The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.
Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD
Abstract
OBJECTIVE: Bile acids are regulators of lipid and glucose metabolism, and modulate inflammation in the liver and other tissues. Primary bile acids such as cholic acid and chenodeoxycholic acid (CDCA) are produced in the liver, and converted into secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid by gut microbiota. Here we investigated the possible roles of bile acids in non-alcoholic fatty liver disease (NAFLD) pathogenesis and the impact of the gut microbiome on bile acid signalling in NAFLD. DESIGN: Serum bile acid levels and fibroblast growth factor 19 (FGF19), liver gene expression profiles and gut microbiome compositions were determined in patients with NAFLD, high-fat diet-fed rats and their controls. RESULTS: -taurocholate cotransporting polypeptide and paraoxonase 1, no change in mRNA expression for small heterodimer partner and bile salt export pump, and reduced serum FGF19 were evidence of impaired FXR and fibroblast growth factor receptor 4 (FGFR4)-mediated signalling in NAFLD. Taurine and glycine metabolising bacteria were increased in the gut of patients with NAFLD, reflecting increased secondary bile acid production. Similar changes in liver gene expression and the gut microbiome were observed in high-fat diet-fed rats. CONCLUSIONS: The serum bile acid profile, the hepatic gene expression pattern and the gut microbiome composition consistently support an elevated bile acid production in NAFLD. The increased proportion of FXR antagonistic bile acid explains, at least in part, the suppression of hepatic FXR-mediated and FGFR4-mediated signalling. Our study suggests that future NAFLD intervention may target the components of FXR signalling, including the bile acid converting gut microbiome.
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“Jiao et al. (2018) found that MAFLD patients present elevated primary and secondary bile acids, among which the proportion of DCA is increased and CDCA is decreased.”
From Akkermansia muciniphila alleviates high‐fat‐diet ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Jiao et al. (2018)
In the citing paper
“Additionally, hepatic CYP7A1 expression is enhanced.”
From Akkermansia muciniphila alleviates high‐fat‐diet ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Jiao et al. (2018)
In the citing paper
“With increasing severity of NASH and fibrosis, BA levels tend to increase and the composition of BAs changes”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [91]
In the citing paper
“First, the gut microbiota may affect gastrointestinal transit through its regulation of BA synthesis. The gut microbiota is equipped with enzymes for the production of secondary BAs, which may suppress the FGF19- and FXR-mediated signaling, leading to the induction of CYP7A1 [ 49 , 50 ], and consequently elevated de novo BA synthesis and improved colonic transit.”
From Role of gut microbiota in functional constipation (2021) · cites this paper as [49]
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Cites
Design and validation of a histological scoring system for nonalcoholic fatty liver disease†
Kleiner, D. E., Brunt, E. M., Van Natta, M., Behling, C., Contos, M. J., Cummings, O. W., Ferrell, L. D., Liu, Y., Torbenson, M. S., Unalp‐Arida, A., et al. (2005) · Hepatology · doi:10.1002/hep.20701 · Cited by 10,791
Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences
Langille, M. G. I., Zaneveld, J., Caporaso, J. G., McDonald, D., Knights, D., Reyes, J. A., Clemente, J. C., Burkepile, D. E., Vega Thurber, R. L., Knight, R., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2676 · Cited by 9,116
Biology of Incretins: GLP-1 and GIP
Baggio, L. L., & Drucker, D. J. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.054 · Cited by 3,639
Vernon, G. C., Baranova, A. V., & Younossi, Z. M. (2011) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2011.04724.x · Cited by 3,116
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
Sayin, S. I., Wahlström, A., Felin, J., Jäntti, S., Marschall, H.-U., Bamberg, K., Angelin, B., Hyötyläinen, T., Orešič, M., & Bäckhed, F. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.01.003 · Cited by 2,331
Bile Acids: Natural Ligands for an Orphan Nuclear Receptor
Parks, D. J., Blanchard, S. G., Bledsoe, R. K., Chandra, G., Consler, T. G., Kliewer, S. A., Stimmel, J. B., Willson, T. M., Zavacki, A. M., Moore, D. D., et al. (1999) · Science · doi:10.1126/science.284.5418.1365 · Cited by 2,274
TGR5-Mediated Bile Acid Sensing Controls Glucose Homeostasis
Thomas, C., Gioiello, A., Noriega, L., Strehle, A., Oury, J., Rizzo, G., Macchiarulo, A., Yamamoto, H., Mataki, C., Pruzanski, M., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.001 · Cited by 1,885
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
Targeted Disruption of the Nuclear Receptor FXR/BAR Impairs Bile Acid and Lipid Homeostasis
Sinal, C. J., Tohkin, M., Miyata, M., Ward, J. M., Lambert, G., & Gonzalez, F. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00062-3 · Cited by 1,819
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Items 301–400 of 736
The Gut‒Liver Axis in Liver Disease: Molecular Mechanisms and Therapeutic Targets
Chen, Z., Liao, S., Wu, S., Chen, S., Tang, Q., Zhou, L., Li, X., Hu, H., Xu, J., Zhang, A., et al. (2025) · MedComm · doi:10.1002/mco2.70458 · Cited by 29
Significance of gut microbiota in alcoholic and non-alcoholic fatty liver diseases
Sharma, S. P., Suk, K. T., & Kim, D. J. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i37.6161 · Cited by 28
Zhang, M., Xiao, B., Chen, X., Ou, B., & Wang, S. (2023) · Acta Physiologica · doi:10.1111/apha.14065 · Cited by 28
“45 In NAFLD patients, changes in gut microbiota were observed to correlate with changes in BA signaling, which was also observed in NAFLD-associated rodent models.”
