Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome
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Bile salt hydrolases (BSHs) catalyze the “gateway” reaction in a wider pathway of bile acid modification by the gut microbiota. Because bile acids function as signaling molecules regulating their own biosynthesis, lipid absorption, cholesterol homeostasis, and local mucosal defenses in the intestine, microbial BSH activity has the potential to greatly influence host physiology. However, the function, distribution, and abundance of BSH enzymes in the gut community are unknown. Here, we show that BSH activity is a conserved microbial adaptation to the human gut environment with a high level of redundancy in this ecosystem. Through metagenomic analyses we identified functional BSH in all major bacterial divisions and archaeal species in the gut and demonstrate that BSH is enriched in the human gut microbiome. Phylogenetic analysis illustrates that selective pressure in the form of conjugated bile acid has driven the evolution of members of the Ntn_CGH-like family of proteins toward BSH activity in gut-associated species. Furthermore, we demonstrate that BSH mediates bile tolerance in vitro and enhances survival in the murine gut in vivo . Overall, we demonstrate the use of function-driven metagenomics to identify functional anchors in complex microbial communities, and dissect the gut microbiome according to activities relevant to survival in the mammalian gastrointestinal tract.
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All major gut-associated bacterial divisions, including Lactobacillus, Bifidobacterium and Bacteroidetes taxa, express bile salt hydrolase (BSH) enzymes which allow de-conjugation of bile acids from taurine and glycine.
“Strikingly, all major gut-associated bacterial divisions, including Lactobacillus, Bifidobacterium and Bacteroidetes taxa, were shown to express bile salt hydrolase (BSH) enzymes which allow de-conjugation of bile acids from taurine and glycine (Begley et al., 2006;Jones et al., 2008).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Jones et al., 2008
Host substrates, such as mucin and bile salts, can be metabolized by the gut microbiota.
“Host substrates, such as mucin and bile salts, can also be metabolized by the gut microbiota [18, 19].”
From Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization (2023) · cites this paper as [18]
Cites
An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444 · see citing works
MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment
Kumar, S. (2004) · Briefings in Bioinformatics · doi:10.1093/bib/5.2.150 · Cited by 11,642 · see citing works
Diversity of the Human Intestinal Microbial Flora
Eckburg, P. B., Bik, E. M., Bernstein, C. N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S. R., Nelson, K. E., & Relman, D. A. (2005) · Science · doi:10.1126/science.1110591 · Cited by 7,913 · see citing works
Host-Bacterial Mutualism in the Human Intestine
Bäckhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A., & Gordon, J. I. (2005) · Science · doi:10.1126/science.1104816 · Cited by 5,277 · see citing works
Metagenomic Analysis of the Human Distal Gut Microbiome
Gill, S. R., Pop, M., DeBoy, R. T., Eckburg, P. B., Turnbaugh, P. J., Samuel, B. S., Gordon, J. I., Relman, D. A., Fraser-Liggett, C. M., & Nelson, K. E. (2006) · Science · doi:10.1126/science.1124234 · Cited by 4,699 · see citing works
Environmental genome shotgun sequencing of the sargasso sea
Venter, J. C., Remington, K., Heidelberg, J. F., Halpern, A. L., Rusch, D., Eisen, J. A., Wu, D., Paulsen, I., Nelson, K. E., Nelson, W., et al. (2004) · Science · doi:10.1126/science.1093857 · Cited by 4,376 · see citing works
Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine
Ley, R. E., Peterson, D. A., & Gordon, J. I. (2006) · Cell · doi:10.1016/j.cell.2006.02.017 · Cited by 3,358 · 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
The gut flora as a forgotten organ
O'Hara, A. M., & Shanahan, F. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400731 · Cited by 2,791 · see citing works
Metagenomics: Application of Genomics to Uncultured Microorganisms
