**5. Efficacy of probiotics on metabolic diseases**

Many hypotheses surround the feasible involvement of the intestinal microbiota in metabolic disorders such as diabetes and obesity.

### **5.1 Diabetes**

Some evidence suggests that in diabetic patients, disruption in antioxidant defenses happens and free radicals are produced in large amounts [99, 100]. Oxidative stress is considered as one of the major factors in insulin resistance [101], the onset of diabetes and the pathogenesis of diabetic retinopathy as well [102, 103]. Evidence recommends that some probiotic strains are effective in reducing inflammation and oxidative stress in pancreatic cells [104, 105], and they play an important role in preventing the destruction of β-pancreatic cells [106, 107]. A preclinical study of the effect of probiotics on diabetic rats showed that the combination of two probiotic strains including *Lactobacillus acidophilus* and *Lactobacillus casei* could significantly suppress oxidative damage by repressing the lipid peroxidation and protecting the antioxidant content of glutathione, superoxide dismutase, catalase and glutathione peroxidase in their pancreases [108]. It has also been demonstrated that *Bifidobacterium adolescentis* enhances insulin sensitivity [109] by increasing the amount of production of glucagon-like peptide 1 (GLP-1) [110]. GLP-1, a growth factor for pancreatic cells, through complicated mechanisms like modulation of insulin secretion, pancreatic cell mass and food consumption improve glucose tolerance [111]. Furthermore, probiotics have also been found to be effective in reducing blood glucose levels [112–114]. This may be because of properties of probiotics that can ameliorate glucose metabolism via increasing the bioavailability of gliclazide, suppressing or postponing the intestinal absorption of glucose and changing the autonomic nervous activity [115–117]. The result of a clinical trial on 79 diabetic people who had used metformin as a daily treatment, and received multi-probiotic strains or placebo two times a day for 12 weeks, indicates glycated hemoglobin (HbA1c), and weight significantly decreased in the probiotic-utilizing group compared to placebo [118].