BackgroundInfluentialColaci, C., Gambardella, M. L., Scarlata, G. G. M., Boccuto, L., Colica, C., Luzza, F., Scarpellini, E., Méndez‐Sánchez, N., & Abenavoli, L. (2024) · Hepatoma Research · doi:10.20517/2394-5079.2023.134 · Cited by 27
Efficacy and safety of drugs for nonalcoholic steatohepatitis
Shen, B., & Lu, L. (2021) · Journal of Digestive Diseases · doi:10.1111/1751-2980.12967 · Cited by 24
“The activation of FXR can indirectly inhibit the expression of cytochrome P450 7A1 (CYP7A1), thereby inhibiting the synthesis of bile acid.(51) In addition, the activation of FXR can inhibit sterol regulatory element-binding protein 1c (SREBP-1c), which is the key transcription factor of lipid regeneration and regulat…”
BackgroundOrabi, D., Berger, N. A., & Brown, J. M. (2021) · Cancers · doi:10.3390/cancers13143473 · Cited by 25
Yang, C.-W., Liu, H.-M., Chang, Z., Liu, G.-H., Chang, H., Huang, P., & Lee, T.-Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25105274 · Cited by 25
Bao, Y., Shang, X., Hu, G., Wang, J., Liu, C., Lv, Q., Che, H., Han, J., Shao, T., & Wang, G. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156680 · Cited by 24
Neurodegeneration in juvenile Iberian pigs with diet-induced nonalcoholic fatty liver disease
Zeltser, N., Meyer, I., Hernandez, G. V., Trahan, M. J., Fanter, R. K., Abo-Ismail, M. K., Glanz, H., Strand, C. R., Burrin, D. G., Frano, M. R. L., et al. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00120.2020 · Cited by 25
Role of microbiota and related metabolites in gastrointestinal tract barrier function in NAFLD
Fernández-Cantos, M. V., García-Morena, D., Iannone, V., El-Nezami, H. S., Kolehmainen, M., & Kuipers, O. P. (2021) · Tissue Barriers · doi:10.1080/21688370.2021.1879719 · Cited by 23
“Some studies have described an increase of total BAs in serum levels in NASH patients.187,188 In addition, an increase in conjugated BAs in serum has been associated with NASH.188–191 However, Puri et al.189 reported an increase of serum levels of total primary BAs and a decrease of total secondary BAs in NASH patient…”
BackgroundInfluentialLu, Y., Hu, L., Song, J., Wan, J., Chen, H., & Yin, J. (2021) · BMC Endocrine Disorders · doi:10.1186/s12902-021-00899-z · Cited by 23
“Furthermore, the increasing bile acids may suppress the farnesoid X receptor (FXR) signaling in the liver and thus reducing serum FGF19 [38].”
BackgroundImpact of Bifidobacterium longum NSP001 on DSS-induced colitis in conventional and humanised mice
Chen, M., Yao, H., Tan, H., Huang, W., Wu, Q., & Nie, S. (2022) · Food Science and Human Wellness · doi:10.1016/j.fshw.2022.10.028 · Cited by 23
Gao, Y., Lin, J., Ye, C., Guo, S., & Jiang, C. (2023) · Liver Research · doi:10.1016/j.livres.2023.09.002 · Cited by 26
“99 e 102 One probable reason could be the elevated CYP7A1 expression level and therefore the increased synthesis of primary BAs.”
