Lamiaa Ahmed

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 (2x10 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.

Dysbiosis has been linked to various diseases ranging from cardiovascular, neurologic, gastrointestinal, respiratory, and metabolic illnesses to cancer. Restoring of gut microbiota balance represents an outstanding clinical target for the management of various multidrug-resistant diseases. Preservation of gut microbial diversity and composition could also improve stem cell therapy which now has diverse clinical applications in the field of regenerative medicine. Gut microbiota modulation and stem cell therapy may be considered a highly promising field that could add up towards the improvement of different diseases, increasing the outcome and efficacy of each other through mutual interplay or interaction between both therapies. Importantly, more investigations are required to reveal the cross-talk between microbiota modulation and stem cell therapy to pave the way for the development of new therapies with enhanced therapeutic outcomes. This review provides an overview of dysbiosis in various diseases and their management. It also discusses microbiota modulation via antibiotics, probiotics, prebiotics, and fecal microbiota transplant to introduce the concept of dysbiosis correction for the management of various diseases. Furthermore, we demonstrate the beneficial interactions between microbiota modulation and stem cell therapy as a way for the development of new therapies in addition to limitations and future challenges regarding the applications of these therapies.