Effects of valerate on intestinal barrier function in cultured Caco-2 epithelial cell monolayers
Abstract
Background Short-chain fatty acids (SCFAs) are a group of microbial metabolites of undigested dietary fiber, protein and unabsorbed amino acids in the colon, well-known for their gut health promoting benefits. A relatively high intestinal level of valerate was found in the healthy human subjects. However, the intestinal protection effects and the underlying mechanism of valerate are waiting to be verified and elucidated.Methods and results In the present study, valerate, a SCFAs mainly converted from proteins or amino acids, was demonstrated to promote intestinal barrier function at its physiological concentrations of 0-4 mM in the Caco-2 cell monolayer model of intestinal barrier using transepithelial electrical resistance (TEER) assay and paracellular permeability assay. Valerate achieved the maximum increase in the TEER at 2 mM and reduced the paracellular permeability. Its intestinal barrier function promoting activity is similar to that of butyrate, with a broader range of effective concentrations than the later. Through western blot analysis, this activity is linked to the valerate-induced AMPK activation and tight junctions (TJs) assembly, but not to the reinforced expression of TJs related proteins.Conclusions It provides direct experimental evidence supporting valerate's function in intestinal health, implying the once under-valued function of valerate and its amino acid precursors. The valerate's role in regulating intestine homeostasis and its possible synergetic effects with other SCFAs warranted to be further investigated.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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 and valerate promote intestinal barrier function, which prevents the translocation of pathogens from the intestine into the bloodstream.
“Butyrate and valerate promote intestinal barrier function, which prevents the translocation of pathogens from the intestine into the bloodstream [45–48].”
From Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization (2023) · cites this paper as [45]
Cites
Santos, A. G., da Rocha, G. O., & de Andrade, J. B. (2019) · Scientific Reports · doi:10.1038/s41598-018-37186-2 · Cited by 8,495 · see citing works
Parada Venegas, D., De la Fuente, M. K., Landskron, G., González, M. J., Quera, R., Dijkstra, G., Harmsen, H. J. M., Faber, K. N., & Hermoso, M. A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00277 · Cited by 3,820 · see citing works
Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health
Ríos-Covián, D., Ruas‐Madiedo, P., Margollés, A., Gueimonde, M., Reyes‐Gavilán, C. G. D. L., & Salazar, N. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00185 · Cited by 2,215 · 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
Correlation between the human fecal microbiota and depression
Naseribafrouei, A., Hestad, K., Avershina, E., Sekelja, M., Linløkken, A., Wilson, R., & Rudi, K. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12378 · Cited by 1,044 · see citing works
Donohoe, 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
Wang, H.-B., Wang, P.-Y., Wang, X., Wan, Y.-L., & Liu, Y.-C. (2012) · Digestive Diseases and Sciences · doi:10.1007/s10620-012-2259-4 · Cited by 827 · see citing works
Self-citationRole of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health
Chambers, E. S., Preston, T., Frost, G., & Morrison, D. J. (2018) · Current Nutrition Reports · doi:10.1007/s13668-018-0248-8 · Cited by 691 · see citing works
Peng, L., He, Z., Chen, W., Holzman, I. R., & Lin, J. (2007) · Pediatric Research · doi:10.1203/01.pdr.0000250014.92242.f3 · Cited by 518 · see citing works
Luu, M., Pautz, S., Kohl, V., Singh, R., Romero, R., Lucas, S., Hofmann, J., Raifer, H., Vachharajani, N., Carrascosa, L. C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08711-2 · Cited by 508 · see citing works
Altered gut microbiota and short chain fatty acids in Chinese children with autism spectrum disorder
Liu, S., Li, E., Sun, Z., Fu, D., Duan, G., Jiang, M., Yu, Y., Mei, L., Yang, P., Tang, Y., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-36430-z · Cited by 457 · see citing works
Lee, B., Moon, K. M., & Kim, C. Y. (2018) · Journal of Immunology Research · doi:10.1155/2018/2645465 · Cited by 405 · see citing works
Ríos-Covián, D., González, S., Nogacka, A. M., Arboleya, S., Salazar, N., Gueimonde, M., & Reyes-Gavilán, C. G. D. L. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.00973 · Cited by 320 · see citing works
Charlton, A. J., May, C., Luikinga, S. J., Burrows, E. L., Kim, J. H., Lawrence, A. J., & Perry, C. J. (2019) · Scientific Reports · doi:10.1038/s41598-019-55095-w · Cited by 315 · see citing works
Regulation of epithelial tight junction assembly and disassembly by AMP-activated protein kinase
Zheng, B., & Cantley, L. C. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610157104 · Cited by 275 · see citing works
Jha, R., & Berrocoso, J. D. (2015) · Animal Feed Science and Technology · doi:10.1016/j.anifeedsci.2015.12.002 · Cited by 272 · see citing works
AMP-activated protein kinase regulates the assembly of epithelial tight junctions
Zhang, L., Li, J., Young, L. H., & Caplan, M. J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608531103 · Cited by 258 · see citing works
Self-citationYuille, S., Reichardt, N., Panda, S., Dunbar, H., & Mulder, I. E. (2018) · PLOS ONE · doi:10.1371/journal.pone.0201073 · Cited by 257 · see citing works
Elamin, E. E., Masclee, A., Jan, D., Pieters, H., & Jonkers, D. M. A. E. (2013) · Journal of Nutrition · doi:10.3945/jn.113.179549 · Cited by 237 · see citing works
