The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
FXR-Dependent Modulation of the Human Small Intestinal Microbiome by the Bile Acid Derivative Obeticholic Acid
Open accessAbstract
Background & Aims: Intestinal bacteria can modify the composition of bile acids and bile acids, which are regulated by the farnesoid X receptor (FXR), affect the survival and growth of gut bacteria. We studied the effects of obeticholic acid (OCA), a bile acid analog and FXR agonist, on the intestinal microbiomes of humans and mice. Methods: We performed a phase 1 study in 24 healthy volunteers given OCA (5 mg, 10 mg, or 25 mg per day, for 17 days). Fecal and plasma specimens were collected at baseline (day 0) and on days 17 (end of dosing) and 37 (end of study). The fecal specimens were analyzed by shotgun metagenomic sequencing. A Uniref90 high stringency genomic analysis was used to assign specific genes to the taxonomic signature of bacteria whose abundance was associated with OCA. Male C57BL/6 mice were gavaged daily with water, vehicle, or OCA (10 mg/kg) for 2 weeks. Small intestine luminal contents were collected by flushing with saline and fecal pellets were collected at baseline and day 14. Mouse samples were analyzed by 16S tagged sequencing. Culture experiments were performed to determine taxonomic-specific effects of bile acids and OCA on bacterial growth. Results: Suppression of endogenous bile acid synthesis by OCA in subjects led to a reversible induction of Gram-positive bacteria that are found in the small intestine and are components of diet and the oral microbiota. We found that bile acids reduced proliferation of these bacteria in minimum inhibitory concentration assays. In these organisms, there was an increase in the representation of microbial genomic pathways involved in DNA synthesis and amino acid metabolism with OCA treatment of subjects. Consistent with these findings, mice fed OCA had reduced endogenous bile acid levels and an increased proportion of Firmicutes, specifically in the small intestine, compared to mice fed water or vehicle. Conclusions: In studying the effects of OCA in humans and mice, we found evidence for interactions between bile acids and features of the small intestinal microbiome. These findings indicate that FXR activation alters the intestinal microbiota and could provide opportunities for microbiome biomarker discovery or new approaches to engineering the human microbiome. Clinical trial information: ClinicalTrials.gov no: NCT01933503.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“In recent years, it has been found that there is an important bidirectional relationship between intestinal microbiota and bile acids.”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [204]
In the citing paper
“Conversely, BAs and FXR ligands alter intestinal microbiota which may add to their therapeutic effects in both entities.53 56”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [56]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
Trimmomatic: a flexible trimmer for Illumina sequence data
Bolger, A. M., Lohse, M., & Usadel, B. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu170 · Cited by 65,548
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
QIIME allows analysis of high-throughput community sequencing data
Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Peña, A. G., Goodrich, J. K., Gordon, J. I., et al. (2010) · Nature Methods · doi:10.1038/nmeth.f.303 · Cited by 34,887
Self-citationSearch and clustering orders of magnitude faster than BLAST
Edgar, R. C. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq461 · Cited by 21,098
Changes of Intestinal Functions in Liver Cirrhosis
Fukui, H., & Wiest, R. (2016) · Inflammatory Intestinal Diseases · doi:10.1159/000444436 · Cited by 6,820
Caspi, R., Billington, R., Ferrer, L., Foerster, H., Fulcher, C. A., Keseler, I. M., Kothari, A., Krummenacker, M., Latendresse, M., Mueller, L. A., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1164 · Cited by 3,395
Personalized nutrition by prediction of glycemic responses
Zeevi, D., Korem, T., Zmora, N., Israeli, D., Rothschild, D., Weinberger, A., Ben-Yacov, O., Lador, D., Avnit-Sagi, T., Lotan-Pompan, M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.11.001 · Cited by 2,929
Alterations of the human gut microbiome in liver cirrhosis
Qin, N., Yang, F., Li, A., Prifti, E., Chen, Y., Shao, L., Guo, J., Le Chatelier, E., Yao, J., Wu, L., et al. (2014) · Nature · doi:10.1038/nature13568 · Cited by 2,177
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
Cited by
Sorted by citations
Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis
Cai, J., Sun, L., & Gonzalez, F. J. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.02.004 · Cited by 892
Gut-liver axis: Pathophysiological concepts and clinical implications
Tilg, H., Adolph, T. E., & Trauner, M. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.09.017 · Cited by 843
Targher, G., Byrne, C. D., & Tilg, H. (2020) · Gut · doi:10.1136/gutjnl-2020-320622 · Cited by 879
“158 In a two phase RCT, a 1-year treatment with elafibranor 120 mg/day (ie, a dual agonist of peroxisome-proliferator activated receptor [PPAR]- α and PPAR-δ ) was significantly associated with a higher rate of NASH resolution than occurred in the placebo arm.”
