ArticleJCI insight2022
Secondary bile acids mediate high-fat diet-induced upregulation of R-spondin 3 and intestinal epithelial proliferation.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Pleiotropic roles of microbial bile acid metabolism in intestinal health and diseases.Cell host & microbe · 2026Review
- Gut microbial metabolites in colorectal cancer: dual roles in tumorigenesis, immune crosstalk, and therapeutic innovation.Frontiers in cellular and infection microbiology · 2026Review
- The impact of a high-fat diet on liver health in pregnant mice and their offspring: The role of the gut-liver axis.iMetaOmics · 2025Article
- Unveiling CTRB2, RSPO3, KLOTB, and ROR1 as obesity-pancreatic disease association proteins: a comprehensive Mendelian randomization study.Gastroenterology report · 2025Article
- Host response to cholestyramine can be mediated by the gut microbiota.Microbiome research reports · 2024Article
- Host-gut microbiota derived secondary metabolite mediated regulation of Wnt/β-catenin pathway: a potential therapeutic axis in IBD and CRC.Frontiers in oncology · 2024Review
- High-fat diet promotes gestational diabetes mellitus through modulating gut microbiota and bile acid metabolism.Frontiers in microbiology · 2024Article
- Are gut dysbiosis, barrier disruption, and endotoxemia related to adipose tissue dysfunction in metabolic disorders? Overview of the mechanisms involved.Internal and emergency medicine · 2023Review
- Review
- Review
- Association between Gut Microbiota and Digestive System Cancers: A Bidirectional Two-Sample Mendelian Randomization Study.Nutrients · 2023Article
- The gut microbiota in obesity and weight management: microbes as friends or foe?Nature reviews. Endocrinology · 2023Review
- Review
- Effects of a Western Diet on Colonic Dysbiosis, Bile Acid Dysmetabolism and Intestinal Inflammation in Clinically Healthy Dogs.Journal of veterinary internal medicineArticle
Corrections and comments
- Retraction · 2024-04-22Falsification/Fabrication of Data · Investigation by Company/Institution · Misconduct - Official Investigation(s) and/or Finding(s) ·
- Retracted
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
A high-fat diet (HFD) contributes to the increased incidence of colorectal cancer, but the mechanisms are unclear. We found that R-spondin 3 (Rspo3), a ligand for leucine-rich, repeat-containing GPCR 4 and 5 (LGR4 and LGR5), was the main subtype of R-spondins and was produced by myofibroblasts beneath the crypts in the intestine. HFD upregulated colonic Rspo3, LGR4, LGR5, and β-catenin gene expression in specific pathogen-free rodents, but not in germ-free mice, and the upregulations were prevented by the bile acid (BA) binder cholestyramine or antibiotic treatment, indicating mediation by both BA and gut microbiota. Cholestyramine or antibiotic treatments prevented HFD-induced enrichment of members of the Lachnospiraceae and Rumincoccaceae, which can transform primary BA into secondary BA. Oral administration of deoxycholic acid (DCA), or inoculation of a combination of the BA deconjugator Lactobacillus plantarum and 7α-dehydroxylase-containing Clostridium scindens with an HFD to germ-free mice increased serum DCA and colonic Rspo3 mRNA levels, indicating that formation of secondary BA by gut microbiota is responsible for HFD-induced upregulation of Rspo3. In primary myofibroblasts, DCA increased Rspo3 mRNA via TGR5. Finally, we showed that cholestyramine or conditional deletion of Rspo3 prevented HFD- or DCA-induced intestinal proliferation. We conclude that secondary BA is responsible for HFD-induced upregulation of Rspo3, which, in turn, mediates HFD-induced intestinal epithelial proliferation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.