Short-Chain Fatty Acids in the Normal Human Feces
Høverstad, T., FAUSA, O., BJØRNEKLETT, A., & Bøhmer, T. (1984) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.1984.12005738 · Cited by 200 · see citing works
McDonald, J. A. K., Mullish, B. H., Pechlivanis, A., Liu, Z., Brignardello, J., Kao, D. H., Holmes, E. C., Li, J. V., Clarke, T. B., Thursz, M. R., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.07.014 · Cited by 189 · see citing works
Gut microbiome and its role in cardiovascular diseases
Ahmadmehrabi, S., & Tang, W. H. W. (2017) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000445 · Cited by 185 · 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
Iino, T., Mori, K., Tanaka, K., Suzuki, K., & Harayama, S. (2007) · INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY · doi:10.1099/ijs.0.64717-0 · Cited by 168 · see citing works
Gomes, S., Oliveira, C. S., Azevedo‐Silva, J., Casanova, M. R., Barreto, J., Pereira, H., Chaves, S. R., Rodrigues, L. R., Casal, M., Côrte‐Real, M., et al. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867325666180530102050 · Cited by 116 · see citing works
Chen, L., Wang, J., You, Q., He, S., Meng, Q., Gao, J., Wu, X., Shen, Y., Sun, Y., Wu, X., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00761 · Cited by 108 · see citing works
Bilotta, A. J., & Cong, Y. (2019) · Precision Clinical Medicine · doi:10.1093/pcmedi/pbz008 · Cited by 108 · see citing works
Mortensen, P. B., Holtug, K., Bonnén, H., & Clausen, M. R. (1990) · Gastroenterology · doi:10.1016/0016-5085(90)90825-l · Cited by 106 · see citing works
An Insight Into the Intestinal Web of Mucosal Immunity, Microbiota, and Diet in Inflammation
Yap, Y. A., & Mariño, E. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02617 · Cited by 97 · see citing works
Campos, A. C. C., Andrade, N. L., Ferdous, M., Chlebowicz, M. A., Santos, C. C., Correal, J. C. D., Foe, J. R. L. T., Rosa, A. C. P., Damasco, P. V., Friedrich, A. W., et al. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.599031 · Cited by 94 · see citing works
Effects of Short-Chain Fatty Acids on the Inflamed Colonic Mucosa
Scheppach, W. M., Christl, S. U., Bartram, H.-P., Richter, F., & Kasper, H. (1997) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.1997.11720719 · Cited by 79 · see citing works
AMPK Activation Promotes Tight Junction Assembly in Intestinal Epithelial Caco-2 Cells
Olivier, S., Leclerc, J., Grenier, A., Foretz, M., Tamburini, J., & Viollet, B. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205171 · Cited by 70 · see citing works
Kim, H., Jeon, B. S., & Sang, B. (2019) · Scientific Reports · doi:10.1038/s41598-019-48591-6 · Cited by 67 · see citing works
Hang, I., Heilmann, R. M., Grützner, N., Suchodolski, J. S., Steiner, J. M., Atroshi, F., Sankari, S., Kettunen, A., de Vos, W. M., Zentek, J., et al. (2013) · BMC Veterinary Research · doi:10.1186/1746-6148-9-201 · Cited by 62 · see citing works
Warburg behind the butyrate paradox?
Burgess, D. J. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3401 · Cited by 33 · see citing works
Colonic Microbiota and Metabolites Response to Different Dietary Protein Sources in a Piglet Model
Li, R., Chang, L., Hou, G., Song, Z., Fan, Z., He, X., & Hou, D. (2019) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00151 · Cited by 33 · see citing works
Metatranscriptome analysis of the microbial fermentation of dietary milk proteins in the murine gut
Hugenholtz, F., Davids, M., Schwarz, J., Müller, M. M., Tomé, D., Schaap, P. J., Hooiveld, G. J. E. J., Smidt, H., & Kleerebezem, M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194066 · Cited by 24 · see citing works
Deb‐Choudhury, S., Bermingham, E. N., Young, W., et al. (2018) · Food & Function · doi:10.1039/c7fo02004j · Cited by 20 · see citing works
Skrzypecki, J., Niewęgłowska, K., & Samborowska, E. (2020) · Nutrients · doi:10.3390/nu12020387 · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Yip, A. Y. G., King, O. G., Omelchenko, O., Kurkimat, S., Horrocks, V., Mostyn, P., Danckert, N., Ghani, R., Satta, G., Jauneikaite, E., et al. (2023) · doi:10.1101/2023.03.25.533086 · Cited by 91 · see citing works
- Authors
- Gao, G., Zhou, J., Wang, H., Ding, Y., Zhou, J., Chong, P. H., Zhu, L., Ke, L., Wang, X., Rao, P., Wang, Q., & Zhang, L.
- Affiliations
- Zhejiang Gongshang University (CN)
- ZheJiang Academy of Agricultural Sciences (CN)
- Institute of Food Science and Technology (CN)
- Fujian Medical University (CN)
- Corresponding author
- Zhu, Liying
- Ke, Lijing
- ORCID
- Venue
- Molecular Biology Reports
- Published
- 2021-11-27
- Volume
- 49
- Issue
- 3
- Pages
- 1817-1825
- ISSN
- 0301-4851 (ISSN-L)
- 1573-4978
- OpenAlex
- W3217667595
- Cited by
- 40
- References
- 39
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 8 · 2023: 4 · 2022: 3
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Biology Reports (publishedVersion)
- PubMed (publishedVersion)
- Funders
- national key research and development plan of china (2016YFD0400202, 2017YFD0400300)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Microbial Metabolites in Food Biotechnology
- Keywords
- valerate, short-chain fatty acids, intestinal barrier function, Caco-2 cell monolayers, transepithelial electrical resistance, paracellular permeability, AMPK activation, tight junctions, butyrate, gut health, intestinal homeostasis
- MeSH terms
- Epithelial Cells, Humans, Intestinal Mucosa, Permeability, Valerates, Caco-2 Cells, Tight Junctions
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