D. A., et al. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.10.009 · Cited by 383 · see citing works
Desulfovibrio Bacterial Species Are Increased in Ulcerative Colitis
Rowan, F., Docherty, N. G., Murphy, M., Murphy, B., Coffey, J. C., & O‘Connell, P. R. (2010) · Diseases of the Colon & Rectum · doi:10.1007/dcr.0b013e3181f1e620 · Cited by 333 · see citing works
Carvalho, F. A., Barnich, N., Sivignon, A., Darcha, C., Chan, C. H. F., Stanners, C. P., & Darfeuille–Michaud, A. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090741 · Cited by 314 · see citing works
Ubeda, C., Lipuma, L., Gobourne, A., Viale, A., Leiner, I., Equinda, M., Khanin, R., & Pamer, E. G. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20120504 · Cited by 310 · see citing works
Castaneda, F. E., Walia, B., Vijay–Kumar, M., Patel, N. R., Roser, S., Kolachala, V. L., Rojas, M., Wang, L., Oprea, G. M., Garg, P., et al. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.09.017 · Cited by 267 · see citing works
Prevalence of Bacteroides and Prevotella spp. in ulcerative colitis
Lucke, K., Miehlke, S., Jacobs, E., & Schuppler, M. (2006) · Journal of Medical Microbiology · doi:10.1099/jmm.0.46198-0 · Cited by 262 · see citing works
AIEC pathobiont instigates chronic colitis in susceptible hosts by altering microbiota composition
Chassaing, B., Koren, O., Carvalho, F. A., Ley, R. E., & Gewirtz, A. T. (2013) · Gut · doi:10.1136/gutjnl-2013-304909 · Cited by 219 · see citing works
Gilbert, J. A., Meyer, F., Jansson, J. K., Gordon, J. I., Pace, N. R., Tiedje, J. M., Ley, R. E., Fierer, N., Field, D., Kyrpides, N. C., et al. (2010) · Standards in Genomic Sciences · doi:10.4056/aigs.1443528 · Cited by 216 · see citing works
Gewirtz, A. T., Vijay–Kumar, M., Brant, S. R., Duerr, R. H., Nicolae, D. L., & Cho, J. H. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00544.2005 · Cited by 197 · see citing works
Glass, E. M., & Meyer, F. (2011) · doi:10.1002/9781118010518.ch37 · Cited by 189 · see citing works
Johansson, M., & Hansson, G. C. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-513-8_13 · Cited by 188 · see citing works
Toll-Like Receptor–Gut Microbiota Interactions: Perturb at Your Own Risk!
Carvalho, F. A., Aitken, J. D., Vijay–Kumar, M., & Gewirtz, A. T. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020911-153330 · Cited by 164 · see citing works
Hydrogen Sulfide Is an Endogenous Potentiator of T Cell Activation
Miller, T. W., Wang, E. A., Gould, S., Stein, E. V., Kaur, S., Lim, L., Amarnath, S., Fowler, D. H., & Roberts, D. D. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.307819 · Cited by 137 · see citing works
Maele, L. V., Carnoy, C., Cayet, D., Songhet, P., Dumoutier, L., Ferrero, I., Janot, L., Erard, F., Bertout, J., Léger, H., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000115 · Cited by 132 · see citing works
Cytosolic flagellin receptor NLRC4 protects mice against mucosal and systemic challenges
Carvalho, F. A., Nalbantoglu, I., Aitken, J. D., Uchiyama, R., Su, Y., Doho, G., Vijay–Kumar, M., & Gewirtz, A. T. (2012) · Mucosal Immunology · doi:10.1038/mi.2012.8 · Cited by 132 · see citing works
Role of Hydrogen Sulfide in the Pathology of Inflammation
Bhatia, M. (2012) · Scientifica · doi:10.6064/2012/159680 · Cited by 74 · see citing works
Carvalho, F. A., Nalbantoglu, I., Ortega-Fernandez, S., Aitken, J. D., Su, Y., Koren, O., Walters, W. A., Knight, R. D., Ley, R. E., Vijay–Kumar, M., et al. (2011) · Gut · doi:10.1136/gut.2011.240556 · Cited by 73 · see citing works
Kim, N., Kunisawa, J., Kweon, M., Ji, G. E., & Kiyono, H. (2007) · Clinical Immunology · doi:10.1016/j.clim.2006.11.005 · Cited by 70 · see citing works
