Microbiota-Derived Indole Metabolites Promote Human and Murine Intestinal Homeostasis through Regulation of Interleukin-10 Receptor
Open accessAbstract
Interactions between the gut microbiota and the host are important for health, where dysbiosis has emerged as a likely component of mucosal disease. The specific constituents of the microbiota that contribute to mucosal disease are not well defined. The authors sought to define microbial components that regulate homeostasis within the intestinal mucosa. Using an unbiased, metabolomic profiling approach, a selective depletion of indole and indole-derived metabolites was identified in murine and human colitis. Indole-3-propionic acid (IPA) was selectively diminished in circulating serum from human subjects with active colitis, and IPA served as a biomarker of disease remission. Administration of indole metabolites showed prominent induction of IL-10R1 on cultured intestinal epithelia that was explained by activation of the aryl hydrocarbon receptor. Colonization of germ-free mice with wild-type Escherichia coli, but not E. coli mutants unable to generate indole, induced colonic epithelial IL-10R1. Moreover, oral administration of IPA significantly ameliorated disease in a chemically induced murine colitis model. This work defines a novel role of indole metabolites in anti-inflammatory pathways mediated by epithelial IL-10 signaling and identifies possible avenues for utilizing indoles as novel therapeutics in mucosal disease.
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?
Indole-3-propionate affects host intestinal inflammation and is reduced in patients with active colitis.
“Indole-3-propionate has been shown to affect host intestinal inflammation and to be reduced in patients with active colitis (Alexeev et al., 2018).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Alexeev et al., 2018
Healthy ageing correlates with increased indoles, gut bacterial tryptophan degradation products that mediate immune homeostasis via aryl hydrocarbon and IL-10 receptors.
“healthy ageing correlates with an increased presence of certain indoles, which are gut bacterial degradation products of tryptophan that mediate immune homeostasis upon binding to aryl hydrocarbon receptors and IL-10 receptors15–17”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [17]
Indolepropionic acid, a microbial metabolite of tryptophan, maintains intestinal homeostasis and protects from experimental colitis.
“indolepropionic acid, a microbial metabolite of tryptophan, maintains intestinal homeostasis and protects from experimental colitis (43).”
From The gut microbiota at the intersection of diet and human health (2018) · cites this paper as [43]
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
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610 · see citing works
Diversity, stability and resilience of the human gut microbiota
Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K., & Knight, R. (2012) · Nature · doi:10.1038/nature11550 · Cited by 5,533 · see citing works
Role of the microbiota in immunity and inflammation.
Belkaid, Y., & Hand, T. W. (2014) · Cell · doi:10.1016/j.cell.2014.03.011 · Cited by 5,385 · see citing works
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 · see citing works
Unravelling the pathogenesis of inflammatory bowel disease
Xavier, R. J., & Podolsky, D. K. (2007) · Nature · doi:10.1038/nature06005 · Cited by 4,364 · see citing works
Interleukin-10-deficient mice develop chronic enterocolitis
Kühn, R., Löhler, J., Rennick, D. M., Rajewsky, K., & Müller, W. (1993) · Cell · doi:10.1016/0092-8674(93)80068-p · Cited by 4,248 · see citing works
Ford Alexander, C., Paul, M., Hanauer Steven, B., 谭蓓, & Dong, W. Z. (2001) · Cited by 3,021 · see citing works
Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites
Wikoff, W. R., Anfora, A. T., Liu, J., Schultz, P. G., Lesley, S. A., Peters, E. C., & Siuzdak, G. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812874106 · Cited by 2,677 · see citing works
Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., Zecchi, R., D’Angelo, C., Massi-Benedetti, C., Fallarino, F., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.003 · Cited by 2,614 · see citing works
Microbial Influences in Inflammatory Bowel Diseases
Sartor, R. B. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.11.059 · Cited by 1,927 · see citing works
Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro
Spence, J. R., Mayhew, C. N., Rankin, S. A., Kuhar, M. F., Vallance, J. E., Tolle, K. A., Hoskins, E. E., Kalinichenko, V. V., Wells, S. I., Zorn, A. M., et al. (2010) · Nature · doi:10.1038/nature09691 · Cited by 1,911 · see citing works
Machiels, K., Joossens, M., Sabino, J., De Preter, V., Arijs, I., Eeckhaut, V., Ballet, V., Claes, K., Van Immerseel, F., Verbeke, K., et al. (2014) · Gut · doi:10.1136/gutjnl-2013-304833 · Cited by 1,904 · see citing works
Low counts of Faecalibacterium prausnitzii in colitis microbiota
Sokol, H., Seksik, P., Furet, J. P., Firmesse, O., Nion-Larmurier, I., Beaugerie, L., Cosnes, J., Corthier, G., Marteau, P., & Doré, J. (2009) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20903 · Cited by 1,275 · see citing works
Dieleman, L. A., Palmen, M. J. H. J., Akol, H., Bloemena, E., Peña, A. S., Meuwissen, S. G. M., & van Rees, E. P. (1998) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1998.00728.x · Cited by 1,167 · see citing works
Manichanh, C., Borruel, N., Casellas, F., & Guarner, F. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.152 · Cited by 1,160 · see citing works
Venkatesh, M., Mukherjee, S., Wang, H., Li, H., Sun, K., Benechet, A. P., Qiu, Z., Maher, L., Redinbo, M. R., Phillips, R. S., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.014 · Cited by 1,066 · see citing works
