Human gut bacteria as potent class I histone deacetylase inhibitors in vitro through production of butyric acid and valeric acid
Open accessAbstract
Overexpression of histone deacetylase (HDAC) isoforms has been implicated in a variety of disease pathologies, from cancer and colitis to cardiovascular disease and neurodegeneration, thus HDAC inhibitors have a long history as therapeutic targets. The gut microbiota can influence HDAC activity via microbial-derived metabolites. While HDAC inhibition (HDI) by gut commensals has long been attributed to the short chain fatty acid (SCFA) butyrate, the potent metabolic reservoir provided by the gut microbiota and its role in host physiology warrants further investigation in a variety of diseases. Cell-free supernatants (CFS) of 79 phylogenetically diverse gut commensals isolated from healthy human donors were screened for their SCFA profile and their total HDAC inhibitory properties. The three most potent HDAC inhibiting strains were further evaluated and subjected to additional analysis of specific class I and class II HDAC inhibition. All three HDAC inhibitors are butyrate producing strains, and one of these also produced substantial levels of valeric acid and hexanoic acid. Valeric acid was identified as a potential contributor to the HDAC inhibitory effects. This bacterial strain, Megasphaera massiliensis MRx0029, was added to a model microbial consortium to assess its metabolic activity in interaction with a complex community. M. massiliensis MRx0029 successfully established in the consortium and enhanced the total and specific HDAC inhibitory function by increasing the capacity of the community to produce butyrate and valeric acid. We here show that single bacterial strains from the human gut microbiota have potential as novel HDI therapeutics for disease areas involving host epigenetic aberrations.
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Pentanoate is a rare bacterial metabolite generated by low-abundant commensals such as Megasphaera massiliensis.
“This SCFA is rather a rare bacterial metabolite generated by low-abundant commensals such as Megasphaera massiliensis, which we have classified as a pentanoate-producing bacterial species21.”
From Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer (2021) · cites this paper as [21]
Among commensal strains tested, only a few bacterial species exhibited strong pan-HDAC inhibitory capacity.
“Our broad screening approach revealed that among the commensal strains tested, only a few bacterial species exhibited a strong pan-HDAC inhibitory capacity21.”
From Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer (2021) · cites this paper as [21]
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Cites
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,949 · see citing works
Gut microbiota, metabolites and host immunity
Rooks, M. G., & Garrett, W. S. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.42 · Cited by 3,409 · see citing works
Formation of propionate and butyrate by the human colonic microbiota
Louis, P., & Flint, H. J. (2017) · Environmental Microbiology · doi:10.1111/1462-2920.13589 · Cited by 3,028 · see citing works
Epigenetic modifications and human disease
Portela, A., & Esteller, M. (2010) · Nature Biotechnology · doi:10.1038/nbt.1685 · Cited by 2,843 · 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
Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota
MetaHIT consortium, Forslund, K., Hildebrand, F., Nielsen, T., Falony, G., Le Chatelier, E., Sunagawa, S., Prifti, E., Vieira-Silva, S., Gudmundsdottir, V., et al. (2015) · Nature · doi:10.1038/nature15766 · Cited by 2,116 · see citing works
New and emerging HDAC inhibitors for cancer treatment
West, A. C., & Johnstone, R. W. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69738 · Cited by 1,404 · see citing works
New evidences on the altered gut microbiota in autism spectrum disorders
Strati, F., Cavalieri, D., Albanese, D., De Felice, C., Donati, C., Hayek, J., Jousson, O., Leoncini, S., Renzi, D., Calabrò, A., et al. (2017) · Microbiome · doi:10.1186/s40168-017-0242-1 · Cited by 1,040 · see citing works
Gut microbes and the brain: paradigm shift in neuroscience
Mayer, E. A., Knight, R., Mazmanian, S. K., Cryan, J. F., & Tillisch, K. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3299-14.2014 · Cited by 1,033 · see citing works