Zhu, X., Xu, P., Zhu, R., Gao, W., Yin, W., Lan, P., Zhu, L., & Jiao, N. (2024) · Communications Biology · doi:10.1038/s42003-023-05714-0 · Cited by 25
“While KO genes involved in metabolism, cysA (K02045) and gctB (K01040), were EBW-CRC speci fi c differential genes (Supplementary Data 14), differential genes gudB (K00260) and metH (K00548) were speci fi c for the lean group (Supplementary Data 15).”
BackgroundSelf-citationQiu, X., Cheng, S., Liu, Y., Li, Y. L., Zhang, R., Li, N., & Li, Z. (2024) · World Journal of Gastroenterology · doi:10.3748/wjg.v30.i8.833 · Cited by 24
“As evidenced by several animal-based studies, FMT could effectively improve the manifestations of NAFLD[14-16].”
InfluentialAppleby, R., Nolan, J., Johnston, I. M., Pattni, S. S., Fox, J. M., & Walters, J. R. F. (2017) · BMJ Open Gastroenterology · doi:10.1136/bmjgast-2017-000178 · Cited by 23
“Another recent study, also in paediatric patients, also showed low serum FGF19 in patients with non-alcoholic steatohepatitis (NASH) and raised levels of serum BAs, which were linked to differences in the gut microbiome.(16) It is of interest to note that both PBAD and NASH respond to the FXR agonist, obeticholic acid…”
Ocker, M. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i3.279 · Cited by 23
Luo, Y., Decato, B. E., Charles, E. D., Shevell, D. E., McNaney, C. A., Shipkova, P. A., Apfel, A., Tirucherai, G., & Sanyal, A. J. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100392 · Cited by 23
Bile acid signaling in MASLD: From pathogenesis to therapeutic applications
Simbrunner, B., Paternostro, R., Reiberger, T., & Trauner, M. (2025) · Hepatology · doi:10.1097/hep.0000000000001539 · Cited by 30
Park, E., Jeong, J., Won, S., Sharma, S. P., Gebru, Y. A., Ganesan, R., Gupta, H., Suk, K. T., & Kim, D. J. (2021) · Cells · doi:10.3390/cells10102634 · Cited by 22
“[↓] CDCA, FXR- and FGFR4-mediated signaling [89]”
BackgroundKimmel, M., Jin, W., Xia, K., Lun, K., Azcárate-Peril, M. A., Plantinga, A., Wu, M. C., Kachouei, S. A., Rackers, H., Carroll, I. M., et al. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113635 · Cited by 22
Li, M., Wang, J., Deng, H., Li, L., Huang, X., Chen, D., Ouyang, P., Geng, Y., Yang, S., Yin, L., et al. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.940576 · Cited by 22
“However, some secondary bile acids, such as deoxycholic acid, can inhibit FXR signaling, leading to increased bile acid synthesis (Jiao et al., 2018).”
BackgroundZhang, B., Luo, X., Han, C., Liu, J., Zhang, L., Qi, J., Gu, J., Tan, R., & Gong, P. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.116082 · Cited by 22
The role of FOXA family transcription factors in glucolipid metabolism and NAFLD
Yu, C., Li, X., Zhao, Y., & Hu, Y. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1081500 · Cited by 25
The Effect of Bioactive Aliment Compounds and Micronutrients on Non-Alcoholic Fatty Liver Disease
Munteanu, C., & Schwartz, B. (2023) · Antioxidants · doi:10.3390/antiox12040903 · Cited by 26
Miao, X., Luo, P., Liu, J., Wang, J., & Chen, Y. (2023) · Lipids in Health and Disease · doi:10.1186/s12944-023-01871-7 · Cited by 23
“High concentration of DCA not only inhibited hepatic glycogen synthesis and promoted gluconeogenesis [10], but also inhibited the growth and reproduction of Bacteroidete that can improve IR [56].”