Indole as an intercellular signal in microbial communities
Lee, J.-H., & Lee, J. (2010) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2009.00204.x · Cited by 1,059 · see citing works
Chaudhry, A., Samstein, R. M., Treuting, P., Liang, Y., Pils, M. C., Heinrich, J.-M., Jack, R. S., Wunderlich, F. T., Brüning, J. C., Müller, W., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.03.018 · Cited by 980 · see citing works
<i>Lactobacillus reuteri</i> induces gut intraepithelial CD4 <sup>+</sup> CD8αα <sup>+</sup> T cells
Cervantes-Barragan, L., Chai, J. N., Tianero, M. D., Di Luccia, B., Ahern, P. P., Merriman, J., Cortez, V. S., Caparon, M. G., Donia, M. S., Gilfillan, S., et al. (2017) · Science · doi:10.1126/science.aah5825 · Cited by 896 · see citing works
Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses Inflammation
Wlodarska, M., Luo, C., Kolde, R., d'Hennezel, E. B., Annand, J. W., Heim, C. E., Krastel, P., Schmitt, E. K., Omar, A. S., Creasey, E. A., et al. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.06.007 · Cited by 890 · see citing works
Exogenous Stimuli Maintain Intraepithelial Lymphocytes via Aryl Hydrocarbon Receptor Activation
Li, Y., Innocentin, S., Withers, D. R., Roberts, N. A., Gallagher, A., Grigorieva, E. F., Wilhelm, C., & Veldhoen, M. (2011) · Cell · doi:10.1016/j.cell.2011.09.025 · Cited by 816 · see citing works
Aryl hydrocarbon receptor control of a disease tolerance defence pathway
Bessede, A., Gargaro, M., Pallotta, M. T., Matino, D., Servillo, G., Brunacci, C., Bicciato, S., Mazza, E. M. C., Macchiarulo, A., Vacca, C., et al. (2014) · Nature · doi:10.1038/nature13323 · Cited by 676 · see citing works
Monteleone, I., Rizzo, A., Sarra, M., Sica, G., Sileri, P., Biancone, L., MacDonald, T. T., Pallone, F., & Monteleone, G. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.04.007 · Cited by 656 · see citing works
Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation
Hubbard, T. D., Murray, I. A., & Perdew, G. H. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.115.064246 · Cited by 646 · see citing works
Kimura, A., Naka, T., Nohara, K., Fujii‐Kuriyama, Y., & Kishimoto, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804231105 · Cited by 540 · see citing works
Roles of indole as an interspecies and interkingdom signaling molecule
Lee, J.-H., Wood, T. K., & Lee, J. (2015) · Trends in Microbiology · doi:10.1016/j.tim.2015.08.001 · Cited by 516 · see citing works
Cis3/Socs3/Ssi3 Plays a Negative Regulatory Role in Stat3 Activation and Intestinal Inflammation
Suzuki, A., Hanada, T., Mitsuyama, K., Yoshida, T., Kamizono, S., Hoshino, T., Kubo, M., Yamashita, A., Okabe, M., Takeda, K., et al. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.4.471 · Cited by 473 · see citing works
Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-α
Mascanfroni, I. D., Takenaka, M. C., Yeste, A., Patel, B., Wu, Y., Kenison, J. E., Siddiqui, S., Basso, A. S., Otterbein, L. E., Pardoll, D. M., et al. (2015) · Nature Medicine · doi:10.1038/nm.3868 · Cited by 441 · see citing works
Generating human intestinal tissue from pluripotent stem cells in vitro
McCracken, K. W., Howell, J. C., Wells, J. M., & Spence, J. R. (2011) · Nature Protocols · doi:10.1038/nprot.2011.410 · Cited by 433 · see citing works
Commensal bacteria-dependent indole production enhances epithelial barrier function in the colon
Shimada, Y., Kinoshita, M., Harada, K., Mizutani, M., Masahata, K., Kayama, H., & Takeda, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080604 · Cited by 404 · see citing works
Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles
Hubbard, T. D., Murray, I. A., Bisson, W. H., Lahoti, T. S., Gowda, K., Amin, S. G., Patterson, A. D., & Perdew, G. H. (2015) · Scientific Reports · doi:10.1038/srep12689 · Cited by 377 · see citing works
Butyricicoccus pullicaecorum in inflammatory bowel disease
Eeckhaut, V., Machiels, K., Perrier, C., Romero, C., Maes, S., Flahou, B., Steppe, M., Haesebrouck, F., Sas, B., Ducatelle, R., et al. (2012) · Gut · doi:10.1136/gutjnl-2012-303611 · Cited by 368 · see citing works
Inflammatory Bowel Disease as a Model for Translating the Microbiome
Huttenhower, C., Kostic, A. D., & Xavier, R. J. (2014) · Immunity · doi:10.1016/j.immuni.2014.05.013 · Cited by 332 · see citing works
Activation of the Ah Receptor by Tryptophan and Tryptophan Metabolites
Heath‐Pagliuso, S., Rogers, W. J., Tullis, K. M., Seidel, S. D., Cenijn, P. H., Brouwer, A., & Denison, M. S. (1998) · Biochemistry · doi:10.1021/bi980087p · Cited by 331 · see citing works
Jin, U.-H., Lee, S., Sridharan, G. V., Lee, K., Davidson, L. A., Jayaraman, A., Chapkin, R. S., Alaniz, R. C., & Safe, S. H. (2014) · Molecular Pharmacology · doi:10.1124/mol.113.091165 · Cited by 330 · see citing works
Modulation of a Circulating Uremic Solute via Rational Genetic Manipulation of the Gut Microbiota
Devlin, A. S., Marcobal, A. M., Dodd, D., Nayfach, S., Plummer, N. S., Meyer, T., Pollard, K. S., Sonnenburg, J. L., & Fischbach, M. A. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.10.021 · Cited by 300 · see citing works
Intestinal antimicrobial peptides during homeostasis, infection, and disease
Muniz, L. R., Knosp, C. A., & Yeretssian, G. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00310 · Cited by 252 · see citing works
Faecal metabolite profiling identifies medium-chain fatty acids as discriminating compounds in IBD
Preter, V. D., Machiels, K., Joossens, M., Arijs, I., Matthys, C., Vermeire, S., Rutgeerts, P. J., & Verbeke, K. (2014) · Gut · doi:10.1136/gutjnl-2013-306423 · Cited by 239 · see citing works