Both Radioresistant and Hemopoietic Cells Promote Innate and Adaptive Immune Responses to Flagellin
Sanders, C. J., Moore, D. A., Williams, I. R., & Gewirtz, A. T. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.11.7184 · Cited by 53 · see citing works
Hobert, M. E., Sands, K. A., Mrsny, R. J., & Madara, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m210466200 · Cited by 39 · see citing works
Flagged first, then by citations
1 of the 48 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome
Chassaing, B., Koren, O., Goodrich, J. K., Poole, A. C., Srinivasan, S., Ley, R. E., & Gewirtz, A. T. (2015) · Nature · doi:10.1038/nature14232 · Cited by 2,055 · see citing works
Human gut microbiome: Hopes, threats and promises
Cani, P. D. (2018) · Gut · doi:10.1136/gutjnl-2018-316723 · Cited by 1,386 · see citing works
Regulation of Intestinal Barrier Function by Microbial Metabolites
Ghosh, S., Whitley, C. S., Haribabu, B., & Jala, V. R. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.02.007 · Cited by 835 · see citing works
Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes
Scheithauer, T. P. M., Rampanelli, E., Nieuwdorp, M., Vallance, B. A., Verchere, C. B., van Raalte, D. H., & Herrema, H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.571731 · Cited by 694 · see citing works
Zou, J., Chassaing, B., Singh, V., Pellizzon, M., Ricci, M. R., Flythe, M. D. D., Kumar, M. V., & Gewirtz, A. T. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.11.003 · Cited by 564 · see citing works
Ussar, S., Griffin, N. W., Bézy, O., Fujisaka, S., Vienberg, S. G., Softic, S., Deng, L., Bry, L., Gordon, J. I., & Kahn, C. R. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.007 · Cited by 529 · see citing works
The Human Microbiome and Obesity: Moving beyond Associations
Maruvada, P., Leone, V., Kaplan, L. M., & Chang, E. B. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.10.005 · Cited by 468 · see citing works
Aron-Wisnewsky, J., Warmbrunn, M. V., Nieuwdorp, M., & Clément, K. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.10.057 · Cited by 452 · see citing works
Price, A. E., Shamardani, K., Lugo, K. A., Deguine, J., Roberts, A. W., Lee, B. L., & Barton, G. M. (2018) · Immunity · doi:10.1016/j.immuni.2018.07.016 · Cited by 379 · see citing works
Epithelial Toll-like receptors and their role in gut homeostasis and disease
Burgueño, J. F., & Abreu, M. T. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0261-4 · Cited by 404 · see citing works
Su, M., Tang, T. F., Tang, W., Yu, L., Wang, L., & Liu, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1243834 · Cited by 344 · see citing works
Toll-like Receptors and Inflammatory Bowel Disease
Lu, Y., Li, X., Liu, S., Zhang, Y., & Zhang, D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00072 · Cited by 342 · see citing works
The gut microbiome, diet, and links to cardiometabolic and chronic disorders
Aron‐Wisnewsky, J., & Clément, K. (2015) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.191 · Cited by 327 · see citing works
Immune-microbiota interactions in health and disease
Palm, N. W., de Zoete, M. R., & Flavell, R. A. (2015) · Clinical Immunology · doi:10.1016/j.clim.2015.05.014 · Cited by 315 · see citing works
Gieryńska, M., Szulc‐Dąbrowska, L., Struzik, J., Mielcarska, M. B., & Gregorczyk-Zboroch, K. P. (2022) · Animals · doi:10.3390/ani12020145 · Cited by 326 · see citing works
Gaudino, S. J., & Kumar, P. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00360 · Cited by 304 · see citing works
Dietary polyphenols to combat the metabolic diseases via altering gut microbiota
