Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile
Open accessAbstract
The gastrointestinal tracts of mammals are colonized by hundreds of microbial species that contribute to health, including colonization resistance against intestinal pathogens. Many antibiotics destroy intestinal microbial communities and increase susceptibility to intestinal pathogens. Among these, Clostridium difficile, a major cause of antibiotic-induced diarrhoea, greatly increases morbidity and mortality in hospitalized patients. Which intestinal bacteria provide resistance to C. difficile infection and their in vivo inhibitory mechanisms remain unclear. Here we correlate loss of specific bacterial taxa with development of infection, by treating mice with different antibiotics that result in distinct microbiota changes and lead to varied susceptibility to C. difficile. Mathematical modelling augmented by analyses of the microbiota of hospitalized patients identifies resistance-associated bacteria common to mice and humans. Using these platforms, we determine that Clostridium scindens, a bile acid 7α-dehydroxylating intestinal bacterium, is associated with resistance to C. difficile infection and, upon administration, enhances resistance to infection in a secondary bile acid dependent fashion. Using a workflow involving mouse models, clinical studies, metagenomic analyses, and mathematical modelling, we identify a probiotic candidate that corrects a clinically relevant microbiome deficiency. These findings have implications for the rational design of targeted antimicrobials as well as microbiome-based diagnostics and therapeutics for individuals at risk of C. difficile infection.
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Certain secondary bile acids serve significant biological functions, including regulation of host metabolism, immunity, and resistance against intestinal pathogen expansion.
“Nevertheless, it is noteworthy that certain secondary BAs serve significant biological functions, including the regulation of host metabolism, immunity, and resistance against intestinal pathogen expansion.21,360–364”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [362]
Previous studies have described that successful FMT treatment of recurrent infection by C. difficile relies on restoration of correct bile acid metabolism, and that antibiotic-induced microbiome depletion reduces the secondary bile acid pool.
“Previous studies have described that successful FMT treatment of recurrent infection by C. difficile relies on restoration of correct bile acid metabolism 35,36 , and that antibioticinduced microbiome depletion reduces the secondary bile acid pool 37 .”
From Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice (2019) · cites this paper as [36]
Bacillus thuringensis secretes thuricin CD, a bacteriocin with narrow-spectrum activity against gram-positive bacteria including C. difficile.
“Bacillus thuringensis secretes a bacteriocin, thuricin CD, with narrow spectrum activity against gram positive bacteria including C. difficile; it is likely other members of the gut microbiota secrete similar antimicrobials.53”
From Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook (2015) · cites this paper as [53]
Other members of the gut microbiota likely secrete antimicrobials similar to thuricin CD.
“it is likely other members of the gut microbiota secrete similar antimicrobials.53”
From Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook (2015) · cites this paper as [53]
C. scindens inhibits growth of C. difficile through generation of secondary bile acids deoxycholic acid and lithocholic acid.
“the commensal bacterium C. scindens can inhibit growth of C. difficile through the generation of secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA) [54].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [54]
Reconstitution with C. scindens alone or within a bacterial consortium protects antibiotic-treated mice from C. difficile intestinal colonization.
“Reconstitution with C. scindens alone or within a bacterial consortium, protected antibiotic-treated mice from C. difficile intestinal colonization.”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [54]
C. scindens is associated with protection from C. difficile colonization in patients receiving allogeneic haematopoietic stem-cell transplantation.
“C. scindens was also associated to protection from C. difficile colonization in patients receiving allogeneic haematopoietic stem-cell transplantation [54].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [54]
Bacterial strains and metabolites associated with protection from C. difficile have been identified.
