A bacterial bile acid metabolite modulates Treg activity through the nuclear hormone receptor NR4A1
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Abstract
Bile acids act as signaling molecules that regulate immune homeostasis, including the differentiation of CD4+ T cells into distinct T cell subsets. The bile acid metabolite isoallolithocholic acid (isoalloLCA) enhances the differentiation of anti-inflammatory regulatory T cells (T reg cells) by facilitating the formation of a permissive chromatin structure in the promoter region of the transcription factor forkhead box P3 (Foxp3). Here, we identify gut bacteria that synthesize isoalloLCA from 3-oxolithocholic acid and uncover a gene cluster responsible for the conversion in members of the abundant human gut bacterial phylum Bacteroidetes. We also show that the nuclear hormone receptor NR4A1 is required for the effect of isoalloLCA on T reg cells. Moreover, the levels of isoalloLCA and its biosynthetic genes are significantly reduced in patients with inflammatory bowel diseases, suggesting that isoalloLCA and its bacterial producers may play a critical role in maintaining immune homeostasis in humans.
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NUR77 is required for isoalloLCA-induced FOXP3 expression in CD4+ T cells.
“Because NUR77 was shown to be required for isoalloLCA–induced FOXP3 expression in CD4+ T cells (32),”
From Bile acid synthesis impedes tumor-specific T cell responses during liver cancer (2025) · cites this paper as [32]
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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 · see citing works
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041 · see citing works
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · see citing works
limma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv007 · Cited by 40,458 · see citing works
clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters
Yu, G., Wang, L.-G., Han, Y., & He, Q.-Y. (2012) · OMICS: A Journal of Integrative Biology · doi:10.1089/omi.2011.0118 · Cited by 36,259 · see citing works
BLAST+: architecture and applications
Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., & Madden, T. L. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-421 · Cited by 22,074 · see citing works
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464 · see citing works
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386 · see citing works
Self-citationRobinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390 · see citing works
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382 · see citing works
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668 · see citing works
Near-optimal probabilistic RNA-seq quantification
Bray, N. L., Pimentel, H., Melsted, P., & Pachter, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3519 · Cited by 9,723 · see citing works
Control of Regulatory T Cell Development by the Transcription Factor <i>Foxp3</i>
Hori, S., Nomura, T., & Sakaguchi, S. (2003) · Science · doi:10.1126/science.1079490 · Cited by 8,187 · see citing works
deepTools2: a next generation web server for deep-sequencing data analysis
Ramírez, F., Ryan, D. P., Grüning, B., Bhardwaj, V., Kilpert, F., Richter, A. S., Heyne, S., Dündar, F., & Manke, T. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw257 · Cited by 8,096 · see citing works
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003) · Nature Immunology · doi:10.1038/ni904 · Cited by 7,745 · see citing works
Enterotypes of the human gut microbiome
MetaHIT Consortium (additional members), Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D. R., Fernandes, G. R., Tap, J., Bruls, T., et al. (2011) · Nature · doi:10.1038/nature09944 · Cited by 7,548 · see citing works
O'Leary, N. A., Wright, M. W., Brister, J. R., Ciufo, S., Haddad, D., McVeigh, R., Rajput, B., Robbertse, B., Smith-White, B., Ako-Adjei, D., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1189 · Cited by 6,357 · see citing works
Self-citationCommensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013) · Nature · doi:10.1038/nature12721 · Cited by 5,549 · see citing works
Revised Estimates for the Number of Human and Bacteria Cells in the Body
Sender, R., Fuchs, S., & Milo, R. (2016) · PLOS Biology · doi:10.1371/journal.pbio.1002533 · Cited by 5,425 · see citing works
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413 · see citing works
Regulatory T Cells and Immune Tolerance
Sakaguchi, S., Yamaguchi, T., Nomura, T., & Ono, M. (2008) · Cell · doi:10.1016/j.cell.2008.05.009 · Cited by 5,357 · see citing works
Letunic, I., & Bork, P. (2016) · Nucleic Acids Res. · doi:10.1093/nar/gkw290 · Cited by 4,851 · see citing works
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J. R., Pfeffer, K., Coffer, P. J., et al. (2013) · Nature · doi:10.1038/nature12726 · Cited by 4,838 · see citing works
The Role of Tumoral FOXP3 on Cell Proliferation, Migration, and Invasion in Gastric Cancer
Zhang, L., Xu, J., Zhang, X., Zhang, Y., Wang, L., Huang, X., & Xu, Z. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479442 · Cited by 4,090 · see citing works
