Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier
Abstract
Production of short-chain fatty acids (SCFA) in the intestinal lumen may play an important role in the maintenance of the intestinal barrier. However, overproduction/accumulation of SCFA in the bowel may be toxic to the intestinal mucosa and has been hypothesized to play a role in the pathogenesis of neonatal necrotizing enterocolitis (NEC). By using a Caco-2 cell monolayer model of intestinal barrier, we report here that the effect of butyrate on the intestinal barrier is paradoxical. Butyrate at a low concentration (2 mM) promotes intestinal barrier function as measured by a significant increase in transepithelial electrical resistance (TER) and a significant decrease in inulin permeability. Butyrate at a high concentration (8 mM) reduces TER and increases inulin permeability significantly. Butyrate induces apoptosis and reduces the number of viable Caco-2 cells in a dose-dependent manner. Intestinal barrier function impairment induced by high concentrations of butyrate is most likely related to butyrate-induced cytotoxicity due to apoptosis. We conclude that the effect of butyrate on the intestinal barrier is paradoxical; i.e. whereas low concentrations of butyrate may be beneficial in promoting intestinal barrier function, excessive butyrate may induce severe intestinal epithelial cell apoptosis and disrupt intestinal barrier.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Butyrate improved barrier function at lower doses, but reduced barrier function at higher doses in Caco-2 cells.
“Similarly, butyrate improved barrier function at lower doses, but reduced barrier function at higher doses in Caco-2 cells.80”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [80]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104 · see citing works
Utilization 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
Sakata, T. (1987) · British Journal Of Nutrition · doi:10.1079/bjn19870073 · Cited by 659 · see citing works
Sangild, P. T., Siggers, R. H., Schmidt, M. H., et al. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.02.026 · Cited by 274 · see citing works
Madara, J. (1990) · The Journal of Membrane Biology · doi:10.1007/bf01868675 · Cited by 242 · see citing works
Fate of soluble carbohydrate in the colon of rats and man.
Bond, J. H., & Levitt, M. D. (1976) · Journal of Clinical Investigation · doi:10.1172/jci108383 · Cited by 198 · see citing works
Jones, B. A., & Gores, G. J. (1997) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1997.273.6.g1174 · Cited by 187 · see citing works
Effect of short-chain fatty acids on paracellular permeability in Caco-2 intestinal epithelium model
Mariadason, J. M., Barkla, D. H., & Gibson, P. R. (1997) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1997.272.4.g705 · Cited by 182 · see citing works
Basuroy, S., Sheth, P., Kuppuswamy, D., Balasubramanian, S., Ray, R. M., & Rao, R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211710200 · Cited by 181 · see citing works
Udall, J. N., Pang, K. Y., Fritze, L. M. S., Kleinman, R. E., & Walker, W. A. (1981) · Pediatric Research · doi:10.1203/00006450-198103000-00008 · Cited by 175 · see citing works
Butyrate induced Caco-2 cell apoptosis is mediated via the mitochondrial pathway
Ruemmele, F. M., Schwartz, S., Seidman, E. G., Dionne, S., Levy, E. H., & Lentze, M. J. (2002) · Gut · doi:10.1136/gut.52.1.94 · Cited by 162 · see citing works
Schumann, A., Nutten, S., Donnicola, D., Comelli, E. M., Mansourian, R., Cherbut, C., Corthesy-Theulaz, I. E., & García‐Ródenas, C. L. (2005) · Physiological Genomics · doi:10.1152/physiolgenomics.00057.2005 · Cited by 156 · see citing works
Total parenteral nutrition adversely affects gut barrier function in neonatal piglets
Kansagra, K., Stoll, B., Rognerud, C. L., Niinikoski, H., Ou, C., Harvey, R. B., & Burrin, D. G. (2003) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00243.2003 · Cited by 144 · see citing works
Koruda, M., Rh, R., Bliss, D., Hastings, J. C., Rombeau, J. L., & Settle, R. G. (1990) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/51.4.685 · Cited by 133 · see citing works
Short Chain Fatty Acid Regulation of Signaling Genes Expressed by the Intestinal Epithelium