Gowd, V., Karim, N., Shishir, M. R. I., Xie, L., & Chen, W. (2019) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2019.09.005 · Cited by 294 · see citing works
β-glucan attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice
Shi, H., Yu, Y., Lin, D., Zheng, P., Zhang, P., Hu, M., Wang, Q., Pan, W., Yang, X., Hu, T., et al. (2020) · Microbiome · doi:10.1186/s40168-020-00920-y · Cited by 264 · see citing works
Ríos, D., Wood, M. B., Li, J., Chassaing, B., Gewirtz, A. T., & Williams, I. R. (2015) · Mucosal Immunology · doi:10.1038/mi.2015.121 · Cited by 266 · see citing works
The gut microbiota: A treasure for human health
Li, D., Wang, P., Wang, P., Hu, X., & Chen, F. (2016) · Biotechnology Advances · doi:10.1016/j.biotechadv.2016.08.003 · Cited by 265 · see citing works
Nutrients Mediate Intestinal Bacteria–Mucosal Immune Crosstalk
Ma, N., Guo, P., Zhang, J., He, T., Kim, S. W., Zhang, G., & Ma, X. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00005 · Cited by 248 · see citing works
Shi, H., Ge, X., Ma, X., Zheng, M., Cui, X., Pan, W., Zheng, P., Yang, X., Zhang, P., Hu, M., et al. (2021) · Microbiome · doi:10.1186/s40168-021-01172-0 · Cited by 249 · see citing works
Liang, Y., Zhan, J., Liu, D., Luo, M., Han, J., Liu, X., Liu, C., Cheng, Z. Z., Zhou, Z., & Wang, P. (2019) · Microbiome · doi:10.1186/s40168-019-0635-4 · Cited by 241 · see citing works
Seo, B., Jeon, K., Moon, S., Lee, K., Kim, W.-K., Jeong, H., Cha, K. H., Lim, M. Y., Kang, W., Kweon, M., et al. (2019) · Cell Host & Microbe · doi:10.1016/j.chom.2019.11.001 · Cited by 238 · see citing works
Truax, A. D., Chen, L., Tam, J. W., Cheng, N., Guo, H., Koblansky, A. A., Chou, W.-C., Wilson, J. E., Brickey, W. J., Petrucelli, A., et al. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.08.009 · Cited by 228 · see citing works
Prevention and cure of rotavirus infection via TLR5/NLRC4–mediated production of IL-22 and IL-18
Zhang, B., Chassaing, B., Shi, Z., Uchiyama, R., Zhang, Z., Denning, T. L., Crawford, S. E., Pruijssers, A. J. P., Iskarpatyoti, J. A., Estes, M. K., et al. (2014) · Science · doi:10.1126/science.1256999 · Cited by 230 · see citing works
Spiljar, M., Merkler, D., & Trajkovski, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01353 · Cited by 219 · see citing works
Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition
Fulde, M., Sommer, F., Chassaing, B., van Vorst, K., Dupont, A., Hensel, M., Basic, M., Klopfleisch, R., Rosenstiel, P., Bleich, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0395-5 · Cited by 206 · see citing works
Li, X., Watanabe, K., & Kimura, I. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01882 · Cited by 209 · see citing works
Interaction between gut microbiota and toll-like receptor: from immunity to metabolism
Yiu, J. H. C., Dorweiler, B., & Woo, C. W. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1474-4 · Cited by 198 · see citing works
Gut microbiome and metabolic syndrome
Mazidi, M., Rezaie, P., Kengne, A. P., Ghayour‐Mobarhan, M., & Ferns, G. A. (2016) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2016.01.024 · Cited by 194 · see citing works
Lack of soluble fiber drives diet-induced adiposity in mice
Chassaing, B., Miles, J. P., Pellizzon, M., Ulman, E. A., Ricci, M. R., Zhang, L., Patterson, A. D., Vijay–Kumar, M., & Gewirtz, A. T. (2015) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00172.2015 · Cited by 185 · see citing works
Nlrp6- and ASC-Dependent Inflammasomes Do Not Shape the Commensal Gut Microbiota Composition
Mamantopoulos, M., Ronchi, F., Van Hauwermeiren, F., Vieira-Silva, S., Yilmaz, B., Martens, L., Saeys, Y., Drexler, S. K., Yazdi, A. S., Raes, J., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.07.011 · Cited by 181 · see citing works