The gut–liver axis and gut microbiota in health and liver disease
Hsu, C. L., & Schnabl, B. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-023-00904-3 · Cited by 737
Molecular physiology of bile acid signaling in health, disease, and aging
Perino, A., Demagny, H., Velazquez-Villegas, L., & Schoonjans, K. (2021) · Physiological Reviews · doi:10.1152/physrev.00049.2019 · Cited by 481
Bile acids as modulators of gut microbiota composition and function
Larabi, A. B., Masson, H. L. P., & Bäumler, A. J. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2172671 · Cited by 443
“In healthy human subjects, the synthetic FXR agonist obeticholic acid (or INT-747) suppresses the synthesis of endogenous bile acids and induces the proliferation of Grampositive bacteria, including Streptococcus thermophilus, Lactobacillus casei, Lactobacillus paracasei, Bifidobacterium breve, and Lactococcus lactis,…”
BackgroundKastl, A., Terry, N. A., Wu, G. D., & Albenberg, L. G. (2019) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2019.07.006 · Cited by 381
Self-citationRole of the Gut Microbiota and Its Metabolites in Tumorigenesis or Development of Colorectal Cancer
Qu, R., Zhang, Y., Ma, Y., Zhou, X., Sun, L., Jiang, C., Zhang, Z., & Fu, W. (2023) · Advanced Science · doi:10.1002/advs.202205563 · Cited by 314
Discovery of farnesoid X receptor and its role in bile acid metabolism
Chiang, J. Y. L., & Ferrell, J. M. (2022) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2022.111618 · Cited by 305
The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options
Wang, Q., Luo, Y., Ray Chaudhuri, K., Reynolds, R., Tan, E.-K., & Pettersson, S. (2021) · Brain · doi:10.1093/brain/awab156 · Cited by 281
Mullish, B. H., McDonald, J. A. K., Pechlivanis, A., Allegretti, J. R., Kao, D., Barker, G. F., Kapila, D., Petrof, E. O., Joyce, S. A., Gahan, C. G. M., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-317842 · Cited by 268
Microbiota and Fatty Liver Disease—the Known, the Unknown, and the Future
Lang, S., & Schnabl, B. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.07.007 · Cited by 244
“OCA leads to alterations in the human gut microbiome (Friedman et al., 2018) and preclinical studies found that OCA prevents disruption of the gut vascular barrier (Mouries et al.”
BackgroundNovel therapeutic targets for cholestatic and fatty liver disease
Trauner, M., & Fuchs, C. D. (2022) · Gut · doi:10.1136/gutjnl-2021-324305 · Cited by 204
Wang, S., Martins, R., Sullivan, M. C., Friedman, E. S., Misic, A. M., El‐Fahmawi, A., Martinis, E. C. P. D., O’Brien, K. M., Chen, Y., Bradley, C. W., et al. (2019) · Microbiome · doi:10.1186/s40168-019-0740-4 · Cited by 208
Self-citationFXR agonists in NASH treatment
Adorini, L., & Trauner, M. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.07.034 · Cited by 200
Self-citationMicrocins in Enterobacteriaceae: Peptide Antimicrobials in the Eco-Active Intestinal Chemosphere
Baquero, F., Lanza, V. F., Baquero, M.-R., del Campo, R., & Bravo-Vázquez, D. A. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02261 · Cited by 174
Targeting the gut-liver-immune axis to treat cirrhosis
Tranah, T. H., Edwards, L. A., Schnabl, B., & Shawcross, D. L. (2020) · Gut · doi:10.1136/gutjnl-2020-320786 · Cited by 168
Effect of different bile acids on the intestine through enterohepatic circulation based on FXR
Xiang, J., Zhang, Z., Xie, H., Zhang, C., Bai, Y., Cao, H., Che, Q., Guo, J., & Su, Z. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1949095 · Cited by 146
Intestinal dysbiosis in nonalcoholic fatty liver disease (NAFLD): focusing on the gut–liver axis
Han, H. L., Jiang, Y., Wang, M., Melaku, M., Liu, L., Zhao, Y. M., Everaert, N., Yi, B., & Zhang, H. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1966738 · Cited by 135
Understanding bile acid signaling in diabetes: From pathophysiology to therapeutic targets
Ferrell, J. M., & Chiang, J. Y. L. (2019) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2019.0043 · Cited by 139
Promises of microbiome-based therapies
Bajaj, J. S., Ng, S. C., & Schnabl, B. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2021.12.003 · Cited by 119
The microbiota and the gut–liver axis in primary sclerosing cholangitis
Hov, J. R., & Karlsen, T. H. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00690-y · Cited by 133
NAFLD and Atherosclerosis: Two Sides of the Same Dysmetabolic Coin?