Self-citationMulti-omics of the gut microbial ecosystem in inflammatory bowel diseases
Lloyd-Price, J., Arze, C., Ananthakrishnan, A. N., Schirmer, M., Avila-Pacheco, J., Poon, T. W., Andrews, E., Ajami, N. J., Bonham, K. S., Brislawn, C. J., et al. (2019) · Nature · doi:10.1038/s41586-019-1237-9 · Cited by 3,143 · see citing works
Self-citationIntestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism
Wahlstrom, A. M., Sayin, S. I., Marschall, H., & Bäckhed, F. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.005 · Cited by 2,903 · see citing works
Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
Atarashi, K., Tanoue, T., Oshima, K., Suda, W., Nagano, Y., Nishikawa, H., Fukuda, S., Saito, T., Narushima, S., Hase, K., et al. (2013) · Nature · doi:10.1038/nature12331 · Cited by 2,872 · see citing works
Bile salt biotransformations by human intestinal bacteria
Ridlon, J. M., Kang, D.-J., & Hylemon, P. B. (2006) · Journal of Lipid Research · doi:10.1194/jlr.r500013-jlr200 · Cited by 2,829 · see citing works
Sakaguchi, S. (2005) · Nature Immunology · doi:10.1038/ni1178 · Cited by 2,669 · see citing works
Multivariable association discovery in population-scale meta-omics studies
Mallick, H., Rahnavard, A., McIver, L. J., Ma, S., Zhang, Y., Nguyen, L. H., Tickle, T. L., Weingart, G., Ren, B., Schwager, E. H., et al. (2021) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1009442 · Cited by 2,596 · see citing works
Self-citationA microbial symbiosis factor prevents intestinal inflammatory disease
Mazmanian, S. K., Round, J. L., & Kasper, D. L. (2008) · Nature · doi:10.1038/nature07008 · Cited by 2,340 · see citing works
Clarridge, J. E. (2004) · Clinical Microbiology Reviews · doi:10.1128/cmr.17.4.840-862.2004 · Cited by 2,198 · see citing works
The Enzymes, Regulation, and Genetics of Bile Acid Synthesis
Russell, D. W. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161712 · Cited by 2,069 · see citing works
Gut microbiome structure and metabolic activity in inflammatory bowel disease
Franzosa, E. A., Sirota-Madi, A., Avila-Pacheco, J., Fornelos, N., Haiser, H. J., Reinker, S., Vatanen, T., Hall, A. B., Mallick, H., McIver, L. J., et al. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0306-4 · Cited by 1,995 · see citing works
Self-citationPrecision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile
Buffie, C. G., Bucci, V., Stein, R. R., McKenney, P. T., Ling, L., Gobourne, A., No, D., Liu, H., Kinnebrew, M., Viale, A., et al. (2015) · Nature · doi:10.1038/nature13828 · Cited by 1,872 · see citing works
Bile acid metabolites control TH17 and Treg cell differentiation
Hang, S., Paik, D., Yao, L., Kim, E., Trinath, J., Lu, J., Ha, S., Nelson, B. N., Kelly, S. P., Wu, L., et al. (2019) · Nature · doi:10.1038/s41586-019-1785-z · Cited by 1,457 · see citing works
Self-citationTargeting bile‐acid signalling for metabolic diseases
Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J., & Schoonjans, K. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2619 · Cited by 1,422 · see citing works
Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate
Zheng, Y., Josefowicz, S. Z., Chaudhry, A., Peng, X. P., Forbush, K. A., & Rudensky, A. Y. (2010) · Nature · doi:10.1038/nature08750 · Cited by 1,170 · 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
Moran, A. E., Holzapfel, K. L., Xing, Y., Cunningham, N. R., Maltzman, J. S., Punt, J. A., & Hogquist, K. A. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20110308 · Cited by 1,035 · see citing works
Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis
Song, X., Sun, X., Oh, S. F., Wu, M., Zhang, Y., Zheng, W., Geva-Zatorsky, N., Jupp, R., Mathis, D., Benoist, C., et al. (2020) · Nature · doi:10.1038/s41586-019-1865-0 · Cited by 1,024 · see citing works
Self-citationBacterial metabolism of bile acids promotes generation of peripheral regulatory T cells
Campbell, C., McKenney, P. T., Konstantinovsky, D., Isaeva, O. I., Schizas, M., Verter, J., Mai, C., Jin, W.-B., Guo, C.-J., Violante, S., et al. (2020) · Nature · doi:10.1038/s41586-020-2193-0 · Cited by 901 · see citing works
Individual intestinal symbionts induce a distinct population of RORγ <sup>+</sup> regulatory T cells
Sefik, E., Geva-Zatorsky, N., Oh, S., Konnikova, L., Zemmour, D., McGuire, A. M., Burzyn, D., Ortiz-Lopez, A., Lobera, M., Yang, J., et al. (2015) · Science · doi:10.1126/science.aaa9420 · Cited by 879 · see citing works
A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients
Hall, A. B., Yassour, M., Sauk, J., Garner, A., Jiang, X., Arthur, T., Lagoudas, G. K., Vatanen, T., Fornelos, N., Wilson, R., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0490-5 · Cited by 777 · see citing works
Self-citationMatsuki, T., Watanabe, K., Fujimoto, J., Takada, T., & Tanaka, R. (2004) · Applied and Environmental Microbiology · doi:10.1128/aem.70.12.7220-7228.2004 · Cited by 656 · see citing works
A User-Friendly Entry to 2-Iodoxybenzoic Acid (IBX)
Frigerio, M., Santagostino, M., & Sputore, S. (1999) · The Journal of Organic Chemistry · doi:10.1021/jo9824596 · Cited by 656 · see citing works
The bile acid receptor FXR is a modulator of intestinal innate immunity
