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Bacterial translocation and changes in the intestinal microbiome in mouse models of liver disease
Open accessAbstract
Background & aims Intestinal dysbiosis and bacterial translocation are common in patients with advanced liver disease, and there is strong evidence that the translocation of bacteria and their products across the epithelial barrier drives experimental liver disease progression. The aims of our study were to investigate dynamics of bacterial translocation and changes in the enteric microbiome in early stages of liver disease.Methods Cholestatic liver injury was induced by ligation of the common bile duct (BDL) and toxic liver injury by injection of carbon tetrachloride (CCl(4)) in mice.Results Increased intestinal permeability and bacterial translocation occurred one day following liver injury in both disease models. This was accompanied by decreased intestinal expression of the tight junction protein occludin. Although BDL resulted in a rapid onset of intestinal bacterial overgrowth, bacterial overgrowth was observed in mice injected with CCl(4) only in advanced stages of liver fibrosis. To further assess the qualitative changes in the intestinal microbiome, massively parallel pyrosequencing of 16S rRNA genes revealed minor microbial changes following BDL, while CCl(4) administration resulted in a relative abundance of Firmicutes and Actinobacteria compared with oil-injected mice. Four different liver disease models (cholestasis, toxic, alcohol, obesity) show few similarities in their intestinal microbiome.Conclusions Acute liver injury is associated with an early onset of increased intestinal permeability and bacterial translocation that precede changes in the microbiome. The enteric microbiome differs with respect to the etiology of liver disease.
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“Increases in blood LPS levels reflect gut leakiness and are mirrored by a number of other alterations such as increased intestinal permeability to high molecular weight polyethylene glycol in patients with ALD26 and to FITC-dextran in mouse models of alcoholic and biliary liver disease27,28.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [28]
In the citing paper
“Decreased bile secretion in rodents by either ligation of the common bile duct or induction of cirrhosis contributes to bacterial translocation, which is not only caused by intestinal bacterial overgrowth but also by increased gut permeability20,28,134.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [28]
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“Moreover, there are very limited available studies focused on characterising the microbiome composition during experimental cholestasis and these studies have shown conflicting results25,26.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [26]
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“In addition, microbiome analysis was performed at later timepoints (10 days) after BDL, while our analyses comprised earlier timepoints after surgery; 3 and 7 days after BDL.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [26]
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“While Fouts et al.26 described that BDL did not alter the microbiome in mice, Alaish et al.25 described changes in Bl6/C57 mice at late stages after BDL (14 days) that the authors discussed to be associated with advanced fibrogenesis (cirrhosis).”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [26]
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“Also, the sequencing methodology used in that study was different that the one we have applied. Fouts and colleagues used pyrosequencing26 while we used Illumina sequencing in our work, which provides a higher number of sequences per sample and greater depth of sequences corresponding to the hypervariable zone V3-V4, as opposed to the hypervariable V1–V3 region targeted in the Fouts et al. work26.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [26]
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Metadata
- Authors
- Fouts, D. E., Torralba, M., Nelson, K. E., Brenner, D. A., & Schnabl, B.
- Affiliations
- J. Craig Venter Institute (US)
- University of California San Diego (US)
- Corresponding author
- Schnabl, Bernd
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 56
- Issue
- 6
- Pages
- 1283-1292
- ISSN
- 0168-8278 (ISSN-L)
- PMC
- PMC3357486
- OpenAlex
- W2153223490
- Cited by
- 311
- References
- 52
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 13 · 2023: 24 · 2022: 21 · 2021: 26 · 2020: 31 · 2019: 27 · 2018: 34 · 2017: 20 · 2016: 21 · 2015: 21 · 2014: 21 · 2013: 18 · 2012: 11
- FWCI
- 9.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of California, San Diego
- National Institute on Alcohol Abuse and Alcoholism (R01AA020703)
- National Institute of General Medical Sciences (R01GM041804)
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK080506, DK 080506, R01DK072237, K08DK081830)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- bacterial translocation, gut microbiota, gut dysbiosis, intestinal permeability, occludin, tight junctions, cholestatic liver injury, common bile duct ligation, carbon tetrachloride, liver fibrosis, Firmicutes, actinobacteria, alcoholic liver disease
- MeSH terms
- Animals, Carbon Tetrachloride, Cholestasis, Disease Models, Animal, Intestines, Liver Diseases, Male, Mice, Inbred BALB C, Permeability, Bacterial Translocation, Mice, Metagenome
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