Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose
Abstract
The mucus layer covering the gastrointestinal mucosa is considered the first line of defense against aggressions arising from the luminal content. It is mainly composed of high molecular weight glycoproteins called mucins. Butyrate, a short-chain fatty acid produced during carbohydrate fermentation, has been shown to increase mucin secretion. The aim of this study was to test 1) whether butyrate regulates the expression of various MUC genes, which are coding for protein backbones of mucins, and 2) whether this effect depends on butyrate status as the major energy source of colonocytes. Butyrate was provided at the apical side of human polarized colonic goblet cell line HT29-Cl.16E in glucose-rich or glucose-deprived medium. In glucose-rich medium, butyrate significantly increased MUC3 and MUC5B expression (1.6-fold basal level for both genes), tended to decrease MUC5AC expression, and had no effect on MUC2 expression. In glucose-deprived medium, i.e., when butyrate was the only energy source available, MUC3 and MUC5B increase persisted, whereas MUC5AC expression was significantly enhanced (3.7-fold basal level) and MUC2 expression was strikingly increased (23-fold basal level). Together, our findings show that butyrate is able to upregulate colonic mucins at the transcriptional level and even better when it is the major energy source of the cells. Thus the metabolism of butyrate in colonocytes is closely linked to some of its gene-regulating effects. The distinct effects of butyrate according to the different MUC genes could influence the composition and properties of the mucus gel and thus its protective function.
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SCFAs support the integrity of the intestinal mucosa in vitro and in vivo.
“which have been shown in vitro and in vivo to support the integrity of the intestinal mucosa in a variety of ways (Fukuda et al., 2011; Gaudier et al., 2004; Macia et al., 2015; Willemsen et al., 2003; Wrzosek et al., 2013).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Gaudier et al., 2004
Butyrate stimulates intestinal mucus production.
“stimulates intestinal mucus production [235]”
From Gut microbiota role in irritable bowel syndrome: New therapeutic strategies (2016) · cites this paper as [235]
Cites
Butyrate inhibits inflammatory responses through NFκB inhibition: implications for Crohn's disease
Segain, J.-P., de la Blétière, D. R., Bourreille, A., Leray, V., Gervois, N., Rosales, C., Ferrier, L., Bonnet, C., Blottière, H. M., & Galmiche, J.-P. (2000) · Gut · doi:10.1136/gut.47.3.397 · Cited by 1,325 · see citing works
Self-citationUtilization of Nutrients by Isolated Epithelial Cells of the Rat Colon
Roediger, W. E. W. (1982) · Gastroenterology · doi:10.1016/s0016-5085(82)80339-9 · Cited by 1,201 · see citing works
Sodium butyrate inhibits histone deacetylation in cultured cells
Candido, E. (1978) · Cell · doi:10.1016/0092-8674(78)90305-7 · Cited by 1,036 · see citing works
Colorectal Cancer in Mice Genetically Deficient in the Mucin Muc2
Velcich, A., Yang, W., Heyer, J., Fragale, A., Nicholas, C., Viani, S., Kucherlapati, R., Lipkin, M., Yang, K., & Augenlicht, L. (2002) · Science · doi:10.1126/science.1069094 · Cited by 936 · see citing works
Kim, Y.-M., Talanian, R. V., & Billiar, T. R. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.49.31138 · Cited by 887 · see citing works
Augeron, C., & LABOISSE, C. L. (1984) · PubMed · Cited by 539 · see citing works
Self-citationThickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis.
Pullan, R. D., Thomas, G. A. O., Rhodes, M. A., Newcombe, R. G., Williams, G. T., Allen, A., & Rhodes, J. M. (1994) · Gut · doi:10.1136/gut.35.3.353 · Cited by 467 · see citing works
Hague, A., Elder, D. J. E., Hicks, D. J., & Paraskeva, C. (1995) · International Journal of Cancer · doi:10.1002/ijc.2910600322 · Cited by 414 · see citing works
Nakano, K., Mizuno, T., Sowa, Y., Orita, T., Yoshino, T., Okuyama, Y., Fujita, T., Ohtani‐Fujita, N., Matsukawa, Y., Tokino, T., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.35.22199 · Cited by 395 · see citing works
Corfield, A. P., MYERSCOUGH, N., LONGMAN, R., SYLVESTER, P., Arul, G. S., & Pignatelli, M. N. (2000) · Gut · doi:10.1136/gut.47.4.589 · Cited by 391 · see citing works
Dekker, J. P., Rossen, J. W. A., Büller, H. A., et al. (2002) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(01)02052-7 · Cited by 387 · see citing works
Mucin secretion is modulated by luminal factors in the isolated vascularly perfused rat colon
Barcelo, A., Claustre, J., Moro, F., Chayvialle, J.-A., Cuber, J.-C., & Plaisancié, P. (2000) · Gut · doi:10.1136/gut.46.2.218 · Cited by 375 · see citing works
Siavoshian, S., Segain, J.-P., Kornprobst, M., Bonnet, C., Cherbut, C., Galmiche, J.-P., & Blottière, H. M. (2000) · Gut · doi:10.1136/gut.46.4.507 · Cited by 277 · see citing works
Self-citationPerrais, M., Pigny, P., Copin, M., Aubert, J., & SEUNINGEN, I. V. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204862200 · Cited by 271 · see citing works
Self-citationMolecular analysis of the effect of short-chain fatty acids on intestinal cell proliferation
Blottière, H. M., Buecher, B., Galmiche, J.-P., & Cherbut, C. (2003) · Proceedings of The Nutrition Society · doi:10.1079/pns2002215 · Cited by 239 · see citing works
Self-citationCell signaling through membrane mucins
Carraway, K. L., Palau, V. E., Haq, B., & Carraway, C. A. C. (2002) · BioEssays · doi:10.1002/bies.10201 · Cited by 234 · see citing works
Colonic mucin synthesis is increased by sodium butyrate.
