Effects of intestinal microbial bile salt sulfatase activity on bile salt kinetics in gnotobiotic rats
Abstract
Hepatic sulfation is thought to promote fecal excretion of lithocholate in humans by impairing the enterohepatic recirculation of the compound. Sulfatases produced by the gut flora may, at least in part, counteract this process. To investigate this interaction, female germfree rats, which are known to excrete considerable amounts of sulfated bile salts, were selectively associated with a bile salt desulfating flora. In these rats nearly all cecal, colonic, and fecal bile salt sulfate esters were hydrolyzed, resulting in a decrease of total fecal bile salt excretion of greater than 25% compared with gnotobiotic rats without a bile salt desulfating flora. Desulfation of allochenodeoxycholate, the major sulfated bile salt in germfree rats, led to an enhanced recirculation and 12 alpha-hydroxylation of the compound in the liver, resulting in an increased fecal output of allocholate. Microbial desulfation of intraperitoneally injected [24-14C]taurolithocholate-3-sulfate caused a fivefold decrease of the fecal plus urinary excretion rate of the isotope to approximately that found for unsulfated [24-14C]taurolithocholate. Coassociation of the gnotobiotic rats with a microflora that normalized the small intestinal transit time and cecal size led to a rise of total fecal bile salt excretion of greater than 30% and a twofold accelerated excretion of both sulfated and unsulfated injected [24-14C]taurolithocholate. We conclude that in rats the gut flora rapidly desulfates intestinal bile salt sulfates, enhancing the enterohepatic recirculation and subsequent hydroxylation of the desulfated bile salts. In addition, these data illustrate the importance of having a well-defined microflora to normalize intestinal transit time and cecal size of gnotobiotic animals when performing kinetic studies of enterohepatic circulating compounds.
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The gut microbiota may influence functional constipation through its impact on bile acid sulfation, in which colonic bacterial bile salt sulfatase may desulfate bile acids, empowering their effect to stimulate colonic secretion and transit and consequently improve colonic fluid transport.
“Another mechanism for the gut microbiota to influence FC is through its impact on BA sulfation, which abolishes the effect of the BAs on fluid transport [ 51 , 52 ]. BA sulfation likely occurred in hepatocytes, while colonic bacterial bile salt sulfatase may desulfate BA, empowering its effect to stimulate colonic secretion and transit, and consequently improve colonic fluid transport [ 53 ].”
From Role of gut microbiota in functional constipation (2021) · cites this paper as [53]
Cites
Almé, B., Bremmelgaard, A., Sjövall, J., & Thomassen, P. A. B. (1977) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41684-0 · Cited by 491 · see citing works
General methods for the analysis of metabolic profiles of bile acids and related compounds in feces.
Setchell, K. D. R., Lawson, A. M., Tanida, N., & Sjövall, J. (1983) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37923-2 · Cited by 285 · see citing works
Effect of the Normal Microbial Flora on Gastrointestinal Motility.
Abrams, G. D., & Bishop, J. E. (1967) · Experimental Biology and Medicine · doi:10.3181/00379727-126-32430 · Cited by 242 · see citing works
Cowen, A. E., Korman, M. G., Hofmann, A. F., & Cass, O. W. (1975) · PubMed · Cited by 189 · see citing works
The formation of bile acid sulfates: a new pathway of bile acid metabolism in humans.
Palmer, R. H. (1967) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.58.3.1047 · Cited by 185 · see citing works
Metabolism of Lithocholate in Healthy Man
Cowen, A. E., Korman, M. G., Hofmann, A. F., & Cass, O. W. (1975) · Gastroenterology · doi:10.1016/s0016-5085(19)32636-8 · Cited by 133 · see citing works
Bile acid sulfates. II. Formation, metabolism, and excretion of lithocholic acid sulfates in the rat
Palmer, R. H. (1971) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39455-4 · Cited by 107 · see citing works
Effects of Sulfation of Taurolithocholic and Glycolithocholic Acids on their Intestinal Transport
Low-Beer, T. S., Tyor, M. P., & Lack, L. C. (1969) · Gastroenterology · doi:10.1016/s0016-5085(69)80033-8 · Cited by 86 · see citing works
The Turnover of Bile Acids in the Rat.1
Lindstedt, S., & Norman, A. (1957) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1957.tb01376.x · Cited by 82 · see citing works
Intestinal transport of bile acids
Wilson, F. A. (1981) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1981.241.2.g83 · Cited by 82 · see citing works
Properties and biological significance of the ileal bile salt transport system.