Sanderson, I. R. (2004) · Journal of Nutrition · doi:10.1093/jn/134.9.2450s · Cited by 115 · see citing works
Permeability of human HT‐29/B6 colonic epithelium as a function of apoptosis
Bojarski, C., Gitter, A. H., Bendfeldt, K., et al. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.00541.x · Cited by 108 · see citing works
Ismail, A. S., & Hooper, L. V. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00203.2005 · Cited by 103 · see citing works
Mandal, M., Olson, D. J., Sharma, T., Vadlamudi, R. K., & Kumar, R. (2001) · Gastroenterology · doi:10.1053/gast.2001.20897 · Cited by 103 · see citing works
Short-chain fatty acids promote the migration of colonic epithelial cells in vitro
Wilson, A., & Gibson, P. (1997) · Gastroenterology · doi:10.1053/gast.1997.v113.pm9247468 · Cited by 101 · see citing works
Rouwet, E. V., Heineman, E., Buurman, W. A., ter Riet, G., Ramsay, G., & Blanco, C. E. (2002) · Pediatric Research · doi:10.1203/00006450-200201000-00012 · Cited by 95 · see citing works
Udall, J. N., Colony, P. C., Fritze, L. M. S., et al. (1981) · Pediatric Research · doi:10.1203/00006450-198103000-00009 · Cited by 88 · see citing works
Necrotizing Enterocolitis: Intraluminal Biochemistry in Human Neonates and a Rabbit Model
Clark, D. A., Thompson, J. E., Weiner, L. B., et al. (1985) · Pediatric Research · doi:10.1203/00006450-198509000-00010 · Cited by 85 · see citing works
Modulation of distal colonic epithelial barrier function by dietary fibre in normal rats
Mariadason, J. M., Catto‐Smith, A. G., & Gibson, P. R. (1999) · Gut · doi:10.1136/gut.44.3.394 · Cited by 84 · see citing works
Too much short chain fatty acids cause neonatal necrotizing enterocolitis
Lin, J. (2003) · Medical Hypotheses · doi:10.1016/s0306-9877(03)00333-5 · Cited by 83 · see citing works
Self-citationLin, J., Nafday, S. M., Chauvin, S. N., Magid, M. S., Pabbatireddy, S., Holzman, I. R., & Babyatsky, M. W. (2002) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-200210000-00016 · Cited by 79 · see citing works
Self-citationCrew, T. E. (2000) · Carcinogenesis · doi:10.1093/carcin/21.1.69 · Cited by 74 · see citing works
Short-Chain Fatty Acids Induce Colonic Mucosal Injury in Rats with Various Postnatal Ages
Nafday, S. M., Chen, W., Peng, L., Babyatsky, M. W., Holzman, I. R., & Lin, J. (2004) · Pediatric Research · doi:10.1203/01.pdr.0000150721.83224.89 · Cited by 73 · see citing works
Self-citationEffect of butyrate on paracellular permeability in rat distal colonic mucosa ex vivo
Mariadason, J. M., Kilias, D., Catto‐Smith, A. G., & Gibson, P. R. (1999) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.1999.01972.x · Cited by 58 · see citing works
Jones, S. A., Butler, R. N., Sanderson, I. R., et al. (2003) · Experimental Cell Research · doi:10.1016/j.yexcr.2003.08.005 · Cited by 40 · see citing works
Early establishment of epithelial apoptosis in the developing human small intestine
Vachon, P. H., Cardin, É., Harnois, C., et al. (2000) · The International Journal of Developmental Biology · doi:10.1387/ijdb.11216457 · Cited by 39 · see citing works
Cytotoxicity of organic acids produced by anaerobic intestinal bacteria on cultured epithelial cells
Sakurazawa, T., & Ohkusa, T. (2005) · Journal of Gastroenterology · doi:10.1007/s00535-005-1594-z · Cited by 38 · see citing works
Nankova, B. B., Chua, J., Mishra, R., Kobasiuk, C. D., & Gamma, E. F. L. (2003) · Pediatric Research · doi:10.1203/00006450-200301000-00019 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The role of short-chain fatty acids in microbiota–gut–brain communication
Dalile, B., Van Oudenhove, L., Vervliet, B., & Verbeke, K. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0157-3 · Cited by 3,357 · 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
Human nutrition, the gut microbiome and the immune system
Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L., & Gordon, J. I. (2011) · Nature · doi:10.1038/nature10213 · Cited by 2,588 · see citing works
The gut microbiota influences blood-brain barrier permeability in mice
Braniste, V., Al-Asmakh, M., Kowal, C., Anuar, F., Abbaspour, A., Tóth, M., Korecka, A., Bakocevic, N., Ng, L. G., Kundu, P., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009759 · Cited by 2,530 · see citing works
