The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Inflammation-independent TL1A-mediated intestinal fibrosis is dependent on the gut microbiome
Open accessAbstract
Tumor necrosis factor-like cytokine 1A (TL1A, TNFSF15) is implicated in inflammatory bowel disease (IBD), modulating the location and severity of intestinal inflammation and fibrosis. TL1A expression is increased in inflamed gut mucosa and associated with fibrostenosing Crohn's disease. Tl1a-overexpression in mice lead to spontaneous ileitis, and exacerbated induced proximal colitis and fibrosis. IBD is associated with shifts in the gut microbiome, but the effect of differing microbial populations and their interaction with TL1A on fibrosis has not been investigated. We demonstrate that the pro-fibrotic and inflammatory phenotype resulting from Tl1a-overexpression is abrogated in the absence of resident microbiota. To evaluate if this is due to the absence of a unique bacterial population, as opposed to any bacteria per se, we gavaged germ-free (GF) wild-type and Tl1a-transgenic (Tl1a-Tg) mice with stool from specific pathogen free (SPF) mice and a healthy human donor (Hu). Reconstitution with SPF, but not Hu microbiota, resulted in increased intestinal collagen deposition and fibroblast activation in Tl1a-Tg mice. Notably, there was reduced fibroblast migration and activation under GF conditions compared to native conditions. We then identified several candidate organisms that correlated directly with increased fibrosis in reconstituted mice and showed that these organisms directly impact fibroblast function in vitro. Thus, Tl1a-mediated intestinal fibrosis and fibroblast activation are dependent on specific microbial populations.
Overview
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
Verification
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?
In the citing paper
“Increased liver ECM deposition was observed in germ free mice compared to conventionally housed mice166, which was also observed in MyD88/TRIF deficient mice.”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [166]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
QIIME 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
Statistical significance for genomewide studies
Storey, J. D., & Tibshirani, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1530509100 · Cited by 9,692
Changes of Intestinal Functions in Liver Cirrhosis
Fukui, H., & Wiest, R. (2016) · Inflammatory Intestinal Diseases · doi:10.1159/000444436 · Cited by 6,820
Frank, D. N., St. Amand, A. L., Feldman, R. A., Boedeker, E. C., Harpaz, N., & Pace, N. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706625104 · Cited by 4,611
Gut microbiota in health and disease
Sekirov, I., Russell, S. L., Antunes, L. C. M., & Finlay, B. B. (2010) · Physiological Reviews · doi:10.1152/physrev.00045.2009 · Cited by 4,182
The Treatment-Naive Microbiome in New-Onset Crohn’s Disease
Gevers, D., Kugathasan, S., Denson, L. A., Vázquez-Baeza, Y., Van Treuren, W., Ren, B., Schwager, E., Knights, D., Song, S. J., Yassour, M., et al. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.02.005 · Cited by 3,220
Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice
Devkota, S., Wang, Y., Musch, M. W., Leone, V., Fehlner-Peach, H., Nadimpalli, A., Antonopoulos, D. A., Jabri, B., & Chang, E. B. (2012) · Nature · doi:10.1038/nature11225 · Cited by 1,904
Self-citationThe Microbiome in Inflammatory Bowel Disease: Current Status and the Future Ahead
Kostic, A. D., Xavier, R. J., & Gevers, D. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.02.009 · Cited by 1,789
Johansson, M., Larsson, J. M. H., & Hansson, G. C. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006451107 · Cited by 1,535
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
Lupp, C., Robertson, M. L., Wickham, M. E., Sekirov, I., Champion, O. L., Gaynor, E. C., & Finlay, B. B. (2007) · Cell Host & Microbe · doi:10.1016/j.chom.2007.06.010 · Cited by 1,310