BackgroundWang, B., Han, D. W., Hu, X., Chen, J., Liu, Y., & Wu, J. (2024) · Microbiological Research · doi:10.1016/j.micres.2024.127865 · Cited by 24
Bile-ology: from bench to bedside
Jin, L., Fang, Z., Fan, M.-J., & Huang, W. (2019) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b1900158 · Cited by 22
Serum metabolic profiling analysis of gout patients based on UPLC-Q-TOF/MS
Zheng, Z., Huang, Y., Huang, Q., Zheng, S., Huang, Z., Deng, W., & LI, T. W. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.12.028 · Cited by 22
A review on the effect of gut microbiota on metabolic diseases
Shi, Q., Dai, L., Zhao, Q., & Zhang, X. (2022) · Archives of Microbiology · doi:10.1007/s00203-022-02802-3 · Cited by 23
Bahitham, W., Alghamdi, S., Omer, I., Alsudais, A. S., Hakeem, I., Alghamdi, A., Abualnaja, R., Sanai, F. M., Rosado, A. S., & Sergi, C. M. (2024) · Biomedicines · doi:10.3390/biomedicines12030550 · Cited by 22
miR-33 deletion in hepatocytes attenuates MASLD-MASH-HCC progression
Fernández-Tussy, P., Cardelo, M. P., Zhang, H., Sun, J., Price, N. L., Boutagy, N. E., Goedeke, L., Cadena-Sandoval, M., Xirouchaki, C. E., Brown, W., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.168476 · Cited by 21
Liu, Z., & You, C. (2024) · Clinica Chimica Acta · doi:10.1016/j.cca.2024.120004 · Cited by 22
Bao, R., Chen, B., Wang, A. Z., Wang, D., Pan, J., Chen, Q., Yu, H., Zhu, Z., Yu, H., Zhang, Y., et al. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.11.040 · Cited by 22
Cheng, Y., Lv, Y., Zhao, X., Lu, Y., Jiao, T., Ma, T., & Fu, Y. (2025) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5c02491 · Cited by 21
Porphyran‐derived oligosaccharides alleviate NAFLD and related cecal microbiota dysbiosis in mice
Wang, X., Liu, D., Wang, Z., Cai, C., Jiang, H., & Yu, G. (2021) · The FASEB Journal · doi:10.1096/fj.202000763rrr · Cited by 21
Fling, R. R., & Zacharewski, T. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212431 · Cited by 21
Lützhøft, D. O., Sinioja, T., Christoffersen, B. Ø., Jakobsen, R. R., Geng, D., Ahmad, H. F., Straarup, E. M., Pedersen, K., Kot, W., Pedersen, H. D., et al. (2022) · BMC Microbiology · doi:10.1186/s12866-022-02704-w · Cited by 23
“Likewise, BA related pathways “glycine, serine, and threonine metabolism” and “taurine and hypotaurine metabolism” were previously identified as being elevated in faecal samples from NASH patients [28].”
BackgroundLockhart, S. M., Mušo, M., Zvetkova, I., Lam, B., Ferrari, A., Schoenmakers, E., Duckett, K., Leslie, J., Collins, A., Romartínez-Alonso, B., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01126-4 · Cited by 23
“Thus, impaired hepatic cholesterol clearance may undermine the therapeutic utility of LXR-inverse agonists in MASLD.”
InfluentialSun, Q., Xin, X., An, Z., Hu, Y., & Feng, Q. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.854879 · Cited by 20
“The content of BAs, especially secondary BAs, increases significantly in the serum of hosts with NAFLD (Jiao et al., 2018).”
BackgroundInfluentialLu, Y., Shao, M., Zhang, C., Xiang, H., Wang, J., Wu, T., & Ji, G. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.946360 · Cited by 20
“Current literature reports on the association between BA components and NASH are inconsistent (Dasarathy et al., 2011; Lake et al., 2013; Jiao et al., 2018; Puri et al., 2018).”
BackgroundZhang, J., Yang, Y., Wang, Z., Zhang, X., Zhang, Y., Lin, J., Du, Y., Wang, S., Si, D., Bao, J., et al. (2023) · Journal of Proteome Research · doi:10.1021/acs.jproteome.3c00009 · Cited by 19
Sheng, X., Zhan, P., Wang, P., He, W., & Tian, H. (2024) · Food & Function · doi:10.1039/d3fo05235d · Cited by 20
Farnesoid X receptor mediates hepatic steatosis induced by PM2.5
Wang, M., Tan, J., Zhou, J., Yi, B., & Huang, Z. (2020) · Environmental Science and Pollution Research · doi:10.1007/s11356-020-09676-2 · Cited by 19
Liu, Y., Xiao, Y., Chen, S., Tian, X., Wang, W., Wang, Y., & Cai, W. (2021) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000003135 · Cited by 20
“Bacteroides and Clostridium produce secondary BAs through the 7adehydroxylation of unconjugated primary BAs (21,36).”
BackgroundDietary nutrients mediate crosstalk between bile acids and gut microbes in animal host metabolism
Lin, Z., & Ma, X. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2067118 · Cited by 20
“Interestingly, BAs appeared to be one of the valuable targets in the research of diseases treatments (Jiao et al. 2018; Li et al. 2018; Wang, Tang, et al. 2021; Gao et al. 2021; Shah et al. 2020).”