Handelsman, J. (2004) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.68.4.669-685.2004 · Cited by 2,454 · see citing works
SEER Cancer Statistics Review, 1975-2008, National Cancer Institute, Bethesda, MD
Howlader, N. (2011) · Medical Entomology and Zoology · Cited by 2,436 · see citing works
Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation
Watanabe, M., Houten, S. M., Mataki, C., Christoffolete, M. A., Kim, B. W., Sato, H., Messaddeq, N., Harney, J. W., Ezaki, O., Kodama, T., et al. (2006) · Nature · doi:10.1038/nature04330 · Cited by 2,220 · see citing works
Comparative Metagenomics of Microbial Communities
Tringe, S. G., von Mering, C., Kobayashi, A., Salamov, A. A., Chen, K., Chang, H. W., Podar, M., Short, J. M., Mathur, E. J., Detter, J. C., et al. (2005) · Science · doi:10.1126/science.1107851 · Cited by 1,694 · see citing works
An ecological and evolutionary perspective on human–microbe mutualism and disease
Dethlefsen, L., McFall-Ngai, M., & Relman, D. A. (2007) · Nature · doi:10.1038/nature06245 · Cited by 1,660 · see citing works
Bile Salt Hydrolase Activity in Probiotics
Begley, M., Hill, C., & Gahan, C. G. M. (2006) · Applied and Environmental Microbiology · doi:10.1128/aem.72.3.1729-1738.2006 · Cited by 1,187 · see citing works
Self-citationRegulation of antibacterial defense in the small intestine by the nuclear bile acid receptor
Inagaki, T., Moschetta, A., Lee, Y.-K., Peng, L., Zhao, G., Downes, M., Yu, R. T., Shelton, J. M., Richardson, J. A., Repa, J. J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509592103 · Cited by 1,164 · see citing works
Rawls, J. F., Mahowald, M. A., Ley, R. E., & Gordon, J. I. (2006) · Cell · doi:10.1016/j.cell.2006.08.043 · Cited by 962 · see citing works
Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes
Kurokawa, K., Itoh, T., Kuwahara, T., Oshima, K., Toh, H., Toyoda, A., Takami, H., Morita, H., Sharma, V. K., Srivastava, T. P., et al. (2007) · DNA Research · doi:10.1093/dnares/dsm018 · Cited by 869 · see citing works
Bile 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
Bile 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
Endocrine functions of bile acids
Houten, S. M., 渡辺, 光., & Auwerx, J. H. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601049 · Cited by 583 · see citing works
A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse model
Martin, F., Dumas, M., Wang, Y., Legido‐Quigley, C., Yap, I. K. S., Tang, H., Zirah, S., Murphy, G. M., Cloarec, O., Lindon, J. C., et al. (2007) · Molecular Systems Biology · doi:10.1038/msb4100153 · Cited by 471 · see citing works
Dussurget, O., Cabanes, D., Dehoux, P., Lecuit, M., Buchrieser, C., Glaser, P., & Cossart, P. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.03080.x · Cited by 356 · see citing works
Park, S. F., & Stewart, G. S. A. B. (1990) · Gene · doi:10.1016/0378-1119(90)90479-b · Cited by 277 · see citing works
Begley, M., Sleator, R. D., Gahan, C. G. M., & Hill, C. (2005) · Infection and Immunity · doi:10.1128/iai.73.2.894-904.2005 · Cited by 264 · see citing works
Self-citationHow bile acids confer gut mucosal protection against bacteria
Hofmann, A. F., & Eckmann, L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600780103 · Cited by 239 · see citing works
Development of a differential medium for bile salt hydrolase-active Lactobacillus spp
Dashkevicz, M. P., & Feighner, S. D. (1989) · Applied and Environmental Microbiology · doi:10.1128/aem.55.1.11-16.1989 · Cited by 202 · see citing works
Begley, M., Gahan, C. G. M., & Hill, C. (2002) · Applied and Environmental Microbiology · doi:10.1128/aem.68.12.6005-6012.2002 · Cited by 196 · see citing works
Self-citationBerr, F., Kullak‐Ublick, G., Paumgartner, G., Münzing, W., & Hylemon, P. (1996) · Gastroenterology · doi:10.1016/s0016-5085(96)70024-0 · Cited by 149 · see citing works
Kumar, R. S., Brannigan, J. A., Prabhune, A. A., Pundle, A. V., Dodson, G. G., Dodson, E. J., & Suresh, C. G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604172200 · Cited by 143 · see citing works
Christiaens, H., Leer, R. J., Pouwels, P. H., & Verstraete, W. (1992) · Applied and Environmental Microbiology · doi:10.1128/aem.58.12.3792-3798.1992 · Cited by 128 · see citing works
Side chain conjugation prevents bacterial 7-dehydroxylation of bile acids.