Lack, L. C. (1979) · Environmental Health Perspectives · doi:10.1289/ehp.793379 · Cited by 79 · see citing works
Mahowald, T. A., Matschiner, J. T., Hsia, S. L., Richter, R., Doisy, E. A., Elliott, W. H., & Doisy, E. A. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64877-x · Cited by 75 · see citing works
Isolation of a bile salt sulfatase-producing Clostridium strain from rat intestinal microflora
Huijghebaert, S., Mertens, J. A., & Eyssen, H. (1982) · Applied and Environmental Microbiology · doi:10.1128/aem.43.1.185-192.1982 · Cited by 61 · see citing works
Self-citationThomas, P. J., Hsia, S. L., Matschiner, J. T., Doisy, E. A., Elliott, W. H., Thayer, S. A., & Doisy, E. A. (1964) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)51754-3 · Cited by 60 · see citing works
Parmentier, G. G., & Eyssen, H. (1977) · Steroids · doi:10.1016/0039-128x(77)90049-6 · Cited by 54 · see citing works
Self-citationEffects of sulfation patterns on intestinal transport of bile salt sulfate esters
Witt, E. H. D., & Lack, L. C. (1980) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1980.238.1.g34 · Cited by 52 · see citing works
Effects of bacterial flora on cecal size and transit rate of intestinal contents in mice.
Iwaï, H., Ishihara, Y., YAMANAKA, J., & Ito, T. (1973) · PubMed · Cited by 51 · see citing works
Wilpart, M., Mainguet, P., Maskens, A. P., & Roberfroid, M. (1983) · Carcinogenesis · doi:10.1093/carcin/4.10.1239 · Cited by 47 · see citing works
Robben, J., Parmentier, G. G., & Eyssen, H. (1986) · Applied and Environmental Microbiology · doi:10.1128/aem.51.1.32-38.1986 · Cited by 38 · see citing works
Self-citationThin-layer chromatography of bile salt sulphates
Parmentier, G. G., & Eyssen, H. (1978) · Journal of Chromatography A · doi:10.1016/s0021-9673(00)85370-4 · Cited by 37 · see citing works
Self-citationEyssen, H., Eldere, J. V., Parmentier, G. G., Huijghebaert, S., & Mertens, J. (1985) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(85)90176-1 · Cited by 36 · see citing works
Self-citationOccurrence of sulfated 5α-cholanoates in rat bile
Eriksson, H., Taylor, W., & Sjövall, J. (1978) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41555-x · Cited by 33 · see citing works
Bile acid conjugation in the chimpanzee: effective sulfation of lithocholic acid
Schwenk, M., Hofmann, A. F., Carlson, G. L., Carter, J. A., Coulston, F., & Greim, H. A. (1978) · Archives of Toxicology · doi:10.1007/bf01891965 · Cited by 28 · see citing works
Bartholomew, T. C., & Billing, B. H. (1983) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(83)90086-3 · Cited by 25 · see citing works
The bile acid composition of rabbit and cat gall-bladder bile
Taylor, W. (1977) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(77)90277-1 · Cited by 24 · see citing works
Sex-linked differences in bile acid metabolism of germfree rats
Eyssen, H., Smets, L., Parmentier, G. G., & Janssen, G. (1977) · Life Sciences · doi:10.1016/0024-3205(77)90079-0 · Cited by 23 · see citing works
Self-citationMui, M. M., & Elliott, W. H. (1971) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)62491-3 · Cited by 22 · see citing works
Intrahepatic cholestasis induced by allo monohydroxy bile acid in rats
Vonk, R. J., Tuchweber, B., Massé, D., Perea, A., Audet, M., ROY, C. C., & Yousef, I. M. (1981) · Gastroenterology · doi:10.1016/0016-5085(81)90710-1 · Cited by 17 · see citing works
Colonic Absorption of Sulfated and Nonsulfated Bile Acids in Rat
Walker, S., Stiehl, A., Raedsch, R., Klöters, P., & Kommerell, B. (2009) · Digestion · doi:10.1159/000199268 · Cited by 17 · see citing works
Riottot, M., SACQUET, E., VILA, J. P., & Leprince, C. (1980) · annales de biologie animale biochimie biophysique · doi:10.1051/rnd:19800110 · Cited by 17 · see citing works
Chenodeoxycholic acid-3-sulfate
Eng, C., & Javitt, N. B. (1983) · Biochemical Pharmacology · doi:10.1016/0006-2952(83)90302-7 · Cited by 15 · see citing works
Effects of Cholesterol Feeding on the Bile Acids of Male and Female Germ-Free Rats
Parmentier, G. G., SMETS, L. M. J., JANNSEN, G. A., & Eyssen, H. (1981) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1981.tb05344.x · Cited by 12 · see citing works
Self-citationBile Acids XLI. Hepatic Microsomal 12 -Hydroxylation of Allochenodeoxycholate to Allocholate
Blaskiewicz, R., O'Neil, G. J., & Elliott, W. H. (1974) · Experimental Biology and Medicine · doi:10.3181/00379727-146-38049 · Cited by 11 · see citing works
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Cited by
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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
Microbial pathways in colonic sulfur metabolism and links with health and disease
Carbonero, F., Benefiel, A. C., Alizadeh-Ghamsari, A. H., & Gaskins, H. R. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00448 · Cited by 544 · see citing works
Azcárate-Peril, M. A., Sikes, M. L., & Bruno-Bárcena, J. M. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00110.2011 · Cited by 252 · 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
Role of gut microbiota in functional constipation
Zhang, S., Wang, R., Li, D., Zhao, L., & Zhu, L. (2021) · Gastroenterology Report · doi:10.1093/gastro/goab035 · Cited by 175 · see citing works
“BA sulfation likely occurred in hepatocytes, while colonic bacterial bile salt sulfatase may desulfate BA, empowering its effect to stimulate colonic secretion and transit, and consequently improve colonic fluid transport [53].”