BackgroundExploring the roles of intestinal flora in enhanced recovery after surgery
Liu, Z., Li, N., Dang, Q., Liu, L., Wang, L., Li, H., & Han, X. (2023) · iScience · doi:10.1016/j.isci.2023.105959 · Cited by 24
“Primary bile acids are synthesized in hepatocytes from cholesterol and transformed into secondary bile acids by intestinal flora.(45) Both categories of bile acids modulate the integration via FGF19/FGF15,(46) whereas they do take on metabolic effects through the nuclear receptor, farnesoid X receptor (FXR), and the m…”
BackgroundChen, L., Zhang, L., Liu, S., Hua, H., Zhang, L., Liu, B., & Wang, R. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.01979-23 · Cited by 19
“In a recent animal study, it was found that LG could inhibit the abundance of Peptococca ceae and odoribacter in rats with nonalcoholic steatoheoatitis (NASH) (17), which aligns with our funding.”
BackgroundInfluentialMurine epithelial sodium (Na+) channel regulation by biliary factors
Wang, X., Im, S. J., Balchak, D. M., Montalbetti, N., Carattino, M. D., Ray, E. C., & Kashlan, O. B. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.007394 · Cited by 19
Zhang, Z., Dai, W., Weng, S., Luo, M., Fu, J., Zadroga, J. A., Spolitu, S., & Peng, D. (2020) · Lipids in Health and Disease · doi:10.1186/s12944-020-1201-6 · Cited by 19
Farnesoid X receptor: a potential therapeutic target in multiple organs.
Zhang, C., Wang, Z., Feng, Q., Chen, W.-D., & Wang, Y.-D. (2021) · Histology and Histopathology · doi:10.14670/hh-18-301 · Cited by 16
“Diseases regulated by gut-microbiota are not limited in the gastrointestinal tract and exist in other organs (Duparc et al., 2017; Jia et al., 2018; Jiao et al., 2018).”
Jiang, M., Tao, X., Pang, Y., Qin, Z., Song, E., & Song, Y. (2024) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2024.136416 · Cited by 18
Systematic identification of secondary bile acid production genes in global microbiome
Yang, Y., Gao, W., Zhu, R., Tao, L., Chen, W., Zhu, X., Shen, M., Xu, T., Zhao, T., Zhang, X., et al. (2024) · mSystems · doi:10.1128/msystems.00817-24 · Cited by 22
“Raw sequencing data were downloaded from the Sequence Read Archive (SRA) using the following identifiers: PRJEB1220 (IBD) for Nielsen et al. (81), PRJEB7774 (CRC) for Feng et al. (82), and PRJNA420817 (NAFLD) for Mardinoglu et al. (83) (in our study, paired “NAFLD” and “Control” samples were obtained from fecal sample…”
InfluentialSelf-citationZeng, W., Sun, M., Cao, J., Chen, C., Jiang, S., Wang, Y., Yang, W.-Q., Zhao, Z., & Jin, J. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156537 · Cited by 21
Che, Z., Xue, W., Zhao, X., Hu, C., & Tian, Y. (2025) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000914 · Cited by 20
“Clinical studies demonstrate characteristic reductions in secondary BA levels coupled with signi fi cant alterations in BA-transforming microbiota in patients with MASLD (80,81).”
Handelman, S. K., Puentes, Y., Kuppa, A., Chen, Y., Du, X., Feitosa, M. F., Palmer, N. D., & Speliotes, E. K. (2022) · Hepatology Communications · doi:10.1002/hep4.2066 · Cited by 19
“Results from animal models[47] of bile acids suggest that NAFLD resolution is contradictory and implicates additional processes[48,49] not addressed here.”
BackgroundZhang, Y., Wang, L., Qi, J., Yu, B., Zhao, J., Pang, L., Zhang, W., & Bin, L. (2023) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-023-01012-1 · Cited by 18
“Studies have shown that IR causes atrial structural remodeling and abnormal intracellular calcium homeostasis, thereby increasing the likelihood of AF [33].”
BackgroundTzeng, H., & Lee, W.-C. (2024) · Nutrients · doi:10.3390/nu16091388 · Cited by 18
“Patients with NAFLD often exhibit increased serum levels of secondary bile acids but reduced hepatic bile acid signaling [75].”
BackgroundHao, Y., Hao, Z., Zeng, X., & Lin, Y. (2024) · Journal of Gastroenterology · doi:10.1007/s00535-024-02134-7 · Cited by 18
“In cirrhotic patients, altered BA composition and functions could impair activation of the intestinal and liver farnesoid X receptor (FXR), lead to aggravation of gut permeability, hepatic fibrosis, and vascular dysfunction [40, 64].”