Dysbiosis in intestinal inflammation: Cause or consequence
Buttó, L. F., & Haller, D. (2016) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2016.02.010 · Cited by 189 · see citing works
Lanis, J. M., Alexeev, E. E., Curtis, V. F., Kitzenberg, D., Kao, D. J., Battista, K. D., Gerich, M. E., Glover, L. E., Kominsky, D., & Colgan, S. P. (2017) · Mucosal Immunology · doi:10.1038/mi.2016.133 · Cited by 189 · see citing works
Self-citationPregnane X receptor as a target for treatment of inflammatory bowel disorders
Cheng, J., Shah, Y. M., & Gonzalez, F. J. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.03.003 · Cited by 159 · see citing works
IL-10 in Humans: Lessons from the Gut, IL-10/IL-10 Receptor Deficiencies, and IL-10 Polymorphisms
Engelhardt, K. R., & Grimbacher, B. (2014) · Current topics in microbiology and immunology · doi:10.1007/978-3-662-43492-5_1 · Cited by 150 · see citing works
CATALYTIC PROPERTIES OF TRYPTOPHANASE, A MULTIFUNCTIONAL PYRIDOXAL PHOSPHATE ENZYME
Newton, W. A., & Snell, E. E. (1964) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.51.3.382 · Cited by 143 · see citing works
Gaitanis, G., Magiatis, P., Σταθοπούλου, Κ., Bassukas, I. D., Alexopoulos, E. C., Velegraki, A., & Skaltsounis, A. (2008) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5701252 · Cited by 134 · see citing works
Interferon-gamma induces a cell surface phenotype switch on T84 intestinal epithelial cells
Colgan, S. P., Parkos, C., Matthews, J. B., D'Andrea, L., Awtrey, C. S., Lichtman, A. H., Delp-Archer, C., & Madara, J. (1994) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1994.267.2.c402 · Cited by 134 · see citing works
Self-citationHarmsen, H. J. M., & de Goffau, M. C. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-31248-4_7 · Cited by 128 · see citing works
High-Resolution Genome-wide Mapping of AHR and ARNT Binding Sites by ChIP-Seq
Lo, R., & Matthews, J. B. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs253 · Cited by 120 · see citing works
A contribution to the chemistry of proteids
Hopkins, F. G., & Cole, S. W. (1903) · The Journal of Physiology · doi:10.1113/jphysiol.1903.sp000968 · Cited by 109 · see citing works
IFN-γ–Mediated Induction of an Apical IL-10 Receptor on Polarized Intestinal Epithelia
Kominsky, D. J., Campbell, E. L., Ehrentraut, S., Wilson, K., Kelly, C. J., Glover, L. E., Collins, C. B., Bayless, A. J., Saeedi, B. J., Dobrinskikh, E., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301757 · Cited by 100 · see citing works
Self-citationVlachos, C., Schulte, B. M., Magiatis, P., Adema, G. J., & Gaitanis, G. (2012) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2012.11014.x · Cited by 96 · see citing works
Martin, K., Morlin, G., Smith, A. L., Nordyke, A., Eisenstark, A., & Golomb, M. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.1.107-118.1998 · Cited by 70 · see citing works
Metabolite profiling reveals new insights into the regulation of serum urate in humans
Albrecht, E., Waldenberger, M., Krumsiek, J., Evans, A. M., Jeratsch, U., Breier, M., Adamski, J., Köenig, W., Kunze, S., Fuchs, C., et al. (2013) · Metabolomics · doi:10.1007/s11306-013-0565-2 · Cited by 67 · see citing works
Mathieu, M., Lapierre, I., Brault, K., & Raymond, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008495200 · Cited by 63 · see citing works
Kominsky, D. J., Keely, S., MacManus, C. F., Glover, L. E., Scully, M. M., Collins, C. B., Bowers, B., Campbell, E. L., & Colgan, S. P. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002805 · Cited by 57 · see citing works
Self-citation
Flagged first, then by citations
1 of the 55 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease
Agus, A., Planchais, J., & Sokol, H. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.05.003 · Cited by 3,180 · see citing works
“Moreover, IPA is decreased in the serum of patients with ulcerative colitis (UC) (Alexeev et al., 2018).”
Microbial tryptophan catabolites in health and disease
Roager, H. M., & Licht, T. R. (2018) · Nature Communications · doi:10.1038/s41467-018-05470-4 · Cited by 2,236 · see citing works
Gut microbiota-derived metabolites as key actors in inflammatory bowel disease
Lavelle, A., & Sokol, H. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0258-z · Cited by 2,015 · see citing works
The gut microbiota at the intersection of diet and human health
Gentile, C. L., & Weir, T. L. (2018) · Science · doi:10.1126/science.aau5812 · Cited by 1,049 · see citing works
Yang, W., & Cong, Y. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00661-4 · Cited by 701 · see citing works
Gut microbiome pattern reflects healthy ageing and predicts survival in humans
Wilmanski, T. M., Diener, C., Rappaport, N., Patwardhan, S., Wiedrick, J. T., Lapidus, J., Earls, J. C., Zimmer, A., Glusman, G., Robinson, M., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00348-0 · Cited by 693 · see citing works
Cullin, N., Azevedo Antunes, C., Straussman, R., Stein-Thoeringer, C. K., & Elinav, E. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.08.006 · Cited by 578 · see citing works
Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis
Wang, J., Zhu, N., Su, L., Gao, Y., & Yang, R. (2023) · Cells · doi:10.3390/cells12050793 · Cited by 624 · see citing works
The Gut Microbiota in Inflammatory Bowel Disease
Qiu, P., Ishimoto, T., Fu, L., Zhang, J., Zhang, Z., & Liu, Y. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.733992 · Cited by 599 · see citing works
“Tryptophan can be metabolized to biologically activate indole by bacteria, which activates aryl hydrocarbon receptors and inhibits the production of inflammatory cytokines (Alexeev et al., 2018; Langan et al., 2021).”