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
Willing, B. P., Dicksved, J., Halfvarson, J., Andersson, A. F., Lucio, M., Zheng, Z., Järnerot, G., Tysk, C., Jansson, J. K., & Engstrand, L. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.08.049 · Cited by 1,032
Meta‐analyses of human gut microbes associated with obesity and IBD
Walters, W. A., Xu, Z., & Knight, R. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.09.039 · Cited by 836
Rath, H. C., Herfarth, H. H., Ikeda, J. S., Grenther, W. B., Hamm, T. E., Balish, E., Taurog, J. D., Hammer, R. E., Wilson, K. H., & Sartor, R. B. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118878 · Cited by 833
Self-citationSartor, R. B., & Wu, G. D. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.10.012 · Cited by 808
Self-citationSignal Transduction by DR3, a Death Domain-Containing Receptor Related to TNFR-1 and CD95
Chinnaiyan, A. M., O’Rourke, K. M., Yu, G.-L., Lyons, R. H., Garg, M., Duan, D. R., Xing, L., Gentz, R., Ni, J., & Dixit, V. M. (1996) · Science · doi:10.1126/science.274.5289.990 · Cited by 653
Kugathasan, S., Denson, L. A., Walters, T. D., Kim, M., Marigorta, U. M., Schirmer, M., Mondal, K., Liu, C., Griffiths, A. M., Noe, J. D., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30317-3 · Cited by 632
CoNet app: inference of biological association networks using Cytoscape
Faust, K., & Raes, J. (2016) · F1000Research · doi:10.12688/f1000research.9050.1 · Cited by 606
The outer mucus layer hosts a distinct intestinal microbial niche
Li, H., Limenitakis, J. P., Fuhrer, T., Geuking, M. B., Lawson, M. A., Wyss, M., Brugiroux, S., Keller, I., Macpherson, J. A., Rupp, S., et al. (2015) · Nature Communications · doi:10.1038/ncomms9292 · Cited by 511
Schaubeck, M., Clavel, T., Calasan, J., Lagkouvardos, I., Haange, S. B., Jehmlich, N., Basic, M., Dupont, A., Hornef, M., Bergen, M. V., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-309333 · Cited by 447
Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD
Sabino, J., Vieira-Silva, S., Machiels, K., Joossens, M., Falony, G., Ballet, V., Ferrante, M., Van Assche, G., Van der Merwe, S., Vermeire, S., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-311004 · Cited by 413
Rooks, M. G., Veiga, P., Wardwell-Scott, L., Tickle, T. L., Segata, N., Michaud, M., Gallini, C. A., Beal, C., van Hylckama-Vlieg, J. E. T., Ballal, S. A., et al. (2014) · The ISME Journal · doi:10.1038/ismej.2014.3 · Cited by 389
A death-domain-containing receptor that mediates apoptosis
Kitson, J., Raven, T., Jiang, Y., Goeddel, D. V., Giles, K. M., Pun, K., Grinham, C. J., Brown, R., & Farrow, S. N. (1996) · Nature · doi:10.1038/384372a0 · Cited by 335
Tan, K. B., Harrop, J., Reddy, M. P., Young, P. R., Terrett, J. A., Emery, J. G., Moore, G. P., & Truneh, A. (1997) · Gene · doi:10.1016/s0378-1119(97)00509-x · Cited by 277
Bodmer, J.-L., Burns, K., Schneider, P., Hofmann, K., Steiner, V., Thome, M., Bornand, T., Hahne, M., Schröter, M., Becker, K., et al. (1997) · Immunity · doi:10.1016/s1074-7613(00)80244-7 · Cited by 262
Intestinal myofibroblasts in innate immune responses of the intestine
Otte, J.-M., Rosenberg, I. M., & Podolsky, D. K. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)00403-7 · Cited by 242
Bibiloni, R., Mangold, M., Madsen, K. L., Fedorak, R. N., & Tannock, G. W. (2006) · Journal of Medical Microbiology · doi:10.1099/jmm.0.46498-0 · Cited by 226
Screaton, G. R., Xu, X.-N., Olsen, A. L., Cowper, A. E., Tan, R., McMichael, A. J., & Bell, J. I. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4615 · Cited by 210
Role of TL1A and its receptor DR3 in two models of chronic murine ileitis
Bamias, G., Mishina, M., Nyce, M. R., Ross, W. G., Kollias, G., Rivera–Nieves, J., Pizarro, T. T., & Cominelli, F. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510903103 · Cited by 169
Dextran Sodium Sulfate-Induced Colitis in Germ-Free IQI/Jic Mice.