Characterization of gut dominant microbiota in obese patients with nonalcoholic fatty liver disease
Jin, L.-T., & Xu, M.-Z. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1113643 · Cited by 18
“In addition, bile acids and gut microbial metabolites may play possible roles in NAFLD (Jiao et al., 2018; Canfora et al., 2019; Chu et al., 2019; Aron-Wisnewsky et al., 2020a; Ortiz-López et al., 2022).”
BackgroundHan, Y., Guo, X., Du, H., Guo, Y., Ding, Q., Li, F., Meng, Y., & Xiao, H. (2025) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2025.105075 · Cited by 20
Liu, A., Huang, M., Xi, Y., Deng, X., & Xu, K. (2025) · Biomedicines · doi:10.3390/biomedicines13061422 · Cited by 17
Zhou, T., Jin, Z., Jiang, R., & Li, W. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1600439 · Cited by 19
Li, B., Ye, L., Zhao, Y., Liu, Y., Chen, Y., & Zhang, H. (2025) · Agricultural Products Processing and Storage · doi:10.1007/s44462-025-00023-7 · Cited by 29
“…into secondary bile acids, which help regulate gut microbiota, facilitate fat absorption, and interact with intestinal bile acid receptors farnesoid X receptor (FXP) and takeda G protein-coupled receptor 5 (TGR5), thereby influencing bile acid synthesis and energy metabolism in the liver [87].”
García-Santos, J. A., Nieto-Ruíz, A., García-Ricobaraza, M., Cerdó, T., & Campoy, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119427 · Cited by 18
“First, gut microbiota composition may alter bile acid (BA) profile in infants with constipation by regulating cholesterol 7α-hydroxylase (CYP7A1)dependent de novo BAs synthesis and/or increasing its sulfation [61,62]; ultimately, this altered BA profile negatively affects both intestinal motility and colonic fluid.”
BackgroundMarine algal polysaccharides as future potential constituents against non-alcoholic steatohepatitis
Lu, S., Tan, K., Zhong, S., & Cheong, K. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.126247 · Cited by 17
Exploring Bile-Acid Changes and Microflora Profiles in Chicken Fatty Liver Disease Model
Yang, W., Chang, P.-E., Li, S., Ding, S., & Lin, Y. (2024) · Animals · doi:10.3390/ani14070992 · Cited by 17
“…have indicated differences in gut microbiota composition between patients with non-alcoholic fatty liver disease and healthy individuals. et al. [13] demonstrated higher levels of bacteria such as Escherichia , Bilophila , and Rhodobacter in the intestines of non-alcoholic fatty liver patients…”
BackgroundNuclear receptors: pathophysiological mechanisms and drug targets in liver disease
Dubois, V., Lefèbvre, P., Staels, B., & Eeckhoute, J. (2024) · Gut · doi:10.1136/gutjnl-2023-331741 · Cited by 17
“For instance, signalling molecules or metabolites issued from the gut or adipose tissue have the ability to modulate the activities of hepatic FXR or PPARs 66–69 and could contribute to their dysfunction in liver diseases.”
Bilson, J., Scorletti, E., Swann, J. R., & Byrne, C. D. (2024) · Biomolecules · doi:10.3390/biom14070841 · Cited by 17
“As mentioned earlier, evidence indicates that the regulation of BAs and several BA signalling pathways is likely to become deranged in individuals with obesity-associated metabolic dysfunction and could have a profound impact on cardiometabolic risk [30,31].”
