Naturally occurring TPE-CA maintains gut microbiota and bile acids homeostasis via FXR signaling modulation of the liver-gut axis
Open accessAbstract
Antibiotics-induceds changes in intestinal flora (dysbiosis) may have various effects on the host. Dysbiosis is associated with numerous metabolites including bile acids, which are produced in the liver from cholesterol and metabolized in the gut by intestinal microbiota. Total phenolic extracts of Citrus aurantium L. (TPE-CA) are rich in dietary flavanones and their glycosyl derivatives, including flavones, flavonols, polymethoxyflavones and coumarins, which exert positive health effects on the microbiota. The aim of this study is to elucidate the interplays between the intestinal microbiota and bile acids metabolism attributed to antibiotics. Mice were exposed to broad-spectrum antibiotics, such as ampicillin, streptomycin and clindamycin, for 14 days. This exposure resulted in reduced bacterial diversity and richness, and destroyed intestinal permeability. The homeostasis of bile acids was also affected. Subsequent TPE-CA administration, counteracted most of the dysbiosis, and reshaped intestinal permeability, these effects occurred via upregulation of zonula occludens 1 and occludin associated proteins and downregulation of serum endotoxin compared to the antibiotics group. TPE-CA maintained the homeostasis of bile acids via modulation of the liver -gut axis related farnesoid X receptor (FXR)/ fibroblast growth factor 15 (FGF15) pathway and FXR-targeted protein. Our findings indicated that TPE-CA exerted a protective effect on the restoration of intestinal microbiota composition, reshaped barrier integrity and maintained bile acid homeostasis via the liver - gut axis with antibiotics-induced dysbiosis.
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TPE-CA treatment induced the expression of tight junction proteins such as ZO-1 and OCLN-associated proteins in these mice and improved the barrier integrity.
“TPE-CA treatment induced the expression of TJ proteins such as ZO-1 and OCLN-associated proteins in these mice and improved the barrier integrity.112”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [112]
Mice exposed to broad-spectrum antibiotics such as ampicillin, clindamycin and streptomycin resulted in reduced gut bacterial diversity and richness and impacted gut barrier integrity.
“It was showed that mice exposed to broad-spectrum antibiotics such as ampicillin, clindamycin and streptomycin resulted in reduced gut bacterial diversity and richness and impacted gut barrier integrity.112”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [112]
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Cites
Bile salt biotransformations by human intestinal bacteria
Ridlon, J. M., Kang, D.-J., & Hylemon, P. B. (2006) · Journal of Lipid Research · doi:10.1194/jlr.r500013-jlr200 · Cited by 2,829 · see citing works
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., Richardson, J. A., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.09.001 · Cited by 1,865 · see citing works
Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation
Lefebvre, P., Cariou, B., Lien, F., Kuipers, F., & Staels, B. (2009) · Physiological Reviews · doi:10.1152/physrev.00010.2008 · Cited by 1,678 · see citing works
Bile acids: regulation of synthesis
Chiang, J. Y. L. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r900010-jlr200 · Cited by 1,567 · see citing works
Long-term ecological impacts of antibiotic administration on the human intestinal microbiota
Jernberg, C., Löfmark, S., Edlund, C., & Jansson, J. K. (2007) · The ISME Journal · doi:10.1038/ismej.2007.3 · Cited by 1,134 · see citing works
Jones, B. V., Begley, M., Hill, C., Gahan, C. G. M., & Marchesi, J. R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804437105 · Cited by 1,098 · see citing works
Ubeda, C., Taur, Y., Jenq, R. R., Equinda, M. J., Son, T., Samstein, M., Viale, A., Socci, N. D., van den Brink, M. R. M., Kamboj, M., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43918 · Cited by 943 · see citing works
Bile acid signaling in metabolic disease and drug therapy
Li, T., & Chiang, J. Y. L. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.008201 · Cited by 935 · see citing works
Systemic gut microbial modulation of bile acid metabolism in host tissue compartments
Swann, J. R., Want, E. J., Geier, F. M., Spagou, K., Wilson, I. D., Sidaway, J. E., Nicholson, J. K., & Holmes, E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006734107 · Cited by 726 · see citing works
Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota
Lee, H. C., Jenner, A. M., Low, C. S., & Lee, Y. K. (2006) · Research in Microbiology · doi:10.1016/j.resmic.2006.07.004 · Cited by 697 · see citing works
Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut
Joyce, S. A., MacSharry, J., Casey, P. G., Kinsella, M., Murphy, E. F., Shanahan, F., Hill, C., & Gahan, C. G. M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323599111 · Cited by 604 · see citing works
Reproducible Community Dynamics of the Gastrointestinal Microbiota following Antibiotic Perturbation
Antonopoulos, D. A., Huse, S. M., Morrison, H. G., Schmidt, T. M., Sogin, M. L., & Young, V. B. (2009) · Infection and Immunity · doi:10.1128/iai.01520-08 · Cited by 545 · see citing works
Assembly of the human intestinal microbiota
Dethlefsen, L., Eckburg, P. B., Bik, E. M., & Relman, D. A. (2006) · Trends in Ecology & Evolution · doi:10.1016/j.tree.2006.06.013 · Cited by 509 · see citing works
Zhao, L., Zhang, Q., Ma, W., Tian, F., Shen, H., & Zhou, M. (2017) · Food & Function · doi:10.1039/c7fo01383c · Cited by 492 · see citing works
Rea, M. C., Dobson, A., O'Sullivan, O., Crispie, F., Fouhy, F., Cotter, P. D., Shanahan, F., Kiely, B., Hill, C., & Ross, R. P. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001224107 · Cited by 377 · see citing works
Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment
Nobel, Y. R., Cox, L. M., Kirigin, F. F., Bokulich, N. A., Yamanishi, S., Teitler, I., Chung, J., Sohn, J., Barber, C. M., Goldfarb, D. S., et al. (2015) · Nature Communications · doi:10.1038/ncomms8486 · Cited by 374 · see citing works
Self-citationGuida, F., Turco, F., Iannotta, M., De Gregorio, D., Palumbo, I., Sarnelli, G., Furiano, A., Napolitano, F., Boccella, S., Luongo, L., et al. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.09.001 · Cited by 367 · see citing works
Jalanka-Tuovinen, J., Salojärvi, J., Salonen, A., Immonen, O., Garsed, K., Kelly, F. M., Zaitoun, A., Palva, A., Spiller, R. C., & de Vos, W. M. (2014) · Gut · doi:10.1136/gutjnl-2013-305994 · Cited by 340 · see citing works
Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells
Yu, A. S. L., McCarthy, K. M., Francis, S. A., McCormack, J. M., Lai, J., Rogers, R. A., Lynch, R. D., & Schneeberger, E. E. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00581.2004 · Cited by 307 · see citing works
Stieger, B. (2010) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-14541-4_5 · Cited by 268 · see citing works
Microbial impact on cholesterol and bile acid metabolism: current status and future prospects
Kriaa, A., Bourgin, M., Potiron, A., Mkaouar, H., Jablaoui, A., Gérard, P., Maguin, E., & Rhimi, M. (2019) · Journal of Lipid Research · doi:10.1194/jlr.r088989 · Cited by 264 · see citing works
d'Aldebert, E., Mve, M.-J. B. B., Mergey, M., Wendum, D., Firrincieli, D., Coilly, A., Fouassier, L., Corpechot, C., Poupon, R. Y., Housset, C., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.12.040 · Cited by 216 · see citing works
Gut microbiota: a key player in health and disease. A review focused on obesity
Villanueva-Millán, M. J., Pérez‐Matute, P., & Oteo, J. A. (2015) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-015-0390-3 · Cited by 185 · see citing works
Munyaka, P. M., Eissa, N., Bernstein, C. N., Khafipour, E., & Ghia, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142536 · Cited by 183 · see citing works
Xue, M.-L., Ji, X.-Q., Liang, H., Liu, Y., Wang, B., Sun, L.-L., & Li, W.-W. (2018) · Food & Function · doi:10.1039/c7fo01677h · Cited by 135 · see citing works
Self-citationSwann, J. R., Tuohy, K. M., Lindfors, P., Brown, D. T., Gibson, G. R., Wilson, I. D., Sidaway, J. E., Nicholson, J. K., & Holmes, E. C. (2011) · Journal of Proteome Research · doi:10.1021/pr200243t · Cited by 125 · see citing works
Deng, H., Yang, S., Zhang, Y., Qian, K., Zhang, Z., Liu, Y., Wang, Y., Bai, Y., Fan, H., Zhao, X., et al. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.02976 · Cited by 121 · see citing works
Self-citationLamousé-Smith, E. S. N., Tzeng, A., & Starnbach, M. N. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027662 · Cited by 107 · see citing works
Lin, J. (2014) · Frontiers in Microbiology · doi:10.3389/fmicb.2014.00033 · Cited by 102 · see citing works
Integrative metabolic and microbial profiling on patients with Spleen-yang-deficiency syndrome
Zhang, L., Ye, W., Zu, X., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-24130-7 · Cited by 99 · see citing works
Hoegenauer, K., Arista, L., Schmiedeberg, N., Werner, G., Jaksche, H., Bouhelal, R., Nguyen, D. G., Bhat, B. G., Raad, L., Rauld, C., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm501052c · Cited by 96 · see citing works
Deng, H., Yang, S., Zhang, Y., Qian, K., Zhang, Z., Liu, Y., Wang, Y., Bai, Y., Fan, H., Zhao, X., et al. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00601 · Cited by 79 · see citing works