Vavassori, P., Mencarelli, A., Renga, B., Distrutti, E., & Fiorucci, S. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803978 · Cited by 655 · see citing works
Peripheral and Intestinal Regulatory CD4+CD25high T Cells in Inflammatory Bowel Disease
Maul, J., Loddenkemper, C., Mundt, P., Berg, E. G., Giese, T., Stallmach, A., Zeitz, M., & Duchmann, R. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.03.043 · Cited by 651 · see citing works
Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians
Sato, Y., Atarashi, K., Plichta, D. R., Arai, Y., Sasajima, S., Kearney, S. M., Suda, W., Takeshita, K., Sasaki, T., Okamoto, S., et al. (2021) · Nature · doi:10.1038/s41586-021-03832-5 · Cited by 632 · see citing works
Human gut bacteria produce ΤΗ17-modulating bile acid metabolites
Paik, D., Yao, L., Zhang, Y., Bae, S., D’Agostino, G. D., Zhang, M., Kim, E., Franzosa, E. A., Avila-Pacheco, J., Bisanz, J. E., et al. (2022) · Nature · doi:10.1038/s41586-022-04480-z · Cited by 594 · see citing works
Self-citationA metabolic pathway for bile acid dehydroxylation by the gut microbiome
Funabashi, M., Grove, T. L., Wang, M., Varma, Y., McFadden, M. E., Brown, L. C., Guo, C., Higginbottom, S., Almo, S. C., & Fischbach, M. A. (2020) · Nature · doi:10.1038/s41586-020-2396-4 · Cited by 590 · see citing works
Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors
Wang, Z., Benoit, G., Liu, J., Prasad, S., Aarnisalo, P., Liu, X., Xu, H., Walker, N. P. C., & Perlmann, T. (2003) · Nature · doi:10.1038/nature01645 · Cited by 583 · see citing works
Bile Acid-Activated Receptors, Intestinal Microbiota, and the Treatment of Metabolic Disorders
Fiorucci, S., & Distrutti, E. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.09.001 · Cited by 539 · see citing works
Andersson, S., & Russell, D. W. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.10.3640 · Cited by 501 · see citing works
A biosynthetic pathway for a prominent class of microbiota-derived bile acids
Devlin, A. S., & Fischbach, M. A. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1864 · Cited by 448 · see citing works
Self-citationComplex host genetics influence the microbiome in inflammatory bowel disease
Knights, D., Silverberg, M. S., Weersma, R. K., Gevers, D., Dijkstra, G., Huang, H., Tyler, A. D., van Sommeren, S., Imhann, F., Stempak, J. M., et al. (2014) · Genome Medicine · doi:10.1186/s13073-014-0107-1 · Cited by 418 · see citing works
Self-citationAntimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation
Cullen, T. W., Schofield, W. B., Barry, N. A., Putnam, E. E., Rundell, E. A., Trent, M. S., Degnan, P. H., Booth, C. J., Yu, H., & Goodman, A. L. (2015) · Science · doi:10.1126/science.1260580 · Cited by 395 · see citing works
High-Specificity Targeted Functional Profiling in Microbial Communities with ShortBRED
Kaminski, J., Gibson, M. K., Franzosa, E. A., Segata, N., Dantas, G. A., & Huttenhower, C. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004557 · Cited by 334 · see citing works
Self-citationNr4a receptors are essential for thymic regulatory T cell development and immune homeostasis
Sekiya, T., Kashiwagi, I., Yoshida, R., Fukaya, T., Morita, R., Kimura, A., Ichinose, H., METZGER, D., Chambon, P., & Yoshimura, A. (2013) · Nature Immunology · doi:10.1038/ni.2520 · Cited by 314 · see citing works
Degnan, P. H., Barry, N. A., Mok, K. C., Taga, M. E., & Goodman, A. L. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2013.12.007 · Cited by 283 · see citing works
Alterations in the gut microbiome of children with severe ulcerative colitis
Michail, S. K., Durbin, M. D., Turner, D., Griffiths, A. M., Mack, D. R., Hyams, J., LeLeiko, N. S., Kenche, H., Stolfi, A., & Wine, E. (2011) · Inflammatory Bowel Diseases · doi:10.1002/ibd.22860 · Cited by 283 · see citing works
A selective gut bacterial bile salt hydrolase alters host metabolism
Yao, L., Seaton, S. C., Ndousse-Fetter, S., Adhikari, A. A., DiBenedetto, N., Mina, A. I., Banks, A. S., Bry, L., & Devlin, A. S. (2018) · eLife · doi:10.7554/elife.37182 · Cited by 274 · see citing works
Human cecal bile acids: concentration and spectrum
Hamilton, J. P., Xie, G., Raufman, J.-P., Hogan, S., Griffin, T. L., Packard, C. A., Chatfield, D. A., Hagey, L. R., Steinbach, J. H., & Hofmann, A. F. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00027.2007 · Cited by 263 · see citing works
Microbiome Dependent Regulation of Tregs and Th17 Cells in Mucosa
Pandiyan, P., Bhaskaran, N., Zou, M., Schneider, E., Jayaraman, S., & Huehn, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00426 · Cited by 231 · see citing works
The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells
Sekiya, T., Kashiwagi, I., Inoue, N., Morita, R., Hori, S., Waldmann, H., Rudensky, A. Y., Ichinose, H., METZGER, D., Chambon, P., et al. (2011) · Nature Communications · doi:10.1038/ncomms1272 · Cited by 215 · see citing works
Karlsson, F. H., Ussery, D. W., Nielsen, J., & Nookaew, I. (2011) · Microbial Ecology · doi:10.1007/s00248-010-9796-1 · Cited by 179 · see citing works
García-Bayona, L., & Comstock, L. E. (2019) · mBio · doi:10.1128/mbio.01762-19 · Cited by 174 · see citing works
Regulatory T cell adaptation in the intestine and skin