Experimental models to study intestinal microbes–mucus interactions in health and disease
Etienne‐Mesmin, L., Chassaing, B., Desvaux, M., Paepe, K. D., Gresse, R., Sauvaitre, T., Forano, É., de Wiele, T. V., Schüller, S., Juge, N., et al. (2019) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuz013 · Cited by 179 · see citing works
The Impact of Plant Phytochemicals on the Gut Microbiota of Humans for a Balanced Life
Santhiravel, S., Bekhit, A. E. A., Mendis, E., Jacobs, J. L., Dunshea, F. R., Rajapakse, N., & Ponnampalam, E. N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158124 · Cited by 171 · see citing works
Intrinsic Defense Mechanisms of the Intestinal Epithelium
Ramanan, D., & Cadwell, K. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.03.003 · Cited by 150 · see citing works
Deconstructing Mechanisms of Diet-Microbiome-Immune Interactions
Alexander, M., & Turnbaugh, P. J. (2020) · Immunity · doi:10.1016/j.immuni.2020.07.015 · Cited by 150 · see citing works
Mucosal Interactions between Genetics, Diet, and Microbiome in Inflammatory Bowel Disease
Basson, A. R., Trotter, A., Rodriguez‐Palacios, A., & Cominelli, F. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00290 · Cited by 136 · see citing works
Targeting gut microbiota as a possible therapy for diabetes
He, C., Shan, Y., & Song, W. (2015) · Nutrition Research · doi:10.1016/j.nutres.2015.03.002 · Cited by 134 · see citing works
Viennois, É., Bretin, A., Dubé, P. E., Maue, A. C., Dauriat, C. J. G., Barnich, N., Gewirtz, A. T., & Chassaing, B. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108229 · Cited by 130 · see citing works
Microbiota and host immune responses: a love–hate relationship
Tomkovich, S., & Jobin, C. (2015) · Immunology · doi:10.1111/imm.12538 · Cited by 128 · see citing works
Colonic Microbiota Encroachment Correlates With Dysglycemia in Humans
Chassaing, B., Raja, S. M., Lewis, J. D., Srinivasan, S., & Gewirtz, A. T. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.04.001 · Cited by 125 · see citing works
Tran, H. Q., Ley, R. E., Gewirtz, A. T., & Chassaing, B. (2019) · Nature Communications · doi:10.1038/s41467-019-13538-y · Cited by 121 · see citing works
Shi, H., Wang, Q., Zheng, M., Hao, S., Lum, J. S., Chen, X., Huang, X., Yu, Y., & Zheng, K. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01760-1 · Cited by 117 · see citing works
Molecular and Cellular Mechanisms Influenced by Postbiotics
Jastrząb, R., Graczyk, D., & Siedlecki, P. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413475 · Cited by 121 · see citing works
Zhao, X., Jiang, Y., Xi, H., Chen, L., & Feng, X. (2020) · Geburtshilfe und Frauenheilkunde · doi:10.1055/a-1081-2036 · Cited by 124 · see citing works
Oriá, R. B., Murray‐Kolb, L. E., Scharf, R. J., Pendergast, L. L., Lang, D., Kolling, G. L., & Guerrant, R. L. (2016) · Nutrition Reviews · doi:10.1093/nutrit/nuw008 · Cited by 110 · see citing works
Moyle, P. M. (2017) · Biotechnology Advances · doi:10.1016/j.biotechadv.2017.03.005 · Cited by 111 · see citing works
Qi-Xiang, M., Yang, F., Ze-Hua, H., Nuo-Ming, Y., Rui-Long, W., Bin-Qiang, X., Jun-Jie, F., Chun-Lan, H., & Yue, Z. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2112882 · Cited by 112 · see citing works
Reichardt, F., Chassaing, B., Nezami, B. G., Li, G., Tabatabavakili, S., Mwangi, S. M., Uppal, K., Liang, B., Vijay–Kumar, M., Jones, D. P., et al. (2016) · The Journal of Physiology · doi:10.1113/jp273269 · Cited by 109 · see citing works
Host genetic control of gut microbiome composition
Bubier, J. A., Chesler, E. J., & Weinstock, G. M. (2021) · Mammalian Genome · doi:10.1007/s00335-021-09884-2 · Cited by 102 · see citing works