Stols‐Gonçalves, D., Hovingh, G. K., Nieuwdorp, M., & Holleboom, A. G. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.08.008 · Cited by 118
Schnabl, B., Damman, C. J., & Carr, R. M. (2025) · Journal of Clinical Investigation · doi:10.1172/jci186423 · Cited by 133
“…demonstrated that there are differences in abundance of these microbes along the intestinal tract, where small intestinal microbiota communities and their metabolites differed from that of the colon, and we suspect that where in the intestinal tract microbes reside has biological consequences (7).”
Self-citationGut-liver axis signaling in portal hypertension
Simbrunner, B., Mandorfer, M., Trauner, M., & Reiberger, T. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i39.5897 · Cited by 113
Bile acid modulators for the treatment of nonalcoholic steatohepatitis (NASH)
Fiorucci, S., Biagioli, M., Sepe, V., Zampella, A., & Distrutti, E. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1763302 · Cited by 99
“Furthermore, obeticholic acid, has been shown effective in shaping the intestinal microbiota [58].”
BackgroundLittmann, E. R., Lee, J.-J., Denny, J. E., Alam, Z., Maslanka, J. R., Zarin, I., Matsuda, R., Carter, R. A., Susac, B., Saffern, M. S., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20793-x · Cited by 88
Self-citationFu, T., Huan, T., Rahman, G., Zhi, H., Xu, Z. Z., Oh, T. G., Guo, J. P., Coulter, S., Tripathi, A., Martino, C., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112997 · Cited by 94
Bile Acids, Their Receptors, and the Gut Microbiota
Poland, J. C., & Flynn, C. R. (2021) · Physiology · doi:10.1152/physiol.00028.2020 · Cited by 93
Jin, P., Duan, X., Huang, Z., Dong, Y., Zhu, J., Guo, H., Tian, H., Zou, C., & Xie, K. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02270-3 · Cited by 88
“487 For example, FXR plays a pivotal role in modulating the gut microbiota and is thereby involved in various biological processes, including the metformin response, 488 bile acid homeostasis, 489 and core metabolic functions.”
Farnesoid X Receptor, Bile Acid Metabolism, and Gut Microbiota
Mori, H., Svegliati‐Baroni, G., Marzioni, M., Nicola, F. D., Santori, P., Maroni, L., Abenavoli, L., & Scarpellini, E. (2022) · Metabolites · doi:10.3390/metabo12070647 · Cited by 82
Novel approaches in IBD therapy: targeting the gut microbiota-bile acid axis
Pan, Y., Zhang, H., Li, M., He, T., Guo, S., Zhu, L., Tan, J., & Wang, B. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2356284 · Cited by 84
“24 A recent study revealed that the gut microbiota of centenarians (average age, 107 years old; n = 160) was enriched in Bacteroides and Alistipes , while the abundance of Streptococcus was reduced compare with older (85–89 years old; n = 112) and young (21–55 years old; n = 47).”