Whibley, N., Tucci, A., & Powrie, F. M. (2019) · Nature Immunology · doi:10.1038/s41590-019-0351-z · Cited by 160 · see citing works
Ridlon, J. M., Kang, D.-J., & Hylemon, P. B. (2009) · Anaerobe · doi:10.1016/j.anaerobe.2009.05.004 · Cited by 138 · see citing works
Muñoz, L., Borrero, M., Cantera, M., Conde, E., del Campo, R., Rodríguez‐Serrano, M., Lario, M., Sánchez‐Díaz, A., Pastor, Ó., Díaz, D., et al. (2018) · Hepatology · doi:10.1002/hep.30349 · Cited by 134 · see citing works
Pols, T. W. H., Puchner, T., Korkmaz, H. I., Vos, M., Soeters, M. R., & de Vries, C. J. M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0176715 · Cited by 132 · see citing works
Nuclear receptor Nr4a1 modulates both regulatory T-cell (Treg) differentiation and clonal deletion
Fassett, M. S., Jiang, W., D'Alise, A. M., Mathis, D., & Benoist, C. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200090109 · Cited by 126 · see citing works
Bile acid induction specificity of 7α-dehydroxylase activity in an intestinal Eubacterium species
A, B., Lipsky, W. R. L., Fricke, R. J., & Hylemon, P. B. (1980) · Steroids · doi:10.1016/0039-128x(80)90115-4 · Cited by 125 · see citing works
Development of a covalent inhibitor of gut bacterial bile salt hydrolases
Adhikari, A. A., Seegar, T. C. M., Ficarro, S. B., McCurry, M. D., Ramachandran, D., Yao, L., Chaudhari, S. N., Ndousse-Fetter, S., Banks, A. S., Marto, J. A., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0467-3 · Cited by 115 · see citing works
Self-citationKANG, D. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2007.10.008 · Cited by 99 · see citing works
Jennings, E., Elliot, T. A. E., Thawait, N., Kanabar, S., Yam-Puc, J. C., Ono, M., Toellner, K.-M., Wraith, D. C., Anderson, G., & Bending, D. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108328 · Cited by 94 · see citing works
Author Correction: Gut microbiome structure and metabolic activity in inflammatory bowel disease
Franzosa, E. A., Sirota‐Madi, A., Ávila-Pacheco, J., Fornelos, N., Haiser, H. J., Reinker, S., Vatanen, T., Hall, A. B., Mallick, H., McIver, L. J., et al. (2019) · Nature Microbiology · doi:10.1038/s41564-019-0442-5 · Cited by 65 · see citing works
Self-citationPlanar bile acids in health and disease
Shiffka, S. J., Kane, M. A., & Swaan, P. W. (2017) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2017.08.019 · Cited by 39 · see citing works
A stereoselective synthesis of the allo-bile acids from the 5β-isomers
Li, Q., & Tochtrop, G. P. (2011) · Tetrahedron Letters · doi:10.1016/j.tetlet.2011.05.140 · Cited by 13 · see citing works
Human gut bacteria produce T H 17-modulating bile acid metabolitesPreprint
Paik, D., Yao, L., Zhang, Y., Bae, S., D’Agostino, G. D., Kim, E., Franzosa, E. A., Ávila-Pacheco, J., Bisanz, J. E., Rakowski, C. K., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.08.425913 · Cited by 9 · see citing works
Self-citationIdentification of unique bile acid-metabolizing bacteria from the microbiome of centenariansPreprint
Honda, K., Sato, Y., Atarashi, K., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-115113/v1 · Cited by 3 · see citing works
New steroid 5Α-reductase type I (SRD5A1) homologous sequences on human chromosomes 6 and 8
Eminović, I., Liović, M., Preželj, J., Kocijančič, A., Rozman, D., & Komel, R. (2001) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s004240100019 · Cited by 2 · see citing works
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Qiu, S., Cai, Y., Yao, H., Lin, C., Xie, Y., Tang, S., & Zhang, A. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01399-3 · Cited by 939 · see citing works
Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis
Cai, J., Sun, L., & Gonzalez, F. J. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.02.004 · Cited by 869 · see citing works
Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians
Sato, Y., Atarashi, K., Plichta, D. R., Arai, Y., Sasajima, S., Kearney, S. M., Suda, W., Takeshita, K., Sasaki, T., Okamoto, S., et al. (2021) · Nature · doi:10.1038/s41586-021-03832-5 · Cited by 632 · 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 621 · see citing works
Bile acid metabolism and signaling, the microbiota, and metabolic disease
Cai, J., Rimal, B., Jiang, C., Chiang, J. Y. L., & Patterson, A. D. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108238 · Cited by 513 · see citing works
Sorbara, M. T., & Pamer, E. G. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-021-00667-9 · Cited by 468 · see citing works
Principles of regulatory T cell function
Dikiy, S., & Rudensky, A. Y. (2023) · Immunity · doi:10.1016/j.immuni.2023.01.004 · Cited by 450 · see citing works
Gut–liver axis: barriers and functional circuits
Pabst, O., Hornef, M. W., Schaap, F. G., Cerovic, V., Clavel, T., & Bruns, T. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00771-6 · Cited by 462 · see citing works
Bile acids as modulators of gut microbiota composition and function
Larabi, A. B., Masson, H. L. P., & Bäumler, A. J. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2172671 · Cited by 412 · see citing works
Bifidobacterium mechanisms of immune modulation and tolerance