Exogenous Stimuli Maintain Intraepithelial Lymphocytes via Aryl Hydrocarbon Receptor Activation
Li, Y., Innocentin, S., Withers, D. R., Roberts, N. A., Gallagher, A., Grigorieva, E. F., Wilhelm, C., & Veldhoen, M. (2011) · Cell · doi:10.1016/j.cell.2011.09.025 · Cited by 822 · see citing works
Miyake, S., Kim, S., Suda, W., Oshima, K., Nakamura, M., Matsuoka, T., Chihara, N., Tomita, A., Sato, W., Kim, S.-W., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137429 · Cited by 809 · see citing works
Epigenetic modifications as therapeutic targets
Kelly, T. K., Carvalho, D. D. D., & Jones, P. A. (2010) · Nature Biotechnology · doi:10.1038/nbt.1678 · Cited by 796 · see citing works
Piekarz, R., Frye, R., Turner, M. L. C., Wright, J. J., Allen, S. L., Kirschbaum, M. H., Zain, J. M., Prince, H. M., Leonard, J. P., Geskin, L. J., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.21.6150 · Cited by 739 · see citing works
Tanaka, T., Kohno, H., Suzuki, R., Yamada, Y., Sugie, S., & Mori, H. (2003) · Cancer Science · doi:10.1111/j.1349-7006.2003.tb01386.x · Cited by 732 · see citing works
Fellows, R., Denizot, J., Stellato, C., Cuomo, A., Jain, P., Stoyanova, E., Balázsi, S., Hajnády, Z., Liebert, A., Kazakevych, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02651-5 · Cited by 568 · see citing works
α-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity
Kontopoulos, E., Parvin, J. D., & Feany, M. Β. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl243 · Cited by 539 · see citing works
Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders
Abel, T. G., & Zukin, R. S. (2008) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.12.002 · Cited by 495 · see citing works
Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma
Piekarz, R., Frye, R., Prince, H. M., Kirschbaum, M. H., Zain, J. M., Allen, S. L., Jaffe, E. S., Ling, A. L., Turner, M. L. C., Peer, C. J., et al. (2011) · Blood · doi:10.1182/blood-2010-10-312603 · Cited by 487 · see citing works
HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases
Yoon, S., & Eom, G. H. (2016) · Chonnam Medical Journal · doi:10.4068/cmj.2016.52.1.1 · Cited by 469 · see citing works
Isoform-selective histone deacetylase inhibitors
Bieliauskas, A. V., & Pflum, M. K. H. (2008) · Chemical Society Reviews · doi:10.1039/b703830p · Cited by 350 · see citing works
Different accessibilities in chromatin to histone acetylase.
Cousens, L. S., Gallwitz, D., & Alberts, B. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37831-6 · Cited by 340 · see citing works
Giloteaux, L., Goodrich, J. K., Walters, W. A., Levine, S. M., Ley, R. E., & Hanson, M. R. (2016) · Microbiome · doi:10.1186/s40168-016-0171-4 · Cited by 338 · see citing works
Gas chromatography – mass spectrometry data processing made easy
Johnsen, L. G., Skou, P. B., Khakimov, B., & Bro, R. (2017) · Journal of Chromatography A · doi:10.1016/j.chroma.2017.04.052 · Cited by 327 · see citing works
Usami, M., Kishimoto, K., Ohata, A., Miyoshi, M., Aoyama, M., Fueda, Y., & Kotani, J. (2008) · Nutrition Research · doi:10.1016/j.nutres.2008.02.012 · Cited by 309 · see citing works
Histone Hyperacetylation Is Associated with Amelioration of Experimental Colitis in Mice
Glauben, R., Batra, A., Fedke, I., Zeitz, M., Lehr, H. A., Leoni, F., Mascagni, P., Fantuzzi, G., Dinarello, C. A., & Siegmund, B. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.8.5015 · Cited by 294 · see citing works
Zhang, H.-L., Yu, L.-X., Yang, W., Tang, L., Lin, Y., Wu, H., Zhai, B., Tan, Y.-X., Shan, L., Liu, Q., et al. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.06.011 · Cited by 281 · see citing works
A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2
Wang, Q., McLoughlin, R. M., Cobb, B. A., Charrel-Dennis, M., Zaleski, K. J., Golenbock, D. T., Tzianabos, A. O., & Kasper, D. L. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20062008 · Cited by 277 · see citing works
Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer
Bultman, S. J. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500902 · Cited by 269 · see citing works
Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis
Alenghat, T., Osborne, L. C., Saenz, S. A., Kobuley, D. E., Ziegler, C. G. K., Mullican, S. E., Choi, I., Grunberg, S., Sinha, R., Wynosky-Dolfi, M. A., et al. (2013) · Nature · doi:10.1038/nature12687 · Cited by 248 · see citing works