“Bacterial strains [54, 118, 119] and metabolites [54] associated with protection from C. difficile have now been identified”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [54]
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Cites
Statistical Power Analysis for the Behavioral Sciences
Muller, K. E., & Cohen, J. (1989) · Technometrics · doi:10.2307/1270020 · Cited by 99,588 · see citing works
Statistical power analysis for the behavioral sciences
Cohen, J. (1990) · Computers Environment and Urban Systems · doi:10.1016/0198-9715(90)90050-4 · Cited by 65,406 · see citing works
QIIME allows analysis of high-throughput community sequencing data
Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Peña, A. G., Goodrich, J. K., Gordon, J. I., et al. (2010) · Nature Methods · doi:10.1038/nmeth.f.303 · Cited by 34,887 · see citing works
Schloss, P. D., Westcott, S. L., Ryabin, T., Hall, J. R., Hartmann, M., Hollister, E. B., Lesniewski, R. A., Oakley, B. B., Parks, D. H., Robinson, C. J., et al. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.01541-09 · Cited by 20,966 · see citing works
UCHIME improves sensitivity and speed of chimera detection
Edgar, R. C., Haas, B. J., Clemente, J. C., Quince, C., & Knight, R. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr381 · Cited by 15,114 · see citing works
Structure, function and diversity of the healthy human microbiome
The Human Microbiome Project Consortium (2012) · Nature · doi:10.1038/nature11234 · Cited by 11,726 · see citing works
Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences
Langille, M. G. I., Zaneveld, J., Caporaso, J. G., McDonald, D., Knights, D., Reyes, J. A., Clemente, J. C., Burkepile, D. E., Vega Thurber, R. L., Knight, R., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2676 · Cited by 9,116 · see citing works
Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms
Caporaso, J. G., Lauber, C. L., Walters, W. A., Berg-Lyons, D., Huntley, J., Fierer, N., Owens, S. M., Betley, J., Fraser, L., Bauer, M., et al. (2012) · The ISME Journal · doi:10.1038/ismej.2012.8 · Cited by 8,839 · see citing works
UniFrac: a New Phylogenetic Method for Comparing Microbial Communities
Lozupone, C., & Knight, R. (2005) · Applied and Environmental Microbiology · doi:10.1128/aem.71.12.8228-8235.2005 · Cited by 8,227 · see citing works
Duodenal Infusion of Donor Feces for Recurrent <i>Clostridium difficile</i>
van Nood, E., Vrieze, A., Nieuwdorp, M., Fuentes, S., Zoetendal, E. G., de Vos, W. M., Visser, C. E., Kuijper, E. J., Bartelsman, J. F. W. M., Tijssen, J. G. P., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1205037 · Cited by 3,708 · 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
Collins, M. D., Lawson, P. A., Willems, A. L., Córdoba, J. J., Fernández‐Garayzábal, J. F., GARCIA, P., Cai, J., Hippe, H., & Farrow, J. A. E. (1994) · International Journal of Systematic Bacteriology · doi:10.1099/00207713-44-4-812 · Cited by 1,670 · see citing works
Microbiota-mediated colonization resistance against intestinal pathogens
Buffie, C. G., & Pamer, E. G. (2013) · Nature reviews. Immunology · doi:10.1038/nri3535 · Cited by 1,564 · see citing works
Self-citationBuilding Phylogenetic Trees from Molecular Data with MEGA
Hall, B. G. (2013) · Molecular Biology and Evolution · doi:10.1093/molbev/mst012 · Cited by 1,547 · see citing works
Clostridium difficile infection: new developments in epidemiology and pathogenesis
Rupnik, M., Wilcox, M. H., & Gerding, D. N. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2164 · Cited by 1,380 · see citing works
Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens
Ng, K. M., Ferreyra, J. A., Higginbottom, S. K., Lynch, J. B., Kashyap, P. C., Gopinath, S., Naidu, N., Choudhury, B., Weimer, B. C., Monack, D. M., et al. (2013) · Nature · doi:10.1038/nature12503 · Cited by 1,035 · see citing works
Taur, Y., Xavier, J. B., Lipuma, L., Ubeda, C., Goldberg, J., Gobourne, A., Lee, Y. J., Dubin, K. A., Socci, N. D., Viale, A., et al. (2012) · Clinical Infectious Diseases · doi:10.1093/cid/cis580 · Cited by 1,020 · see citing works
Self-citationChang, J. Y., Antonopoulos, D. A., Kalra, A., Tonelli, A., Khalife, W. T., Schmidt, T. M., & Young, V. B. (2008) · The Journal of Infectious Diseases · doi:10.1086/525047 · Cited by 1,010 · see citing works