Self-citationShi, Y., Kellingray, L., Zhai, Q., Gall, G. L., Narbad, A., Zhao, J., Zhang, H., & Chen, W. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01948 · Cited by 78 · see citing works
INT-767 prevents NASH and promotes visceral fat brown adipogenesis and mitochondrial function
Comeglio, P., Cellai, I., Mello, T., Filippi, S., Maneschi, E., Corcetto, F., Corno, C., Sarchielli, E., Morelli, A., Rapizzi, E., et al. (2018) · Journal of Endocrinology · doi:10.1530/joe-17-0557 · Cited by 74 · see citing works
Jin, M. J., Kim, U., Kim, I., Kim, Y., Kim, D., Han, S. B., Kim, D., Kwon, O., & Yoo, H. H. (2010) · Journal of Toxicology and Environmental Health · doi:10.1080/15287394.2010.511549 · Cited by 70 · see citing works
Zhao, S., Liu, Z., Wang, M., He, D., Liu, L., Shu, Y., Song, Z., Li, H., Liu, Y., & Lü, A. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.09.184 · Cited by 65 · see citing works
Self-citationShi, Y., Zhao, X., Zhao, J., Zhang, H., Zhai, Q., Narbad, A., & Chen, W. (2018) · Journal of Applied Microbiology · doi:10.1111/jam.13687 · Cited by 61 · see citing works
Kong, B., Sun, R., Huang, M., Chow, M. D., Zhong, X., Xie, W., Lee, Y., & Guo, G. L. (2018) · Hepatology · doi:10.1002/hep.30041 · Cited by 52 · see citing works
Gao, X., Wang, C., Ning, C., Liu, K., Wang, X., Liu, Z., Sun, H., Ma, X., Sun, P., & Meng, Q. (2018) · Food & Function · doi:10.1039/c8fo00107c · Cited by 44 · see citing works
Self-citationJu, T., Shoblak, Y., Gao, Y., Yang, K., Fouhse, J. M., Finlay, B. B., So, Y. W., Stothard, P., & Willing, B. P. (2017) · Applied and Environmental Microbiology · doi:10.1128/aem.01107-17 · Cited by 40 · see citing works
Shu, Y., Liu, Z., Zhao, S., Song, Z., He, D., Wang, M., Zeng, H., Lu, C. C., Lü, A., & Liu, Y. (2017) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-017-0428-1 · Cited by 36 · see citing works
Self-citationInhibition of farnesoid X receptor signaling shows beneficial effects in human obesity
Gonzalez, F. J., Jiang, C., Bisson, W. H., & Patterson, A. D. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.043 · Cited by 29 · see citing works
Organic Anion Uptake by Hepatocytes
Wolkoff, A. W. (2014) · Comprehensive physiology · doi:10.1002/cphy.c140023 · Cited by 21 · see citing works
Tao, X., Guo, F., Zhou, Q., Hu, F., Xiang, H., Xiao, G. G., & Shang, D. (2019) · RSC Advances · doi:10.1039/c8ra09547g · Cited by 21 · see citing works
An in vitro metabolic system of gut flora and the metabolism of ginsenoside Rg3 and cholic acid
Zhao, C., Sun, R., Cao, B., Gu, S., Zhao, J., Liu, L., Wang, X., Zha, W., Yu, X., Xiao, W., et al. (2013) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/s13318-013-0143-z · Cited by 14 · see citing works
Self-citationLi, H., Zeng, H., He, D., Wang, M., Liu, L., Liang, W., Shu, Y., Zhao, S., Sun, G., Lv, C., et al. (2018) · Journal of Chromatography B · doi:10.1016/j.jchromb.2018.09.017 · Cited by 12 · see citing works
Self-citationHe, D., Liu, Z., Wang, M., et al. (2019) · Phytotherapy Research · doi:10.1002/ptr.6306 · Cited by 12 · see citing works
Self-citationMinamisawa, M., Suzuki, K., Kawai, G., Yamaguchi, A., & Yamanaka, S. (2017) · Journal of Functional Foods · doi:10.1016/j.jff.2017.09.043 · Cited by 9 · see citing works
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Regulation of Intestinal Barrier Function by Microbial Metabolites
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Li, S., Chen, F., Zou, Y., Ning, L., Zhang, G., Zhang, S., & Yao, Q. (2022) · Annals of Translational Medicine · doi:10.21037/atm-21-4809 · Cited by 10 · see citing works
- Authors
- Liu, L., Liu, Z., Li, H., Cao, Z., Li, W., Song, Z., Li, X., Lu, A., Lu, C., & Liu, Y.
- Affiliations
- Beijing University of Chinese Medicine (CN)
- China Academy of Chinese Medical Sciences (CN)
- Corresponding author
- Liu, Zhenli
- Lu, Cheng
- Liu, Yuanyan
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2020-02-06
- Volume
- 11
- Pages
- 12-12
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC7015895
- OpenAlex
- W2998935115
- Cited by
- 68
- References
- 48
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 17 · 2023: 12 · 2022: 14 · 2021: 10 · 2020: 5
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Beijing University of Chinese Medicine
- National Science and Technology Major Project (2018ZX10101001-005-003, 2018ZX10101‐001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Citrus aurantium, gut microbiota, bile acid homeostasis, FXR signaling, FGF15, gut-liver axis, antibiotic-induced dysbiosis, intestinal permeability, tight junction proteins, endotoxin, flavanones, coumarins, zonula occludens-1, occludin
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