Progression of Parkinson's disease is associated with gut dysbiosis: Two-year follow-up study
Minato, T., Maeda, T., Fujisawa, Y., Tsuji, H., Nomoto, K., Ohno, K., & Hirayama, M. (2017) · PLOS ONE · doi:10.1371/journal.pone.0187307 · Cited by 248 · see citing works
Emerging roles of the microbiome in cancer
Bultman, S. J. (2014) · Carcinogenesis · doi:10.1093/carcin/bgt392 · Cited by 239 · see citing works
Ly, N. P., Litonjua, A. A., Gold, D. R., & Celedon, J. C. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.02.015 · Cited by 214 · see citing works
Butyrate Histone Deacetylase Inhibitors
Steliou, K., Boosalis, M. S., Perrine, S. P., Sangerman, J., & Faller, D. V. (2012) · BioResearch open access · doi:10.1089/biores.2012.0223 · Cited by 209 · see citing works
Polyamines: Emerging players in bacteria–host interactions
Martino, M. L. D., Campilongo, R., Casalino, M., Micheli, G., Colonna, B., & Prosseda, G. (2013) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2013.06.008 · Cited by 175 · see citing works
The gut microbiota and Type 1 Diabetes
Gülden, E., Wong, F. S., & Li, W. (2015) · Clinical Immunology · doi:10.1016/j.clim.2015.05.013 · Cited by 165 · see citing works
Angiolilli, C., Kabala, P. A., Grabiec, A. M., van Baarsen, I. M., Ferguson, B. S., García, S., Malvar‐Fernández, B., McKinsey, T. A., Tak, P. P., Fossati, G., et al. (2016) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2015-209064 · Cited by 149 · 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
Wang, C., Henkes, L. M., Doughty, L. B., He, M., Wang, D., Meyer‐Almes, F., & Cheng, Y. (2011) · Journal of Natural Products · doi:10.1021/np200324x · Cited by 120 · see citing works
Sivaprakasam, S., Bhutia, Y. D., Ramachandran, S., & Ganapathy, V. (2017) · Nutrients · doi:10.3390/nu9080856 · Cited by 78 · see citing works
Inhibition of Histone Deacetylases in Inflammatory Bowel Diseases
Glauben, R., & Siegmund, B. (2011) · Molecular Medicine · doi:10.2119/molmed.2011.00069 · Cited by 77 · see citing works
Inhibiting Histone Deacetylase 2 (HDAC2) Promotes Functional Recovery From Stroke
Tang, Y., Lin, Y., Ni, H., Dong, J. P., Yuan, H., Zhang, Y., Liang, H., Yao, M., Zhou, Q., Wu, H., et al. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.007236 · Cited by 76 · see citing works
Wang, C.-C., Chen, P. S., Hsu, C.-W., Wu, S.-J., Lin, C.-T., & Gean, P. W. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.01.017 · Cited by 47 · see citing works
Hegazi, R. A. F., Mady, H. H., Melhem, M. F., Sepulveda, A. R., Mohi, M., & Kandil, H. M. (2003) · Inflammatory Bowel Diseases · doi:10.1097/00054725-200307000-00003 · Cited by 34 · see citing works
Wilson, A. J., Cheng, Y., & Khabele, D. (2012) · Journal of Ovarian Research · doi:10.1186/1757-2215-5-12 · Cited by 32 · see citing works
The histone deacetylase Hdac1 regulates inflammatory signalling in intestinal epithelial cells
Gonneaud, A., Gagné, J. M., Turgeon, N., & Asselin, C. (2014) · Journal of Inflammation · doi:10.1186/s12950-014-0043-2 · Cited by 30 · see citing works
Short-chain fatty acids and thyroid hormone interact in regulating enterocyte gene transcription
Meng, S., Wu, J. T., Archer, S. Y., & Hodin, R. A. (1999) · Surgery · doi:10.1016/s0039-6060(99)70168-6 · Cited by 27 · see citing works
Can intestinal microbiota be associated with non-intestinal cancers?
Jacqueline, C. M., Brazier, L., Faugère, D., Renaud, F., Frédéric Thomas, A., & Roche, B. (2017) · Scientific Reports · doi:10.1038/s41598-017-11644-9 · Cited by 23 · see citing works
Flagged first, then by citations
1 of the 48 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The Effect of Probiotics on the Production of Short-Chain Fatty Acids by Human Intestinal Microbiome
Markowiak‐Kopeć, P., & Śliżewska, K. (2020) · Nutrients · doi:10.3390/nu12041107 · Cited by 1,241 · see citing works
Luu, M., Riester, Z., Baldrich, A., Reichardt, N., Yuille, S., Busetti, A., Klein, M., Wempe, A., Leister, H., Raifer, H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24331-1 · Cited by 771 · see citing works
Self-citationThe gut-bone axis: How bacterial metabolites bridge the distance
Zaiss, M. M., Jones, R. M., Schett, G., & Pacifici, R. (2019) · Journal of Clinical Investigation · doi:10.1172/jci128521 · Cited by 403 · see citing works