Batta, A. K., Salen, G., Arora, R., Shefer, S., Batta, M., & Person, A. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)38535-7 · Cited by 116 · see citing works
Improvement and Optimization of Two Engineered Phage Resistance Mechanisms in Lactococcus lactis
McGrath, S., Fitzgerald, G. F., & van Sinderen, D. (2001) · Applied and Environmental Microbiology · doi:10.1128/aem.67.2.608-616.2001 · Cited by 115 · see citing works
Transposon-aided capture (TRACA) of plasmids resident in the human gut mobile metagenome
Jones, B. V., & Marchesi, J. R. (2006) · Nature Methods · doi:10.1038/nmeth964 · Cited by 114 · see citing works
Self-citationHill, M. J. (1990) · Mutation Research/Reviews in Genetic Toxicology · doi:10.1016/0165-1110(90)90023-5 · Cited by 92 · see citing works
Tauroconjugation of cholic acid stimulates 7 alpha-dehydroxylation by fecal bacteria
Eldere, J. V., Celis, P., Pauw, G. D., Lesaffre, E., & Eyssen, H. (1996) · Applied and Environmental Microbiology · doi:10.1128/aem.62.2.656-661.1996 · Cited by 86 · see citing works
Delpino, M. V., Marchesini, M. I., Estein, S. M., Comerci, D. J., Cassataro, J., Fossati, C. A., & Baldi, P. C. (2006) · Infection and Immunity · doi:10.1128/iai.00952-06 · Cited by 82 · see citing works
Stamp, D. (2002) · Medical Hypotheses · doi:10.1016/s0306-9877(02)00125-1 · Cited by 62 · see citing works
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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
Host-gut microbiota metabolic interactions
Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., & Pettersson, S. (2012) · Science · doi:10.1126/science.1223813 · Cited by 4,760 · see citing works
Gut microbiota functions: metabolism of nutrients and other food components
Rowland, I., Gibson, G., Heinken, A., Scott, K., Swann, J., Thiele, I., & Tuohy, K. (2018) · European Journal of Nutrition · doi:10.1007/s00394-017-1445-8 · Cited by 2,878 · 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
Gut microbiome and health: mechanistic insights
de Vos, W. M., Tilg, H., Van Hul, M., & Cani, P. D. (2022) · Gut · doi:10.1136/gutjnl-2021-326789 · Cited by 2,388 · see citing works
Unravelling the effects of the environment and host genotype on the gut microbiome
Spor, A., Koren, O., & Ley, R. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2540 · Cited by 1,509 · 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
Genomic variation landscape of the human gut microbiome
Schloissnig, S., Arumugam, M., Sunagawa, S., Mitreva, M., Tap, J., Zhu, A., Waller, A., Mende, D. R., Kultima, J. R., Martin, J., et al. (2013) · Nature · doi:10.1038/nature11711 · Cited by 907 · see citing works
Commensal bacteria at the interface of host metabolism and the immune system
Brestoff, J. R., & Artis, D. (2013) · Nature Immunology · doi:10.1038/ni.2640 · Cited by 945 · see citing works
Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases
Duboc, H., Rajca, S., Rainteau, D., Benarous, D., Maubert, M.-A., Quervain, E., Thomas, G., Barbu, V., Humbert, L., Despras, G., et al. (2013) · Gut · doi:10.1136/gutjnl-2012-302578 · Cited by 930 · see citing works
Bile acid signaling in metabolic disease and drug therapy
Li, T., & Chiang, J. Y. L. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.008201 · Cited by 935 · see citing works
Stress Physiology of Lactic Acid Bacteria.
