adverse effects may occur with the use of metformin 8. Alternatively, the potential role of modifications in the gut microbiome had been explored as a new complementary therapeutic strategy 9. Clinical evidence supports the hypothesis that the modulation of the gut microbiota by probiotics could be effective in prevention and management of diabetes 10,11. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The healthy human body contains such microbes physiologically; and they can be obtained in forms of over-the-counter food supplements as well. Over the last few years, probiotics, especially the lactobacillus species were shown to be effective in the therapy of type 2 diabetes 12. In type 2 diabetes, gut microbiome is found to be different from that in the healthy population. In a human study, the amount of Firmicutes bacteria was lower, whereas the number of Bacteroides and Proteobacteria is higher in the gastrointestinal tract of patients with type 2 diabetes compared to non-diabetic persons 13. According to the study 13 , the ratio of Bacteriodes and Firmicutes species had positive correlation with decreased insulin resistance, however, causality has not been proven yet. Following innovative dietary strategies, it seems possible to maintain euglycemia by normalizing the altered microbiome, and to prevent long-term micro-and macrovascular complications of type 2 diabetes 9. Although, there have been numerous bacterial species investigated in the therapy of type 2 diabetes, no consensus has been obtained regarding the effectivity and the most effective species. For instance, an earlier meta-analysis suggested, that the intake of certain Lactobacillus species, such as L. fermentum, L. ingluviei and L. acidophilus can lead to weight gain, while the ingestion of L. gasseri and L. plantarum might end up in weight loss both in animal and human studies 14. Previous meta-analysis in this field were not conducted with assessment of the evidence quality levels and the number of identified trials that met their inclusion criteria was relatively low (7-12 trials) 15-19. Two meta-analysis found no significant effects of probiotics on lipid profile 16,19 and two meta-analysis found decreased indexes of lipid profiles 17,18. These contradictory reports on the effect of probiotics inspired us to conduct an updated meta-analysis to assess the effect of probiotic therapies in diabetes mellitus type 2 exclusively from randomized controlled trials. Materials and methods Protocol and registration. This meta-analysis was reported according to the recommendation of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines 20. Pre-specified protocol of this meta-analysis was published in the Prospero Center for Reviews and Dissemination (PROSPERO) under the registration number of CRD42019137997.
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