Finnie, I. A., Dwarakanath, A. D., Taylor, B. A., & Rhodes, J. M. (1995) · Gut · doi:10.1136/gut.36.1.93 · Cited by 231 · see citing works
Mucin gene expression in intestinal epithelial cells in Crohn's disease
Buisine, M.-P., Desreumaux, P., Leteurtre, E., Copin, M.-C., Colombel, J.-F., Porchet, N., & Aubert, J.-P. (2001) · Gut · doi:10.1136/gut.49.4.544 · Cited by 195 · see citing works
Self-citationCRC Handbook of Dietary Fiber in Human Nutrition, Third Edition
Spiller, G. A. (1992) · Cited by 188 · see citing works
Quantitative Analysis of MUC2 Synthesis in Ulcerative Colitis
Tytgat, K. M. A. J., van der Wal, J. G., Einerhand, A. W. C., Büller, H. A., & Dekker, J. P. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1039 · Cited by 176 · see citing works
Short chain fatty acids but not lactate or succinate stimulate mucus release in the rat colon
Shimotoyodome, A., Meguro, S., Hase, T., Tokimitsu, I., & Sakata, T. (2000) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/s1095-6433(00)00183-5 · Cited by 172 · see citing works
Immunohistology of the Antigenic Pattern of a Continuous Cell Line From a Human Colon Tumor
von Kleist, S., Chany, E., Burtin, P., et al. (1975) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/55.3.555 · Cited by 147 · see citing works
Kohlgraf, K. G., Gawron, A. J., Higashi, M., et al. (2003) · PubMed · Cited by 138 · see citing works
A gene expression profile that defines colon cell maturation in vitro.
Mariadason, J. M., Arango, D., Corner, G. A., Aranes, M., Hotchkiss, K. A., Yang, W., & Augenlicht, L. H. (2002) · PubMed · Cited by 125 · see citing works
Guo, W., Lonardo, F., Ueda, T., Kim, T. K., Huvos, A. G., Healey, J. H., & Ladanyi, M. (1999) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19990118)80:2 · Cited by 120 · see citing works
Mariadason, J. M., Velcich, A., Wilson, A. J., Augenlicht, L. H., & Gibson, P. R. (2001) · Gastroenterology · doi:10.1053/gast.2001.22472 · Cited by 118 · see citing works
Aberrant expression of a human mucin gene (MUC5AC) in rectosigmoid villous adenoma
Mp, B., Janin, A., Maunoury, V., et al. (1996) · Gastroenterology · doi:10.1053/gast.1996.v110.pm8536891 · Cited by 114 · see citing works
Lee, H.-W., Ahn, D., Crawley, S., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200353200 · Cited by 107 · see citing works
Siavoshian, S., Blottière, H. M., Cherbut, C., & Galmiche, J. P. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6255 · Cited by 103 · see citing works
Self-citationShort Chain Fatty Acids and Colon Cancer
Augenlicht, L. H., Mariadason, J. M., Wilson, A., Arango, D., Yang, W., Heerdt, B. G., & Velcich, A. (2002) · Journal of Nutrition · doi:10.1093/jn/132.12.3804s · Cited by 99 · see citing works
Lessor, T. J., Yoo, J.-Y., Xia, X., Woodford, N., & Hamburger, A. W. (2000) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(200006)183:3 · Cited by 93 · see citing works
Stein, J. M., Zores, M., & Schröder, O. (2000) · European Journal of Nutrition · doi:10.1007/s003940070028 · Cited by 89 · see citing works
The MUC3 Gene Encodes a Transmembrane Mucin and Is Alternatively Spliced
Williams, S. J., Munster, D. J., Quin, R. J., et al. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1001 · Cited by 87 · see citing works
Molecular analysis of short-chain fatty acids on intestinal cell proliferation
Blottière, H. (2003) · Medical Entomology and Zoology · Cited by 87 · see citing works
Self-citationLeschelle, X., Delpal, S., Goubern, M., Blottière, H. M., & Blachier, F. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01731.x · Cited by 79 · see citing works
Self-citationOligosaccharide structures of mucins secreted by the human colonic cancer cell line CL.16E.