Kitajima, S., MORIMOTO, M., Sagara, E., SHIMIZU, C., & IKEDA, Y. (2001) · EXPERIMENTAL ANIMALS · doi:10.1538/expanim.50.387 · Cited by 168
The T Cell Costimulator TL1A Is Induced by FcγR Signaling in Human Monocytes and Dendritic Cells
Prehn, J., Thomas, L. S., Landers, C. J., Yu, Q., Michelsen, K. S., & Targan, S. R. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.7.4033 · Cited by 160
Self-citationThe TNF-family cytokine TL1A drives IL-13-dependent small intestinal inflammation
Meylan, F., Song, Y.-J., Fuss, I. J., Villarreal, S., Kahle, E., Malm, I.-J., Acharya, K., Ramos, H. L., Lo, L., Mentink‐Kane, M. M., et al. (2010) · Mucosal Immunology · doi:10.1038/mi.2010.67 · Cited by 154
Microbial Dysbiosis in Pediatric Patients with Crohn's Disease
Kaakoush, N. O., Day, A. S., Huinao, K. D., Leach, S. T., Lemberg, D. A., Dowd, S. E., & Mitchell, H. M. (2012) · Journal of Clinical Microbiology · doi:10.1128/jcm.01396-12 · Cited by 147
Eun, C. S., Mishima, Y., Wohlgemuth, S., Liu, B., Bower, M., Carroll, I. M., & Sartor, R. B. (2014) · Infection and Immunity · doi:10.1128/iai.01513-13 · Cited by 128
Self-citationCrucial steps in the natural history of inflammatory bowel disease
Latella, G. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i29.3790 · Cited by 115
Inhibition of a novel fibrogenic factor Tl1a reverses established colonic fibrosis
Shih, D. Q., Zheng, L., Zhang, X., Zhang, H., Kanazawa, Y., Ichikawa, R., Wallace, K. L., Chen, J., Pothoulakis, C., Koon, H. W., et al. (2014) · Mucosal Immunology · doi:10.1038/mi.2014.37 · Cited by 106
Self-citationIBD-Associated TL1A Gene (TNFSF15) Haplotypes Determine Increased Expression of TL1A Protein
Michelsen, K. S., Thomas, L. S., Taylor, K. D., Yu, Q., Mei, L., Landers, C. J., Derkowski, C. A., McGovern, D. P. B., Rotter, J. I., & Targan, S. R. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004719 · Cited by 104
Self-citationShih, D. Q., Barrett, R. J., Zhang, X., Yeager, N., Koon, H. W., Phaosawasdi, P., Song, Y., Ko, B., Wong, M. H., Michelsen, K. S., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016090 · Cited by 103
Self-citationTaraban, V. Y., Ślebioda, T. J., Willoughby, J. E., Buchan, S. L., James, S., Sheth, B., Smyth, N. R., Thomas, G. J., Wang, E. C. Y., & Al‐Shamkhani, A. (2010) · Mucosal Immunology · doi:10.1038/mi.2010.70 · Cited by 102
TNFSF15 is an ethnic-specific IBD gene
Picornell, Y., Mei, L., Taylor, K. D., Yang, H., Targan, S. R., & Rotter, J. I. (2007) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20223 · Cited by 91
Self-citationDrygiannakis, I., Valatas, V., Sfakianaki, O., Bourikas, L. A., Manousou, P., Kambas, K., Ritis, K., Kolios, G. C., & Kouroumalis, E. (2012) · Journal of Crohn s and Colitis · doi:10.1016/j.crohns.2012.04.008 · Cited by 91
Barrett, R. J., Zhang, X., Koon, H. W., Vu, M., Chang, J.-Y., Yeager, N., Nguyen, M. A., Michelsen, K. S., Berel, D., Pothoulakis, C., et al. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.10.026 · Cited by 90
Self-citationShih, D. Q., Kwan, L. Y., Chavez, V., Cohavy, O., Gonsky, R., Chang, E. Y., Chang, C. C.-C., Elson, C. O., & Targan, S. R. (2009) · European Journal of Immunology · doi:10.1002/eji.200839087 · Cited by 86
Self-citationTL1A Both Promotes and Protects from Renal Inflammation and Injury
Al‐Lamki, R. S., Wang, J., Tolkovsky, A. M., Bradley, J. A., Griffin, J. L., Thiru, S., Wang, E. C. Y., Bolton, E. M., Wang, M., Moore, P. A., et al. (2008) · Journal of the American Society of Nephrology · doi:10.1681/asn.2007060706 · Cited by 78
Association Study of 71 European Crohnʼs Disease Susceptibility Loci in a Japanese Population
Hirano, A., Yamazaki, K., Umeno, J., Ashikawa, K., Aoki, M., Matsumoto, T., Nakamura, S., Ninomiya, T., Matsui, T., Hirai, F., et al. (2013) · Inflammatory Bowel Diseases · doi:10.1097/mib.0b013e31828075e7 · Cited by 68