Insights into Secondary Metabolism from a Global Analysis of Prokaryotic Biosynthetic Gene Clusters
Cimermančič, P., Medema, M. H., Claesen, J., Kurita, K. L., Brown, L. C. W., Mavrommatis, K., Pati, A., Godfrey, P. A., Koehrsen, M., Clardy, J., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.034 · Cited by 984 · see citing works
Ubeda, C., Taur, Y., Jenq, R. R., Equinda, M. J., Son, T., Samstein, M., Viale, A., Socci, N. D., van den Brink, M. R. M., Kamboj, M., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43918 · Cited by 943 · see citing works
Self-citationBile Salts and Glycine as Cogerminants for <i>Clostridium difficile</i> Spores
Sorg, J. A., & Sonenshein, A. L. (2008) · Journal of Bacteriology · doi:10.1128/jb.01765-07 · Cited by 711 · see citing works
Stein, R. R., Bucci, V., Toussaint, N. C., Buffie, C. G., Rätsch, G., Pamer, E. G., Sander, C., & Xavier, J. B. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003388 · Cited by 619 · see citing works
Self-citationBile acids as carcinogens in human gastrointestinal cancers
Bernstein, H., Bernstein, C., Payne, C. M., Dvorakova, K., & Garewal, H. (2005) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2004.08.001 · Cited by 611 · see citing works
Buffie, C. G., Jarchum, I., Equinda, M., Lipuma, L., Gobourne, A., Viale, A., Ubeda, C., Xavier, J., & Pamer, E. G. (2012) · Infection and Immunity · doi:10.1128/iai.05496-11 · Cited by 596 · see citing works
Self-citationYutin, N., & Galperin, M. Y. (2013) · Environmental Microbiology · doi:10.1111/1462-2920.12173 · Cited by 569 · see citing works
Rea, M. C., Sit, C. S., Clayton, E., O'Connor, P. M., Whittal, R. M., Zheng, J., Vederas, J. C., Ross, R. P., & Hill, C. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913554107 · Cited by 530 · see citing works
A mouse model of clostridium difficile-associated disease
Chen, X., Katchar, K., Goldsmith, J. D., Nanthakumar, N., Cheknis, A., Gerding, D. N., & Kelly, C. P. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.09.002 · Cited by 510 · see citing works
Ubeda, C., Bucci, V., Caballero, S., Djukovic, A., Toussaint, N. C., Equinda, M., Lipuma, L., Ling, L., Gobourne, A., No, D., et al. (2013) · Infection and Immunity · doi:10.1128/iai.01197-12 · Cited by 466 · see citing works
Self-citationWeingarden, A. R., Chen, C., Bobr, A., Yao, D., Lu, Y., Nelson, V. M., Sadowsky, M. J., & Khoruts, A. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00282.2013 · Cited by 423 · see citing works
Zhao, Y.-A., Tang, H.-X., & Ye, Y.-Z. (2011) · Bioinform. · doi:10.1093/bioinformatics/btr595 · Cited by 415 · see citing works
Metabolism of Bile Salts in Mice Influences Spore Germination in Clostridium difficile
Giel, J. L., Sorg, J. A., Sonenshein, A. L., & Zhu, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008740 · Cited by 195 · see citing works
Wilson, K. H. (1983) · Journal of Clinical Microbiology · doi:10.1128/jcm.18.4.1017-1019.1983 · Cited by 188 · see citing works
Clearcut: a fast implementation of relaxed neighbor joining
Sheneman, L., Evans, J., & Foster, J. A. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btl478 · Cited by 185 · see citing works
Wells, J. E., & Hylemon, P. B. (2000) · Applied and Environmental Microbiology · doi:10.1128/aem.66.3.1107-1113.2000 · Cited by 154 · see citing works
Critical Role for MyD88-Mediated Neutrophil Recruitment during Clostridium difficile Colitis
Jarchum, I., Liu, M., Shi, C., Equinda, M. J., & Pamer, E. G. (2012) · Infection and Immunity · doi:10.1128/iai.00448-12 · Cited by 153 · see citing works
Self-citationKitahara, M., Takamine, F., Imamura, T., & Benno, Y. (2000) · INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY · doi:10.1099/00207713-50-3-971 · Cited by 146 · see citing works
Toll-Like Receptor 5 Stimulation Protects Mice from Acute Clostridium difficile Colitis
Jarchum, I., Liu, M., Lipuma, L., & Pamer, E. G. (2011) · Infection and Immunity · doi:10.1128/iai.01196-10 · Cited by 130 · 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
Early Clostridium difficile Infection during Allogeneic Hematopoietic Stem Cell Transplantation