BackgroundMicrobiome and Human Health: Current Understanding, Engineering, and Enabling Technologies
Aggarwal, N., Kitano, S., Puah, G. R. Y., Kittelmann, S., Hwang, I. Y., & Chang, M. W. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00431 · Cited by 544 · see citing works
The role of inflammation and the gut microbiome in depression and anxiety
Peirce, J. M., & Alviña, K. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24476 · Cited by 466 · see citing works
“Lactobacillus spp., especially L. reuteris, can catabolize tryptophan into indole‐3‐aldehyde (Zelante et al., 2014), which exerts anti‐inflammatory effects by increasing expression of the IL‐10 receptor in intestinal epithelial cells (Alexeev et al., 2018).”
BackgroundMicrobiota-derived metabolites as drivers of gut–brain communication
Ahmed, H., Leyrolle, Q., Koistinen, V., Kärkkäinen, O., Layé, S., Delzenne, N., & Hanhineva, K. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2102878 · Cited by 462 · see citing works
The Gut Microbiome and Inflammatory Bowel Diseases
Shan, Y., Lee, M., & Chang, E. B. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-042320-021020 · Cited by 420 · see citing works
Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis
Su, X., Gao, Y., & Yang, R. (2022) · Cells · doi:10.3390/cells11152296 · Cited by 424 · see citing works
The gut metabolite indole-3 propionate promotes nerve regeneration and repair
Serger, E., Luengo-Gutierrez, L., Chadwick, J., Kong, G., Zhou, L., Crawford, G., Danzi, M. C., Myridakis, A., Brandis, A. S., Bello, A. T., et al. (2022) · Nature · doi:10.1038/s41586-022-04884-x · Cited by 381 · see citing works
Gut Microbial Metabolites of Aromatic Amino Acids as Signals in Host–Microbe Interplay
Liu, Y., Hou, Y., Wang, G., Zheng, X., & Hao, H. (2020) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2020.02.012 · Cited by 357 · see citing works
Tryptophan in health and disease
Comai, S., Bertazzo, A., Brughera, M., & Crotti, S. (2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.08.005 · Cited by 300 · see citing works
Dual Role of Indoles Derived From Intestinal Microbiota on Human Health
Ye, X., Li, H., Anjum, K., Zhong, X., Miao, S., Zheng, G., Liu, W., & Li, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.903526 · Cited by 282 · see citing works
“regulated intestinal immune homeostasis by significantly inducing IL-10 receptor ligand-binding subunit (IL-10R1) on intestinal epithelial cells through activation of AhR (75).”
BackgroundInfluentialXiao, H., Cui, M., Li, Y., Dong, J., Zhang, S., Zhu, C., Jiang, M., Zhu, T., Wang, B., Wang, H., et al. (2020) · Microbiome · doi:10.1186/s40168-020-00845-6 · Cited by 254 · see citing works
Macrophage immunometabolism in inflammatory bowel diseases: From pathogenesis to therapy
Pan, X., Zhu, Q., Pan, L., & Sun, J. T. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108176 · Cited by 251 · see citing works
Mitrea, L., Nemeș, S. A., Szabo, K., Teleky, B., & Vodnar, D. C. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.813204 · Cited by 242 · see citing works
Hosseinkhani, F., Heinken, A., Thiele, I., Lindenburg, P. W., Harms, A. C., & Hankemeier, T. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1882927 · Cited by 244 · see citing works
“Furthermore, indole promotes epithelial barrier functions of intestinal cells by inducing increased expression of tight junction proteins between cells, thereby contributing to trans epithelial resistance to inflammation.(62) Additionally, indole administration attenuated multiple deleterious effects of nonsteroidal a…”
BackgroundJi, Y. S., Yin, Y., Li, Z., & Zhang, W. (2019) · Nutrients · doi:10.3390/nu11081712 · Cited by 230 · see citing works
“As a ligand of aryl hydrocarbon receptor (AhR), IAld induces the production of IL-22, thereby providing a protection against candidiasis and mucosal damage [86].”
BackgroundInfluentialNew Insights Into Gut-Bacteria-Derived Indole and Its Derivatives in Intestinal and Liver Diseases
Li, X., Zhang, B., Hu, Y., & Zhao, Y. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.769501 · Cited by 235 · see citing works
Konopelski, P., & Mogilnicka, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031222 · Cited by 218 · see citing works
“Moreover, IPA acts as a ligand of the aryl hydrocarbon receptor (AhR) present in colonic epithelial cells, activation of which is associated with anti-inflammatory and anticancer effects [119] Interestingly, it has been observed that in patients suffering from colitis serum, IPA concentration decreases significantly […”
BackgroundHou, Y., Li, J., & Ying, S. (2023) · Metabolites · doi:10.3390/metabo13111166 · Cited by 225 · see citing works
“Administration of IPA has been shown to significantly induce expressionof IL-10 receptor protein 1 in cultured intestinal epithelial T84 cells, which further supports the role of IPA in the maintenance of intestinal immunity [82].”
BackgroundResultBosi, A., Banfi, D., Bistoletti, M., Giaroni, C., & Baj, A. (2020) · International Journal of Tryptophan Research · doi:10.1177/1178646920928984 · Cited by 221 · see citing works
Wernimont, S. M., Radosevich, J., Jackson, M. I., Ephraim, E., Badri, D. V., MacLeay, J. M., Jewell, D. E., & Suchodolski, J. S. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.01266 · Cited by 220 · see citing works
“For example, indole, a degradation product of the amino acid tryptophan, has been shown to improve host-microbiome immune homeostasis (Alexeev et al., 2018), decrease markers of inflammation, and increase epithelial-cell tight-junction resistance (Bansal et al.”
