Early intervention with probiotics and metformin alleviates liver injury in NAFLD rats via targeting gut microbiota dysbiosis and p-AKT/mTOR/LC-3II pathways

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Seif el-Din S.H.; Salem M.B.; El-Lakkany N.M.; Hammam O.A.; Nasr S.M.; Okasha H.; Ahmed L.A.; Saleh S.; Botros S.S.

Journal: Human and Experimental Toxicology

Publisher: SAGE Publications Ltd

Publication Date: 8 March 2021

Volume / Issue: Volume 40 / Issue 9

Pages: 1496–1509

ISSN: 9603271

DOI: 10.1177/0960327121999445

Scopus: View on Scopus

PubMed: 33678036

Document Type: Article

Authors and Affiliations

Seif el-Din S.H., Pharmacology Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, Giza, Egypt; Salem M.B., Pharmacology Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, Giza, Egypt; El-Lakkany N.M., Pharmacology Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, Giza, Egypt; Hammam O.A., Pathology Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, Giza, Egypt; Nasr S.M., Biochemistry Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, Giza, Egypt; Okasha H., Biochemistry Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, Giza, Egypt; Ahmed L.A., Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; Saleh S., Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; Botros S.S., Pharmacology Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, Giza, Egypt

Abstract

Non-alcoholic fatty liver disease (NAFLD) constitutes a major health problem worldwide and intimately links with obesity and diabetes. This study aimed to explore the therapeutic impact of early treatment with metformin (MTF) alone or in combination with Lactobacillus reuteri DSM 17938 (L. reuteri) + metronidazole (MTZ) in male Sprague Dawley rats with high-fat diet (HFD)-induced NAFLD. Hepatic steatosis was induced by feeding rats HFD for 6 weeks. MTF (150 mg/kg/day) or L. reuteri (2 × 109 colony forming unit/day) were given orally for 4 weeks; meanwhile, MTZ (15 mg/kg/day, p.o.) was administered for 1 week. Administration of L. reuteri + MTZ in combination with MTF produced a superior effect concerning insulin resistance (IR), lipid profile, liver function, oxidative stress, inflammatory and autophagic markers than using each treatment alone. Besides, this combination resulted in disappearance of steatosis, inflammation and vacuolation within hepatic architecture. Moreover, it normalized short chain fatty acids (SCFAs) as well as Firmicutes and Bacteroidetes faecal contents. In conclusion, early treatment with L. reuteri + MTZ in combination with MTF could prevent NAFLD progression and liver injury through targeting gut dysbiosis, inflammation and autophagic pathways. © The Author(s) 2021.

Keywords

Autophagy; dysbiosis; inflammation; Lactobacillus reuteri; NAFLD; Animals; Disease Models, Animal; Drug Therapy, Combination; Gastrointestinal Microbiome; Humans; Hypoglycemic Agents; Male; Metformin; Metronidazole; Non-alcoholic Fatty Liver Disease; Probiotics; Rats; Rats, Sprague-Dawley; lipid; mammalian target of rapamycin; probiotic agent; protein kinase B; short chain fatty acid; antidiabetic agent; animal experiment; animal model; animal tissue; Article; autophagy (cellular); Bacteroidetes; clinical effectiveness; colony forming unit; controlled study; dose response; drug effect; drug efficacy; drug mechanism; early intervention; fatty liver; feces analysis; Firmicutes; immunohistochemistry; insulin resistance; intestine flora; lipid blood level; lipid diet; liver function; liver injury; nonalcoholic fatty liver; nonhuman; oxidative stress; rat; signal transduction; Sprague Dawley rat; treatment outcome; animal; chemistry; combination drug therapy; disease model; human

Citation Information

Scopus Citations: 29

For comprehensive information about the Theodor Bilharz Research Institute (TBRI), its institutional activities, scientific and research achievements, clinical and hospital services, and the diverse expertise offered through its 22 specialized research and clinical departments, as well as opportunities for professional training, specialized workshops, and scientific conferences, readers are invited to visit the Institute’s official website.