Papadimitriou, K., Alegría, Á., Bron, P. A., de Angelis, M., Gobbetti, M., Kleerebezem, M., Lemos, J. A., Linares, D. M., Ross, P., Stanton, C., et al. (2016) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00076-15 · Cited by 914 · see citing works
Deschasaux, M., Bouter, K. E., Prodan, A., Levin, E., Groen, A. K., Herrema, H., Tremaroli, V., Bakker, G. J., Attaye, I., Pinto-Sietsma, S.-J., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0160-1 · Cited by 695 · see citing works
Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children
Korpela, K., Salonen, A., Virta, L. J., Kekkonen, R. A., Forslund, K., Bork, P., & de Vos, W. M. (2016) · Nature Communications · doi:10.1038/ncomms10410 · Cited by 698 · see citing works
Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut
Joyce, S. A., MacSharry, J., Casey, P. G., Kinsella, M., Murphy, E. F., Shanahan, F., Hill, C., & Gahan, C. G. M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323599111 · Cited by 604 · see citing works
Self-citationMetabolism of Cholesterol and Bile Acids by the Gut Microbiota
Gérard, P. (2013) · Pathogens · doi:10.3390/pathogens3010014 · Cited by 580 · see citing works
“BSH genes have been detected in the main bacterial genera of the gut microbiota [32] and the enzyme has been purified from Bacteroides fragilis, B.”
BackgroundIntestinal transport and metabolism of bile acids
Dawson, P. A., & Karpen, S. J. (2015) · Journal of Lipid Research · doi:10.1194/jlr.r054114 · Cited by 598 · see citing works
Bile resistance mechanisms in Lactobacillus and Bifidobacterium
Ruiz, L., Margolles, A., & Sánchez, B. (2013) · Frontiers in Microbiology · doi:10.3389/fmicb.2013.00396 · Cited by 548 · see citing works
Metabolic fate of polyphenols in the human superorganism
van Duynhoven, J., Vaughan, E. E., Jacobs, D. M., A. Kemperman, R., van Velzen, E. J. J., Gross, G., Roger, L. C., Possemiers, S., Smilde, A. K., Doré, J., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000098107 · Cited by 540 · see citing works
Song, Z., Cai, Y., Lao, X., Wang, X., Lin, X., Cui, Y., Kalavagunta, P. K., Liao, J., Jin, L., Shang, J., et al. (2019) · Microbiome · doi:10.1186/s40168-019-0628-3 · Cited by 505 · 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
Self-citationTheriot, C. M., Bowman, A. A., & Young, V. B. (2016) · mSphere · doi:10.1128/msphere.00045-15 · Cited by 481 · see citing works
Interactions between Bacteria and Bile Salts in the Gastrointestinal and Hepatobiliary Tracts
Urdaneta, V., & Casadesús, J. (2017) · Frontiers in Medicine · doi:10.3389/fmed.2017.00163 · Cited by 449 · see citing works
The role of the gut microbiota in nonalcoholic fatty liver disease
Abu-Shanab, A., & Quigley, E. M. M. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.172 · Cited by 457 · see citing works
Archaea and the Human Gut: New Beginning of an Old Story
Gaci, N., Borrel, G., Tottey, W., O’Toole, P. W., & Brugère, J.-F. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i43.16062 · Cited by 422 · see citing works
Role of the Microbiome in Energy Regulation and Metabolism
Nieuwdorp, M., Gilijamse, P. W., Pai, N., & Kaplan, L. M. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.02.008 · Cited by 421 · see citing works
A healthy gastrointestinal microbiome is dependent on dietary diversity
Heiman, M. L., & Greenway, F. L. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.02.005 · Cited by 370 · see citing works
Degirolamo, C., Rainaldi, S., Bovenga, F., Murzilli, S., & Moschetta, A. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.02.032 · Cited by 356 · see citing works