Gavzy, S. J., Kensiski, A., Lee, Z. L., Mongodin, E. F., Ma, B., & Bromberg, J. S. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2291164 · Cited by 375 · see citing works
Cong, J., Liu, P., Han, Z., Ying, W., Li, C., Yang, Y., Wang, S., Yang, J., Cao, F., Shen, J., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.02.014 · Cited by 319 · see citing works
Lipid metabolism in T cell signaling and function
Lim, S. A., SU, W. W., Chapman, N. M., & Chi, H. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01017-3 · Cited by 287 · see citing works
The changing metabolic landscape of bile acids – keys to metabolism and immune regulation
Mohanty, I., Allaband, C., Mannochio-Russo, H., Abiead, Y. E., Hagey, L. R., Knight, R. D., & Dorrestein, P. C. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00914-3 · Cited by 225 · see citing works
Jia, B., Zou, Y., Han, X., Bae, J., & Jeon, C. O. (2022) · Trends in Microbiology · doi:10.1016/j.tim.2022.08.003 · Cited by 220 · see citing works
The underappreciated diversity of bile acid modifications
Mohanty, I., Mannochio-Russo, H., Schweer, J. V., Abiead, Y. E., Bittremieux, W., Xing, S., Schmid, R., Zuffa, S., Vasquez, F. J. D. A., Muti, V. B., et al. (2024) · Cell · doi:10.1016/j.cell.2024.02.019 · Cited by 202 · see citing works
The Current and Future Perspectives of Postbiotics
Liang, B., & Xing, D. (2023) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-023-10045-x · Cited by 217 · see citing works
Another renaissance for bile acid gastrointestinal microbiology
Ridlon, J. M., & Gaskins, H. R. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00896-2 · Cited by 193 · see citing works
Bile acid synthesis impedes tumor-specific T cell responses during liver cancer
Varanasi, S. K., Chen, D., Liu, Y., Johnson, M. A., Miller, C. M., Ganguly, S., Lande, K., LaPorta, M. A., Hoffmann, F. A., Mann, T. H., et al. (2025) · Science · doi:10.1126/science.adl4100 · Cited by 177 · see citing works
The microbial landscape of colorectal cancer
White, M., & Sears, C. L. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-023-00973-4 · Cited by 169 · see citing works
Gut microbiota derived bile acid metabolites maintain the homeostasis of gut and systemic immunity
Su, L., Gao, Y., & Yang, R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1127743 · Cited by 167 · see citing works
The Emerging Role of Bile Acids in the Pathogenesis of Inflammatory Bowel Disease
Thomas, J. P., Módos, D., Rushbrook, S., Powell, N., & Korcsmaros, T. D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.829525 · Cited by 160 · see citing works
Gut microbiota shapes cancer immunotherapy responses
Lei, W., Zhou, K., Lei, Y., Li, Q., & Zhu, H. (2025) · npj Biofilms and Microbiomes · doi:10.1038/s41522-025-00786-8 · Cited by 166 · see citing works
Periportal macrophages protect against commensal-driven liver inflammation
Miyamoto, Y., Kikuta, J., Matsui, T., Hasegawa, T., Fujii, K., Okuzaki, D., Liu, Y.-C., Yoshioka, T., Seno, S., Motooka, D., et al. (2024) · Nature · doi:10.1038/s41586-024-07372-6 · Cited by 135 · see citing works
How bile acids and the microbiota interact to shape host immunity
Lee, M. H., Nuccio, S.-P., Mohanty, I., Hagey, L. R., Dorrestein, P. C., Chu, H., & Raffatellu, M. (2024) · Nature Reviews Immunology · doi:10.1038/s41577-024-01057-x · Cited by 143 · see citing works
Microbial Metabolites and Gut Immunology
Takeuchi, T., Nakanishi, Y., & Ohno, H. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090222-102035 · Cited by 130 · see citing works
Regulatory T cells in the face of the intestinal microbiota
Ramanan, D., Pratama, A., Zhu, Y., Venezia, O., Sassone-Corsi, M., Chowdhary, K., Galván-Peña, S., Sefik, E., Brown, C., Gélineau, A., et al. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00890-w · Cited by 126 · see citing works
T Cell Responses to the Microbiota
Ivanov, I. I., Tuganbaev, T., Skelly, A. N., & Honda, K. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101320-011829 · Cited by 128 · see citing works
Regulatory T cells in the tumour microenvironment
Imianowski, C. J., Chen, Q., Workman, C. J., & Vignali, D. A. A. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-025-00832-9 · Cited by 117 · see citing works
Traxinger, B. R., Richert-Spuhler, L. E., & Lund, J. M. (2021) · Mucosal Immunology · doi:10.1038/s41385-021-00471-x · Cited by 101 · see citing works
Ma, Y., Kong, C., Guo, Z., Wang, M., Wang, P., Liu, F., Yang, D., Zheng, Y., & Tang, Q. (2024) · Nature Communications · doi:10.1038/s41467-024-48970-2 · Cited by 105 · see citing works
Nutrients: Signal 4 in T cell immunity
Raynor, J. L., & Chi, H. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20221839 · Cited by 94 · see citing works
A biosynthetic pathway for the selective sulfonation of steroidal metabolites by human gut bacteria
Yao, L., D’Agostino, G. D., Park, J., Hang, S., Adhikari, A. A., Zhang, Y., Li, W., Ávila-Pacheco, J., Bae, S., Clish, C. B., et al. (2022) · Nature Microbiology · doi:10.1038/s41564-022-01176-y · Cited by 94 · see citing works
Self-citationGut microbiota as a key regulator of intestinal mucosal immunity
Wang, J., He, M., Yang, M., & Ai, X. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122612 · Cited by 96 · see citing works