The website provides regularly updated information on the Institute’s latest news, research activities, scientific initiatives, clinical services, institutional programs, and academic and professional opportunities.

English Website: https://www.tbri.sci.eg/en/

Arabic Website: https://www.tbri.sci.eg/ar/

Prepared and Uploaded by:

Abdalla F. Abdalla

Electronic Portal Unit

Electronic Portal Unit

Popular Posts

A cost-performance index for nano-optical biosensor evaluation: Systematic evaluation of europium–salicylate luminescent platforms for GPC3-targeted early HCC diagnosis

Image
Bibliographic Information Authors: Hassan Y.M.; El-Tantawi H.; Ali I.R.; Attia M.S. Journal: Talanta Publisher: Elsevier B.V. Publication Date: January 2027 Volume / Issue: Volume 311 Article No.: 130103 ISSN: 399140 DOI: 10.1016/j.talanta.2026.130103 Scopus: View on Scopus PubMed: 42391698 Document Type: Review Authors and Affiliations Hassan Y.M., Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt; El-Tantawi H., Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt; Ali I.R., Department of Immunology and Treatment Evaluation, Theodore Bilharz Research Institute, Giza, Egypt; Attia M.S., Chemistry Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia Abstract Comparative evaluation of nano-optical biosensor platforms lacks a standardised, multi-parameter quantitative framework that integrates analytical performance...
Read more

Interpretation of liver stiffness measurement in patients with mixed liver disease etiologies

Image
Bibliographic Information Authors: El Ray A.; El Ghannam M.; Rautou P.E. Journal: Arab Journal of Gastroenterology Publisher: Elsevier Ltd Publication Date: August 2026 ISSN: 16871979 DOI: 10.1016/j.ajg.2026.05.002 Scopus: View on Scopus PubMed: 42362465 Document Type: Letter Authors and Affiliations El Ray A., Theodor Bilharz Research Institute, Hepatogastroenterology Department, Giza, Egypt, Faculty of Medicine, October 6 University, Egypt; El Ghannam M., Theodor Bilharz Research Institute, Hepatogastroenterology Department, Giza, Egypt; Rautou P.E., Université Paris-Cité, Inserm, Centre de recherche sur l’inflammation, UMR 1149, Paris, France, AP-HP, Hôpital Beaujon, Service d’Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France Abstract Vibration-controlled transient elastography (VCTE)–based liver stiffness measurement (LSM) is widely used for non-invasive assessment of liver fibrosis and p...
Read more

Holothuria arenicola Extract-Loaded Polycaprolactone Nanocapsules Attenuate Bile Duct Ligation-Induced Acute Liver Injury

Image
Bibliographic Information Authors: Mansour E.M.; Shemis M.; Fahmy S.R.; Amer M.A.; Mohamed A.S. Journal: Current Nanomedicine Publisher: Bentham Science Publishers Publication Date: September 2026 Volume / Issue: Volume 16 / Issue 5 Pages: 771–786 ISSN: 24681873 DOI: 10.2174/0124681873401484250924125945 Scopus: View on Scopus Document Type: Article Authors and Affiliations Mansour E.M., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt; Shemis M., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt; Fahmy S.R., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; Amer M.A., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; Mohamed A.S., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt Abstract Introduction: Cholestatic liver diseases are characterized by jaundice and cholestasis with various conseq...
Read more

Mytilus edulis-mediated green synthesis of selenium nanoparticles with antimicrobial and molluscicidal applications