Peng, L., Li, Z.-R., Green, R. S., Holzmanr, I. R., & Lin, J. (2009) · The Journal of Nutrition · doi:10.3945/jn.109.104638 · Cited by 2,130 · see citing works
Self-citationCausal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases
Sanna, S., van Zuydam, N. R., Mahajan, A., Kurilshikov, A., Vich Vila, A., Võsa, U., Mujagic, Z., Masclee, A. A. M., Jonkers, D. M. A. E., Oosting, M., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0350-x · Cited by 1,539 · 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
Kelly, J. R., Kennedy, P. J., Cryan, J. F., Dinan, T. G., Clarke, G., & Hyland, N. P. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00392 · Cited by 1,110 · see citing works
The neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis
Stilling, R. M., van de Wouw, M., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2016) · Neurochemistry International · doi:10.1016/j.neuint.2016.06.011 · Cited by 891 · see citing works
Obesity, inflammation, and the gut microbiota
Cox, A. J., West, N. P., & Cripps, A. W. (2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(14)70134-2 · Cited by 869 · see citing works
Regulation of Intestinal Barrier Function by Microbial Metabolites
Ghosh, S., Whitley, C. S., Haribabu, B., & Jala, V. R. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.02.007 · Cited by 835 · see citing works
Brown, C. T., Davis-Richardson, A. G., Giongo, A., Gano, K. A., Crabb, D. B., Mukherjee, N., Casella, G., Drew, J. C., Ilonen, J., Knip, M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025792 · Cited by 778 · see citing works
Michielan, A., & D’Incà, R. (2015) · Mediators of Inflammation · doi:10.1155/2015/628157 · Cited by 709 · 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
Gut microbiota, obesity and diabetes
Patterson, E., Ryan, P. M., Cryan, J. F., Dinan, T. G., Ross, R. P., Fitzgerald, G. F., & Stanton, C. (2016) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2015-133285 · Cited by 552 · see citing works
Feeding the microbiota–gut–brain axis: Diet, microbiome, and neuropsychiatry
Sandhu, K. V., Sherwin, E., Schellekens, H., Stanton, C., Dinan, T. G., & Cryan, J. F. (2017) · Translational Research · doi:10.1016/j.trsl.2016.10.002 · Cited by 491 · see citing works
Yan, H., & Ajuwon, K. M. (2017) · PLOS ONE · doi:10.1371/journal.pone.0179586 · Cited by 456 · see citing works
Macfarlane, G. T., & Macfarlane, S. (2011) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e31822fecfe · Cited by 406 · see citing works
The Immunomodulatory Functions of Butyrate
Siddiqui, M. T., & Cresci, G. A. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s300989 · Cited by 381 · see citing works
Gut-brain Axis and migraine headache: a comprehensive review
On behalf of the School of Advanced Studies of the European Headache Federation (EHF-SAS), Arzani, M., Jahromi, S. R., Ghorbani, Z., Vahabizad, F., Martelletti, P., Ghaemi, A., Sacco, S., & Togha, M. (2020) · The Journal of Headache and Pain · doi:10.1186/s10194-020-1078-9 · Cited by 366 · see citing works
Irritable bowel syndrome: a gut microbiota-related disorder?
Bhattarai, Y., Muniz Pedrogo, D. A., & Kashyap, P. C. (2017) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00338.2016 · Cited by 294 · see citing works
Collino, S., Montoliu, I., Martin, F.-P. J., Scherer, M., Mari, D., Salvioli, S., Bucci, L., Ostan, R., Monti, D., Biagi, E., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056564 · Cited by 270 · see citing works
Mao, S., Huo, W., & Zhu, W. (2016) · Environmental Microbiology · doi:10.1111/1462-2920.12724 · Cited by 257 · see citing works
Causality of small and large intestinal microbiota in weight regulation and insulin resistance
Scheithauer, T. P. M., Dallinga-Thie, G. M., de Vos, W. M., Nieuwdorp, M., & van Raalte, D. H. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.06.002 · Cited by 188 · see citing works
“For example, butyrate is mainly used as an energy source for colonic epithelial cells and, at low doses, improves the intestinal barrier function [37] but has also been implicated in regulation of (murine) insulin sensitivity [38].”