BackgroundLi, B., Zhang, J., Chen, Y., Wang, Q., Li, Y., Wang, R., Wei, Y., You, Z., Li, Y., Miao, Q., et al. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1946366 · Cited by 74
“The use of a bile acid analog, obeticholic acid (OCA), led to a reversible induction of gram-positive bacteria in rodents and humans.(7) Of note, our previous work revealed the presence of a microbial perturbation in naïve PBC patients, and UDCA treatment can partially reverse this dysbiosis.”
BackgroundSelf-citationCarino, A., Biagioli, M., Marchianò, S., Fiorucci, C., Zampella, A., Monti, M. C., Scarpelli, P. T., Ricci, P., Distrutti, E., & Fiorucci, S. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2019.07.006 · Cited by 70
Bile Salt Hydrolase-Competent Probiotics in the Management of IBD: Unlocking the “Bile Acid Code”
Gadaleta, R. M., Cariello, M., Crudele, L., & Moschetta, A. (2022) · Nutrients · doi:10.3390/nu14153212 · Cited by 67
Nuclear Receptors Regulate Intestinal Inflammation in the Context of IBD
Klepsch, V., Moschen, A. R., Tilg, H., Baier, G., & Hermann‐Kleiter, N. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01070 · Cited by 63
“AOM/APCmin LRH-1+/− mice show reduced intestinal tumorigenesis (26)”
BackgroundThe contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection
Mullish, B. H., & Allegretti, J. R. (2021) · Therapeutic Advances in Gastroenterology · doi:10.1177/17562848211017725 · Cited by 61
Zhao, M., Jiafeng, Z., Yang, H., Ouyang, Z., Lv, C., Geng, Z., & Zhao, J. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118182 · Cited by 69
Targeting nonalcoholic fatty liver disease via gut microbiome-centered therapies
Koning, M., Herrema, H., Nieuwdorp, M., & Meijnikman, A. S. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2226922 · Cited by 56
Research progress on the relationship between bile acid metabolism and type 2 diabetes mellitus
Hou, Y., Zhai, X., Wang, X., Wu, Y., Wang, H., Qin, Y., Han, J., & Meng, Y. (2023) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-023-01207-6 · Cited by 59
Zazueta, A., Valenzuela-Pérez, L., Ortiz‐López, N., Pinto-León, A., Torres, V., Guiñez, D., Aliaga, N., Merino, P., Sandoval, A., Covarrubías, N., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084387 · Cited by 57
“In humans, the administration of obeticholic acid has been shown to increase the abundance of Gram-positive bacteria [16], while these effects in mice were reversed using BA sequestrants [17].”
BackgroundYao, Y., Li, X., Xu, B., Luo, L., Guo, Q., Wang, X., Sun, L., Zhang, Z., & Li, P. (2022) · Cell Communication and Signaling · doi:10.1186/s12964-022-00890-8 · Cited by 50
Xiang, D., Yang, J., Liu, L., Yu, H., Gong, X., & Liu, D. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115606 · Cited by 51
Gut microbiota and their metabolites in the progression of non-alcoholic fatty liver disease
Zhou, J., Tripathi, M., Sinha, R. A., Singh, B. K., & Yen, P. M. (2021) · Hepatoma Research · doi:10.20517/2394-5079.2020.134 · Cited by 49
“Consistent with this finding, mice fed OCA showed increased proportion of firmicutes in the small intestine([91]).”
ResultKastl, A., Zong, W., Gershuni, V. M., Friedman, E. S., Tanes, C., Boateng, A., Mitchell, W. J., O’Connor, K., Bittinger, K. L., Terry, N. A., et al. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2083417 · Cited by 49
“Small intestinal contents and feces were sequenced, and bile acid levels were quantified in the systemic blood, small intestinal contents, and feces as previously described.(45)”
MethodSelf-citationEthanol-induced changes to the gut microbiome compromise the intestinal homeostasis: a review
Sosnowski, K., & Przybyłkowski, A. M. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2393272 · Cited by 52
“151 Interestingly, individuals with inflammatory bowel disease (IBD) often exhibit diminished primary bile acid conversion into secondary bile acids by their gut microbiome.”