BackgroundLiu, C., Ruan, F., Chen, Z., Han, J.-R., Ding, X., Han, C., Ye, L., Yang, C., Yu, Y., Zuo, Z., et al. (2024) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2024.174923 · Cited by 21
Gao, S., Zhang, Q., Tian, C., Li, C., Lin, Y., Gao, W., Wu, D., Jiao, N., Zhu, L., Li, W., et al. (2019) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2019.112372 · Cited by 17
Self-citationHe, D., Su, Y., Meng, D., Wang, X., Wang, J., & Ye, H. (2021) · Journal of Mass Spectrometry and Advances in the Clinical Lab · doi:10.1016/j.jmsacl.2021.10.001 · Cited by 17
Wang, X., Klaassen, C. D., Chen, X., & Zhang, Y. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100073 · Cited by 17
Beneficial effects of inorganic nitrate in non-alcoholic fatty liver disease
Liu, Y., Croft, K. D., Caparros-Martin, J. A., O’Gara, F., Mori, T. A., & Ward, N. C. (2021) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2021.109032 · Cited by 16
Manjarín, R., Dillard, K., Coffin, M., Hernandez, G. V., Smith, V. A. O., Noland-Lidell, T., Gehani, T. R., Smart, H. J., Wheeler, K., Sprayberry, K. A., et al. (2022) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00052.2022 · Cited by 16
Lithocholic acid promotes rosacea-like skin inflammation via G protein-coupled bile acid receptor 1
Xiao, W., Chen, M., Peng, Q., Sha, K., Liu, T., Xia, J., Xie, H., Li, J., Xu, S., & Deng, Z. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2022.166563 · Cited by 16
Bao, Z., Guo, C., Chen, Y., Li, C., Lei, T., Zhou, S., Qi, D., & Xiang, Z. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112718 · Cited by 17
Skeletal muscles and gut microbiota-derived metabolites: novel modulators of adipocyte thermogenesis
Tang, Y., Wang, Y., Wang, Y. Y., Liao, Z., & Xiao, X. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1265175 · Cited by 17
Liu, H., Wang, X., Deng, H., Huang, H., Liu, Y., Zhong, Z., Shen, L., Cao, S., Ma, X., Zhou, Z., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216086 · Cited by 16
“The occurrence of a variety of liver diseases is accompanied by the disorder of BA metabolism [34,35].”
BackgroundIndole alleviates nonalcoholic fatty liver disease in an ACE2 ‐dependent manner
Gao, Y., Chen, Q., Yang, S., Cao, J., Li, F., Li, R., Wu, Z., Wang, Y., & Li, Y. (2024) · The FASEB Journal · doi:10.1096/fj.202401172rr · Cited by 16
“10,11 The flora metabolites, TMA, 12 short-chain fatty acids (SCFAs), and ethanol, 13,14 can enter the intestine-hepatic circulation through the weak intestinal barrier, thereby accelerating the progression of liver disease.”
Liver metabolism in human MASLD: A review of recent advancements using human tissue metabolomics
Flam, E. L., Haas, J. T., & Staels, B. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.119054 · Cited by 17
Quantification of common and planar bile acids in tissues and cultured cells
Shiffka, S. J., Jones, J. W., Li, L., Farese, A. M., MacVittie, T. J., Wang, H., Swaan, P. W., & Kane, M. A. (2020) · Journal of Lipid Research · doi:10.1194/jlr.d120000726 · Cited by 15
Revealing metabolic pathways relevant to prediabetes based on metabolomics profiling analysis
Ouyang, Y., Jin, Y., Zhao, X., Chen, M., Yang, P., Zheng, X., Zeng, L., Chen, L., & Tian, Z. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.09.016 · Cited by 16
Circulating Bile Acid Profiles: A Need for Further Examination
Li, Q., Tian, Y., & Chen, Y. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab531 · Cited by 16
Role of gut microbiota in the development of non-alcoholic fatty liver disease
Wang, X., Xia, J., & Jiang, C. (2019) · Liver Research · doi:10.1016/j.livres.2019.01.006 · Cited by 17
Wang, G., Wu, B., Cui, Y., Zhang, B., Jiang, C., & Wang, H. (2020) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.0c00192 · Cited by 15
Zhao, L., Jiang, Q., Lei, J., Cui, J., Pan, X., Yuan, Y., & Zhang, B. (2024) · Poultry Science · doi:10.1016/j.psj.2024.104422 · Cited by 18
Impact of Gut Microbiome on Gut Permeability in Liver and Gut Diseases
Saha, P., & Hartmann, P. (2025) · Microorganisms · doi:10.3390/microorganisms13061188 · Cited by 16
“An increase in deoxycholic acid, and concomitant decreases in FXR-agonistic chenodeoxycholic acid, are also reported in patients with MASLD, indicating the importance of the bile acid–FXR axis [139].”
Gut microbiota in non-alcoholic fatty liver disease: Pathophysiology, diagnosis, and therapeutics
Pandey, H., Goel, P., Srinivasan, V. M., Tang, D. W. T., Wong, S. H., & Lal, D. (2025) · World Journal of Hepatology · doi:10.4254/wjh.v17.i6.106849 · Cited by 20
Gut microbiome in liver pathophysiology and cholestatic liver disease
Yan, S., & Yin, X. (2021) · Liver Research · doi:10.1016/j.livres.2021.08.001 · Cited by 16
Xu, J., Xu, F., Wang, W., Wang, P.-P., Xian, J., Han, X., Shang, M., Liu, G., Wang, X., & Cai, S. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1002922 · Cited by 18
“Meanwhile, the increase in the levels of these two genera and the activity of BSH and 7α-HSHD causes the accumulation of secondary bile acids, which is one of the mechanisms of cholestatic liver diseases (Jiao et al., 2018).”
