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Gut microbiota modulation as a promising therapy with metformin in rats with non-alcoholic steatohepatitis: Role of LPS/TLR4 and autophagy pathways.
Ahmed, Lamiaa A; Salem, Maha B; Seif El-Din, Sayed H; El-Lakkany, Naglaa M; Ahmed, Hend O; Nasr, Sami M; Hammam, Olfat A; Botros, Sanaa S; Saleh, Samira.
Afiliación
  • Ahmed LA; Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: lamiaa.ahmed@pharma.cu.edu.eg.
  • Salem MB; Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: drmahabadr86@gmail.com.
  • Seif El-Din SH; Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: s.seifeldin@tbri.gov.eg.
  • El-Lakkany NM; Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: n.ellakkany@tbri.gov.eg.
  • Ahmed HO; Biochemistry, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: hend.oaa@gmail.com.
  • Nasr SM; Biochemistry, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: samitbri@gmail.com.
  • Hammam OA; Pathology, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: totoali1@hotmail.com.
  • Botros SS; Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: sanaabotros113@gmail.com.
  • Saleh S; Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: samira.saleh@pharma.cu.edu.eg.
Eur J Pharmacol ; 887: 173461, 2020 Nov 15.
Article en En | MEDLINE | ID: mdl-32758573
Gut microbiota is a crucial factor in pathogenesis of non-alcoholic steatohepatitis (NASH). Therefore, targeting the gut-liver axis might be a novel therapeutic approach to treat NASH. This study aimed to investigate the therapeutic effects of a probiotic (Lactobacillus reuteri) and metronidazole (MTZ) (an antibiotic against Bacteroidetes) either alone or in combination with metformin (MTF) in experimentally-induced NASH. NASH was induced by feeding rats high fat diet (HFD) for 12 weeks. MTF (150 mg/kg/day) or L. reuteri (2x109 colony forming unit/day) were given orally for 8 weeks; meanwhile, MTZ (15 mg/kg/day, p.o.) was administered for 1 week. Treatment with L. reuteri and MTZ in combination with MTF showed additional benefit compared to MTF alone concerning lipid profile, liver function, oxidative stress, inflammatory and autophagic markers. Furthermore, combined regimen succeeded to modulate acetate: propionate: butyrate ratios as well as Firmicutes and Bacteroidetes fecal contents with improvement of insulin resistance (IR). Yet, the administration of MTF alone failed to normalize Bacteriodetes and acetate contents which could be the reason for its moderate effect. In conclusion, gut microbiota modulation may be an attractive therapeutic avenue against NASH. More attention should be paid to deciphering the crosstalk mechanisms linking gut microbiota to non-alcoholic fatty liver disease (NAFLD) to identify new therapeutic targets for this disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Receptor Toll-Like 4 / Enfermedad del Hígado Graso no Alcohólico / Microbioma Gastrointestinal / Hipoglucemiantes / Metformina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2020 Tipo del documento: Article Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Receptor Toll-Like 4 / Enfermedad del Hígado Graso no Alcohólico / Microbioma Gastrointestinal / Hipoglucemiantes / Metformina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2020 Tipo del documento: Article Pais de publicación: Países Bajos