Unlocking gut-liver-brain axis communication metabolites: energy metabolism, immunity and barriers
Sun, X., Shukla, M., Wang, W., & Li, S. (2024) · npj Biofilms and Microbiomes · doi:10.1038/s41522-024-00610-9 · Cited by 98 · see citing works
Immunology of bile acids regulated receptors
Fiorucci, S., Marchianò, S., Urbani, G., Giorgio, C. D., Distrutti, E., Zampella, A., & Biagioli, M. (2024) · Progress in Lipid Research · doi:10.1016/j.plipres.2024.101291 · Cited by 84 · see citing works
The bridge of the gut–joint axis: Gut microbial metabolites in rheumatoid arthritis
Xu, X., Wang, M., Wang, Z., Chen, Q., Chen, X., Xu, Y., Dai, M., Wu, B., & Li, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1007610 · Cited by 85 · see citing works
Messengers From the Gut: Gut Microbiota-Derived Metabolites on Host Regulation
Li, C., Liang, Y., & Qiao, Y. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.863407 · Cited by 86 · see citing works
The intestinal immune system and gut barrier function in obesity and ageing
Shemtov, S. J., Emani, R., Bielska, O., Covarrubias, A. J., Verdin, E. M., Andersen, J. K., & Winer, D. A. (2022) · FEBS Journal · doi:10.1111/febs.16558 · Cited by 83 · see citing works
The impact of gut microbial short-chain fatty acids on colorectal cancer development and prevention
Thulasinathan, B., Suvilesh, K. N., Maram, S., Grossmann, E. M., Ghouri, Y. A., Teixeiro, E., Chan, J., Kaifi, J. T., & Rachagani, S. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2483780 · Cited by 81 · see citing works
Bile acids in immunity: Bidirectional mediators between the host and the microbiota
Godlewska, U., Bulanda, E., & Wypych, T. P. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.949033 · Cited by 77 · see citing works
Kiriyama, Y., & Nochi, H. (2023) · Microorganisms · doi:10.3390/microorganisms11112730 · Cited by 75 · see citing works
Exploring the Relationship between the Gut Microbiota and Ageing: A Possible Age Modulator
Salazar, J., Durán, P., Díaz, M. P., Chacín, M., Santeliz, R., Mengual, E., Gutiérrez, E., León, X., Díaz, A., Bernal, M., et al. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20105845 · Cited by 71 · see citing works
Formation of secondary allo-bile acids by novel enzymes from gut Firmicutes
Lee, J., Cowley, E. S., Wolf, P. G., Doden, H. L., Murai, T., Caicedo, K. Y. O., Ly, L. K., Sun, F.-R., Takei, H., Nittono, H., et al. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2132903 · Cited by 68 · see citing works
Lindner, S., Miltiadous, O., Ramos, R. J. J. F., Paredes, J., Kousa, A. I., Dai, A., Fei, T., Lauder, E., Frame, J., Waters, N. R., et al. (2024) · Nature Microbiology · doi:10.1038/s41564-024-01617-w · Cited by 68 · see citing works
Xiao, F., Dong, F., Li, X., Li, Y., Yu, G., Liu, Z., Wang, Y., & Zhang, T. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.902337 · Cited by 66 · see citing works
Stutz, M. R., Dylla, N. P., Pearson, S. D., Lecompte-Osorio, P. A., Nayak, R., Khalid, M., Adler, E., Boissiere, J. C., Lin, H., Leiter, W. E., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34260-2 · Cited by 65 · see citing works
Shi, J., Wang, Y., Cheng, L., Wang, J., & Raghavan, V. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2160962 · Cited by 70 · see citing works
Zhang, H., Xie, Y., Cao, F., & Song, X. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2382336 · Cited by 68 · see citing works
Wang, J., Hou, Y., Mu, L., Yang, M., & Ai, X. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113570 · Cited by 65 · see citing works
Wang, M., Guo, J., Hart, A. L., & Li, J. V. (2023) · Journal of Inflammation Research · doi:10.2147/jir.s432747 · Cited by 63 · see citing works
Kim, G., Yoon, Y., Park, J., Park, J. W., Noh, M., Kim, H., Park, C.-H., Kwon, H., Park, J. H., Kim, Y., et al. (2022) · Microbiome · doi:10.1186/s40168-022-01374-0 · Cited by 61 · see citing works
Antigen-presenting cells as specialized drivers of intestinal T cell functions
Kedmi, R., & Littman, D. R. (2024) · Immunity · doi:10.1016/j.immuni.2024.09.011 · Cited by 60 · see citing works
Gut Microbial Metabolites on Host Immune Responses in Health and Disease
Yoon, J.-H., Do, J.-S., Velankanni, P., Lee, C., & Kwon, H. (2023) · Immune Network · doi:10.4110/in.2023.23.e6 · Cited by 58 · see citing works
Zhao, Q. C., Ren, H., Nian, Y., Xia, X., Chen, Q., Zhou, D., Liu, Z., Chen, X., Chen, Y., Huang, W., et al. (2023) · Nutrients · doi:10.3390/nu15020255 · Cited by 56 · see citing works
Srirat, T., Hayakawa, T., Mise-Omata, S., Nakagawara, K., Ando, M., Shichino, S., Ito, M., & Yoshimura, A. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113898 · Cited by 56 · see citing works
Gut microbiota in regulatory T cell generation and function: mechanisms and health implications
Sharma, A., Sharma, G., & Im, S. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2516702 · Cited by 65 · see citing works
Paine, A., Brookes, P. S., Bhattacharya, S., Li, D., García-Hernández, M. D. L. L., Tausk, F., & Ritchlin, C. T. (2022) · Arthritis & Rheumatology · doi:10.1002/art.42288 · Cited by 55 · see citing works
Yntema, T., Koonen, D. P. Y., & Kuipers, F. (2023) · Nutrients · doi:10.3390/nu15081850 · Cited by 55 · see citing works