BackgroundWang, W. J., Zhai, T., Luo, P., Miao, X., Wang, J., & Chen, Y. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1257158 · Cited by 15
“Our results showed that SIL significantly increased the abundance of intestinal Akkermansiaceae in MCD mice, and its abundance was negatively correlated with serum levels of UDCA, 3-oxo-CA, and 23-norDCA, suggesting that SIL treatment affected the competition of bile acid agonists and antagonists for FXR signaling in il…”
BackgroundInfluentialSuárez, M., Martínez, R., Torres, A., Ramón, A., Blasco, P., & Mateo, J. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12206489 · Cited by 15
“After cholecystectomy, this feedback disappears, causing an increase in FGF19 concentrations and alterations in the enterohepatic circulation of bile acids, thereby exposing the liver to higher amounts of various lipids that may lead to the development of MASLD [50].”
BackgroundDelik, A., Dinçer, S., Ülger, Y., Akkız, H., & Karaoğullarından, Ü. (2022) · Gene · doi:10.1016/j.gene.2022.146587 · Cited by 15
Yan, L.-S., Kang, J.-Y., Gu, C.-Y., Qiu, X., Li, J., Cheng, B. C., Wang, Y., Luo, G., & Zhang, Y. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.119801 · Cited by 14
Shen, S., Liu, Y., Wang, N., Huang, Z., & Deng, G. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1621583 · Cited by 17
Qiu, Y., Laguna, J. C., Alegret, M., & Vilà, L. (2026) · Nutrients · doi:10.3390/nu18040679 · Cited by 14
“…and Ruminococcus, are reduced in MASLD patients [82], and changes in the abundance of bile acid metabolizing bacteria result in an imbalance in the ratio of primary to secondary bile acids, and alteration of the farnesoid X receptor (FXR) signalling pathway in liver and ileum tissues [83].”
Effect of Gender and Various Diets on Bile Acid Profile and Related Genes in Mice
Ma, C., Guo, Y., & Klaassen, C. D. (2020) · Drug Metabolism and Disposition · doi:10.1124/dmd.120.000166 · Cited by 14
“BAs are often quantified in serum and it is often assumed that BA concentrations in the serum reflects BA concentrations in the liver (Jiao et al., 2018).”
BackgroundWang, T., Huang, S., Wu, C., Wang, N., Zhang, R., Wang, M., & Mao, D. (2021) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2021/6682581 · Cited by 14
“microbes in HFD-fed rats and NASH patients suggests that HFD may be an important cause of the initiation of elevated intestinal bile acid [65].”
BackgroundThe molecular insights of bile acid homeostasis in host diseases
Zhang, J., Lü, A., & Wang, C. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121919 · Cited by 15
Metadata
- Authors
- Jiao, N., Baker, S. S., Chapa-Rodriguez, A., Liu, W., Nugent, C. A., Tsompana, M., Mastrandrea, L., Buck, M. J., Baker, R. D., Genco, R. J., Zhu, R., & Zhu, L.
- Affiliations
- Tongji University (CN)
- University at Buffalo, State University of New York (US)
- Department of Pediatrics, Digestive Diseases and Nutrition Center, The State University of New York at Buffalo, Buffalo, New York, USA
- Corresponding author
- Baker, Susan S
- Zhu, Lixin
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2017-08-03
- Volume
- 67
- Issue
- 10
- Pages
- 1881-1891
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2605955022
- Cited by
- 737
- References
- 50
- Citations by year
- 2026: 81 · 2025: 112 · 2024: 128 · 2023: 105 · 2022: 93 · 2021: 83 · 2020: 68 · 2019: 44 · 2018: 17 · 2017: 4
- FWCI
- 15.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- GEM Community of Excellence, the University at Buffalo
- the University at Buffalo Departmental Start-Up Fund
- Natural Science Foundation of Shanghai
- National Natural Science Foundation of China
- the Peter and Tommy Fund, Inc., Buffalo, NY
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- non-alcoholic fatty liver disease, bile acids, bile acid signaling, farnesoid X receptor, FGFR4, FGF19, gut microbiota, secondary bile acids, deoxycholic acid, lithocholic acid, taurine metabolism, hepatic gene expression, high-fat diet
- MeSH terms
- Gastrointestinal Microbiome, Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Cholesterol 7-alpha-Hydroxylase, Female, Fibroblast Growth Factors, Humans, Male, Middle Aged, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Gene Expression Profiling, Rats, Diet, High-Fat, Non-alcoholic Fatty Liver Disease
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