BackgroundReview of the Relationships Between Human Gut Microbiome, Diet, and Obesity
Patloka, O., Komprda, T., & Franke, G. (2024) · Nutrients · doi:10.3390/nu16233996 · Cited by 50
“The data of Friedman et al. [85] indicate that the FXR activation modulates the gut microbiota composition via the BAs-dependent mechanism, suppressing BAs synthesis in the liver and stimulating the proliferation of the Gram-positive species, such as Streptococcus thermophilus , Lactobacillus casei…”
Crosstalk between Gut Microbiota and Bile Acids in Cholestatic Liver Disease
Shi, Q., Yuan, X., Zeng, Y., Wang, J., Zhang, Y., Chen, X., & Li, L. (2023) · Nutrients · doi:10.3390/nu15102411 · Cited by 41
The Influence of the Microbiome on NAFLD and NASH
Albhaisi, S. A. M., & Bajaj, J. S. (2021) · Clinical Liver Disease · doi:10.1002/cld.1010 · Cited by 40
Bile Acids: Key Regulators and Novel Treatment Targets for Type 2 Diabetes
Wu, Y., Zhou, A., Tang, L., Lei, Y., Tang, B., & Zhang, L. (2020) · Journal of Diabetes Research · doi:10.1155/2020/6138438 · Cited by 38
“The remaining 5% of BAs are excreted in the feces or serve as substrates for biotransformation, where they will be converted into secondary bile acids by the intestinal microbiota: deoxycholic acid (DCA) is formed from CA, lithocholic acid (LCA) is formed from CDCA, and ursodeoxycholic acid (UDCA) is formed in humans…”
BackgroundObeticholic Acid and Other Farnesoid-X-Receptor (FXR) Agonists in the Treatment of Liver Disorders
Fiorucci, S., Urbani, G., Distrutti, E., & Biagioli, M. (2025) · Pharmaceuticals · doi:10.3390/ph18091424 · Cited by 42
The Role of the Intestinal Microbiota in Nonalcoholic Steatohepatitis
Xiang, H., Sun, D., Liu, X., She, Z., & Chen, Y. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.812610 · Cited by 37
Regulating bile acids signaling for NAFLD: molecular insights and novel therapeutic interventions
Wei, M., Tu, W., & Huang, G. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1341938 · Cited by 39
Intestinal barrier in chronic gut and liver diseases: Pathogenesis and therapeutic targets
Zhang, Y., Liu, Y., Liang, X., Wen, Y., Zhao, J., He, Y., Xie, Q., & Xie, C. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.08.028 · Cited by 40
“…agonist obeticholic acid (OCA) can increase the proportion of microbes involved in DNA synthesis and amino acid metabolism, reduce the proliferation of certain Gram-positive bacteria, and decrease the concentrations of endogenous bile acids, thus effectively improving gut ecological disorders 164 .”
Bile acid and its bidirectional interactions with gut microbiota: a review
He, S., Li, L., Yao, Y., Su, J., Lei, S., Zhang, Y., & Zeng, H. (2023) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2023.2262020 · Cited by 36
“Friedman et al. also demonstrated that FXR can be activated by bile acid treatment, thereby inhibiting the overgrowth of gram-positive bacteria (Friedman et al. 2018).”