The Hylemon-Björkhem pathway of bile acid 7-dehydroxylation: history, biochemistry, and microbiology
Ridlon, J. M., Daniel, S. L., & Gaskins, H. R. (2023) · Journal of Lipid Research · doi:10.1016/j.jlr.2023.100392 · Cited by 50 · see citing works
Wang, Y., Li, Y., Lin, Y., Cao, C.-Y., Chen, D., Huang, X., Li, C., Xu, H., Lai, H., Chen, H., et al. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02413-z · Cited by 55 · see citing works
Tan, J., Taitz, J., Sun, S. M., Langford, L., Ni, D., & Macia, L. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.878382 · Cited by 48 · see citing works
Effect of gut flora mediated‐bile acid metabolism on intestinal immune microenvironment
Zhang, Y., Gao, X., Gao, S., Liu, Y., Wang, W., Feng, Y., Pei, L., Sun, Z., Liu, L., & Wang, C. (2023) · Immunology · doi:10.1111/imm.13672 · Cited by 49 · see citing works
Self-citationBiagioli, M., Giorgio, C. D., Massa, C., Marchianò, S., Bellini, R., Bordoni, M., Urbani, G., Roselli, R., Lachi, G., Morretta, E., et al. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117731 · Cited by 50 · see citing works
Lipid metabolism in homeostasis and disease
Li, Z., Deng, W., Yang, L., Tang, C., Yue, J.-M., Monteiro, O., Baptista‐Hon, D. T., & Li, T. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02357-x · Cited by 51 · see citing works
Li, Y., Ye, Z., Zhu, J., Fang, S., Meng, L., & Zhou, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.844335 · Cited by 45 · see citing works
The impact of the gut microbiome on tumor immunotherapy: from mechanism to application strategies
Guo, C., Kong, L., Xiao, L., Liu, K., Cui, H., Xin, Q., Gu, X., Jiang, C., & Wu, J. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01135-y · Cited by 46 · see citing works
Mechanisms of gut microbiota-immune-host interaction on glucose regulation in type 2 diabetes
Zhou, Y.-D., Liang, F.-X., Tian, H.-R., Luo, D., Wang, Y., & Yang, S. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1121695 · Cited by 45 · see citing works
Dai, J., Jiang, M., Wang, X., Lang, T., Wan, L., & Wang, J. (2024) · BMC Microbiology · doi:10.1186/s12866-024-03216-5 · Cited by 44 · see citing works
Zhang, Y., Jing, Y., He, J., Dong, R., Li, T., Li, F., Zheng, X., Liu, G., Jia, R., Xu, J., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.02.003 · Cited by 44 · see citing works
Self-citationOlder, E. A., Zhang, J., Ferris, Z. E., Xue, D., Zhong, Z., Mitchell, M. K., Madden, M. D., Wang, Y.-Z., Chen, H.-X., Nagarkatti, P., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53670-y · Cited by 39 · see citing works
The role of gut microbial metabolites in the T cell lifecycle
Tran, M. T., Huh, J. R., & Devlin, A. S. (2025) · Nature Immunology · doi:10.1038/s41590-025-02227-2 · Cited by 49 · see citing works
Self-citationLi, G., Xiong, Y., Li, Z., Yu, Q., Li, S., Xie, J., Zeng, S., Yu, D., Yang, Y., & Yu, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1710733 · Cited by 44 · see citing works
The triple interactions between gut microbiota, mycobiota and host immunity
Yang, J., Yang, H., & Li, Y. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2094888 · Cited by 43 · see citing works
Orberg, E. T., Meedt, E., Hiergeist, A., Xue, J., Heinrich, P., Ru, J., Ghimire, S., Miltiadous, O., Lindner, S., Tiefgraber, M., et al. (2024) · Nature Cancer · doi:10.1038/s43018-023-00669-x · Cited by 42 · see citing works
Influence of human gut microbiome on the healthy and the neurodegenerative aging
Borrego-Ruiz, A., & Borrego, J. J. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112497 · Cited by 42 · see citing works
Song, M., Zhang, F., Fu, Y., Yi, X., Feng, S., Liu, Z., Deng, D., Yang, Q., Yu, M., Zhu, C., et al. (2022) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-022-00713-3 · Cited by 37 · see citing works
Skin microbe-dependent TSLP-ILC2 priming axis in early life is co-opted in allergic inflammation
Cha, J., Kim, T., Bhae, E., Gwak, H., Ju, Y., Choe, Y. H., Jang, I.-H., Jung, Y., Moon, S., Kim, T. H., et al. (2024) · Cell Host & Microbe · doi:10.1016/j.chom.2023.12.006 · Cited by 35 · see citing works
Bai, Z., Liu, Y., Zhao, Y., Yan, R., Yang, L., Ma, H., Wang, J., Wang, T., Li, Y., Zhang, G., et al. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110296 · Cited by 35 · see citing works
Maternal microbiota and gestational diabetes: impact on infant health
Singh, P., Elhag, D. A., Ibrahim, I., Abdullahi, H., & Khodor, S. A. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04230-3 · Cited by 38 · see citing works
Kim, H., Nelson, P., Nzabarushimana, É., Shen, J., Jensen, J., Bhosle, A., Li, C., Lee, N., Everett, C., Berdy, B. M., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01318-6 · Cited by 36 · see citing works
Self-citationTREGking From Gut to Brain: The Control of Regulatory T Cells Along the Gut-Brain Axis
Choi, J., Kim, B., Akuzum, B., Chang, L., Lee, J., & Kwon, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.916066 · Cited by 36 · see citing works
Li, D., Zhou, J., Wang, L., Gong, Z., Le, H., Huang, Y., Xu, C., Tian, C., Cai, W., & Wu, J. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01109-0 · Cited by 35 · see citing works