The interaction among gut microbes, the intestinal barrier and short chain fatty acids
Ma, J., Piao, X., Mahfuz, S. U., Long, S., & Wang, J. (2021) · Animal nutrition · doi:10.1016/j.aninu.2021.09.012 · Cited by 409 · see citing works
Nomura, M., Nagatomo, R., Doi, K., Shimizu, J., Baba, K., Saito, T., Matsumoto, S., Inoue, K., & Muto, M. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.2895 · Cited by 396 · see citing works
Gut microbiota-derived short chain fatty acids are potential mediators in gut inflammation
Akhtar, M. F., Chen, Y., Ma, Z., Zhang, X., Shi, D., Khan, J. A., & Liu, H. (2021) · Animal nutrition · doi:10.1016/j.aninu.2021.11.005 · Cited by 368 · see citing works
Nishida, K., Sawada, D., Kuwano, Y., Tanaka, H., & Rokutan, K. (2019) · Nutrients · doi:10.3390/nu11081859 · Cited by 292 · see citing works
Ashaolu, T. J., Ashaolu, J. O., & Adeyeye, S. A. O. (2020) · Journal of Applied Microbiology · doi:10.1111/jam.14843 · Cited by 215 · see citing works
Mechanisms of Short-Chain Fatty Acids Derived from Gut Microbiota in Alzheimer's Disease
Qian, X., Xie, R.-Y., Liu, X., Chen, S., & Tang, H. (2022) · Aging and Disease · doi:10.14336/ad.2021.1215 · Cited by 212 · see citing works
O’Keefe, S. J. (2019) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(19)30257-2 · Cited by 190 · see citing works
Gut commensal derived-valeric acid protects against radiation injuries
Li, Y., Dong, J., Xiao, H., Zhang, S., Wang, B., Cui, M., & Fan, S. (2020) · Gut Microbes · doi:10.1080/19490976.2019.1709387 · Cited by 174 · see citing works
The Gut Microbiome and Sex Hormone-Related Diseases
He, S., Li, H., Yu, Z., Zhang, F., Liang, S., Liu, H., Chen, H., & Lü, M. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.711137 · Cited by 176 · see citing works
Gut Microbiota Dysbiosis Drives the Development of Colorectal Cancer
Fan, X., Jin, Y., Chen, G., Ma, X., & Zhang, L. (2020) · Digestion · doi:10.1159/000508328 · Cited by 169 · see citing works
Fawad, J. A., Luzader, D., Hanson, G. F., Moutinho, T. J., McKinney, C. A., Mitchell, P., Brown-Steinke, K., Kumar, A., Park, M., Lee, S., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2022.07.051 · Cited by 167 · see citing works
The role of short-chain fatty acids in inflammatory skin diseases
Xiao, X., Hu, X., Yao, J., Cao, W., Zou, Z., Wang, L., Qin, H., Zhong, D., Li, Y., Xue, P., et al. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1083432 · Cited by 163 · see citing works
Chang, Y., Chen, Y., Zhou, Q., Wang, C., Chen, L., Di, W. J., & Zhang, Y. (2020) · Clinical Science · doi:10.1042/cs20191253 · Cited by 161 · see citing works
The Epigenetic Connection Between the Gut Microbiome in Obesity and Diabetes
Sharma, M., Li, Y., Stoll, M. L., & Tollefsbol, T. O. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2019.01329 · Cited by 152 · see citing works
Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy
Thomas, A. M., Fidelle, M., Routy, B., Kroemer, G., Wargo, J. A., Segata, N., & Zitvogel, L. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00785-8 · Cited by 141 · see citing works
Therapeutic Potential of Butyrate for Treatment of Type 2 Diabetes
Arora, T., & Tremaroli, V. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.761834 · Cited by 124 · see citing works
Masse, K. E., & Lu, V. B. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1169624 · Cited by 120 · see citing works
Kaur, H., & Ali, S. A. (2022) · Food & Function · doi:10.1039/d2fo00911k · Cited by 121 · see citing works
Dong, Y., Zhang, K., Wei, J., Ding, Y., Wang, X., Hou, H., Wu, J., Liu, T., Wang, B., & Cao, H. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1158200 · Cited by 107 · see citing works
Huang, Y., Wang, Z., Ye, B., Hongjie, J., Ji, S., Sheng, W., Ye, S., Ou, Y., Peng, Y., Xu, Y., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04259-4 · Cited by 109 · see citing works
COPD and Gut–Lung Axis: How Microbiota and Host Inflammasome Influence COPD and Related Therapeutics
Qu, L., Cheng, Q., Wang, Y., Mu, H., & Zhang, Y. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.868086 · Cited by 104 · see citing works
Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways
Lin, X., Xiao, H.-M., Liu, H.-M., Lv, W.-Q., Greenbaum, J., Gong, R., Zhang, Q., Chen, Y.-C., Peng, C., Xu, X.-J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42005-y · Cited by 101 · see citing works
