Probiotics targeting the cellular and molecular mechanism of type 2 diabetes mellitus (T2DM). The left part of figure represents the normal glucose metabolism and regulation that occurs in a healthy nondiabetic individual (when a human ingest food, it gets digested and carbohydrate breakdowns into glucose in the intestine. Then glucose enters the bloodstream. The β cells of pancreas releases sufficient amount of insulin into the bloodstream inresponse to the glucose content. Glucose uptake by cells of muscle and adipose tissues are promoted by the insulin. The endogenous insulin secretion suppresses the secretion of glucagon in pancreas. The unused remaining glucose are stored as glycogen mainly in liver. Glycogenolysis and gluconeogenesis in liver is suppressed by the insulin. And finally, the blood glucose level reaches the normal level. When blood glucose concentration is reduced than a normal level during fasting, the α cells of pancreas secretes glucagon and releases glucagon in to liver. Glucagon catalyses the conversion of glycogen into glucose and liver releases the glucose in to the bloodstream. Glucose uptake by cells of muscle and adipose tissues are controlled by the basal level of insulin and the blood glucose level is maintained. Glycogenolysis and gluconeogenesis in the liver is minimally suppressed due to to the low level of insulin secretion). The right part of the figure represents the impared glucose metabolism and regulation in individuals with T2DM (genetic and constitutional factors affect the secretion and action of insulin. β cell dysfunction in diabetic (T2DM) individual is caused due to the effect of FFAs, insulin resistance, obesity, and inflammation. The β cell function is affected by long term exposure of FFAs. Initially, the short term exposure of FFAs after ingestion of mixed meal causes an increase in the level of insulin secretion and allows the storage of extra calories as fat, which eventually results in overweight and leads to obesity. It also accounts for the increased secretion of insulin in response to insulin resistance. But glucose induced insulin secretion is suppressed due to the long term exposure of FFAs. Insulin resistance in obese individual causes increased demand on β cell function that leads to metabolic exhaustion of β cells and accelerates the loss of β cell mass. Incase of β cell dysfunction, the insulin secretion is reduced due to loss of β cell mass. The low level of endogenous insulin secretion does not effectively suppress the rate of glucagon secretion in pancreas. Resulting in increased glycogenolysis and gluconeogenesis in liver and releasing more glucose in bloodstream, which occurs both at fasting and fed state. Incase of insulin resistance, the insulin mediated uptake of glucose is reduced in skeletal muscles and adipose tissues that results in increased blood glucose level following the ingestion of food. The upregulated accumulation of fat in the cells of adipose tissues increases the release of pro-inflammatory mediators and causes increased lipolysis, which results in releasing more FFAs that induces glucose production in liver and leads to progressive hyperglycemia) and probiotics targeting the mechanism of T2DM to improve the health status of individuals with T2DM (probiotics improves the glycemic status by reducing the blood glucose level, insulin resistance, the production of inflammatory markers and increasing fasting insulin level, improvement of lipid profile by increasing LDL and decreasing TC, TG, HDL, and improvement of hypertension by decreasing the systolic and diastolic blood pressure in individuals with T2DM). The orange lines indicate the mechanism involved in T2DM. Green lines indicate the targets of probiotic. T2DM: Type 2 diabetic mellitus; Ecologic®Barrier is a probiotic mixture of Bifidobacterium bifidum W23, B. lactis W52, Lactobacillus acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24, L. lactis W19, and Lactococcus lactis W58; VSL#3 is a probiotic mixture of L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii subsp. Bulgaricus, B. breve, B. longum, B. infantis, and S. thermophiles; BMI: Body mass index; TG: Triglycerides; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; TC: Total cholesterol; FFA: Free fatty acid.