Context-Dependent Regulation of Type17 Immunity by Microbiota at the Intestinal Barrier
Akuzum, B., & Lee, J. (2022) · Immune Network · doi:10.4110/in.2022.22.e46 · Cited by 34 · see citing works
Gut microbiota and healthy longevity
Luo, J., Liang, S., & Jin, F. (2024) · Science China Life Sciences · doi:10.1007/s11427-023-2595-5 · Cited by 35 · see citing works
Unraveling the Gut–Liver–Brain Axis: Microbiome, Inflammation, and Emerging Therapeutic Approaches
Aghara, H., Patel, M., Chadha, P., Parwani, K., Chaturvedi, R., & Mandal, P. (2025) · Mediators of Inflammation · doi:10.1155/mi/6733477 · Cited by 35 · see citing works
Microbiota-derived bile acid metabolic enzymes and their impacts on host health
Ma, H., Wang, K., & Jiang, C. (2025) · Cell Insight · doi:10.1016/j.cellin.2025.100265 · Cited by 34 · see citing works
Translating Microbiome Research From and To the Clinic
Zhang, Z. J., Lehmann, C. J., Cole, C. G., & Pamer, E. G. (2022) · Annual Review of Microbiology · doi:10.1146/annurev-micro-041020-022206 · Cited by 32 · see citing works
Gut microbiota: A double-edged sword in immune checkpoint blockade immunotherapy against tumors
Wang, J., Zhu, N., Su, L., & Yang, R. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216582 · Cited by 32 · see citing works
Petakh, P., Kamyshna, I. I., Nykyforuk, A., Yao, R., Imbery, J. F., Oksenych, V., Korda, M. M., & Kamyshnyi, O. (2022) · Viruses · doi:10.3390/v14030477 · Cited by 32 · see citing works
Progress and opportunities in microbial community metabolomics
Bhosle, A., Wang, Y., Franzosa, E. A., & Huttenhower, C. (2022) · Current Opinion in Microbiology · doi:10.1016/j.mib.2022.102195 · Cited by 33 · see citing works
Self-citationInterkingdom signaling between gastrointestinal hormones and the gut microbiome
Zhao, X., Qiu, Y., Liang, L., & Fu, X. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2456592 · Cited by 30 · see citing works
Nr4a nuclear receptors: markers and modulators of antigen receptor signaling
Bending, D., & Zikherman, J. (2023) · Current Opinion in Immunology · doi:10.1016/j.coi.2023.102285 · Cited by 29 · see citing works
Immunologic role of macrophages in sepsis-induced acute liver injury
Xu, W., Hou, H., Yang, W., Tang, W., & Sun, L. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113492 · Cited by 29 · see citing works
Gut-lung axis in allergic asthma: microbiota-driven immune dysregulation and therapeutic strategies
Lv, J., Zhang, Y., Liu, S., Wang, R., & Zhao, J. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1617546 · Cited by 29 · see citing works
Self-citationXia, B., Liu, X., Li, Z., Ren, J., & Liu, X. (2022) · Current Opinion in Food Science · doi:10.1016/j.cofs.2022.100956 · Cited by 31 · see citing works
Kisthardt, S. C., Thanissery, R., Pike, C. M., Foley, M. H., & Theriot, C. M. (2023) · Journal of Bacteriology · doi:10.1128/jb.00180-23 · Cited by 29 · see citing works
Enriquez, A. B., ten-Caten, F., Ghneim, K., Sékaly, R., & Sharma, A. (2023) · Annual Review of Virology · doi:10.1146/annurev-virology-040323-082822 · Cited by 29 · see citing works
Cheng, W., Li, F., & Yang, R. (2024) · Gastro Hep Advances · doi:10.1016/j.gastha.2024.05.012 · Cited by 28 · see citing works
Microbiota-dependent metabolites – New engine for T cell warriors
Tang, Y., Fu, A., Wang, L., & Ge, Q. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2523815 · Cited by 28 · see citing works
Gillard, J., & Leclercq, I. A. (2023) · Clinical Science · doi:10.1042/cs20220697 · Cited by 27 · see citing works
- Authors
- Li, W., Hang, S., Fang, Y., Bae, S., Zhang, Y., Zhang, M., Wang, G., McCurry, M. D., Bae, M., Paik, D., Franzosa, E. A., Rastinejad, F., Huttenhower, C., Yao, L., Devlin, A. S., & Huh, J. R.
- Affiliations
- Harvard University (US)
- Broad Institute (US)
- University of Oxford (GB)
- Brigham and Women's Hospital (US)
- Corresponding author
- Yao, Lina
- Devlin, A. Sloan
- Huh, Jun R.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 29
- Issue
- 9
- Pages
- 1366-1377.e9
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC9064000
- OpenAlex
- W3193797930
- Cited by
- 306
- References
- 81
- Citations by year
- 2026: 70 · 2025: 74 · 2024: 68 · 2023: 40 · 2022: 48 · 2021: 6
- FWCI
- 12.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 373 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Host & Microbe (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 DK110559, MIRA R35 GM128618)
- Harvard Medical School
- Seres Therapeutics
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- bile acid metabolites, regulatory T cells, Foxp3, Nur77, nuclear receptors, gut microbiota, Bacteroidetes, inflammatory bowel disease, immune homeostasis, CD4+ T cell differentiation, chromatin structure
- MeSH terms
- Bile Acids and Salts, Cell Differentiation, Chromatin, Multigene Family, Humans, Phenanthrenes, Promoter Regions, Genetic, Inflammatory Bowel Diseases, Signal Transduction, T-Lymphocyte Subsets, Bacteroidetes, T-Lymphocytes, Regulatory, Forkhead Transcription Factors, Nuclear Receptor Subfamily 4, Group A, Member 1
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 ›
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