The Intestinal Microenvironment and Functional Gastrointestinal Disorders
Barbara, G., Feinle-Bisset, C., Ghoshal, U. C., Santos, J., Vanner, S. J., Vergnolle, N., Zoetendal, E. G., & Quigley, E. M. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.02.028 · Cited by 335 · 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
Hartmann, P., Hochrath, K., Horvath, A., Chen, P., Seebauer, C. T., Llorente, C., Wang, L., Alnouti, Y., Fouts, D. E., Stärkel, P., et al. (2018) · Hepatology · doi:10.1002/hep.29676 · Cited by 290 · see citing works
Jones, M. L., Martoni, C. J., & Prakash, S. (2012) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2012.126 · Cited by 277 · 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
Foley, M. H., O’Flaherty, S., Barrangou, R., & Theriot, C. M. (2019) · PLOS Pathogens · doi:10.1371/journal.ppat.1007581 · Cited by 271 · see citing works
The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism
Just, S., Mondot, S., Ecker, J., Wegner, K., Rath, E., Gau, L., Streidl, T., Hery-Arnaud, G., Schmidt, S., Lesker, T. R., et al. (2018) · Microbiome · doi:10.1186/s40168-018-0510-8 · Cited by 269 · see citing works
Banerjee, S., Sindberg, G., Wang, F., Meng, J., Sharma, U., Zhang, L., Dauer, P., Chen, C., Dalluge, J., Johnson, T., et al. (2016) · Mucosal Immunology · doi:10.1038/mi.2016.9 · Cited by 266 · 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
Self-citationMicrobial impact on cholesterol and bile acid metabolism: current status and future prospects
Kriaa, A., Bourgin, M., Potiron, A., Mkaouar, H., Jablaoui, A., Gérard, P., Maguin, E., & Rhimi, M. (2019) · Journal of Lipid Research · doi:10.1194/jlr.r088989 · Cited by 264 · see citing works
Lelouvier, B., Servant, F., Païssé, S., Brunet, A., Benyahya, S., Serino, M., Valle, C., Ortiz, M. R., Puig, J., Courtney, M., et al. (2016) · Hepatology · doi:10.1002/hep.28829 · 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
Self-citationMartínez-del Campo, A., Bodea, S., Hamer, H. A., Marks, J. A., Haiser, H. J., Turnbaugh, P. J., & Balskus, E. P. (2015) · mBio · doi:10.1128/mbio.00042-15 · Cited by 224 · see citing works
Wu, T., Zhang, Z., Liu, B., Hou, D., Liang, Y., Zhang, J., & Shi, P. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-669 · Cited by 234 · see citing works
Bustos, A. Y., Font de Valdez, G., Fadda, S., & Taranto, M. P. (2018) · Food Research International · doi:10.1016/j.foodres.2018.06.035 · Cited by 232 · 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
You’ve got male: Sex and the microbiota-gut-brain axis across the lifespan
Jaggar, M., Rea, K., Spichak, S., Dinan, T. G., & Cryan, J. F. (2020) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.100815 · Cited by 200 · see citing works
Foley, M. H., O’Flaherty, S., Allen, G., Rivera, A. J., Stewart, A. K., Barrangou, R., & Theriot, C. M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2017709118 · Cited by 205 · see citing works
Sun, R., Yang, N., Kong, B., Cao, B., Feng, D., Yu, X., Ge, C., Huang, J., Shen, J., Wang, P., et al. (2017) · Molecular Pharmacology · doi:10.1124/mol.116.106617 · Cited by 199 · see citing works
Jones, M. L., Tomaro-Duchesneau, C., Martoni, C. J., & Prakash, S. (2013) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2013.758706 · Cited by 190 · see citing works
Molecular basis of bile acid-FXR-FGF15/19 signaling axis
Katafuchi, T., & Makishima, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116046 · Cited by 193 · see citing works