BackgroundZhang, Y., Chen, R., Zhang, D., Qi, S., & Liu, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114295 · Cited by 209 · see citing works
Berberine improves colitis by triggering AhR activation by microbial tryptophan catabolites
Jing, W., Dong, S., Luo, X., Liu, J., Wei, B., Wei, D., Yang, L. W., Luo, H., Wang, Y., Wang, S., et al. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105358 · Cited by 194 · see citing works
The aryl hydrocarbon receptor as a mediator of host-microbiota interplay
Dong, F., & Perdew, G. H. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1859812 · Cited by 193 · see citing works
“Not only the use of AHR agonist-producing probiotics, but also direct oral administration of microbial AHR agonists, such as IPA, indole, and IPyA, have been shown to reduce experimental intestinal inflammation in an experimental colitis model.(105,137,138) A recent study demonstrated that a diet supplemented with the…”
BackgroundGut microbiota bridges dietary nutrients and host immunity
Fan, L., Xia, Y., Wang, Y., Han, D., Liu, Y., Li, J., Fu, J., Wang, L., Gan, Z., Liu, B., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2346-1 · Cited by 197 · see citing works
“…example, indole propionic acid (IPA), the final metabolite of the microbial reduction pathway of Trp, has been demonstrated as an endogenous ligand for PXR, functions to strengthen the gut barrier through Toll-like receptor 4 (TLR4) signaling or epithelial IL-10 receptor 1 (Alexeev et al., 2018).”
BackgroundTryptophan Metabolic Pathways Are Altered in Obesity and Are Associated With Systemic Inflammation
Cussotto, S., Delgado, I., Anesi, A., Dexpert, S., Aubert, A., Beau, C., Forestier, D., Ledaguenel, P., Magne, E., Mattivi, F., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00557 · Cited by 189 · see citing works
Identification of the novel role of butyrate as AhR ligand in human intestinal epithelial cells
Marinelli, L., Martin‐Gallausiaux, C., Bourhis, J., Béguet-Crespel, F., Blottière, H. M., & Lapaque, N. (2019) · Scientific Reports · doi:10.1038/s41598-018-37019-2 · Cited by 190 · see citing works
Fu, Y., Lyu, J., & Wang, S. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1277102 · Cited by 175 · see citing works
Indole-3-Acetic Acid Alters Intestinal Microbiota and Alleviates Ankylosing Spondylitis in Mice
Shen, J., Yang, L., You, K., Chen, T., Su, Z., Cui, Z., Wang, M., Zhang, W., Liu, B., Zhou, K., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.762580 · Cited by 168 · see citing works
“IPA has antineoplastic features in breast cancer (60) and effect on astrocytes to limit central nervous system (CNS) inflammation (61), as well as inhibit colonic inflammation induced by dextran sodium sulfate (DSS) in mice (62).”
BackgroundZhang, H.-Y., Tian, J., Lian, F., Li, M., Liu, W., Zhong, Z., Liao, J., & Tong, X. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110857 · Cited by 163 · see citing works
Ala, M. (2021) · International Reviews of Immunology · doi:10.1080/08830185.2021.1954638 · Cited by 162 · see citing works
“IPA, in an AHR-dependent manner, could increase the expression of IL-10R1 (Interleukin-10 receptor subunit 1) on cultured intestinal epithelia and similarly improved colitis in vivo [13].”
BackgroundTennoune, N., Andriamihaja, M., & Blachier, F. (2022) · Microorganisms · doi:10.3390/microorganisms10050930 · Cited by 159 · see citing works
“In such an experimental context, it is of interest to note that circulating indole-3-propionate acid is reduced in patients suffering from ulcerative colitis when compared with their healthy counterparts, whereas an increased level of this bacterial metabolite is associated with remission [54].”
BackgroundMa, N., He, T., Johnston, L. J., & Ma, X. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1758008 · Cited by 158 · see citing works
Impact of Microbial Metabolites on Microbiota–Gut–Brain Axis in Inflammatory Bowel Disease
Banfi, D., Moro, E., Bosi, A., Bistoletti, M., Cerantola, S., Crema, F., Maggi, F., Giron, M. C., Giaroni, C., & Baj, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041623 · Cited by 159 · see citing works
“A beneficial effect on chemically-induced inflammatory injury in mouse small and large intestine was obtained after oral administration of indole and IPA [332,333].”
BackgroundInfluentialPowell, D. N., Swimm, A. I., Sonowal, R., Bretin, A., Gewirtz, A. T., Jones, R. M., & Kalman, D. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003004117 · Cited by 151 · see citing works
“2B), indoles also improve transepithelial resistance (17, 35) and regulate expression of the IL-10 receptor (IL-10R) on intestinal epithelial cells, perhaps as a means of further promoting IL-10 signaling (35).”
BackgroundJiang, H., Chen, C., & Gao, J. (2022) · Nutrients · doi:10.3390/nu15010151 · Cited by 149 · see citing works
“1 mg/mL Drinking water 9 days [25] C57BL/6 mice 6–8 weeks 10.”
BackgroundResultInfluentialLai, Y., Liu, C., Yang, Y., Hsiao, Y.-C., Ru, H., & Lü, K. (2021) · Nature Communications · doi:10.1038/s41467-021-26209-8 · Cited by 144 · see citing works
Lai, W., Deng, W.-F., Xu, S., Zhao, J., Xu, D., Liu, Y., Guo, Y., Wang, M., He, F.-S., Ye, S.-W., et al. (2019) · Psychological Medicine · doi:10.1017/s0033291719003027 · Cited by 141 · see citing works
Optimizing therapeutic outcomes of immune checkpoint blockade by a microbial tryptophan metabolite
Renga, G., Nunzi, E., Pariano, M., Puccetti, M., Bellet, M. M., Pieraccini, G., D’Onofrio, F., Santarelli, I., Stincardini, C., Aversa, F., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003725 · Cited by 144 · see citing works
Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy
Thomas, A. M., Fidelle, M., Routy, B., Kroemer, G., Wargo, J. A., Segata, N., & Zitvogel, L. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00785-8 · Cited by 141 · see citing works
Microbial Metabolites Determine Host Health and the Status of Some Diseases
Sittipo, P., Shim, J., & Lee, Y. K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215296 · Cited by 138 · see citing works
Microbiota-derived tryptophan metabolites in vascular inflammation and cardiovascular disease
Paeslack, N., Mimmler, M., Becker, S., Gao, Z., Khuu, M. P., Mann, A., Malinarich, F., Regen, T., & Reinhardt, C. (2022) · Amino Acids · doi:10.1007/s00726-022-03161-5 · Cited by 139 · see citing works
Zhou, Y., Chen, Y., He, H., Peng, M., Zeng, M., & Sun, H. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109690 · Cited by 141 · see citing works
Man, A. W. C., Zhou, Y., Xia, N., & Li, H. (2020) · Nutrients · doi:10.3390/nu12103054 · Cited by 136 · see citing works
“Moreover, administration of IPA significantly ameliorates colitis and induces IL-10-mediated anti-inflammatory pathway in vitro [178].”