Programmed and environmental determinants driving neonatal mucosal immune development
Torow, N., Hand, T. W., & Hornef, M. W. (2023) · Immunity · doi:10.1016/j.immuni.2023.02.013 · Cited by 107 · see citing works
Lin, H., Guo, Q., Wen, Z., Tan, S., Chen, J., Lin, L., Chen, P., He, J., Wen, J., & Chen, Y. (2021) · Microbial Cell Factories · doi:10.1186/s12934-021-01720-1 · Cited by 102 · see citing works
Gut Microbiota in Patients with Polycystic Ovary Syndrome: a Systematic Review
Guo, J., Shao, J., Yang, Y., Niu, X., Liao, J., Zhao, Q. S., Wang, D., Li, S., & Hu, J. (2021) · Reproductive Sciences · doi:10.1007/s43032-020-00430-0 · Cited by 98 · see citing works
Etienne‐Mesmin, L., Vijay–Kumar, M., Gewirtz, A. T., & Chassaing, B. (2016) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2016.04.007 · Cited by 98 · see citing works
Chen, H., Ma, X., Liu, Y., Ma, L., Chen, Z., Lin, X., Si, L., Ma, X., & Chen, X. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01662 · Cited by 96 · see citing works
Roseburia intestinalis stimulates TLR5-dependent intestinal immunity against Crohn's disease
Shen, Z., Luo, W., Tan, B., Nie, K., Deng, M., Wu, S., Xiao, M., Wu, X., Meng, X., Tong, T., et al. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104285 · Cited by 97 · see citing works
Molecular pathways controlling barrier function in IBD
Atreya, R. N., & Neurath, M. F. (2014) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2014.201 · Cited by 96 · see citing works
Toll-like receptors and metabolic (dysfunction)-associated fatty liver disease
Khanmohammadi, S., & Kuchay, M. S. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106507 · Cited by 93 · see citing works
TLR5: beyond the recognition of flagellin
Yang, J., & Yan, H. (2017) · Cellular and Molecular Immunology · doi:10.1038/cmi.2017.122 · Cited by 92 · see citing works
The short-chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis
Fuller, M. H., Priyadarshini, M., Gibbons, S. M., Angueira, A. R., Brodsky, M. R., Hayes, M. G., Kovatcheva‐Datchary, P., Bäckhed, F., Gilbert, J. A., Lowe, W. L., et al. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00171.2015 · Cited by 87 · see citing works
Cereal fiber, fruit fiber, and type 2 diabetes: Explaining the paradox
Davison, K., & Temple, N. J. (2017) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2017.11.002 · Cited by 88 · see citing works
McPhee, J. B., & Schertzer, J. D. (2015) · Clinical Science · doi:10.1042/cs20150431 · Cited by 83 · see citing works
Physical exercise, gut, gut microbiota, and atherosclerotic cardiovascular diseases
Chen, J., Guo, Y., Gui, Y., & Xu, D. (2018) · Lipids in Health and Disease · doi:10.1186/s12944-017-0653-9 · Cited by 88 · see citing works
The opportunistic nature of gut commensal microbiota
Dey, P., & Chaudhuri, S. R. (2022) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2022.2133987 · Cited by 82 · see citing works
Compartmentalized Antimicrobial Defenses in Response to Flagellin
Vijayan, A., Rumbo, M., Carnoy, C., & Sirard, J. (2017) · Trends in Microbiology · doi:10.1016/j.tim.2017.10.008 · Cited by 79 · see citing works
Wu, X., Pan, S., Luo, W., Shen, Z., Meng, X., Xiao, M., Tan, B., Nie, K., Tong, T., & Wang, X. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.11351 · Cited by 76 · see citing works
Xie, R., Gu, Y., Li, M., Li, L., Yang, Y., Sun, Y., Zhou, B., Liu, T., Wang, S., Liu, W., et al. (2024) · Microbiome · doi:10.1186/s40168-023-01722-8 · Cited by 69 · see citing works
Crosstalk between the immune receptors and gut microbiota
Mu, C., Yang, Y., & Zhu, W. (2015) · Current Protein & Peptide Science · doi:10.2174/1389203716666150630134356 · Cited by 66 · see citing works