Ahmed, S., Busetti, A., Fotiadou, P., Jose, N. V., Reid, S., Georgieva, M., Brown, S., Dunbar, H., Beurket-Ascencio, G., Delday, M. I., et al. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00402 · Cited by 99 · see citing works
Self-citationMoutsoglou, D., Tatah, J., Prisco, S. Z., Prins, K. W., Staley, C. M., Lopez, S., Blake, M. L., Teigen, L. M., Kazmirczak, F., Weir, Ε. K., et al. (2022) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202203-0490oc · Cited by 98 · see citing works
Bacterial Natural Compounds with Anti-Inflammatory and Immunomodulatory Properties (Mini Review)
Jenab, A., Roghanian, R., & Emtiazi, G. (2020) · Drug Design Development and Therapy · doi:10.2147/dddt.s261283 · Cited by 97 · see citing works
Dürholz, K., Hofmann, J., Iljazović, A., Häger, J., Lucas, S., Sarter, K., Strowig, T., Bang, H., Rech, J., Schett, G. A., et al. (2020) · Nutrients · doi:10.3390/nu12103207 · Cited by 96 · see citing works
Shinde, T., Perera, A. P., Vemuri, R., Gondalia, S. V., Karpe, A. V., Beale, D. J., Shastri, S., Southam, B., Eri, R. D., & Stanley, R. A. (2019) · Nutrients · doi:10.3390/nu11040818 · Cited by 88 · see citing works
Shinde, T., Perera, A. P., Vemuri, R., Gondalia, S. V., Beale, D. J., Karpe, A. V., Shastri, S., Basheer, W., Southam, B., Eri, R. D., et al. (2020) · European Journal of Nutrition · doi:10.1007/s00394-020-02200-9 · Cited by 88 · see citing works
The gut-eye-lacrimal gland-microbiome axis in Sjögren Syndrome
Trujillo-Vargas, C. M., Schaefer, L., Alam, J., Pflugfelder, S. C., Britton, R. A., & de Paiva, C. S. (2019) · The Ocular Surface · doi:10.1016/j.jtos.2019.10.006 · Cited by 87 · see citing works
Huang, Y., Ning, Z. H., Xing, Z., Liu, Y., Lu, H., Yin, X., Hao, H., Tan, Y. Q., Wang, D., Hu, H., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.785422 · Cited by 89 · see citing works
Bacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases
Stec, A., Sikora, M., Maciejewska, M., Paralusz-Stec, K., Michalska, M. N., Sikorska, E., & Rudnicka, L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043494 · Cited by 85 · see citing works
Vemuri, R., Gundamaraju, R., Shinde, T., Perera, A. P., Basheer, W., Southam, B., Gondalia, S. V., Karpe, A. V., Beale, D. J., Tristram, S. G., et al. (2019) · Nutrients · doi:10.3390/nu11061297 · Cited by 83 · see citing works
Trachsel, J., Briggs, C., Gabler, N. K., Allen, H. K., & Loving, C. L. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01381 · Cited by 81 · see citing works
Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor
Wang, R. X., Henen, M. A., Lee, J. S., Vögeli, B., & Colgan, S. P. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1938380 · Cited by 86 · see citing works
Metabolism, HDACs, and HDAC Inhibitors: A Systems Biology Perspective
King, J., Patel, M., & Chandrasekaran, S. (2021) · Metabolites · doi:10.3390/metabo11110792 · Cited by 75 · see citing works
The heightened importance of the microbiome in cancer immunotherapy
Villemin, C., Six, A., Neville, B. A., Lawley, T. D., Robinson, M. J., & Bakdash, G. (2022) · Trends in Immunology · doi:10.1016/j.it.2022.11.002 · Cited by 75 · see citing works
Implication of Obesity and Gut Microbiome Dysbiosis in the Etiology of Colorectal Cancer
Singh, S., Sharma, P., Sarma, D. K., Kumawat, M., Tiwari, R. R., Verma, V., Nagpal, R., & Kumar, M. (2023) · Cancers · doi:10.3390/cancers15061913 · Cited by 80 · see citing works
Qing, Y., Xie, H., Su, C. H., Wang, Y., Yu, Q., Pang, Q., & Cui, F. (2018) · Digestive Diseases and Sciences · doi:10.1007/s10620-018-5428-2 · Cited by 74 · see citing works
Kaur, H., Singh, Y., Singh, S., & Singh, R. B. (2020) · Genome · doi:10.1139/gen-2020-0136 · Cited by 72 · see citing works
Microbiome as an immune regulator in health, disease, and therapeutics
Juarez, V. M., Montalbine, A. N., & Singh, A. K. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114400 · Cited by 76 · see citing works
Zhao, Q., Wang, Z., Wang, X., Yan, X., Guo, Q., Yue, Y., Yue, T., & Yuan, Y. (2023) · Food Research International · doi:10.1016/j.foodres.2023.112493 · Cited by 69 · see citing works
Ratajczak, W., Mizerski, A., Rył, A., Słojewski, M., Sipak‐Szmigiel, O., Piasecka, M., & Laszczyńska, M. (2021) · Aging · doi:10.18632/aging.202968 · Cited by 67 · see citing works