Targeting Nuclear Receptors for Cancer Therapy: Premises, Promises, and Challenges
Yang, Z., Gimple, R. C., Zhou, N., Zhao, L., Gustafsson, J.-Α., & Zhou, S. (2020) · Trends in cancer · doi:10.1016/j.trecan.2020.11.007 · Cited by 36
Immunomodulation by foods and microbes: Unravelling the molecular tango
Forde, B. M., Yao, L., Shaha, R., Murphy, S., Lunjani, N., & O’Mahony, L. (2022) · Allergy · doi:10.1111/all.15455 · Cited by 35
Wu, L. M., Han, Y., Zheng, Z., Zhu, S., Chen, J., Yao, Y., Yue, S., Teufel, A., Weng, H., Li, L., et al. (2021) · Nutrients · doi:10.3390/nu13030940 · Cited by 36
Disruption of intestinal oxygen balance in acute colitis alters the gut microbiome
Zong, W., Friedman, E. S., Allu, S., Firrman, J., Tu, V., Daniel, S. G., Bittinger, K. L., Liu, L., Vinogradov, S. A., & Wu, G. D. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2361493 · Cited by 33
“8,45,46”
Self-citationFecal microbiome and bile acid metabolome in adult short bowel syndrome
Boutte, H. J., Chen, J., Wylie, T. N., Wylie, K. M., Xie, Y., Geisman, M., Prabu, A., Gazit, V., Tarr, P. I., Levin, M. S., et al. (2022) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00091.2021 · Cited by 33
Carr, R. M., Li, Y., Chau, L., Friedman, E. S., Lee, J., Adorini, L., Erickson, M., Zaru, L., Shringarpure, R., MacConell, L., et al. (2023) · Hepatology · doi:10.1097/hep.0000000000000474 · Cited by 34
“[30] Briefly, fecal samples were suspended in methanol (5 μ L/mg stool), vortexed for 1 minute, centrifuged twice at 13,000 g for 5 minutes, and quantified against known standards using a Waters Acquity uPLC System with a Cortecs UPLC C-18 + 1.6 μ m 2.1 × 50 mm column and a Qda single quadrupole…”
BackgroundMethodResultInfluentialSelf-citationBile Acid Receptor Therapeutics Effects on Chronic Liver Diseases
Meadows, V., Kennedy, L. L., Kundu, D., Alpini, G. D., & Francis, H. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00015 · Cited by 31
Mouzaki, M., & Loomba, R. S. (2019) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756284819858470 · Cited by 31
Role of Farnesoid X Receptor in the Pathogenesis of Respiratory Diseases
Wu, J., Chen, J., & Chen, J. (2020) · Canadian Respiratory Journal · doi:10.1155/2020/9137251 · Cited by 31
“1), which is mainly expressed in various digestible tissues, including the liver [24] and small intestine [25].”
BackgroundGuo, Z., He, K., Pang, K., Yang, D., Lyu, C., Xu, H., & Wu, D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084321 · Cited by 29
“Changes in the intestinal microbiota were observed in both healthy humans and mice after OCA treatment [107].”
BackgroundPotential of Intestine-Selective FXR Modulation for Treatment of Metabolic Disease
van Zutphen, T., Bertolini, A., de Vries, H. D., Bloks, V. W., de Boer, J. F., Jonker, J. W., & Kuipers, F. (2019) · Handbook of experimental pharmacology · doi:10.1007/164_2019_233 · Cited by 31
Xiong, F., Zheng, Z., Xiao, L., Su, C., Chen, J., Gu, X., Tang, J., Zhao, Y., Luo, H., & Zha, L. (2021) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202100067 · Cited by 29
Nuclear Receptors in the Pathogenesis and Management of Inflammatory Bowel Disease
Ning, L., Lou, X., Zhang, F., & Xu, G. (2019) · Mediators of Inflammation · doi:10.1155/2019/2624941 · Cited by 27
“FXR activation by obeticholic acid (OCA) is associated with the retention of dendritic cells in the spleen, but not inmesenteric lymphnodes, thereby alleviating inflammatory cell infiltration of the colon [89].”
ResultRetroperfusion studies of the aqueous outflow system. Part 2: Studies in human eyes.
Ethier, C. R., Coloma, F. M., de Kater, A. W., & Allingham, R. R. (1995) · PubMed · Cited by 28
Intestine-specific FXR agonists as potential therapeutic agents for colorectal cancer
Yin, Y., Wang, M., Gu, W., & Chen, L. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114430 · Cited by 27
Emerging roles of bile acids in control of intestinal functions
Yang, J., Palmiotti, A., & Kuipers, F. (2020) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000709 · Cited by 28
“The clinical use of FXR agonist OCA and secondary bile acid UDCA for the treatment of liver diseases modulates intestinal microbiome [32,36].”
BackgroundThe 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
Zeng, Z., Zhou, Y., Xu, Y., Wang, S., Wang, B., Zeng, Z., Wang, Q., Ye, X., Lu, J., Yue, M., et al. (2022) · Food & Function · doi:10.1039/d1fo03170h · Cited by 24
Bile acid–gut microbiota crosstalk in irritable bowel syndrome
Gu, Y., Li, L., Yang, M., Liu, T., Song, X., Qin, X., Xu, X. J., Liu, J., Wang, B., & Cao, H. (2022) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2022.2058353 · Cited by 26
“Notably, an increased Firmicutes to Bacteroidetes ratio, along with a higher level of Clostridium XIVa, have been widely discovered in IBS populations (Rajili c-Stojanovi c et al. 2015).”