Intestinal Ralstonia pickettii augments glucose intolerance in obesity
Udayappan, S. D., Kovatcheva‐Datchary, P., Bakker, G. J., Havik, S. R., Herrema, H., Cani, P. D., Bouter, K. E. C., Belzer, C., Witjes, J. J., Vrieze, A., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181693 · Cited by 66 · see citing works
Jalanka, J., Salonen, A., Fuentes, S., & de Vos, W. M. (2015) · Gut Microbes · doi:10.1080/19490976.2015.1096486 · Cited by 61 · see citing works
Layunta, E., Buey, B., Mesonero, J. E., & Latorre, E. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.748254 · Cited by 67 · see citing works
Osteoprotegerin-dependent M cell self-regulation balances gut infection and immunity
Kimura, S., Nakamura, Y., Kobayashi, N., Shiroguchi, K., Kawakami, E., Mutoh, M., Takahashi‐Iwanaga, H., Yamada, T., Hisamoto, M., Nakamura, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13883-y · Cited by 62 · see citing works
Heavy arch: from inflammatory bowel diseases to metabolic disorders
Adolph, T. E., Meyer, M., Jukic, A., & Tilg, H. (2024) · Gut · doi:10.1136/gutjnl-2024-331914 · Cited by 65 · see citing works
Bessac, A., Cani, P. D., Meunier, É., Dietrich, G., & Knauf, C. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00725 · Cited by 61 · see citing works
Quraishi, M. N., Shaheen, W., Oo, Y. H., & Iqbal, T. H. (2019) · Clinical & Experimental Immunology · doi:10.1111/cei.13397 · Cited by 62 · see citing works
The Gut Microbial Endocrine Organ in Type 2 Diabetes
Massey, W. J., & Brown, J. M. (2020) · Endocrinology · doi:10.1210/endocr/bqaa235 · Cited by 61 · see citing works
Pai, Y.-C., Li, Y.-H., Turner, J. R., & Yu, L. C. (2023) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjad064 · Cited by 55 · see citing works
Epithelial-derived interleukin-23 promotes oral mucosal immunopathology
Kim, T. S., Ikeuchi, T., Theofilou, V. I., Williams, D. W., Greenwell‐Wild, T., June, A., Adade, E. E., Li, L., Abusleme, L., Dutzan, N., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.02.020 · Cited by 55 · see citing works
Yu, L., Lǐ, Y., Du, C., Zhao, W., Zhang, H., Yang, Y., Sun, A., Song, X., & Feng, Z. (2019) · Mediators of Inflammation · doi:10.1155/2019/5271295 · Cited by 56 · see citing works
Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice
Schroeder, B. O., Birchenough, G. M. H., Pradhan, M., Nyström, E. E. L., Henricsson, M., Hansson, G. C., & Bäckhed, F. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.015771 · Cited by 54 · see citing works
How diet can impact gut microbiota to promote or endanger health
Chassaing, B., Vijay-Kumar, M., & Gewirtz, A. T. (2017) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000401 · Cited by 52 · see citing works
Self-citationTLR5 Signaling in the Regulation of Intestinal Mucosal Immunity
Feng, S., Zhang, C., Chen, S., He, R., Chao, G., & Zhang, S. (2023) · Journal of Inflammation Research · doi:10.2147/jir.s407521 · Cited by 51 · see citing works
A gut sense for a microbial pattern regulates feeding
Liu, W. W., Reicher, N., Alway, E., Rupprecht, L. E., Weng, P., Schaefgen, C., Klein, M. E., Villalobos, J. A., Puerto-Hernández, C., Altún, Y. G. K., et al. (2025) · Nature · doi:10.1038/s41586-025-09301-7 · Cited by 56 · see citing works
Cheng, D., Song, J., Xie, M., & Song, D. (2019) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2019.07.044 · Cited by 53 · see citing works
Sauvaitre, T., Etienne‐Mesmin, L., Sivignon, A., Mosoni, P., Courtin, C. M., de Wiele, T. V., & Blanquet‐Diot, S. (2020) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaa052 · Cited by 53 · see citing works
Alterations in Gut Microbiota and Immunity by Dietary Fat