Ma, J., Hong, Y., Zheng, N., Xie, G., Lyu, Y., Gu, Y., Xi, C., Chen, L., Wu, G., Li, Y., et al. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1763770 · Cited by 171 · see citing works
Bile salt hydrolase/aminoacyltransferase shapes the microbiome
Guzior, D., Okros, M., Hernandez, C. M., Shivel, M., Armwald, B., Hausinger, R., & Quinn, R. (2022) · doi:10.21203/rs.3.rs-2050406/v1 · Cited by 187 · see citing works
Targeting fatty acid metabolism to improve glucose metabolism
Stinkens, R., Goossens, G. H., Jocken, J. W. E., & Blaak, E. E. (2015) · Obesity Reviews · doi:10.1111/obr.12298 · Cited by 183 · see citing works
Chen, W., Wei, Y., Xiong, A., Li, Y., Guan, H., Wang, Q., Miao, Q., Bian, Z., Xiao, X., Lian, M., et al. (2020) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-019-08731-2 · Cited by 166 · see citing works
Beneficial Bile Acid Metabolism from Lactobacillus plantarum of Food Origin
Prete, R., Long, S. L., Gallardo, A. L., Gahan, C. G., Corsetti, A., & Joyce, S. A. (2020) · Scientific Reports · doi:10.1038/s41598-020-58069-5 · Cited by 165 · see citing works
Self-citationLucas, L. N., Barrett, K., Kerby, R. L., Zhang, Q., Cattaneo, L. E., Stevenson, D., Rey, F. E., & Amador-Noguez, D. (2021) · mSystems · doi:10.1128/msystems.00805-21 · Cited by 168 · see citing works
Barrangou, R., Briczinski, E. P., Traeger, L. L., Loquasto, J. R., Richards, M., Horvath, P., Coûté-Monvoisin, A.-C., Leyer, G., Rendulic, S., Steele, J. L., et al. (2009) · Journal of Bacteriology · doi:10.1128/jb.00155-09 · Cited by 150 · see citing works
Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes
Russell, B. J., Brown, S. D., Siguenza, N., Mai, I., Saran, A. R., Lingaraju, A., Maissy, E. S., Dantas Machado, A. C., Pinto, A. F. M., Sanchez, C., et al. (2022) · Cell · doi:10.1016/j.cell.2022.06.050 · Cited by 151 · see citing works
The human microbiome and bile acid metabolism: Dysbiosis, dysmetabolism, disease and intervention
Jones, M. L., Martoni, C. J., Ganopolsky, J. G., Labbé, A., & Prakash, S. (2014) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2014.880420 · Cited by 150 · see citing works
The gut microbiota and the metabolic health of the host
Joyce, S. A., & Gahan, C. G. M. (2014) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000039 · Cited by 147 · see citing works
Self-citationJoyce, S. A., Shanahan, F., Hill, C., & Gahan, C. G. (2014) · Gut Microbes · doi:10.4161/19490976.2014.969986 · Cited by 139 · see citing works
Self-citationThe human microbiome: A hot spot of microbial horizontal gene transfer
Liu, L., Chen, X., Skogerbø, G., Zhang, P., Chen, R., He, S., & Huang, D.-W. (2012) · Genomics · doi:10.1016/j.ygeno.2012.07.012 · Cited by 131 · 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
Baars, A., Oosting, A., Knol, J., Garssen, J., & Van Bergenhenegouwen, J. (2015) · Microorganisms · doi:10.3390/microorganisms3040641 · Cited by 135 · see citing works
The <i>Lactobacillus</i> Bile Salt Hydrolase Repertoire Reveals Niche-Specific Adaptation
O’Flaherty, S., Briner Crawley, A., Theriot, C. M., & Barrangou, R. (2018) · mSphere · doi:10.1128/msphere.00140-18 · Cited by 118 · see citing works
Masse, K. E., & Lu, V. B. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1169624 · Cited by 120 · see citing works
“At the phyla level, bacterial populations encoding BSH, such as Bacillota, Bacteroidota and Actinomycetota, have been shown to play an important role in the production of secondary bile acids (61).”
