Butyrate modulating effects on pro-inflammatory pathways in human intestinal epithelial cells
Abstract
Butyrate acts as energy source for intestinal epithelial cells and as key mediator of several immune processes, modulating gene expression mainly through histone deacetylation inhibition. Thanks to these effects, butyrate has been proposed for the treatment of many intestinal diseases. Aim of this study was to investigate the effect of butyrate on the expression of a large series of target genes encoding proteins involved in pro-inflammatory pathways. We performed quantitative real-time-PCR analysis of the expression of 86 genes encoding proteins bearing to pro-inflammatory pathways, before and after butyrate exposure, in primary epithelial cells derived from human small intestine and colon. Butyrate significantly down-regulated the expression of genes involved in inflammatory response, among which nuclear factor kappa beta, interferon-gamma, Toll like 2 receptor and tumour necrosis factor-alpha. Further confirmations of these data, including studies at protein level, would support the use of butyrate as effective therapeutic strategy in intestinal inflammatory disorders.
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Butyrate downregulates expression of genes involved in inflammatory pathways in non-inflamed intestinal tissue.
“In addition, butyrate has also been shown to downregulate the expression of genes involved in inflammatory pathways in non-inflamed intestinal tissue [37].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [37]
Preclinical and clinical studies have demonstrated a link between the Standard American diet and an increase in markers of systemic immune activation, a phenomenon referred to as metabolic endotoxemia.
“A number of preclinical and clinical studies have demonstrated a link between the Standard American diet (SAD), and an increase in markers of systemic immune activation, a phenomenon referred to as metabolic endotoxemia [37, 40]”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [37]
Cites
Frank, D. N., St. Amand, A. L., Feldman, R. A., Boedeker, E. C., Harpaz, N., & Pace, N. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706625104 · Cited by 4,611 · 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
Potential beneficial effects of butyrate in intestinal and extraintestinal diseases
Canani, R. B. (2011) · World Journal of Gastroenterology · doi:10.3748/wjg.v17.i12.1519 · Cited by 1,381 · see citing works
Self-citationDonohoe, D. R., Collins, L. B., Wali, A., Bigler, R., Sun, W., & Bultman, S. J. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.08.033 · Cited by 993 · see citing works
From the gut to the peripheral tissues: the multiple effects of butyrate
Guilloteau, P., Martin, L., Eeckhaut, V., Ducatelle, R., Zabielski, R., & Immerseel, F. V. (2010) · Nutrition Research Reviews · doi:10.1017/s0954422410000247 · Cited by 813 · see citing works
Ito, H., Takazoe, M., Fukuda, Y., Hibi, T., Kusugami, K., Andoh, A., Matsumoto, T., Yamamura, T., Azuma, J., & Nishimoto, N. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.01.012 · Cited by 636 · see citing works
Butyrate Inhibits NF-κB Activation in Lamina Propria Macrophages of Patients with Ulcerative Colitis
Lührs, H., Gerke, T., Müller, J. G., Melcher, R., Schauber, J., Boxberger, F., Scheppach, W. M., & Menzel, T. (2002) · Scandinavian Journal of Gastroenterology · doi:10.1080/003655202317316105 · Cited by 468 · see citing works
Schenk, M., Bouchon, A., Seibold, F., & Mueller, C. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30602 · Cited by 365 · see citing works
Inflammatory Bowel Disease: Mechanisms, Redox Considerations, and Therapeutic Targets
Biasi, F., Leonarduzzi, G., Oteiza, P. I., & Poli, G. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4530 · Cited by 301 · see citing works
(2008) · PubMed · Cited by 274 · see citing works
Zhou, D. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.10.2003 · Cited by 269 · see citing works
Master regulator of intestinal disease: IL-6 in chronic inflammation and cancer development
Waldner, M. J., & Neurath, M. F. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2013.12.003 · Cited by 193 · see citing works
Ock, C. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i4.302 · Cited by 150 · see citing works
Felice, C., Lewis, A., Armuzzi, A., Lindsay, J., & Silver, A. R. (2014) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13008 · Cited by 120 · see citing works
Dual roles for HMGB1: DNA binding and cytokine
Czura, C. J., Wang, H., & Tracey, K. J. (2001) · Journal of Endotoxin Research · doi:10.1177/09680519010070041401 · Cited by 120 · see citing works
Vitali, R., Stronati, L., Negroni, A., Nardo, G. D., Pierdomenico, M., Giudice, E. D., Rossi, P., & Cucchiara, S. (2011) · The American Journal of Gastroenterology · doi:10.1038/ajg.2011.231 · Cited by 115 · see citing works
Butyrate as an effective treatment of congenital chloride diarrhea
Canani, R. B., Terrin, G., Cirillo, P., Castaldo, G., Salvatore, F., Cardillo, G., Coruzzo, A., & Troncone, R. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.03.071 · Cited by 113 · see citing works
Self-citationHigh mobility group box 1 protein, a cue for stem cell recruitment
Palumbo, R., & Bianchi, M. E. (2004) · Biochemical Pharmacology · doi:10.1016/j.bcp.2004.03.048 · Cited by 98 · see citing works
SODIUM BUTYRATE PREVENTS LETHALITY OF SEVERE SEPSIS IN RATS
Zhang, L., Yao, Y.-M., Lu, J.-Q., Yan, X.-J., Yu, Y., & Sheng, Z. (2007) · Shock · doi:10.1097/shk.0b013e31802e3f4c · Cited by 76 · see citing works