Verdugo‐Meza, A., Ye, J., Dadlani, H., Ghosh, S., & Gibson, D. L. (2020) · Nutrients · doi:10.3390/nu12051434 · Cited by 69 · see citing works
Gut Microbiota Composition Is Associated with the Global DNA Methylation Pattern in Obesity
Ramos-Molina, B., Sánchez-Alcoholado, L., Cabrera-Mulero, A., Lopez-Dominguez, R., Carmona-Saez, P., Garcia-Fuentes, E., Moreno-Indias, I., & Tinahones, F. J. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00613 · Cited by 64 · see citing works
Accelerated Vascular Aging in Chronic Kidney Disease: The Potential for Novel Therapies
Hobson, S., Arefin, S., Witasp, A., Hernandez, L. N., Kublickiene, K. R., Shiels, P. G., & Stenvinkel, P. (2023) · Circulation Research · doi:10.1161/circresaha.122.321751 · Cited by 64 · see citing works
Gio-Batta, M., Sjöberg, F., Jonsson, K., Barman, M., Lundell, A., Adlerberth, I., Hesselmar, B., Sandberg, A., & Wold, A. E. (2020) · Scientific Reports · doi:10.1038/s41598-020-79737-6 · Cited by 63 · see citing works
Rosés, C., Cuevas‐Sierra, A., Quintana, S., Riezu‐Boj, J. I., Martínez, J. A., Milagro, F. I., & Barceló, A. (2021) · Nutrients · doi:10.3390/nu13020636 · Cited by 63 · see citing works
Martínez-Gili, L., McDonald, J. A. K., Liu, Z., Kao, D. H., Allegretti, J. R., Monaghan, T. M., Barker, G. F., Blanco, J. M., Williams, H. R. T., Holmes, E. C., et al. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1810531 · Cited by 62 · see citing works
A Link between Chronic Kidney Disease and Gut Microbiota in Immunological and Nutritional Aspects
Mertowska, P., Mertowski, S., Wojnicka, J., Korona‐Głowniak, I., Grywalska, E., Błażewicz, A., & Załuska, W. (2021) · Nutrients · doi:10.3390/nu13103637 · Cited by 61 · see citing works
Drugs and Bugs: The Gut-Brain Axis and Substance Use Disorders
Simpson, S., Mclellan, R., Wellmeyer, E., Matalon, F., & George, O. (2021) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-021-10022-7 · Cited by 60 · see citing works
Chiu, L., & Gilbert, S. F. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-817996-3.00015-3 · Cited by 55 · see citing works
Galow, A.-M., & Peleg, S. (2022) · Cells · doi:10.3390/cells11030468 · Cited by 58 · see citing works
The Immunomodulatory Potential of Short-Chain Fatty Acids in Multiple Sclerosis
Bărcuţean, L., Maier, S., Patrascu, M. B., Farczádi, L., & Bălașa, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063198 · Cited by 56 · see citing works
Thompson, K. N., Bonham, K. S., Ilott, N. E., Britton, G. J., Colmenero, P., Bullers, S. J., McIver, L. J., Ma, S., Nguyen, L. H., Filer, A. D., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abn4722 · Cited by 56 · see citing works
Impact of Steviol Glycosides and Erythritol on the Human and Cebus apella Gut Microbiome
Mahalak, K. K., Firrman, J., Tomasula, P. M., Núñez, A., Lee, J., Bittinger, K. L., Rinaldi, W. J., & Liu, L. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b06181 · Cited by 54 · see citing works
Tuck, C. J., Palma, G. D., Takami, K., Brant, B. J., Caminero, A., Reed, D. E., Muir, J. G., Gibson, P. R., Winterborn, A., Verdu, E. F., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-74460-8 · Cited by 52 · see citing works
Zeng, X., Li, J., Shan, W., Lai, Z., & Zuo, Z. (2023) · Microbiome · doi:10.1186/s40168-023-01648-1 · Cited by 49 · see citing works
Colorectal Cancer and Probiotics: Are Bugs Really Drugs?
Lamichhane, P., Maiolini, M., Alnafoosi, O., Hussein, S., Alnafoosi, H., Umbela, S., Richardson, T., Alla, N., Lamichhane, N., Subhadra, B. G., et al. (2020) · Cancers · doi:10.3390/cancers12051162 · Cited by 50 · see citing works
Inamoto, T., Furuta, K., Cheng, H., Uneme, M., Kano, T., Ishikawa, K., & Kaito, C. (2023) · FEBS Journal · doi:10.1111/febs.16945 · Cited by 46 · see citing works
Thenappan, T., Khoruts, A., Chen, Y., & Weir, Ε. K. (2019) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00416.2019 · Cited by 45 · see citing works
Heppert, J. K., Davison, J. M., Kelly, C., Mercado, G. P., Lickwar, C. R., & Rawls, J. F. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00357-6 · Cited by 43 · see citing works
Dothel, G., Barbaro, M. R., Vito, A. D., Ravegnini, G., Gorini, F., Monesmith, S., Coschina, E., Benuzzi, E., Fuschi, D., Palombo, M., et al. (2023) · Journal of Gastroenterology · doi:10.1007/s00535-023-01997-6 · Cited by 46 · see citing works