Kinnebrew, M. A., Lee, Y. J., Jenq, R. R., Lipuma, L., Littmann, E. R., Gobourne, A., No, D. J., van den Brink, M. R. M., Pamer, E. G., & Taur, Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090158 · Cited by 77 · see citing works
Self-citationWells, J. E., Williams, K. B., Whitehead, T. R., Heuman, D. M., & Hylemon, P. B. (2003) · Clinica Chimica Acta · doi:10.1016/s0009-8981(03)00115-3 · Cited by 65 · see citing works
Bile acid sequestrants: more than simple resins
Out, C., Groen, A. K., & Brufau, G. (2012) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32834f0ef3 · Cited by 36 · see citing works
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Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis
Yano, J. M., Yu, K., Donaldson, G. P., Shastri, G. G., Ann, P., Ma, L., Nagler, C. R., Ismagilov, R. F., Mazmanian, S. K., & Hsiao, E. Y. (2015) · Cell · doi:10.1016/j.cell.2015.02.047 · Cited by 3,614 · see citing works
The Human Intestinal Microbiome in Health and Disease
Lynch, S. V., & Pedersen, O. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1600266 · Cited by 3,637 · see citing works
Gut microbiota, metabolites and host immunity
Rooks, M. G., & Garrett, W. S. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.42 · Cited by 3,409 · see citing works
Dysbiosis and the immune system
Levy, M., Kolodziejczyk, A. A., Thaiss, C. A., & Elinav, E. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.7 · Cited by 1,769 · see citing works
Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease
Pickard, J. M., Zeng, M. Y., Caruso, R., & Núñez, G. (2017) · Immunological Reviews · doi:10.1111/imr.12567 · Cited by 1,699 · see citing works
Gut microbiome–mediated bile acid metabolism regulates liver cancer via NKT cells
Ma, C., Han, M., Heinrich, B., Fu, Q., Zhang, Q., Sandhu, M., Agdashian, D., Terabe, M., Berzofsky, J. A., Fako, V., et al. (2018) · Science · doi:10.1126/science.aan5931 · Cited by 1,508 · see citing works
Interactions between the microbiota and pathogenic bacteria in the gut
Bäumler, A. J., & Sperandio, V. (2016) · Nature · doi:10.1038/nature18849 · Cited by 1,420 · 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
Garrett, W. S. (2015) · Science · doi:10.1126/science.aaa4972 · Cited by 1,404 · see citing works
Proton pump inhibitors affect the gut microbiome
Imhann, F., Bonder, M. J., Vich Vila, A., Fu, J., Mujagic, Z., Vork, L., Tigchelaar, E. F., Jankipersadsing, S. A., Cenit, M. C., Harmsen, H. J. M., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-310376 · Cited by 1,371 · see citing works
Homeostatic Immunity and the Microbiota
Belkaid, Y., & Harrison, O. J. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.008 · Cited by 1,261 · see citing works
Bile acids and the gut microbiota: metabolic interactions and impacts on disease
Collins, S. L., Stine, J. G., Bisanz, J. E., Okafor, C. D., & Patterson, A. D. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00805-x · Cited by 1,214 · see citing works
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells
Benakis, C., Brea, D., Caballero, S., Faraco, G., Moore, J., Murphy, M., Sita, G., Racchumi, G., Ling, L., Pamer, E. G., et al. (2016) · Nature Medicine · doi:10.1038/nm.4068 · Cited by 1,114 · see citing works
Self-citationChemical transformation of xenobiotics by the human gut microbiota
Koppel, N., Maini Rekdal, V., & Balskus, E. P. (2017) · Science · doi:10.1126/science.aag2770 · Cited by 1,080 · see citing works
Antibiotic-Induced Changes in the Intestinal Microbiota and Disease
Becattini, S., Taur, Y., & Pamer, E. G. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.04.003 · Cited by 901 · see citing works
Self-citationThe Human Gut Microbiome: From Association to Modulation
Schmidt, T. S. B., Raes, J., & Bork, P. (2018) · Cell · doi:10.1016/j.cell.2018.02.044 · Cited by 845 · see citing works
The intestinal microbiota: Antibiotics, colonization resistance, and enteric pathogens
Kim, S., Covington, A., & Pamer, E. G. (2017) · Immunological Reviews · doi:10.1111/imr.12563 · Cited by 741 · see citing works
Self-citationThe microbial pharmacists within us: a metagenomic view of xenobiotic metabolism
Spanogiannopoulos, P., Bess, E. N., Carmody, R. N., & Turnbaugh, P. J. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.17 · Cited by 717 · see citing works