BackgroundDunleavy, K. A., Raffals, L. E., & Camilleri, M. (2023) · Digestive Diseases and Sciences · doi:10.1007/s10620-023-08122-w · Cited by 132 · see citing works
Li, X., Zhang, Z., Zabed, H. M., Yun, J., Zhang, G., & Qi, X. (2020) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202000461 · Cited by 124 · see citing works
Altomare, A., Rosa, C. D., Imperia, E., Emerenziani, S., Cicala, M., & Guarino, M. P. L. (2021) · Nutrients · doi:10.3390/nu13051506 · Cited by 132 · see citing works
“Trp metabolism in the gut includes the direct transformation of Trp by intestinal microorganisms into several molecules, such as indole and its derivates, many of which are ligands for aryl hydrocarbon receptor (AhR) [77].”
BackgroundDietary protein and the intestinal microbiota: An understudied relationship
Bartlett, A., & Kleiner, M. (2022) · iScience · doi:10.1016/j.isci.2022.105313 · Cited by 124 · see citing works
“Additionally, indole concentrations were found to be lower in mice upon induction of colitis (Alexeev et al., 2018).”
Wu, R., Xiong, R., Li, Y., Chen, J., & Yan, R. (2023) · Journal of Autoimmunity · doi:10.1016/j.jaut.2023.103062 · Cited by 121 · see citing works
Matei, D. E., Menon, M., Alber, D., Smith, A. M., Nedjat-Shokouhi, B., Fasano, A., Magill, L., Duhlin, A., Bitoun, S., Gleizes, A., et al. (2021) · Med · doi:10.1016/j.medj.2021.04.013 · Cited by 119 · see citing works
“In vitro, IL-10 signaling inhibits IFNg-mediated disruption of epithelial cell tight junctions and loss of cell viability.(21,43,63) However, IFNg has been reported to upregulate IL-10R expression by epithelial cells, making them more sensitive to IL-10-mediated protection.”
BackgroundRegulation of common neurological disorders by gut microbial metabolites
Park, J., & Kim, C. H. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00703-x · Cited by 120 · see citing works
Zhang, B., Jiang, M., Zhao, J., Song, Y., Du, W., & Shi, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.841703 · Cited by 115 · see citing works
Greathouse, K. L., & Wyatt, M. (2021) · Nutrients · doi:10.3390/nu13041189 · Cited by 111 · see citing works
“Indolic compounds can also act as AhR ligands to promote both pro- and antiinflammatory effects [17,96].”
BackgroundDiverse roles of microbial indole compounds in eukaryotic systems
Kumar, P., Lee, J., & Lee, J. (2021) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12765 · Cited by 112 · see citing works
Zhong, S., Sun, Y.-Q., Huo, J.-X., Xu, W., Yang, Y.-N., Yang, J.-B., Wu, W.-J., Liu, Y.-X., Wu, C.-M., & Li, Y.-G. (2024) · iMeta · doi:10.1002/imt2.180 · Cited by 109 · see citing works
“…evidence has revealed that AhR can mitigate colitis by decreasing the serum inflammatory cytokines/chemo-kines (e.g., TNF ‐ α , IFN ‐ γ , MCP ‐ 1, and IL ‐ 17) [47], enhancing the expression of IL ‐ 10 and IL ‐ 22 [12, 48], and strengthening the intestinal epithelial cell barrier [11, 14].”
BackgroundAmino Acid Trp: The Far Out Impacts of Host and Commensal Tryptophan Metabolism
Grifka‐Walk, H. M., Jenkins, B. R., & Kominsky, D. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.653208 · Cited by 112 · see citing works
“The importance of AHR signaling is exemplified by numerous in vivo studies utilizing endogenously produced (93, 96, 103), exogenously acquired (67, 101, 118), and microbe-derived ligands (7, 9, 65, 119) to ameliorate pathologies associated with IBD and gastrointestinal infection.”
BackgroundInfluentialSelf-citationGao, H., Sun, M., Ai, L., Gu, Q., Kang, D., Feng, Z., Li, X., Wang, X., Chen, L., Hong, Y., et al. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2467235 · Cited by 113 · see citing works
Chen, C., Cao, Z., Lei, H., Zhang, C., Wu, M., Huang, S., Li, X., Xie, D., Liu, M., Zhang, L., et al. (2024) · Advanced Science · doi:10.1002/advs.202404545 · Cited by 105 · see citing works
Vila, A. V., Zhang, J., Liu, M., Faber, K. N., & Weersma, R. K. (2024) · Gut · doi:10.1136/gutjnl-2023-329969 · Cited by 109 · see citing works
“…AhR activation has been shown to protect against dextran suldate sodium (DSS)- induced colitis by regulating the IL22 and IL10 signalling pathways 109 ; modulating the differentiation and function of key immune cells like Th17, Treg, macrophages and dendritic cells in mice 110 and enhancing…”
Aa, L., Fei, F., Qi, Q., Sun, R., Gu, S., Di, Z., Aa, J., Wang, G., & Liu, C. (2019) · Acta Pharmacologica Sinica · doi:10.1038/s41401-019-0279-8 · Cited by 101 · see citing works
Mamic, P., Chaikijurajai, T., & Tang, W. H. W. (2020) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2020.12.001 · Cited by 99 · see citing works
“Indoles (including indole-3-propionate (IPA)), which are produced from dietary tryptophan by some specific gut microbes (such as Clostridium sporogenes in case of IPA [58]), fortify the intestinal barrier decreasing the gut wall permeability and circulating inflammatory cytokines [59-63].”