Głowacka, P., Oszajca, K., Pudlarz, A. M., Szemraj, J., & Witusik‐Perkowska, M. (2024) · Nutrients · doi:10.3390/nu16142244 · Cited by 48 · see citing works
The Urine Metabolome of Young Autistic Children Correlates with Their Clinical Profile Severity
Mussap, M., Siracusano, M., Noto, A., Fattuoni, C., Riccioni, A., Rajula, H. S. R., Fanos, V., Curatolo, P., Barberini, L., & Mazzone, L. (2020) · Metabolites · doi:10.3390/metabo10110476 · Cited by 43 · see citing works
Microbiota-assisted iron uptake promotes immune tolerance in the intestine
Zhu, L., Li, G., Liang, Z., Qi, T., Deng, K., Yu, J., Peng, Y., Zheng, J., Song, Y., & Chang, X. (2023) · Nature Communications · doi:10.1038/s41467-023-38444-2 · Cited by 46 · see citing works
Butyrate-producing colonic clostridia: picky glycan utilization specialists
Leth, M. L., Pichler, M. J., & Hachem, M. A. (2022) · Essays in Biochemistry · doi:10.1042/ebc20220125 · Cited by 42 · 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
The Many Faces of Microbiota-Gut-Brain Axis in Autism Spectrum Disorder
Gonçalves, C. L., Doifode, T., Rezende, V. L., Costa, M. A., Rhoads, J. M., & Soutullo, C. A. (2024) · Life Sciences · doi:10.1016/j.lfs.2023.122357 · Cited by 42 · see citing works
Bashir, B., Gulati, M., Vishwas, S., Gupta, G., Dhanasekaran, M., Paudel, K. R., Chellappan, D. K., Anand, K., Negi, P., Singh, P. K., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102689 · Cited by 43 · see citing works
Kim, G., Bae, J.-H., Cheon, S., Lee, D. H., Kim, D. H., Lee, D., Park, S., Shim, S., Seo, J., & Han, N. S. (2022) · Food & Function · doi:10.1039/d1fo03287a · Cited by 40 · see citing works
Revisiting the Role of Valeric Acid in Manipulating Ulcerative Colitis
Liu, M., Zhang, Y., Liu, J., Xiang, C., Lu, Q., Lu, H., Yang, T., Wang, X., Zhang, Q., Fan, C., et al. (2024) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izad187 · Cited by 39 · see citing works
Cho, J. H., Chae, C. W., Lim, J. R., Jung, Y. H., Han, S. J., Yoon, J. H., Park, J. Y., & Han, H. J. (2024) · Autophagy · doi:10.1080/15548627.2024.2323785 · Cited by 39 · see citing works
The Effect of Probiotic Supplementation on the Gut–Brain Axis in Psychiatric Patients
Sabit, H., Kassab, A., Alaa, D., Mohamed, S., Abdel-Ghany, S. E., mansy, M. I. A., Said, O. A. M., Khalifa, M. A., Hafiz, H., & Abushady, A. M. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45050260 · Cited by 37 · see citing works
How gut microbiota may impact ocular surface homeostasis and related disorders
Labétoulle, M., Baudouin, C., del Castillo, J. M. B., Rolando, M., Rescigno, M., Messmer, E. S. B. M., & Aragona, P. (2024) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2024.101250 · Cited by 37 · see citing works
Shinde, T., Vemuri, R., Shastri, S., Perera, A. P., Gondalia, S. V., Beale, D. J., Karpe, A. V., Eri, R. D., & Stanley, R. A. (2020) · Nutrients · doi:10.3390/nu12082380 · Cited by 36 · see citing works
Jones, L., Kumar, J., Mistry, A., Sankar Chittoor Mana, T., Perry, G., Reddy, V. P., & Obrenovich, M. (2019) · Biomedicines · doi:10.3390/biomedicines7020024 · Cited by 34 · see citing works
Jeong, J., Ganesan, R., Jin, Y.-J., Park, H., Min, B. H., Jeong, M. K., Yoon, S. J., Choi, M., Choi, J., Moon, J. H., et al. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1174968 · Cited by 34 · see citing works
Song, T., Guan, X., Wang, X., Qu, S., Zhang, S., Hui, W., Men, L., & Chen, X. (2021) · The FASEB Journal · doi:10.1096/fj.201903129rrr · Cited by 34 · see citing works
The Role and Mechanism of Gut Microbiota in Pulmonary Arterial Hypertension
Chen, Y.-H., Wen, Y., Meng, L., Zhong, J., & Liu, X.-Y. (2022) · Nutrients · doi:10.3390/nu14204278 · Cited by 36 · see citing works
Gut microbiota and myocardial fibrosis
Han, X., Yang, F., & Bao, Z. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175355 · Cited by 34 · see citing works
Chen, L., Sun, X., Khalsa, A. S., Bailey, M. T., Kelleher, K. J., Spees, C., & Zhu, J. (2021) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2021.114066 · Cited by 31 · see citing works
Dąbek, A., Kaczmarczyk, O., Woźniakiewicz, M., Paśko, P., Dobrowolska‐Iwanek, J., Woźniakiewicz, A., Piątek-Guziewicz, A., Zagrodzki, P., & Zwolinska-Wcislo, M. M. (2022) · Biology · doi:10.3390/biology11010108 · Cited by 33 · see citing works