Zheng, D., Dong, S., Li, T., Yang, F., Yu, X., Wu, J., Zhong, X., Zhao, Y., Wang, L., Xu, C., et al. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000430266 · Cited by 58
Jacobs, J. P., Lin, L., Goudarzi, M., Ruegger, P. M., McGovern, D. P. B., Fornace, A. J., Borneman, J., Xia, L., & Braun, J. G. (2016) · Gut Microbes · doi:10.1080/19490976.2016.1257469 · Cited by 55
Self-citationZheng, L., Zhang, X., Chen, J., Ichikawa, R., Wallace, K. L., Pothoulakis, C., Koon, H. W., Targan, S. R., & Shih, D. Q. (2013) · European Journal of Microbiology and Immunology · doi:10.1556/eujmi.3.2013.1.2 · Cited by 45
Self-citationZeng, O., Fang, L., Li, Y., Li, L., Xiao, T., Chu, C., & Yang, J. (2016) · Bioengineered · doi:10.1080/21655979.2016.1197743 · Cited by 25
Cited by
Sorted by citations
Fibrosis: from mechanisms to medicines
Henderson, N. C., Rieder, F., & Wynn, T. A. (2020) · Nature · doi:10.1038/s41586-020-2938-9 · Cited by 1,868
Fibroblasts as immune regulators in infection, inflammation and cancer
Davidson, S., Coles, M. C., Thomas, T. R., Kollias, G. A., Ludewig, B., Turley, S. J., Brenner, M. B., & Buckley, C. D. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00540-z · Cited by 639
Revisiting fibrosis in inflammatory bowel disease: the gut thickens
D’Alessio, S., Ungaro, F., Noviello, D., Lovisa, S., Peyrin‐Biroulet, L., & Danese, S. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00543-0 · Cited by 262
Shao, X., Sun, C., Tang, X., Zhang, X., Han, D., Liang, S., Qu, R., Hui, X., Shan, Y., Hu, L., et al. (2020) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.0c04773 · Cited by 249
Fibrosis in IBD: from pathogenesis to therapeutic targets
Rieder, F., Mukherjee, P. K., Massey, W. J., Wang, Y., & Fiocchi, C. (2024) · Gut · doi:10.1136/gutjnl-2023-329963 · Cited by 218
Metadata
- Authors
- Jacob, N., Jacobs, J. P., Kumagai, K., Ha, C. W. Y., Kanazawa, Y., Lagishetty, V., Altmayer, K., Hamill, A. M., Von Arx, A., Sartor, R. B., Devkota, S., Braun, J., Michelsen, K. S., Targan, S. R., & Shih, D. Q.
- Affiliations
- Cedars-Sinai Medical Center (US)
- University of California, Los Angeles (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Jacob, Noam
- Shih, David Q.
- ORCID
- Venue
- Mucosal Immunology
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 11
- Issue
- 5
- Pages
- 1466-1476
- ISSN
- 1933-0219 (ISSN-L)
- PMC
- PMC6162160
- OpenAlex
- W2863875449
- Cited by
- 102
- References
- 51
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 18 · 2023: 10 · 2022: 12 · 2021: 21 · 2020: 12 · 2019: 5 · 2018: 2
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Mucosal Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Crohn's and Colitis Foundation
- National Institutes of Health (NIH T32, NIH-R01, DK034987, DK056328, T32DK07180—40, P40OD010995)
- Inflammatory Bowel and Immunobiology Research Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK046763, K08DK093578, P01DK094779, P30DK041301, R01DK056328, L30 DK110927, T32DK007180, P30DK034987)
- Topics
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Microscopic Colitis
- Keywords
- TL1A, TNFSF15, intestinal fibrosis, gut microbiota, inflammatory bowel disease, Crohn's disease, fibroblast activation, fibroblast migration, germ-free mice, transgenic mice, collagen deposition
- MeSH terms
- Gastrointestinal Microbiome, Animals, Colitis, Collagen, Crohn Disease, Fibroblasts, Fibrosis, Humans, Ileitis, Inflammation, Intestinal Mucosa, Intestines, Mice, Inbred C57BL, Mice, Transgenic, Inflammatory Bowel Diseases, Mice, Tumor Necrosis Factor Ligand Superfamily Member 15
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