BackgroundModulation of immunity by tryptophan microbial metabolites
Li, S. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1209613 · Cited by 101 · see citing works
Ghiboub, M., Verburgt, C. M., Sovran, B., Benninga, M. A., de Jonge, W. J., & Limbergen, J. V. (2020) · Nutrients · doi:10.3390/nu12092846 · Cited by 94 · see citing works
Huang, Z., Hu, Z., Lu, C.-X., Luo, S.-D., Chen, Y., Zhou, Z.-P., Hu, J., Zhang, F.-L., Deng, F., & Liu, K. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.1015386 · Cited by 91 · see citing works
“Indole 3propionic acid (IPA) is a tryptophan deamination product derived from Lactobacillus reuteri, Akkermansia and Clostiridum genus, which mediate intracellular signaling activity (Dodd et al., 2017; Alexeev et al., 2018; Konopelski and Mogilnicka, 2022).”
BackgroundNguyen, H. D., Aljamaei, H. M., & Stadnyk, A. W. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.07.005 · Cited by 91 · see citing works
Hyland, N. P., Cavanaugh, C. R., & Hornby, P. J. (2022) · Amino Acids · doi:10.1007/s00726-022-03123-x · Cited by 89 · see citing works
“Circulating IPA levels are reduced in patients suffering from Inflammatory Bowel Disease and increased levels are associated with remission (Alexeev et al. 2018).”
BackgroundPotdar, A. A., Dube, S., Naito, T., Li, K., Botwin, G. J., Haritunians, T., Li, D., Casero, D., Yang, S., Bilsborough, J., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.10.041 · Cited by 88 · see citing works
Modulating AHR function offers exciting therapeutic potential in gut immunity and inflammation
Chen, Y., Wang, Y., Fu, Y., Yin, Y., & Xu, K. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01046-y · Cited by 91 · see citing works
“Indole metabolites enhance intestinal homeostasis through AHR-mediated regulation of the IEC IL-10R1 [110].”
BackgroundYang, J., Liang, J., Hu, N., He, N., Liu, B., Liu, G., & Qin, Y. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70091 · Cited by 100 · see citing works
“Additionally, microbiota-derived metabolic products like taurocholic acid, histamine, indole, and spermine influence downstream neuro-peptides, regulating NLRP6 inflammasomes, IL-10, and IL-18 secretion, which correlate with inflammatory factor levels and Alzheimer's severity [14, 121].”
BackgroundMicrobiota-derived tryptophan metabolism: Impacts on health, aging, and disease
Gupta, S. K., Vyavahare, S. S., Blanes, I. L. D., Berger, F. G., Isales, C. M., & Fulzele, S. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112319 · Cited by 85 · see citing works
“Recently, several groups confirmed the decreased production of IPA in the serum of patients suffering from UC compared to average healthy persons (Alexeev et al., 2018).”
BackgroundMolecular and Pathophysiological Links between Metabolic Disorders and Inflammatory Bowel Diseases
Hyun, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179139 · Cited by 84 · see citing works
Liu, Y., Pei, Z., Pan, T., Wang, H., Chen, W., & Lu, W. (2023) · Microbiological Research · doi:10.1016/j.micres.2023.127392 · Cited by 87 · see citing works
Limosilactobacillus reuteri in immunomodulation: molecular mechanisms and potential applications
Luo, Z., Chen, A., Xie, A., Liu, X., Jiang, S., & Yu, R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1228754 · Cited by 82 · see citing works
Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease
Pandey, H., Jain, D., Tang, D. W. T., Wong, S. H., & Lal, D. (2023) · Intestinal Research · doi:10.5217/ir.2023.00080 · Cited by 89 · see citing works
Gut health: The results of microbial and mucosal immune interactions in pigs
Peng, J., Tang, Y., & Huang, Y. (2021) · Animal nutrition · doi:10.1016/j.aninu.2021.01.001 · Cited by 80 · see citing works
Iyer, N. R., & Corr, S. C. (2021) · Nutrients · doi:10.3390/nu13124259 · Cited by 80 · see citing works
“GPR35 (predicted), Aryl hydrocarbon receptor (AHR), Pregnane X receptor (PXR) [106,111] - Indole derivatives promote expression of anti-microbials [108] - Indoles regulate epithelial repair and differentiation [109,112] - Indoles promote IL-10 signalling to increase goblet cell differentiation and strengthen mucus bar…”
BackgroundXie, Y., Zou, X., Han, J., Zhang, Z., Feng, Z., Ouyang, Q., Hua, S., Liu, Z., Li, C., Cai, Y., et al. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114081 · Cited by 80 · see citing works
Cao, C., Wang, L., Ai, C., Gong, G., Wang, Z., Huang, L., Song, S., & Zhu, B. (2022) · Food & Function · doi:10.1039/d2fo01283a · Cited by 79 · see citing works
Gut-microbiota derived bioactive metabolites and their functions in host physiology
Debnath, N., Kumar, R., Kumar, A., Mehta, P. K., & Yadav, A. K. (2021) · Biotechnology and Genetic Engineering Reviews · doi:10.1080/02648725.2021.1989847 · Cited by 77 · see citing works
“This signalling system actively participates in epithelial cell renewal, intensify the integrity of epithelial barrier, and activates several immune cell types, such as intraepithelial lymphocytes, T helper 17 (Th17) cells, innate lymphoid cells, macrophages, DCs, and neutrophils (Alexeev et al., 2018).”