Frankel, A. E., Coughlin, L. A., Kim, J., Froehlich, T. W., Xie, Y., Frenkel, E. P., & Koh, A. Y. (2017) · Neoplasia · doi:10.1016/j.neo.2017.08.004 · Cited by 709 · see citing works
Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice
Bárcena, C., Valdés-Mas, R., Mayoral, P., Garabaya, C., Durand, S., Rodríguez, F., Fernández-García, M. T., Salazar, N., Nogacka, A. M., Garatachea, N., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0504-5 · Cited by 661 · 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
Dynamic modulation of the gut microbiota and metabolome by bacteriophages in a mouse model
Hsu, B. B., Gibson, T. E., Yeliseyev, V., Liu, Q., Lyon, L., Bry, L., Silver, P. A., & Gerber, G. K. (2019) · Cell Host & Microbe · doi:10.1016/j.chom.2019.05.001 · Cited by 573 · see citing works
A 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
Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook
Kelly, C. R., Kahn, S., Kashyap, P., Laine, L., Rubin, D., Atreja, A., Moore, T., & Wu, G. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.05.008 · Cited by 572 · see citing works
Gut Microbiota and Colonization Resistance against Bacterial Enteric Infection
Ducarmon, Q. R., Zwittink, R. D., Hornung, B. V. H., van Schaik, W., Young, V. B., & Kuijper, E. J. (2019) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00007-19 · Cited by 566 · 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
A Gut Commensal-Produced Metabolite Mediates Colonization Resistance to Salmonella Infection
Jacobson, A., Lam, L., Rajendram, M., Tamburini, F., Honeycutt, J., Pham, T., Van Treuren, W., Pruss, K., Stabler, S. R., Lugo, K., et al. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.07.002 · Cited by 507 · see citing works
Interactions between gut bacteria and bile in health and disease
Long, S. L., Gahan, C. G. M., & Joyce, S. A. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.06.002 · Cited by 495 · see citing works
Theriot, C. M., Bowman, A. A., & Young, V. B. (2016) · mSphere · doi:10.1128/msphere.00045-15 · Cited by 481 · see citing works
Molecular physiology of bile acid signaling in health, disease, and aging
Perino, A., Demagny, H., Velazquez-Villegas, L., & Schoonjans, K. (2021) · Physiological Reviews · doi:10.1152/physrev.00049.2019 · Cited by 481 · see citing works
Microbiota-mediated colonization resistance: mechanisms and regulation
Caballero-Flores, G., Pickard, J. M., & Núñez, G. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00833-7 · Cited by 474 · 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
Immune regulation by microbiome metabolites
Kim, C. H. (2018) · Immunology · doi:10.1111/imm.12930 · Cited by 375 · see citing works
Fachi, J. L., Felipe, J. D. S., Pral, L. P., da Silva, B. K., Corrêa, R. O., de Andrade, M. C. P., da Fonseca, D. M., Basso, P. J., Câmara, N. O. S., de Sales e Souza, É. L., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.054 · Cited by 364 · see citing works
Taurocholic acid metabolism by gut microbes and colon cancer
Ridlon, J. M., Wolf, P. G., & Gaskins, H. R. (2016) · Gut Microbes · doi:10.1080/19490976.2016.1150414 · Cited by 327 · see citing works
Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium
Caballero, S., Kim, S., Carter, R. A., Leiner, I. M., Sušac, B., Miller, L., Kim, G. J., Ling, L., & Pamer, E. G. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.04.002 · Cited by 308 · see citing works
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Coyte, K. Z., & Rakoff-Nahoum, S. (2019) · Current Biology · doi:10.1016/j.cub.2019.04.017 · Cited by 329 · see citing works
Mining the microbiota for microbial and metabolite-based immunotherapies
Skelly, A. N., Sato, Y., Kearney, S., & Honda, K. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0144-5 · Cited by 306 · see citing works
Freedberg, D. E., Toussaint, N. C., Chen, S. P., Ratner, A. J., Whittier, S., Wang, T. C., Wang, H. H., & Abrams, J. A. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.06.043 · Cited by 322 · see citing works
Self-citationA bacterial bile acid metabolite modulates Treg activity through the nuclear hormone receptor NR4A1
