The Gut Impacts Diabetic Management Tomorrow: The Recent Messages from Intestine and Microbiota

Abstract

The number of diabetic patients tremendously increased worldwide constituting a grave health problem at present. Life style changes including high-fat highsugar diet and poor physical activity affect diabetes risk. Persistent, lowgrade inflammatory responses in obese patients with metabolic syndrome are considered to play a cardinal role in the development and progression of type 2 diabetes. Emerging experimental and clinical evidence indicates that gut dysbiosis, intestinal barrier dysfunction and resultant metabolic endotoxaemia are closely related to the inflammation, insulin resistance and finally cardiovascular events in patients with type 2 diabetes. Gut microbiome transmitted from mother to child at birth is profoundly affected by eating habits in life thereafter. In the feces of type 2 diabetics, relatively higher abundance in endotoxin producing gram-negative bacteria and lower abundance in butyrate-producing bacteria were reported. As butyrate is an important energy source and protector of intestinal barrier, its defect may enhance intestinal hyperpermeability and endotoxaemia. Inflammation in the adipose tissue provokes detrimental effects on other organs through secreted pro-inflammatory cytokines. Activation of Toll-like receptor 4 in immune cells such as macrophages evokes inflammation and insulin resistance, finally leading to an impairment of insulin signalling and β-cell failure. Inflammatory changes in the arterial vessels and liver lead to two life-threatening states, ischemic heart disease and liver cirrhosis, respectively. Meticulous management strategies to improve gut dysbiosis may pave the way for effective pharmacotherapy and lower the morbidity and mortality of type 2 diabetes. Biguanide derivative metformin is known to have an anti-inflammatory effect in addition to its glucoregulatory function. There is a possibility that two newly developed diabetic drugs, dipeptydilpeptidase- 4 (DPP-4) inhibitors and sodium-glucose co-transporter 2 (SGLT2) inhibitors, may have some undetermined effect on inflammation, which is worth investigating. This review summarizes the bulk of latest information on type 2 diabetes, endotoxaemia and gut dysfunction.