Huang, S., He, Y., Chen, P., Liu, K., & Shaukat, A. (2023) · Animal Diseases · doi:10.1186/s44149-023-00089-5 · Cited by 33 · see citing works
The emerging role of microbiota derived SCFAs in neurodegenerative disorders
Wachamo, S., & Gaultier, A. (2025) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2025.101012 · Cited by 34 · see citing works
In Vitro Evaluation of Apoptotic Induction of Butyric Acid Derivatives in Colorectal Carcinoma Cells
PATTAYIL, L., & BALAKRISHNAN-SARASWATHI, H.-T. (2019) · Anticancer Research · doi:10.21873/anticanres.13528 · Cited by 32 · see citing works
Chen, S.-M., Guo, B.-J., Feng, A.-Q., Wang, X., Zhang, S.-L., & Miao, C. (2024) · Molecular Biomedicine · doi:10.1186/s43556-024-00211-0 · Cited by 31 · see citing works
Gio-Batta, M., Spetz, K., Barman, M., Bråbäck, L., Norin, E. L., Björkstén, B., Wold, A. E., & Sandin, A. (2021) · International Archives of Allergy and Immunology · doi:10.1159/000520149 · Cited by 29 · see citing works
The gut–heart axis: a review of gut microbiota, dysbiosis, and cardiovascular disease development
Abdulrahim, A. O., Doddapaneni, N. S. P., Salman, N., Giridharan, A., Thomas, J., Sharma, K., Abboud, E., Rochill, K., Shreelakshmi, B., Gupta, V., et al. (2024) · Annals of Medicine and Surgery · doi:10.1097/ms9.0000000000002789 · Cited by 31 · see citing works
Members of Lachnospiraceae produce valerate and caproate in response to short-chain fatty acids
Fitzgerald, B. G., Govind, M., Firth, I. J., Herold, L., Froment, J., Vancuren, S. J., Allen‐Vercoe, E., Kimber, M. S., & Sorbara, M. T. (2025) · Microbiome · doi:10.1186/s40168-025-02220-9 · Cited by 33 · see citing works
Paciolla, C., Manganelli, M., Chiano, M. D., Montenegro, F., Gallone, A., Sallustio, F., & Guida, G. (2025) · Cells · doi:10.3390/cells14221823 · Cited by 32 · see citing works
Hersi, F., Elgendy, S. M., Shamma, S. A. A., Altell, R. T., Sadiek, O., & Omar, H. A. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120573 · Cited by 29 · see citing works
Shegani, A., Kealey, S., Luzi, F., Basagni, F., Machado, J. D. M., Ekici, S. D., Ferocino, A., Gee, A. D., & Bongarzone, S. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00398 · Cited by 27 · see citing works
Epigenetic Aberrations in Major Psychiatric Diseases Related to Diet and Gut Microbiome Alterations
Nohesara, S., Abdolmaleky, H. M., & Thiagalingam, S. (2023) · Genes · doi:10.3390/genes14071506 · Cited by 29 · see citing works
Inflammatory Bowel Diseases: The Role of Gut Microbiota
Musis, C. D., Granata, L., Dallio, M., Miranda, A., Gravina, A. G., & Romano, M. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666200420144128 · Cited by 27 · see citing works
Kumari, B., Kumari, U., Singh, D. K., Husain, G. M., Patel, D. K., Shakya, A., Singh, R. B., Modi, G. P., & Singh, G. K. (2024) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/0118715303262653231120043819 · Cited by 26 · see citing works
González‐Bosch, C., Zunszain, P. A., & Mann, G. E. (2023) · Pathogens · doi:10.3390/pathogens12030486 · Cited by 27 · see citing works
Immune System Efficiency in Cancer and the Microbiota Influence
Barbosa, A. M., Gomes-Gonçalves, A., Castro, A. G., & Torrado, E. (2021) · Pathobiology · doi:10.1159/000512326 · Cited by 25 · see citing works
- Authors
- Yuille, S., Reichardt, N., Panda, S., Dunbar, H., & Mulder, I. E.
- Corresponding author
- Mulder, Imke E.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-07-27
- Volume
- 13
- Issue
- 7
- Pages
- e0201073
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC6063406
- OpenAlex
- W2884838967
- Cited by
- 257
- References
- 48
- Citations by year
- 2026: 23 · 2025: 23 · 2024: 46 · 2023: 48 · 2022: 34 · 2021: 27 · 2020: 37 · 2019: 18 · 2018: 1
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- 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 › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- histone deacetylase inhibitors, gut microbiota, class I HDACs, class II HDACs, short-chain fatty acids, butyrate, valeric acid, hexanoic acid, cell-free supernatant, microbial consortia, epigenetic regulation, host-microbe interactions
- MeSH terms
- Gastrointestinal Microbiome, Culture Media, Histone Deacetylases, Humans, Pentanoic Acids, Cell Culture Techniques, HT29 Cells, Butyric Acid, Megasphaera, Histone Deacetylase Inhibitors
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