Li, W., Hang, S., Fang, Y., Bae, S., Zhang, Y., Zhang, M., Wang, G., McCurry, M. D., Bae, M., Paik, D., et al. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2021.07.013 · Cited by 306 · see citing works
Dzutsev, A., Badger, J. H., Perez-Chanona, E., Roy, S., Salcedo, R., Smith, C. K., & Trinchieri, G. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052133 · Cited by 302 · see citing works
Dietary zinc alters the microbiota and decreases resistance to Clostridium difficile infection
Zackular, J. P., Moore, J. L., Jordan, A. T., Juttukonda, L. J., Noto, M. J., Nicholson, M. R., Crews, J. D., Semler, M. W., Zhang, Y., Ware, L. B., et al. (2016) · Nature Medicine · doi:10.1038/nm.4174 · Cited by 275 · see citing works
An integrative view of microbiome-host interactions in inflammatory bowel diseases
Wlodarska, M., Kostic, A. D., & Xavier, R. J. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.008 · Cited by 287 · see citing works
Haak, B. W., Littmann, E. R., Chaubard, J.-L., Pickard, A. J., Fontana, E., Adhi, F., Gyaltshen, Y., Ling, L., Morjaria, S. M., Peled, J. U., et al. (2018) · Blood · doi:10.1182/blood-2018-01-828996 · Cited by 273 · see citing works
Self-citationUniversality of human microbial dynamics
Bashan, A., Gibson, T. E., Friedman, J., Carey, V. J., Weiss, S. T., Hohmann, E. L., & Liu, Y.-Y. (2016) · Nature · doi:10.1038/nature18301 · Cited by 270 · see citing works
Mullish, B. H., McDonald, J. A. K., Pechlivanis, A., Allegretti, J. R., Kao, D., Barker, G. F., Kapila, D., Petrof, E. O., Joyce, S. A., Gahan, C. G. M., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-317842 · Cited by 268 · see citing works
Problems with the concept of gut microbiota dysbiosis
Brüssow, H. (2020) · Microbial Biotechnology · doi:10.1111/1751-7915.13479 · Cited by 250 · see citing works
A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility
Wei, M., Huang, F., Zhao, L., Zhang, Y., Yang, W., Wang, S., Li, M., Han, X., Ge, K., Qu, C., et al. (2020) · eBioMedicine · doi:10.1016/j.ebiom.2020.102766 · Cited by 253 · see citing works
Linking the Microbiota, Chronic Disease, and the Immune System
Hand, T. W., Vujkovic-Cvijin, I., Ridaura, V. K., & Belkaid, Y. (2016) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.08.003 · Cited by 247 · see citing works
Thanissery, R., Winston, J. A., & Theriot, C. M. (2017) · Anaerobe · doi:10.1016/j.anaerobe.2017.03.004 · Cited by 242 · see citing works
Joyce, S. A., & Gahan, C. G. M. (2016) · Annual Review of Food Science and Technology · doi:10.1146/annurev-food-041715-033159 · Cited by 241 · see citing works
Morphine induces changes in the gut microbiome and metabolome in a morphine dependence model
Wang, F., Meng, J., Zhang, L., Johnson, T., Chen, C., & Roy, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-21915-8 · Cited by 238 · see citing works
Adjusting for age improves identification of gut microbiome alterations in multiple diseases
Ghosh, T. S., Das, M., Jeffery, I. B., & O'Toole, P. W. (2020) · eLife · doi:10.7554/elife.50240 · Cited by 233 · see citing works
The promise of the gut microbiome as part of individualized treatment strategies
Schupack, D. A., Mars, R. A. T., Voelker, D. H., Abeykoon, J. P., & Kashyap, P. C. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00499-1 · Cited by 217 · see citing works
The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics
Ridlon, J. M., & Bajaj, J. S. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2015.01.006 · Cited by 210 · see citing works
Lewis, B. B., Buffie, C. G., Carter, R. A., Leiner, I., Toussaint, N. C., Miller, L. C., Gobourne, A., Ling, L., & Pamer, E. G. (2015) · Journal of Infectious Diseases · doi:10.1093/infdis/jiv256 · Cited by 197 · see citing works
Deciphering the Chemical Lexicon of Host–Gut Microbiota Interactions
Nicolas, G. R., & Chang, P. V. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.04.006 · Cited by 195 · see citing works
Beresford-Jones, B. S., Forster, S. C., Stares, M. D., Notley, G., Viciani, E., Browne, H. P., Boehmler, D. J., Soderholm, A. T., Kumar, N., Vervier, K., et al. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2021.12.003 · Cited by 194 · see citing works
Self-citationTherapeutic pipeline for atopic dermatitis: End of the drought?