Gao, M., Bu, L., Ma, Y., & Liu, D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065641 · Cited by 61 · see citing works
Górka, P., Pietrzak, P., Kotunia, A., et al. (2013) · Journal of Dairy Science · doi:10.3168/jds.2013-7251 · Cited by 58 · see citing works
Enteric microbiota leads to new therapeutic strategies for ulcerative colitis
Chen, W.-X. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i42.15657 · Cited by 51 · see citing works
Steppe, M., Nieuwerburgh, F. V., Vercauteren, G., Boyen, F., Eeckhaut, V., Deforce, D. L. D., Haesebrouck, F., Ducatelle, R., & Immerseel, F. V. (2014) · Food and Chemical Toxicology · doi:10.1016/j.fct.2014.06.024 · Cited by 45 · see citing works
TREM-1 inhibition attenuates inflammation and tumor within the colon
Zhou, J., Chai, F., Lu, G. X., Hang, G., Chen, C., Chen, X., & Shi, J. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.06.009 · Cited by 43 · see citing works
Genotype-dependency of butyrate efficacy in children with congenital chloride diarrhea
Canani, R. B., Terrin, G., Elce, A., Pezzella, V., Heinz‐Erian, P., Pedrolli, A., Centenari, C., Amato, F., Tomaiuolo, R., Calignano, A., et al. (2013) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-8-194 · Cited by 42 · see citing works
Self-citationSodium butyrate protects against toxin-induced acute liver failure in rats
Yang, F., Wang, L.-K., Li, X., Wang, L.-W., Han, X.-Q., & Gong, Z. (2014) · Hepatobiliary & pancreatic diseases international · doi:10.1016/s1499-3872(14)60044-8 · Cited by 27 · see citing works
The effect of oxidative stress upon the intestinal epithelial uptake of butyrate
Gonçalves, P., Gregório, I., Catarino, T. A., et al. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.11.029 · Cited by 26 · see citing works
Gene-Diet Interactions on Colorectal Cancer Risk
Wang, L., Kuo, C., Huang, Y., Stoner, G. D., & Lechner, J. F. (2012) · Current Nutrition Reports · doi:10.1007/s13668-012-0023-1 · Cited by 25 · see citing works
Danger-Associated Molecular Patterns and Inflammatory Bowel Disease: Is There a Connection?
Mueller, C. (2012) · Digestive Diseases · doi:10.1159/000342600 · Cited by 24 · see citing works
Stojčev, Z., Krokowicz, Ł., Krokowicz, P., et al. (2013) · International Journal of Colorectal Disease · doi:10.1007/s00384-013-1682-0 · Cited by 13 · see citing works
Kimura, R., Takahashi, N., Goto, T., Murota, K., & Kawada, T. (2013) · Obesity Research & Clinical Practice · doi:10.1016/j.orcp.2013.05.005 · Cited by 12 · see citing works
Importance of monovalent ions for the fast axonal transport of proteins
Lavoie, D. (1981) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y81-006 · Cited by 8 · see citing works
Analysis of inflammatory signals in J apanese children with C rohn's disease
Fujitake, Y., Ohtsuka, Y., Ikuse, T., et al. (2013) · Pediatrics International · doi:10.1111/ped.12159 · Cited by 5 · see citing works
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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
Impact of Diet-Modulated Butyrate Production on Intestinal Barrier Function and Inflammation
Bach Knudsen, K. E., Lærke, H. N., Hedemann, M. S., Nielsen, T. S., Ingerslev, A. K., Gundelund Nielsen, D. S., Theil, P. K., Purup, S., Hald, S., Schioldan, A. G., et al. (2018) · Nutrients · doi:10.3390/nu10101499 · Cited by 572 · see citing works
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Siddiqui, M. T., & Cresci, G. A. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s300989 · Cited by 381 · see citing works
Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders
Horn, J., Mayer, D. E., Chen, S., & Mayer, E. A. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01922-0 · Cited by 193 · see citing works
Checa-Ros, A., Jeréz-Calero, A., Molina-Carballo, A., Campoy, C., & Muñoz-Hoyos, A. (2021) · Nutrients · doi:10.3390/nu13010249 · Cited by 164 · see citing works
Beneficial effects of butyrate on brain functions: A view of epigenetic
Alpino, G. D. C. Á., Pereira-Sol, G. A., Dias, M. D. M. E., Aguiar, A. S. D., & Peluzio, M. D. C. G. (2024) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2137776 · Cited by 110 · see citing works
Scannell, N., Villani, A., Moran, L., & Mantzioris, E. (2025) · Proceedings of the Nutrition Society · doi:10.1017/s0029665124007584 · Cited by 12 · see citing works
- Authors
- Elce, A., Amato, F., Zarrilli, F., Calignano, A., Troncone, R., Castaldo, G., & Canani, R. B.
- Affiliations
- Pegaso University (IT)
- CEINGE Biotecnologie Avanzate Franco Salvatore (Italy) (IT)
- University of Molise (IT)
- University of Naples Federico II (IT)
- Venue
- Beneficial Microbes
- Publisher
- Walter de Gruyter GmbH
- Published
- 2017-10-13
- Volume
- 8
- Issue
- 5
- Pages
- 841-848
- ISSN
- 1876-2883 (ISSN-L)
- 1876-2891
- OpenAlex
- W2752199747
- Cited by
- 81
- References
- 33
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 11 · 2023: 10 · 2022: 18 · 2021: 9 · 2020: 8 · 2019: 6 · 2018: 1
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Beneficial Microbes (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
- Funders
- Regione Campania
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- butyrate, intestinal epithelial cells, pro-inflammatory pathways, gene expression regulation, NF-κB, interferon-gamma, TLR2, TNF-α, histone deacetylation, intestinal inflammation, short-chain fatty acids, small intestine, colon
- MeSH terms
- Anti-Inflammatory Agents, Butyrates, Cells, Cultured, Colon, Epithelial Cells, Humans, Immunologic Factors, Intestine, Small, Gene Expression Profiling, Real-Time Polymerase Chain Reaction
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