BackgroundInfluentialSaid, I., Ahad, H., & Said, A. (2022) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v14.i5.947 · Cited by 27
Jiang, J., Zhang, H., Hussain, M., Abdullah, Feng, F., Guan, R., & Zhong, H. (2025) · Biology · doi:10.3390/biology14070802 · Cited by 28
“For example, the FXR agonist obeticholic acid (OCA) suppresses endogenous BA synthesis while promoting gram-positive bacteria (e.g., Streptococcus salivarius subsp. thermophilus , Lacticaseibacillus paracasei , Bifidobacterium breve , and Lactococcus lactis [28]).”
Self-citationSecondary bile acids as immune and metabolic mediators
Fiorucci, S., Biagioli, M., Marchianò, S., Zampella, A., & Distrutti, E. (2026) · Trends in Immunology · doi:10.1016/j.it.2025.12.008 · Cited by 25
Nonalcoholic fatty liver disease and the gut microbiome: Are bacteria responsible for fatty liver?
Dong, T. S., & Jacobs, J. P. (2019) · Experimental Biology and Medicine · doi:10.1177/1535370219836739 · Cited by 22
“The administration of obeticholic acid also led to a reversible induction of Grampositive bacteria in the human small intestine and increased proportion of Firmicutes in mice.(98) While initial results are promising, ongoing studies and phase 3 trials are underway in order to better understand the complex relationship…”
Sun, 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
Li, Y., Wang, K., Ding, J., Sun, S., Ni, Z., & Yu, C. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.954684 · Cited by 21
“In recent years, studies have shown that OCA can change the characteristics of the GM of mice and humans and reduce the level of endogenous BAs by activating FXR (Friedman et al., 2018).”
BackgroundSelf-citationLiu, 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
“Elliot et al (38) reported that FXR activation induced by oral OCA altered the composition of ileal microbiota and endogenous BA levels.”
BackgroundMarzano, M., Fosso, B., Colliva, C., Notario, E., Passeri, D., Intranuovo, M., Gioiello, A., Adorini, L., Pesole, G., Pellicciari, R., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113380 · Cited by 21
Self-citationEffects of bile acid metabolism on intestinal health of livestock and poultry
Jia, H., & Dong, N. (2024) · Journal of Animal Physiology and Animal Nutrition · doi:10.1111/jpn.13969 · Cited by 19
Metabolic Analysis of Regionally Distinct Gut Microbial Communities Using an In Vitro Platform
Firrman, J., Liu, L., Tanes, C., Friedman, E. S., Bittinger, K. L., Daniel, S. G., den Abbeele, P. V., & Evans, B. S. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b05202 · Cited by 19
Self-citationChen, P., Jiang, X., Fu, J., Ou, C., Li, Y., Jia, J., & Liao, C. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1419160 · Cited by 19
Self-citationFarnesoid 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
“Friedma et al. reported that FXR ligand OCA increased Gram-positive bacteria through the regulation of BA synthesis (Friedman et al., 2018).”
Antibiotic exposure is associated with minimal gut microbiome perturbations in healthy term infants
Benitez, A., Tanes, C., Friedman, E. S., Zackular, J. P., Ford, E., Gerber, J. S., DeRusso, P. A., Kelly, A. T., Li, H., Elovitz, M. A., et al. (2025) · Microbiome · doi:10.1186/s40168-024-01999-3 · Cited by 19
Self-citationSecretory IgM regulates gut microbiota homeostasis and metabolism
Ding, Y., Fernández-Montero, Á., Mani, A., Casadei, E., Miyazawa, R., Zhou, C., Chaumont, L., Posavi, M., Cole, S. D., Shibasaki, Y., et al. (2025) · Nature Microbiology · doi:10.1038/s41564-025-02013-8 · Cited by 17
“69.”