Capon, C., LABOISSE, C. L., Wieruszeski, J. M., et al. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41768-1 · Cited by 74 · see citing works
Self-citationVelcich, A., Palumbo, L., Jarry, A., LABOISSE, C. L., Racevskis, J., & Augenlicht, L. H. (1995) · PubMed · Cited by 72 · see citing works
Self-citationAugenlicht, L. H., Shi, L., Mariadason, J. M., LABOISSE, C. L., & Velcich, A. (2003) · Oncogene · doi:10.1038/sj.onc.1206521 · Cited by 67 · see citing works
Self-citationRegulated expression of an intestinal mucin gene in HT29 colonic carcinoma cells
Velcich, A., & Augenlicht, L. H. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85195-5 · Cited by 61 · see citing works
Differential expression of the chromosome 11 mucin genes in colorectal cancer
Sylvester, P. A., Myerscough, N., Warren, B. F., et al. (2001) · The Journal of Pathology · doi:10.1002/path.951 · Cited by 61 · see citing works
The Sp family of transcription factors in the regulation of the human and mouse MUC2 gene promoters.
Aslam, F., Palumbo, L., Augenlicht, L. H., & Velcich, A. (2001) · PubMed · Cited by 54 · see citing works
Identification of genes responsive to sodium butyrate in colonic epithelial cells
Tabuchi, Y., Arai, Y. O., Kondo, T., et al. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00365-0 · Cited by 53 · see citing works
Sakata, T., & Setoyama, H. (1995) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(95)00033-4 · Cited by 52 · see citing works
Charrier, L., Jarry, A., Toquet, C. S., et al. (2002) · PubMed · Cited by 46 · see citing works
Self-citation[MUC genes: a superfamily of genes? Towards a functional classification of human apomucins].
Porchet, N., Mp, B., Desseyn, J., et al. (1999) · PubMed · Cited by 42 · see citing works
Jouany, J. P., & Sénaud, J. (1982) · PubMed · Cited by 40 · see citing works
Porchet, N., Buisine, M., Desseyn, J., et al. (1999) · Journal de la Société de Biologie · doi:10.1051/jbio/1999193010085 · Cited by 33 · see citing works
Self-citationJarry, A., Merlin, D., Velcich, A., et al. (1994) · European Journal of Pharmacology Molecular Pharmacology · doi:10.1016/0922-4106(94)90229-1 · Cited by 31 · see citing works
Self-citationJouany, J. P., & Sénaud, J. (1982) · annales de biologie animale biochimie biophysique · doi:10.1051/rnd:19820602 · Cited by 31 · see citing works
Colonic mucus and ulcerative colitis.
Rhodes, J. M. (1997) · Gut · doi:10.1136/gut.40.6.807 · Cited by 27 · see citing works
Schröder, O., Opritz, J., & Stein, J. M. (2000) · Digestion · doi:10.1159/000007807 · Cited by 25 · see citing works
Regulation of Mucin MUC2 Gene Expression during Colon Carcinogenesis
Gratchev, A. N., Böhm, C., Riede, E., et al. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb11122.x · Cited by 12 · see citing works
Response of HT29 cells to butyrate depends on time of exposure and glucose deprivation
Kučerová, D., Štokrová, J., Korb, J., et al. (2002) · International Journal of Molecular Medicine · doi:10.3892/ijmm.10.6.779 · Cited by 8 · see citing works
Fleming, S. E., & Kobayashi, H. (2001) · CRC Press eBooks · doi:10.1201/9781420038514.ch4.9 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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Rooks, M. G., & Garrett, W. S. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.42 · Cited by 3,409 · see citing works
Review article: the role of butyrate on colonic function
HAMER, H. M., JONKERS, D., VENEMA, K., VANHOUTVIN, S., TROOST, F. J., & BRUMMER, R. ‐. (2008) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2007.03562.x · Cited by 2,721 · see citing works
Short-chain fatty acids: Linking diet, the microbiome and immunity
Mann, E. R., Lam, Y. K., & Uhlig, H. H. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-01014-8 · Cited by 1,595 · see citing works
Microbes, Metabolites, and the Gut-Lung Axis
Dang, A. T., & Marsland, B. J. (2019) · Mucosal Immunology · doi:10.1038/s41385-019-0160-6 · Cited by 1,028 · see citing works
Immunological aspects of intestinal mucus and mucins
Johansson, M. E. V., & Hansson, G. C. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.88 · Cited by 1,007 · see citing works
Bacteria, Colonic Fermentation, and Gastrointestinal Health
Macfarlane, G. T., & Macfarlane, S. (2012) · Journal of AOAC INTERNATIONAL · doi:10.5740/jaoacint.sge_macfarlane · Cited by 970 · see citing works
Nogal, A., Valdes, A. M., & Menni, C. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1897212 · Cited by 917 · see citing works
Postler, T. S., & Ghosh, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.008 · Cited by 876 · see citing works
“…levels of short-chain fatty acids (SCFAs, discussed in detail below), which have been shown in vitro and in vivo to support the integrity of the intestinal mucosa in a variety of ways (Fukuda et al., 2011; Gaudier et al., 2004; Macia et al., 2015; Willemsen et al., 2003; Wrzosek et al., 2013).”