Paller, A. S., Kabashima, K., & Bieber, T. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.07.006 · Cited by 192 · see citing works
Targeting the gut‐skin axis—Probiotics as new tools for skin disorder management?
Szántó, M., Dózsa, A., Antal, D., Szabó, K., Kemény, L., & Bai, P. (2019) · Experimental Dermatology · doi:10.1111/exd.14016 · Cited by 189 · see citing works
The "Gut Feeling": Breaking Down the Role of Gut Microbiome in Multiple Sclerosis
Freedman, S. N., Shahi, S. K., & Mangalam, A. K. (2018) · Neurotherapeutics · doi:10.1007/s13311-017-0588-x · Cited by 168 · see citing works
Horiguchi, H., Loftus, T. J., Hawkins, R. B., Raymond, S. L., Stortz, J. A., Hollen, M. K., Weiss, B. P., Miller, E. S., Bihorac, A., Larson, S. D., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00595 · Cited by 164 · see citing works
Feeding the microbiota: Transducer of nutrient signals for the host
Shanahan, F., van Sinderen, D., O’Toole, P. W., & Stanton, C. (2017) · Gut · doi:10.1136/gutjnl-2017-313872 · Cited by 157 · see citing works
Faecal microbiota transplantation for Clostridioides difficile: mechanisms and pharmacology
Khoruts, A., Staley, C., & Sadowsky, M. J. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0350-4 · Cited by 155 · see citing works
Recipient factors in faecal microbiota transplantation: one stool does not fit all
Danne, C., Rolhion, N., & Sokol, H. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00441-5 · Cited by 154 · see citing works
Friedman, E. S., Li, Y., Shen, T.-C. D., Jiang, J., Chau, L., Adorini, L., Babakhani, F., Edwards, J., Shapiro, D., Zhao, C., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.08.022 · Cited by 149 · see citing works
Kim, B., Wang, Y.-C., Hespen, C. W., Espinosa, J., Salje, J., Rangan, K. J., Oren, D. A., Kang, J. Y., Pedicord, V. A., & Hang, H. C. (2019) · eLife · doi:10.7554/elife.45343 · Cited by 120 · 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
Fecal microbiota transplantation reverses antibiotic and chemotherapy-induced gut dysbiosis in mice
Le Bastard, Q., Ward, T., Sidiropoulos, D., Hillmann, B. M., Chun, C. L., Sadowsky, M. J., Knights, D., & Montassier, E. (2018) · Scientific Reports · doi:10.1038/s41598-018-24342-x · Cited by 134 · see citing works
Gut microbiome as a clinical tool in gastrointestinal disease management: are we there yet?
Quigley, E. M. M. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.29 · Cited by 125 · see citing works
Metabolic network modeling of microbial communities
Biggs, M. B., Medlock, G. L., Kolling, G. L., & Papin, J. A. (2015) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1308 · Cited by 124 · see citing works
In vivo commensal control of Clostridioides difficile virulence
Girinathan, B. P., DiBenedetto, N., Worley, J. N., Peltier, J., Arrieta-Ortiz, M. L., Immanuel, S. R. C., Lavin, R., Delaney, M. L., Cummins, C. K., Hoffman, M., et al. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2021.09.007 · Cited by 114 · see citing works
An ecological framework to understand the efficacy of fecal microbiota transplantation
Xiao, Y., Angulo, M. T., Lao, S., Weiss, S. T., & Liu, Y.-Y. (2020) · Nature Communications · doi:10.1038/s41467-020-17180-x · Cited by 89 · see citing works
O’Donovan, S. M., Crowley, E. K., Brown, J. R. ‐., O’Sullivan, O., O’Leary, O. F., Timmons, S., Nolan, Y. M., Clarke, D. J., Hyland, N. P., Joyce, S. A., et al. (2020) · Neurogastroenterology & Motility · doi:10.1111/nmo.13726 · Cited by 86 · see citing works
Djukovic, A., Garzón, M. J., Canlet, C., Cabral, V., Lalaoui, R., García-Garcerá, M., Rechenberger, J., Tremblay-Franco, M., Peñaranda, I., Puchades-Carrasco, L., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33313-w · Cited by 85 · see citing works
Self-citationGut-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
Kong, L., Lloyd-Price, J., Vatanen, T., Seksik, P., Beaugerie, L., Simon, T., Vlamakis, H., Sokol, H., & Xavier, R. J. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.08.045 · Cited by 69 · see citing works
Kazemian, N., Ramezankhani, M., Sehgal, A., Khalid, F. M., Kalkhoran, A. H. Z., Narayan, A., Wong, G. K.-S., Kao, D., & Pakpour, S. (2020) · Scientific Reports · doi:10.1038/s41598-020-75162-x · Cited by 61 · see citing works
Bile acids: Key players in inflammatory bowel diseases?