Lin, X., Zhu, X., Xin, Y., Zhang, P., Xiao, Y., He, T., & Guo, H. (2023) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202200595 · Cited by 18
Mo, Q., Deng, X., Zhou, Z., & Yin, L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104777 · Cited by 20
“Concurrently, preclinical and clinical evidence shows that HFD-induced alterations in secondary bile acid metabolism exacerbate hepatic lipid accumulation and suppress GLP-1 secretion through farnesoid X receptor (FXR) signaling activation [184,185].”
Wu, Y., Wang, Z., Zhao, Z., Song, X., Miao, M., & Zhang, X. (2023) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15104 · Cited by 17
Mao, J., Wei, Y., Ni, Z., Zhang, J., Zhu, J., & Wang, H. (2025) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-025-01169-x · Cited by 16
Wang, L. J., Sun, J., Chen, S., Sun, Y., Zheng, Y., & Feng, J. C. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2024.1490929 · Cited by 19
Zhang, C., Gan, Y., Lv, J.-W., Qin, M.-Q., Hu, W., Liu, Z.-B., Ma, L., Song, B., Li, J., Jiang, W., et al. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106442 · Cited by 15
Hou, M., Song, P., Chen, Y., Yang, X., Chen, P., Cao, A., & Ni, Y. (2024) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2024.117313 · Cited by 15
Chewing the Fat with Microbes: Lipid Crosstalk in the Gut
Lemons, J. M. S., & Liu, L. (2022) · Nutrients · doi:10.3390/nu14030573 · Cited by 14
“Bile acids can influence the composition of the gut microbiota of the intestine, and this composition influences the species of secondary bile acids available for host metabolism [123].”
BackgroundHistamine Causes Pyroptosis of Liver by Regulating Gut-Liver Axis in Mice
Luo, Q., Shi, R., Liu, Y., Huang, L., Chen, W., & Wang, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073710 · Cited by 14
“Meanwhile, the liver components can affect liver health via influencing the community and function of the gut microbiota [13].”
BackgroundTang, Q., & Evans, R. M. (2021) · Essays in Biochemistry · doi:10.1042/ebc20210038 · Cited by 14
Dietary Fiber Modulates the Window of Susceptibility to Clostridioides difficile Infection
Hewlett, K. K., PeBenito, A., Hecht, A. L., Tiffany, C. R., Tanes, C., Glover, R. C., Fawad, J. A., Friedman, E. S., Reynolds, J. C., Bittinger, K. L., et al. (2025) · Gastroenterology · doi:10.1053/j.gastro.2025.04.027 · Cited by 13
Self-citationNew insights into gut-liver axis in advanced liver diseases: A promising therapeutic target
Xing, Y., Ou, Y., Wang, Y., Hou, L., & Zhu, J. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117284 · Cited by 13
Metadata
- Authors
- Friedman, E. S., Li, Y., Shen, T.-C. D., Jiang, J., Chau, L., Adorini, L., Babakhani, F., Edwards, J., Shapiro, D., Zhao, C., Carr, R. M., Bittinger, K., Li, H., & Wu, G. D.
- Affiliations
- University of Pennsylvania (US)
- Intercept Pharmaceuticals (United States) (US)
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Wu, Gary D.
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 155
- Issue
- 6
- Pages
- 1741-1752.e5
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC6279623
- OpenAlex
- W2888639734
- Semantic Scholar
- 112d9c4c64a59c5fa23a506e2249278055eca2ff
- Cited by
- 149
- References
- 44
- Citations by year
- 2026: 15 · 2025: 28 · 2024: 19 · 2023: 16 · 2022: 19 · 2021: 17 · 2020: 16 · 2019: 17
- FWCI
- 4.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (K08AA021424, R01AA026302)
- National Institute of General Medical Sciences (R01GM123056)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK106457, P30DK019525, P30DK050306)
- 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
- obeticholic acid, farnesoid X receptor, bile acids, gut microbiota, bile acid synthesis inhibition, Gram-positive bacteria, Firmicutes, bacterial growth inhibition, microbiome biomarkers
- MeSH terms
- Gastrointestinal Microbiome, Receptor, Farnesoid X-Activated, Adult, Animals, Bile Acids and Salts, Chenodeoxycholic Acid, Female, Humans, Intestine, Small, Male, Mice, Inbred C57BL, Receptors, Cytoplasmic and Nuclear, Mice, Healthy Volunteers
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