BackgroundMicrobiota and Host Nutrition across Plant and Animal Kingdoms
Hacquard, S., Garrido-Oter, R., González, A., Spaepen, S., Ackermann, G., Lebeis, S., McHardy, A. C., Dangl, J. L., Knight, R., Ley, R., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.009 · Cited by 779 · see citing works
Macfarlane, G. T., & Macfarlane, S. (2011) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e31822fecfe · Cited by 406 · see citing works
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Blacher, E., Levy, M., Tatirovsky, E., & Elinav, E. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601247 · Cited by 354 · see citing works
Gut microbiota role in irritable bowel syndrome: New therapeutic strategies
Distrutti, E., Monaldi, L., Ricci, P., & Fiorucci, S. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i7.2219 · Cited by 320 · see citing works
Spiljar, M., Merkler, D., & Trajkovski, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01353 · Cited by 219 · see citing works
The effects of butyrate enemas on visceral perception in healthy volunteers
Vanhoutvin, S. A. L. W., Troost, F. J., Kilkens, T. O. C., Lindsey, P. J., Hamer, H. M., Jonkers, D. M. A. E., Venema, K., & Brummer, R. ‐. M. (2009) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2009.01324.x · Cited by 171 · see citing works
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Toden, S., Bird, A. R., Topping, D. L., & Conlon, M. A. (2006) · Cancer Biology & Therapy · doi:10.4161/cbt.5.3.2382 · Cited by 113 · see citing works
Colonic butyrate- algesic or analgesic?: Colonic butyrate function
Kannampalli, P., Shaker, R., & Sengupta, J. N. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2011.01775.x · Cited by 50 · see citing works
De Sales-Millán, A., Aguirre-Garrido, J. F., González-Cervantes, R. M., & Velázquez-Aragón, J. A. (2023) · doi:10.20944/preprints202305.1223.v1 · Cited by 44 · see citing works
- Authors
- Gaudier, E., Jarry, A., Blottière, H. M., de Coppet, P., Buisine, M. P., Aubert, J. P., Laboisse, C., Cherbut, C., & Hoebler, C.
- Affiliations
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Nantes Université (FR)
- Département Alimentation Humaine (FR)
- Inserm (FR)
- PhysioPathologie des Adaptations Nutritionnelles (FR)
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2004-12
- Volume
- 287
- Issue
- 6
- Pages
- G1168-G1174
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2136633470
- Cited by
- 365
- References
- 54
- Citations by year
- 2026: 22 · 2025: 34 · 2024: 30 · 2023: 37 · 2022: 32 · 2021: 37 · 2020: 21 · 2019: 19 · 2018: 12 · 2017: 21 · 2016: 15 · 2015: 7 · 2014: 7 · 2013: 12 · 2012: 13
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- World Cancer Research Fund International
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Health Sciences › Nursing › Nutrition and Dietetics › Microbial Metabolites in Food Biotechnology
- Keywords
- butyrate, MUC genes, mucin, goblet cells, colonic epithelium, glucose deprivation, MUC3, MUC5B, MUC5AC, MUC2, gene expression regulation, short-chain fatty acids, mucus layer
- MeSH terms
- Butyrates, Culture Media, Dose-Response Relationship, Drug, Enzyme Inhibitors, Fatty Acids, Gene Expression Regulation, Glucose, Humans, Hydrogen-Ion Concentration, Hydroxamic Acids, Intestinal Mucosa, L-Lactate Dehydrogenase, Mucins, RNA, Messenger, Time Factors, Cell Death, HT29 Cells, Reverse Transcriptase Polymerase Chain Reaction, Goblet Cells, Mucin-2, Mucin-3
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