Kriaa, A., Mariaule, V., Jablaoui, A., Rhimi, S., Mkaouar, H., Hernandez, J., Korkmaz, B., Lesner, A., Maguin, E., Aghdassi, A., et al. (2022) · Cells · doi:10.3390/cells11050901 · Cited by 53 · see citing works
Gut microbiota dysbiosis associated with bile acid metabolism in neonatal cholestasis disease
Li, M., Liu, S., Wang, M., Hu, H., Yin, J., Liu, C., & Huang, Y. (2020) · Scientific Reports · doi:10.1038/s41598-020-64728-4 · Cited by 41 · see citing works
Reed, A. D., & Theriot, C. M. (2021) · Microorganisms · doi:10.3390/microorganisms9020371 · Cited by 39 · see citing works
Jenkins, S. V., Robeson, M. S., Griffin, R. J., Quick, C. M., Siegel, E. R., Cannon, M. J., Vang, K. B., & Dings, R. P. M. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-4108 · Cited by 41 · see citing works
Pathogenesis of Clostridium difficile Infection and Its Potential Role in Inflammatory Bowel Disease
Monaghan, T. M., Cockayne, A., & Mahida, Y. R. (2015) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000461 · Cited by 38 · see citing works
Corver, J., Cordo’, V., van Leeuwen, H. C., Klychnikov, O. I., & Hensbergen, P. J. (2017) · Molecular Microbiology · doi:10.1111/mmi.13736 · Cited by 20 · see citing works
Arase, S., Watanabe, Y., Setoyama, H., Nagaoka, N., Kawai, M., & Matsumoto, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0160736 · Cited by 18 · see citing works
Li, S., Zhang, H., Xiao, J., Yuan, T., Shu, Z., Min, Y., Xu, W., Yin, Y., & Zhang, X. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00358 · Cited by 8 · see citing works
The gut microbiome takes center stage in critical care
Wiersinga, W. J. (2017) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000000390 · Cited by 4 · see citing works
- Authors
- Buffie, C. G., Bucci, V., Stein, R. R., McKenney, P. T., Ling, L., Gobourne, A., No, D., Liu, H., Kinnebrew, M., Viale, A., Littmann, E., van den Brink, M. R. M., Jenq, R. R., Taur, Y., Sander, C., Cross, J. R., Toussaint, N. C., Xavier, J. B., & Pamer, E. G.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- University of Massachusetts Dartmouth (US)
- Corresponding author
- Pamer, Eric G.
- ORCID
- Venue
- Nature
- Published
- 2014-10-22
- Volume
- 517
- Issue
- 7533
- Pages
- 205-208
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4354891
- OpenAlex
- W1993830991
- Cited by
- 1,872
- References
- 41
- Citations by year
- 2026: 130 · 2025: 140 · 2024: 146 · 2023: 154 · 2022: 197 · 2021: 197 · 2020: 164 · 2019: 150 · 2018: 165 · 2017: 156 · 2016: 168 · 2015: 94 · 2014: 9
- FWCI
- 100.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (4r37ai039031-21, 5k23ai095398-05, DP2OD008440)
- Weill Cornell Medical College
- NIH Office of the Director
- National Cancer Institute (P01CA023766, T32CA009149, U54CA148967, P30CA008748)
- National Institute of General Medical Sciences (T32GM07739, T32GM007739)
- National Institute of Allergy and Infectious Diseases (R01 AI42135, R37-AI039031, AI95706, R01AI095706, K23-AI095398, R01AI042135)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Keywords
- Clostridium difficile infection, Clostridium scindens, bile acids, secondary bile acids, colonization resistance, antibiotic-induced dysbiosis, probiotics, fecal microbiota transplantation, Clostridium difficile colitis, hospitalized patients
- MeSH terms
- Animals, Anti-Bacterial Agents, Bile Acids and Salts, Clostridium, Colitis, Disease Susceptibility, Biological Evolution, Feces, Female, Humans, Intestinal Mucosa, Intestines, Mice, Inbred C57BL, Symbiosis, Clostridioides difficile, Mice, Metagenome, Microbiota
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