BackgroundGut microbiota, cirrhosis, and alcohol regulate bile acid metabolism in the gut
Ridlon, J. M., Kang, D.-J., Hylemon, P. B., & Bajaj, J. S. (2015) · Digestive Diseases · doi:10.1159/000371678 · Cited by 109 · see citing works
Cholesterol-lowering effects of Lactobacillus species
Khare, A., & Gaur, S. (2020) · Current Microbiology · doi:10.1007/s00284-020-01903-w · Cited by 100 · see citing works
Horrocks, V., King, O. G., Yip, A. Y. G., Marques, I. M., & McDonald, J. A. K. (2023) · Microbiology · doi:10.1099/mic.0.001377 · Cited by 104 · see citing works
Wise, J. L., & Cummings, B. P. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1093420 · Cited by 94 · see citing works
Bile salt hydrolases: Structure and function, substrate preference, and inhibitor development
Dong, Z., & Lee, B. H. (2018) · Protein Science · doi:10.1002/pro.3484 · Cited by 92 · see citing works
Agolino, G., Pino, A., Vaccalluzzo, A., Cristofolini, M., Solieri, L., Caggia, C., & Randazzo, C. L. (2024) · Journal of Functional Foods · doi:10.1016/j.jff.2024.106357 · Cited by 87 · see citing works
Martoni, C. J., Labbé, A., Ganopolsky, J. G., Prakash, S., & Jones, M. L. (2015) · Gut Microbes · doi:10.1080/19490976.2015.1005474 · Cited by 87 · see citing works
Gu, X., Zhou, J., Zhou, Y., Wang, H., Si, N., Ren, W., Zhao, W., Fan, X., Gao, W., Wei, X., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00779-7 · Cited by 81 · see citing works
Liu, L., Liu, Z., Li, H., Cao, Z., Li, W., Song, Z., Li, X., Lu, A., Lu, C., & Liu, Y. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00012 · Cited by 68 · see citing works
Bariatric surgery: remission of inflammation, cardiometabolic benefits, and common adverse effects
Biobaku, F., Ghanim, H., Monte, S. V., Caruana, J. A., & Dandona, P. (2020) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaa049 · Cited by 68 · see citing works
New insights into microbial bile salt hydrolases: from physiological roles to potential applications
Dong, Z., Yang, S., Tang, C., Li, D., Kan, Y., & Yao, L. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1513541 · Cited by 64 · 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
Kathiriya, M. R., Vekariya, Y. V., & Hati, S. (2023) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-023-10104-3 · Cited by 50 · see citing works
Ru, X., Zhang, C.-C., Yuan, Y.-H., Yue, T.-L., & Guo, C.-F. (2019) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-018-9492-5 · Cited by 45 · see citing works
Yang, S., Li, D., Yu, Z., Li, Y., & Wu, M. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.709629 · Cited by 40 · see citing works
Functional and Phylogenetic Diversity of BSH and PVA Enzymes
Daly, J. W., Keely, S. J., & Gahan, C. G. M. (2021) · Microorganisms · doi:10.3390/microorganisms9040732 · Cited by 40 · see citing works
Self-citationSun, X., Chen, Z., Yu, L., Zeng, W., Sun, B., Fan, H., & Bai, Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1205323 · Cited by 33 · see citing works
“Gut microbiota analyses revealed that Firmicutes, Actinobacteria, and Erysipelotrichaceae have high BSH activity (Jones et al., 2008; Labbé et al., 2014).”
BackgroundKusada, H., Arita, M., Tohno, M., & Tamaki, H. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.858263 · Cited by 29 · see citing works
Functional food addressing heart health: do we have to target the gut microbiota?
Ryan, P. M., Ross, R. P., Fitzgerald, G. F., Caplice, N. M., & Stanton, C. (2015) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0000000000000224 · Cited by 28 · see citing works
- Authors
- Jones, B. V., Begley, M., Hill, C., Gahan, C. G. M., & Marchesi, J. R.
- Affiliations
- University College Cork (IE)
- Teagasc - The Irish Agriculture and Food Development Authority (IE)
- *Alimentary Pharmabiotic Centre and Department of Microbiology, and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-09-09
- Volume
- 105
- Issue
- 36
- Pages
- 13580-13585
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2533232
- OpenAlex
- W2035779227
- Cited by
- 1,098
- References
- 38
- Citations by year
- 2026: 78 · 2025: 95 · 2024: 101 · 2023: 92 · 2022: 114 · 2021: 102 · 2020: 74 · 2019: 76 · 2018: 61 · 2017: 41 · 2016: 38 · 2015: 41 · 2014: 54 · 2013: 43 · 2012: 25
- FWCI
- 8.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Brighton Repository (University of Brighton) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- bile salt hydrolase, human gut microbiome, bile acid metabolism, functional metagenomics, bile tolerance, selection pressure, bile acid conjugates, archaea, bacterial diversity, host-microbe interactions
- MeSH terms
- Amidohydrolases, Amino Acid Sequence, Humans, Phylogeny, Evolution, Molecular, Methanobrevibacter, Gastrointestinal Tract, Metagenome
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