Yang, B., Hur, K. Y., & Lee, M. (2017) · Yonsei Medical Journal · doi:10.3349/ymj.2017.58.6.1083 · Cited by 49 · see citing works
Khan, A. A., Khan, Z., & Warnakulasuriya, S. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw053 · Cited by 48 · see citing works
Microbial sensing in the intestine
Wan, T., Wang, Y., He, K., & Zhu, S. (2023) · Protein & Cell · doi:10.1093/procel/pwad028 · Cited by 49 · see citing works
Lu, P., Sodhi, C. P., Yamaguchi, Y., Jia, H., Prindle, T., Fulton, W. B., Vikram, A., Bibby, K. J., Morowitz, M. J., & Hackam, D. J. (2018) · Mucosal Immunology · doi:10.1038/mi.2017.114 · Cited by 48 · see citing works
Crosstalk between microbiota, pathogens and the innate immune responses
Günther, C., Josenhans, C., & Wehkamp, J. (2016) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2016.03.003 · Cited by 48 · see citing works
Adeshirlarijaney, A., Zou, J., Tran, H. Q., Chassaing, B., & Gewirtz, A. T. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00245.2019 · Cited by 46 · see citing works
Dietary Fatty Acids and Microbiota-Brain Communication in Neuropsychiatric Diseases
Marrone, M. C., & Coccurello, R. (2019) · Biomolecules · doi:10.3390/biom10010012 · Cited by 46 · see citing works
Wrześniewska, M., Wołoszczak, J., Świrkosz, G., Szyller, H. P., & Gomułka, K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126539 · Cited by 47 · see citing works
Wahida, A., Müller, M., Hiergeist, A., Popper, B., Steiger, K., Branca, C., Tschurtschenthaler, M., Engleitner, T., Donakonda, S., Coninck, J. D., et al. (2021) · Science Immunology · doi:10.1126/sciimmunol.abf7235 · Cited by 44 · see citing works
Ting, C.-H., Pan, C., Chen, Y.-C., Lin, Y.-C., Chen, T.-Y., Rajanbabu, V., & Chen, J. (2019) · Scientific Reports · doi:10.1038/s41598-019-55509-9 · Cited by 43 · see citing works
Arya, V. S., Kanthlal, S. K., & Linda, G. (2020) · Journal of Food Biochemistry · doi:10.1111/jfbc.13369 · Cited by 42 · see citing works
Zhou, Z., Kim, J.-W., Qi, J., Eo, S. K., Lim, C. W., & Kim, B. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2019.11.012 · Cited by 41 · see citing works
Investigating local and systemic intestinal signalling in health and disease with Drosophila
Medina, A. B., Bellec, K., Polcowñuk, S., & Cordero, J. B. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049332 · Cited by 35 · see citing works
- Authors
- Chassaing, B., Ley, R. E., & Gewirtz, A. T.
- Affiliations
- Cornell University (US)
- Georgia State University (US)
- Corresponding author
- Gewirtz, Andrew T.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 147
- Issue
- 6
- Pages
- 1363-1377.e17
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC4253564
- OpenAlex
- W2090488505
- Cited by
- 326
- References
- 48
- Citations by year
- 2026: 20 · 2025: 25 · 2024: 38 · 2023: 31 · 2022: 29 · 2021: 39 · 2020: 33 · 2019: 28 · 2018: 23 · 2017: 23 · 2016: 17 · 2015: 18 · 2014: 2
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DK083890, DK099071)
- Crohn's and Colitis Foundation of America (DK083890, DK099071)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- TLR5, intestinal epithelial cells, dendritic cells, gut microbiota, flagellin, low-grade inflammation, metabolic syndrome, colitis, IL-22, lipopolysaccharide, pathobionts, DSS-induced colitis, high-fat diet, antibiotic therapy, cohousing, host-microbe interactions
- MeSH terms
- Animals, Colitis, Enteritis, Female, Flagellin, Intestinal Mucosa, Male, Mice, Inbred C57BL, Signal Transduction, Mice, Knockout, Metabolic Syndrome, Toll-Like Receptor 4, Toll-Like Receptor 5, Diet, High-Fat, Microbiota
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
