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
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