BackgroundResultDiao, H., Jiao, A. R., Yu, B., Mao, X. B., & Chen, D. W. (2019) · Genes & Nutrition · doi:10.1186/s12263-019-0626-x · Cited by 139 · see citing works
Liver-on-a-Chip models of fatty liver disease
Hassan, S., Sebastian, S., Maharjan, S., Lesha, A., Carpenter, A., Liu, X., Xie, X., Livermore, C., Zhang, Y. S., & Zarrinpar, A. (2020) · Hepatology · doi:10.1002/hep.31106 · Cited by 127 · see citing works
Nielsen, D. S. G., Jensen, B. B., Theil, P. K., Nielsen, T. S., Knudsen, K. E. B., & Purup, S. (2018) · Journal of Functional Foods · doi:10.1016/j.jff.2017.10.023 · Cited by 115 · see citing works
Ikeda-Ohtsubo, W., Brugman, S., Warden, C. H., Rebel, J. M. J., Folkerts, G., & Pieterse, C. M. J. (2018) · Frontiers in Nutrition · doi:10.3389/fnut.2018.00090 · Cited by 115 · see citing works
Featured article: Structure moderation of gut microbiota in liraglutide-treated diabetic male rats
Zhang, Q., Xiao, X., Zheng, J., Li, M., Yu, M., Ping, F., Wang, T., & Wang, X. (2018) · Experimental Biology and Medicine · doi:10.1177/1535370217743765 · Cited by 101 · see citing works
Gutiérrez‐Repiso, C., Hernández‐García, C., García‐Almeida, J. M., Bellido, D., Martín‐Núñez, G. M., Sánchez‐Alcoholado, L., Alcaide‐Torres, J., Sajoux, I., Tinahones, F. J., & Moreno‐Indias, I. (2019) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900167 · Cited by 80 · see citing works
Salami, M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.613120 · Cited by 67 · see citing works
Son, Y. S., Ki, S. J., Thanavel, R., Kim, J., Lee, M., Kim, J., Jung, C., Han, T., Cho, H., Ryu, C., et al. (2020) · The FASEB Journal · doi:10.1096/fj.202000063r · Cited by 45 · see citing works
The Role of Fatty Acid Metabolites in Vaginal Health and Disease: Application to Candidiasis
Baldewijns, S., Sillen, M., Palmans, I., Vandecruys, P., Van Dijck, P., & Demuyser, L. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.705779 · Cited by 44 · see citing works
Effects of valerate on intestinal barrier function in cultured Caco-2 epithelial cell monolayers
Gao, G., Zhou, J., Wang, H., Ding, Y., Zhou, J., Chong, P. H., Zhu, L., Ke, L., Wang, X., Rao, P., et al. (2022) · Molecular Biology Reports · doi:10.1007/s11033-021-06991-w · Cited by 40 · see citing works
Zhu, X., Li, Y., Jiang, Y., Zhang, J., Duan, R., Liu, L., Liu, C., Xu, X., Yu, L., Wang, Q., et al. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.665406 · Cited by 32 · see citing works
The role of microbiota in allogeneic hematopoietic stem cell transplantation
Chang, C.-C., Hayase, E., & Jenq, R. R. (2021) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2021.1872541 · Cited by 20 · see citing works
- Authors
- Peng, L., He, Z., Chen, W., Holzman, I. R., & Lin, J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Lin, Jing
- Venue
- Pediatric Research
- Published
- 2007-01
- Volume
- 61
- Issue
- 1
- Pages
- 37-41
- ISSN
- 0031-3998 (ISSN-L)
- 1530-0447
- OpenAlex
- W2004506978
- Cited by
- 518
- References
- 32
- Citations by year
- 2026: 39 · 2025: 49 · 2024: 32 · 2023: 40 · 2022: 46 · 2021: 54 · 2020: 46 · 2019: 36 · 2018: 37 · 2017: 29 · 2016: 24 · 2015: 17 · 2014: 21 · 2013: 10 · 2012: 10
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r03hd049881-02)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (1-R03-HD049881)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- butyrate, intestinal barrier function, short-chain fatty acids, Caco-2 cell monolayers, transepithelial electrical resistance, inulin permeability, apoptosis, necrotizing enterocolitis, dose-dependent effects
- MeSH terms
- Butyrates, Dose-Response Relationship, Drug, Humans, Intestinal Mucosa, Inulin, Models, Biological, Permeability, Electric Impedance, Apoptosis, Caco-2 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
