Titel
Antibiotics attenuate diet-induced nonalcoholic fatty liver disease without altering intestinal barrier dysfunction
Autor*in
Angélica Hernández-Arriaga
Livestock Microbial Ecology Department, Institute of Animal Science, University of Hohenheim
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Abstract
To date the role of the alterations of intestinal microbiota in the development of intestinal barrier dysfunction in settings of nonalcoholic fatty liver disease (NAFLD) has not been fully understood. Here, we assessed the effect of antibiotics on development of NAFLD and their impact on intestinal barrier dysfunction. Male C57BL/6J mice were either pair-fed a liquid control diet (C) or fat- and fructose-rich diet (FFr) +/- antibiotics (AB, ampicillin/vancomycin/metronidazole/gentamycin) for 7 weeks. Fasting blood glucose was determined and markers of liver damage, inflammation, intestinal barrier function, and microbiota composition were assessed. The development of hepatic steatosis with early signs of inflammation found in FFr-fed mice was significantly abolished in FFr+AB-fed mice. Also, while prevalence of bacteria in feces was not detectable and TLR4 ligand levels in portal plasma were at the level of controls in FFr+AB-fed mice, impairments of intestinal barrier function like an increased permeation of xylose and iNOS protein levels persisted to a similar extent in both FFr-fed groups irrespective of AB use. Exposure of everted small intestinal tissue sacs of naïve mice to fructose resulted in a significant increase in tissue permeability and loss of tight junction proteins, being not affected by the presence of AB, whereas the concomitant treatment of tissue sacs with the NOS inhibitor aminoguanidine attenuated these alterations. Taken together, our data suggest that intestinal barrier dysfunction in diet-induced NAFLD in mice may not be predominantly dependent on changes in intestinal microbiota but rather that fructose-induced alterations of intestinal NO-homeostasis might be critically involved.
Stichwort
AntibioticIntestinal barrier functionFatty liverTight junctionEndotoxinNitric oxide
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
https://phaidra.univie.ac.at/o:2044432
Erschienen in
Titel
The Journal of Nutritional Biochemistry
Band
123
ISSN
0955-2863
Erscheinungsdatum
2024
Verlag
Elsevier BV
Projektnummer
864199 – Österreichische Forschungsförderungsgesellschaft mbH (FFG)
Erscheinungsdatum
2024
Zugänglichkeit
Rechteangabe
© 2023 The Author(s)

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