BackgroundMcbain, A. J., & Macfarlane, G. T. (1998) · Journal of Medical Microbiology · doi:10.1099/00222615-47-5-407 · Cited by 179 · see citing works
Chen, J., Thomsen, M., & Vitetta, L. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.27635 · Cited by 152 · see citing works
Methods for Diagnosis of Bile Acid Malabsorption in Clinical Practice
Vijayvargiya, P., Camilleri, M., Shin, A., & Saenger, A. K. (2013) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2013.04.029 · Cited by 126 · see citing works
New Insights into the Pathogenesis and Pathophysiology of Irritable Bowel Syndrome
Collins, S. M. (1992) · Springer eBooks · doi:10.1007/978-1-4615-3314-6_9 · Cited by 115 · see citing works
Hofmann, A. F., Loening‐Baucke, V., Lavine, J. E., Hagey, L. R., Steinbach, J. H., Packard, C. A., Griffin, T. L., & Chatfield, D. A. (2008) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0b013e31816920a6 · Cited by 75 · see citing works
Camilleri, M., & Fealey, R. D. (1990) · Digestive Diseases and Sciences · doi:10.1007/bf01540409 · Cited by 73 · see citing works
GUI, X. (1998) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.1998.tb00558.x · Cited by 66 · see citing works
Role of Bile Acids in Dysbiosis and Treatment of Nonalcoholic Fatty Liver Disease
Wang, C., Zhu, C., Shao, L., Ye, J., Shen, Y., & Ren, Y. (2019) · Mediators of Inflammation · doi:10.1155/2019/7659509 · Cited by 64 · see citing works
The site-specific delivery of ursodeoxycholic acid to the rat colon by sulfate conjugation
Rodrigues, C. M. P., Kren, B. T., Steer, C. J., & Setchell, K. D. R. (1995) · Gastroenterology · doi:10.1016/0016-5085(95)90750-5 · Cited by 59 · see citing works
Role of bile acids in liver diseases mediated by the gut microbiome
Shao, J., Ge, T., Chen, S., Wang, G., Yang, Q., Huang, C., Xu, L., & Chen, Z. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i22.3010 · Cited by 60 · see citing works
Biotransformation of Bile Acids, Cholesterol, and Steroid Hormones
Baron, S. F., & Hylemon, P. B. (1997) · Springer eBooks · doi:10.1007/978-1-4615-4111-0_13 · Cited by 50 · see citing works
Zimniak, P., Holsztynska, E. J., Lester, R., Waxman, D. J., & Radominska-p, A. (1989) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38317-6 · Cited by 39 · see citing works
Menghan, L., & Nazzal, L. (2019) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000518 · Cited by 33 · see citing works
Lee, S. H., An, J. H., Park, H., & Jung, B. H. (2012) · Journal of Chromatography B · doi:10.1016/j.jchromb.2011.12.030 · Cited by 31 · see citing works
Gut feelings: the microbiota-gut-brain axis on steroids
So, S. Y., & Savidge, T. (2021) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00294.2021 · Cited by 29 · see citing works
Zhang, T., Liu, W., Lu, H., Cheng, T., Wang, L., Wang, G., Zhang, H., & Chen, W. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2278155 · Cited by 28 · see citing works
Bile acids and their receptors in hepatic immunity
Fiorucci, S., Marchianò, S., Distrutti, E., & Biagioli, M. (2025) · Liver Research · doi:10.1016/j.livres.2025.01.005 · Cited by 28 · see citing works
Thompson, M. B., Davis, D., & Morris, R. (1993) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39978-8 · Cited by 26 · see citing works
Review: Bacterial transformations of bile acids
Prabha, V., & Ohri, M. (2005) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-005-9019-y · Cited by 23 · see citing works
Caderni, G., Dolara, P., Spagnesi, M. T., Luceri, C., Bianchini, F., MASTRANDREA, V., & Morozzi, G. (1993) · Journal of Nutrition · doi:10.1093/jn/123.4.704 · Cited by 22 · see citing works
Microbial Biotransformations of Bile Acids as Detected by Electrospray Mass Spectrometry
Hagey, L. R., & Krasowski, M. D. (2013) · Advances in Nutrition · doi:10.3945/an.112.003061 · Cited by 20 · see citing works
Functional Disorders of the Small Intestine