Image
Bibliographic Information Authors: Dokmak H.-A.A.; AlSedawy M.; Ramadan M.A.; Amin B.H.; Faid A.H.; Abdelmaksoud H.F.; El-Sayed S.M. Journal: Scientific Reports Publisher: Nature Research Publication Date: 7 September 2026 Volume / Issue: Volume 16 / Issue 1 Article No.: 27918 ISSN: 20452322 DOI: 10.1038/s41598-026-65860-3 Scopus: View on Scopus PubMed: 42706305 Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Dokmak H.-A.A., Department of Medical Malacology, Theodor Bilharz Research Institute, Giza, Egypt; AlSedawy M., Microbiology and Immunology Department, Faculty of Pharmacy (For Boys), Al-Azhar University, Cairo, Egypt; Ramadan M.A., Department of Laser Application in Metrology, Photochemistry and Agriculture, National Institute of Laser Enhanced Science (NILES) Cairo University (CU), Giza, Egypt; Amin B.H., The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, 11787,...
Read more

Microbial levan potentiates hepatic retention and antitumor activity of a PEGylated benzimidazole–curcumin nanocomplex through TLR2–FXR/FGF15-associated immunometabolic remodeling in experimental liver cancer

Image
Bibliographic Information Authors: Shawky H.; Ibrahim N.E.; Amer M.N.; Al-Ashmawy A.A.K.; Hammam O.A.; Fayed D.B.; Maghraby A.S. Journal: Scientific Reports Publisher: Nature Research Publication Date: 12 August 2026 Volume / Issue: Volume 16 / Issue 1 Article No.: 25094 ISSN: 20452322 DOI: 10.1038/s41598-026-64576-8 Scopus: View on Scopus PubMed: 42581056 Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Shawky H., Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, 12622, Egypt; Ibrahim N.E., Microbial Biotechnology Department, Biotechnology Research Institute, National Research Centre, Dokki, Cairo, 12622, Egypt; Amer M.N., Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, 12622, Egypt; Al-Ashmawy A.A.K., Therapeutic Chem...
Read more

Variable clinical presentations of pulmonary hydatid cysts: a four-case series from a single center in United Arab Emirates, non-endemic region

Image
Bibliographic Information Authors: Yehya M.; Abdallah M.F.H.; Ajeka S.; Al-Masalmeh F.H.; Albaghdadi M.O.J. Journal: Journal of Surgical Case Reports Publisher: Oxford University Press Publication Date: 29 July 2026 Volume / Issue: Volume 2026 / Issue 7 Article No.: rjag658 ISSN: 20428812 DOI: 10.1093/jscr/rjag658 Scopus: View on Scopus Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Yehya M., Department of Thoracic Surgery, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates; Abdallah M.F.H., Department of Radiology, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates, Theodor Bilharz Research Institute, Mahad Al Abhas Al bahari St, Kornish Al Nile, Warraq Al Arab, Al Warak, Governorate, Giza, 3863341, Egypt; Ajeka S., Department of General Surgery, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates; Al-Masalmeh F.H., Department of ...
Read more

Corrigendum to ‘Eco-friendly approach for the removal and simultaneous detection of cyanide toxins from drinking and wastewater sources’ [Environ. Pollut. 385 (2025) 127094]

Image
Bibliographic Information Authors: El-Sewify I.M.; Shenashen M.A.; Gomaa H.; Selim M.S.; Akhtar N.; Azzam A.; Mekawy M.; Emran M.Y.; Khairy M.; Shahat A.; Hasan M.; Elmarakbi A.; El-Safty S.A. Journal: Environmental Pollution Publisher: Elsevier Ltd Publication Date: September 2026 Volume / Issue: Volume 405 Article No.: 128412 ISSN: 2697491 DOI: 10.1016/j.envpol.2026.128412 Scopus: View on Scopus PubMed: 42259729 Document Type: Erratum Authors and Affiliations El-Sewify I.M., Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1–2-1 Sengen, Ibaraki-ken, Tsukubashi, 305–0047, Japan, Chemistry Department, Faculty of Science, Ain Shams University, Abbasia, Cairo, 11566, Egypt; Shenashen M.A., Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1–2-1 Sengen, Ibaraki-ken, Tsukubashi, 305–0047, Japan; Gomaa H., Research Center for Macromolecules and Biomaterials, Na...
Read more