BackgroundLefèvre, A., Mavel, S., Nadal‐Desbarats, L., Galineau, L., Attucci, S., Dufour, D. F., Sokol, H., & Emond, P. (2018) · Talanta · doi:10.1016/j.talanta.2018.11.094 · Cited by 74 · see citing works
“the immune response, although their functions are not fully understood [6,7].”
BackgroundA dysbiotic microbiome promotes head and neck squamous cell carcinoma
Frank, D. N., Qiu, Y., Cao, Y. Q., Zhang, S., Lu, L., Kofonow, J. M., Robertson, C. E., Liu, Y., Wang, H., Levens, C. L., et al. (2022) · Oncogene · doi:10.1038/s41388-021-02137-1 · Cited by 77 · see citing works
Mar, J. S., Ota, N., Pokorzynski, N. D., Peng, Y., Jaochico, A., Sangaraju, D., Skippington, E., Lekkerkerker, A., Rothenberg, M. E., Tan, M., et al. (2023) · Microbiome · doi:10.1186/s40168-023-01486-1 · Cited by 74 · see citing works
“These observations are in line with prior studies describing depleted indole concentration, increased L-Kyn levels, and reduced AhR activity accompanying microbial dysbiosis in the stool of IBD patients [13, 23, 28].”
ResultClostridium sporogenes-derived metabolites protect mice against colonic inflammation
Krause, F. F., Mangold, K., Ruppert, A.-L., Leister, H., Hellhund-Zingel, A., Krol, A. L., Pesek, J., Watzer, B., Winterberg, S., Raifer, H., et al. (2024) · Gut microbes · doi:10.1080/19490976.2024.2412669 · Cited by 74 · see citing works
“60 By colonizing mice with C. sporogenes we were able to restore IPA levels, promoting survival and alleviation of colitis.”
BackgroundIn vitro models and ex vivo systems used in inflammatory bowel disease
Joshi, A., Soni, A., & Acharya, S. R. (2022) · In vitro models · doi:10.1007/s44164-022-00017-w · Cited by 75 · see citing works
Sehgal, R., de Mello, V. D., Männistö, V., Lindström, J., Tuomilehto, J. O., Pihlajamäki, J., & Uusitupa, M. I. J. (2022) · Nutrients · doi:10.3390/nu14214695 · Cited by 73 · see citing works
“IPA is a biomarker of active ulcerative colitis and for disease, remission based on a study in human patients with intestinal bowel disorder [35].”
BackgroundMicrobiota and IBD: Current knowledge and future perspectives
Foppa, C., Rizkala, T., Repici, A., Hassan, C., & Spinelli, A. (2023) · Digestive and Liver Disease · doi:10.1016/j.dld.2023.11.015 · Cited by 79 · see citing works
Old Friends, immunoregulation, and stress resilience
Langgartner, D., Lowry, C. A., & Reber, S. O. (2018) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2228-7 · Cited by 73 · see citing works
Intestinal Dysbiosis and Tryptophan Metabolism in Autoimmunity
Brown, J., Robusto, B. A., & Morel, L. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01741 · Cited by 67 · see citing works
Molecular interactions between the intestinal microbiota and the host
Hertli, S., & Zimmermann, P. (2022) · Molecular Microbiology · doi:10.1111/mmi.14905 · Cited by 76 · see citing works
“Wrzosek, L., Miquel, S., Noordine, M.- L., Bouet, S., Chevalier- Curt, M.J., Robert, V. et al. (2013) Bacteroides thetaiotaomicron and Faecalibacterium prausnitziiinfluence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent.”
BackgroundInfluentialLangan, D., Perkins, D. J., Vogel, S. N., & Moudgil, K. D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042017 · Cited by 70 · see citing works
“This observation contrasts with other reports where in vitro effects of IAld are described at 10 to 100 times higher concentration [24].”
BackgroundResultLi, N., Ma, P.-G., Li, Y., Shang, X., Nan, X., Shi, L., Han, X., Liu, J., Hong, Y., Li, Q., et al. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2290315 · Cited by 74 · see citing works
Beyond the Gut: The intratumoral microbiome's influence on tumorigenesis and treatment response
Zhang, H., Fu, L., Leiliang, X., Qu, C., Wu, W., Wen, R., Huang, N., He, Q., Cheng, Q., Liu, G., et al. (2024) · 癌症：英文版 · doi:10.1002/cac2.12597 · Cited by 71 · see citing works
- Authors
- Alexeev, E. E., Lanis, J. M., Kao, D. J., Campbell, E. L., Kelly, C. J., Battista, K. D., Gerich, M. E., Jenkins, B. R., Walk, S. T., Kominsky, D. J., & Colgan, S. P.
- Affiliations
- University of Colorado Anschutz (US)
- Queen's University Belfast (GB)
- Montana State University (US)
- Corresponding author
- Kominsky, Douglas J.
- Colgan, Sean P.
- ORCID
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 188
- Issue
- 5
- Pages
- 1183-1194
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC5906738
- OpenAlex
- W2788222993
- Cited by
- 532
- References
- 55
- Citations by year
- 2026: 65 · 2025: 84 · 2024: 76 · 2023: 90 · 2022: 68 · 2021: 74 · 2020: 43 · 2019: 22 · 2018: 8
- FWCI
- 13.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion, cc-by-nc-nd)
- Funders
- NIH (DK1047893, DK50189, DK095491, DK103639, DK103712)
- VA Merit (BX002182)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut microbiota, indole metabolites, indole-3-propionic acid, interleukin-10 receptor, IL-10 signaling, aryl hydrocarbon receptor, intestinal homeostasis, colitis, germ-free mice, Escherichia coli, intestinal epithelium, mucosal disease, anti-inflammatory therapy
- MeSH terms
- Animals, Cell Line, Colitis, Disease Models, Animal, Homeostasis, Humans, Indoles, Intestinal Mucosa, Dextran Sulfate, Mice, Receptors, Interleukin-10, Metabolomics, 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