Kellow, J. E., & Phillips, S. F. (1989) · Springer eBooks · doi:10.1007/978-1-4684-5694-3_9 · Cited by 19 · see citing works
Microbial bile acid modifications: current understandings, key problems, and future perspectives
Zhang, H., Wen, J., Liu, X., Feng, Y., Liu, X., & Ning, K. (2025) · Science China Life Sciences · doi:10.1007/s11427-025-3019-2 · Cited by 18 · see citing works
Eldere, J. V., Robben, J., Caenepeel, P., & Eyssen, H. (1988) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(88)90373-1 · Cited by 15 · see citing works
Self-citationKayahara, T., Tamura, T., Amuro, Y., Higashino, K., Igimi, H., & Uchida, K. (1994) · Lipids · doi:10.1007/bf02536334 · Cited by 15 · see citing works
Kakiyama, G., Iida, T., Yoshimoto, A., Goto, T., Mano, N., Goto, J., Nambara, T., Hagey, L. R., & Hofmann, A. F. (2004) · Journal of Lipid Research · doi:10.1194/jlr.d300027-jlr200 · Cited by 14 · see citing works
Wang, P., Yuan, P., Lin, S., Zhong, H., Zhang, X., Zhuo, Y., Li, J., Che, L., Feng, B., Lin, Y., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126496 · Cited by 14 · see citing works
Robben, J., Janssen, G., Merckx, R., & Eyssen, H. (1989) · Applied and Environmental Microbiology · doi:10.1128/aem.55.11.2954-2959.1989 · Cited by 13 · see citing works
Self-citationWang, P., Chen, Q., Yuan, P., Lin, S., Chen, H., Li, R., Zhang, X., Zhuo, Y., Li, J., Che, L., et al. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1023623 · Cited by 10 · see citing works
Effects of Psychological Factors on Gastrointestinal Function
Whitehead, W. E. (1989) · Springer eBooks · doi:10.1007/978-1-4684-5694-3_3 · Cited by 9 · see citing works
Microbial transformation of secondary bile acids: roles in gut ecology and autoimmune diseases
Ren, L., Li, M., Wu, L., Lin, Z. M., & Chen, A. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1769792 · Cited by 8 · see citing works
The Indigenous Microflora and the Intestinal Metabolism of Cholesterol, Bile Acids and Steroids
Eyssen, H., & Robben, J. (1989) · Palgrave Macmillan UK eBooks · doi:10.1007/978-1-349-10723-0_6 · Cited by 6 · see citing works
Self-citationEldere, J. V., Mertens, J., & Eyssen, H. (1990) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(90)90087-9 · Cited by 4 · see citing works
Self-citationUne, M., Konishi, M., Yoshii, M., Kuramoto, T., & Hoshita, T. (1996) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37459-9 · Cited by 4 · see citing works
Bile Acids: A Bridge Linking Gut Microbiota and NAFLD
Zhang, J., Wang, C., Ji, X., Wu, F., Lin, Z., Zhou, Y., Xu, C., & Wang, F. (2022) · Advanced Gut & Microbiome Research · doi:10.1155/2022/4752148 · Cited by 3 · see citing works
Wang, M. M., Hu, B., Ni, J., Liu, K., Tian, S., Zheng, J., Liu, S., & Liu, H. (2025) · Food Research International · doi:10.1016/j.foodres.2025.118085 · Cited by 2 · see citing works
Teitelbaum, J. E. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4377-0774-8.10004-1
- Authors
- Robben, J., Caenepeel, P., Van Eldere, J., & Eyssen, H.
- Affiliations
- Rega Institute for Medical Research (BE)
- ORCID
- Robben, J.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 1988-02
- Volume
- 94
- Issue
- 2
- Pages
- 494-502
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W1660647916
- Cited by
- 43
- References
- 33
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 3 · 2019: 3 · 2018: 1 · 2017: 1 · 2013: 2 · 2012: 2
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- gut microbiota, enterohepatic circulation, lithocholic acid, taurolithocholate, germ-free rats, gnotobiotic rats, intestinal transit time
- MeSH terms
- Animals, Bacteria, Bile Acids and Salts, Biotransformation, Cecum, Clostridium, Enterohepatic Circulation, Feces, Female, Germ-Free Life, Intestines, Rats, Inbred Strains, Sulfatases, Sulfates, Rats
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