Type 2 diabetes mellitus is a metabolic disorder, characterized by heperglycemia and elevated levels of free radicals that can cause lipid peroxidation.[4] In addition, antioxidant defense is disturbed in diabetic patients leading to the expansion of diabetes complications, such as retinopathy, nephropathy and neuropathy[32]. So the promotion in antioxidant status can contribute to diabetes management.[4]
The aim of our study was to investigate the effect of consumption of probiotic supplements on antioxidant biomarkers, including total antioxidant capacity (TAC), total oxidant status (TOS) and PON in type 2 diabetic patients. The results of this study showed that consumption of multispecies probiotic supplement for 6 weeks among subjects with type 2 diabetic patients improved antioxidant status and TAC level and significantly decreased fasting blood glucose; however, MDA and PON levels remained unchanged in the intervention group.
In the present study, the intake of polyunsaturated fatty acid, vitamin E and total fat were significantly different between probiotic and placebo groups at baseline so we adjust them. There were no statistically significant differences in energy, carbohydrate, protein, saturated fatty acid, monounsaturated fatty acid, cholesterol, dietary fiber and vitamin C intakes between groups. However, at the end of study, there were statistically significant difference between the two groups with respect to dietary intakes of energy, saturated fatty acid, monounsaturated fatty acid, polyunsaturated fatty acid and dietary fiber.
Several studies showed the antioxidant and anti-diabetic properties of probiotics.[16, 24-27] The imbalance of microbiota in the gastrointestinal tract has been demonstrated in T2DM.[33]
According to Larsen et al. diabetic patients increased gram-negative bacteria in their intestinal tract. The gut microbiota in patient with T2DM can result in a decreased ratio of Firmicutes to Clostridia, an increased ratio of Betaproteobacteria and an increased ratio of Bacteroidetes to Firmicutes.It has been demonstrated that Probiotics may improve intestinal microbiota composition by increasing gram positive bacteria.[34]
In fact, probiotics can modulate the composition of microbiota and inhibit the excessive proliferation of harmful bacteria that can cause oxidative stress. Some species of probiotics can reduce intestinal PH and subjugate the growth of harmful bacteria through producing lactic acid, propionic acid and acetic acid.[22, 23]
Some of the similar studies have shown improved antioxidant status in animal models after consuming probiotics. For example, Yadav et al. demonstrated that treatment with probiotic dahi can suppress oxidative damage in the pancreatic tissues of diabetic rats by inhibiting lipid peroxidation, producing nitric oxide and improving the activities of SOD, CAT and GPX.[26]
The feeding of the probiotic dahi significantly delayed the onset of glucose intolerance, hyperglycemia, hyperinsulinemia, and oxidative stress in high fructose induced diabetic rats.[25]
Harisa et al. reported that treatment with L. acidophilus improved the antioxidant potential activity of aryl esterase enzyme and decreased fasting blood sugar, HbA1c, and MDA concentrations in diabetic rats.[24]
Amar et al. found that treatment with Bifidobacterium animalis subsp. Lactis 420 reversed bacterial translocation to mesenteric adipose tissue, decreased the expression of pro-inflammatory cytokines in liver, muscle and adipose tissue and improved insulin sensitivity in HFD mice.[35]
In the present study, supplementation with multispecies probiotics led to an increase in TAC level. However, the lack of significant changes in plasma TOS and PON levels could be explained by the short duration of the study and dosage of bacteria used in the study.
The results of this study confirm previous reports on the antioxidant property of probiotics in human models. A clinical trial performed by Ejtahed et al. indicated that consumption of probiotic yogurt improved fasting blood glucose the erythrocyte superoxide dismutase and glutathione peroxidase activities, and total antioxidant status.[16] However, it should be noted that fermented milks because of the presence of antioxidant peptides have both radical scavenging activity and inhibited lipid peroxidation.[28]
Asemi et al. showed that multispecies probiotic supplementation for 8 weeks in diabetic patients decreased serum hs-CRP and increased plasma total GSH, but no significant changes were observed in TAC level.[27] In the present study, TAC level was increased in the probiotic group.
The lack of significant changes in TAC levels and differences in previous studies might be explained by the different characteristics of the subjects.
Several mechanisms are involved in antioxidant effects of probiotics. Some strains of probiotic bacteria have antioxidant activity through scavenging reactive oxygen species, metal ion chelating, and inhibition of ascorbate autoxidation, enzyme inhibition, inhibiting cytotoxic activity and capturing ROS.[18-20] Regulation of the level of antioxidant metabolites such as GSH,[36] butyrate[37] and folate[38] are other antioxidant mechanisms of probiotics.
In deed Probiotics by expressing antioxidant enzymes, up-regulate antioxidant activities of the host,[36, 39, 40] down-regulate activities of ROS-producing enzymes, and ameliorate antioxidant status.[41]
It is revealed that vitamin B12 and folate deficiency can raise oxidative stress in diabetic patient.[42] The consumption of probiotics could improve the level of vitamin B12 and folate and ameliorate antioxidant defense.[38]
Moreover, some strains of probiotic bacteria have been reported as mediator in antioxidant signaling pathway by inhibiting NFκB and ROS production,[43] decreasing ROS level, regulating Nrf2 expressions,[44] and inhibiting PKC[45]. This result showed that consumption of probiotic was effective in increasing antioxidant activity in diabetes.
The limitations of our study were as follows: a low sample size, short duration of intervention and alteration in dietary intake. This highlights that studies need to be conducted with a higher dosage at a longer duration. In addition, further studies are needed to assess the effect of probiotics lipid peroxidation. Further investigations are needed to survey the effects of probiotics on intestinal microbiota composition and free lipopolysaccharides and short chain fatty acids.