Jornal de Microbiologia Alimentar e Industrial

The Gut affects Pathophysiology and Management of Diabetes Mellitus Type 2: The Recent Messages from Intestine and Gastrointestinal Microbiota

Abstract

Hiroshi Fukui

The number of diabetic patients rapidly increased in the world constituting a serious health problem. Daily life alterations such as high-fat high-sugar diet and insufficient physical exercise augment diabetes risk. Long-lasting low-grade inflammatory reactions in obese patients with metabolic syndrome are considered as an important role in the occurrence and advance in the stage of type 2 diabetes. Emerging clinical and experimental evidence reveals that gut dysbiosis, intestinal barrier disturbance and following metabolic endotoxemia are firmly related to the low-grade inflammatory, insulin resistance and resultant cardiovascular complications in patients with type 2 diabetes. Gut microbiome transmitted from mother to child at birth is deeply affected by dietary habits in life thereafter. In the feces of type 2 diabetics, relatively frequent abundance in endotoxin producing gram-negative bacteria and lower abundance in butyrate-producing bacteria were noted. Butyrate as an important energy source and a protector of intestinal barrier, its defect is considered to enhance intestinal hyperpermeability and metabolic endotoxemia. Inflammation in the adipose tissue induces detrimental effects on other organs and tissues 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 signal and β-cell failure. Inflammatory changes in the arterial vessels and liver lead to two life-threatening conditions, ischemic heart disease and liver cirrhosis, respectively. Careful management strategies to improve gut dysbiosis may stimulate effective drug treatment and lower the morbidity and mortality of patients who suffers from type 2 diabetes. A kind of biguanide metformin is considered as an anti-inflammatory influence in addition to its glucoregulatory effect. Two newly developed diabetic drugs, Dipeptydil-Peptidase-4 (DPP-4) inhibitors and Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors may in combination with reasonable dietary therapy have some undetermined effect on inflammatory changes. This systemic review summarizes the bulk of latest information published until 2021 on the pathogenesis and treatment of type 2 diabetes, especially related to gut microbial alterations. This manuscript in addition to my previous review includes up-to-date information in diabetes mellitus type 2.