The Impact of Microbiota-Gut-Brain Axis on Diabetic Cognition Impairment

Abstract

Progressive cognitive dysfunction is a central characteristic of diabetic encephalopathy (DE). With an aging population, the incidence of DE is rising and it has become a major threat that seriously affects public health. Studies within this decade have indicated the important role of risk factors such as oxidative stress and inflammation on the development of cognitive impairment. With the recognition of the two-way communication between gut and brain, recent investigation suggests that "microbiota-gut-brain axis" also plays a pivotal role in modulating both cognition function and endocrine stability. This review aims to systemically elucidate the underlying impact of diabetes on cognitive impairment.

Keywords: advanced glycation end products; diabetic encephalopathy; gut; hypothalamic-pituitary-adrenal axis; inflammation; microbiota.

Figure 1

Proposed pathogenesis of diabetic encephalopathy. Hyperglycemia, insulin resistance and metabolic disorder are characteristics of diabetes; they may promote dysfunction of blood brain barrier, induce neuron loss, hamper synaptic transmission, and thereafter contribute to the development of diabetic cognitive impairment.

Figure 2

The two-way cross-talk of MGBA. In healthy population, the glucose metabolism is strictly controlled by both neuropeptides originated from the brain and endocrine factors secreted from the digestive system. CRF and cortisol modulates the secretion of insulin from islet β cells and maintains blood glucose at reasonable level. Microbiota in the gut digest dietary fiber and “co-metabolize” with gut epithelial cells to keep gut epithelial cell barrier and promote the secretion of neuropeptides, SCFAs originated from Microbiota and neuropeptides generated from the epithelial cells will further circulate to the brain and affect brain function. ACTH, adrenocorticotrophin hormone; AGEs, advanced glycation end products; BBB, blood brain barrier; CRF, corticotropin releasing factor; GABA, γ-aminobutyric acid; ROS, reactive oxygen species; SCFAs, short chain fatty acids.

Figure 3

MGBA modulated DCI. In diabetic population, metabolic disorder and hypercortisolism will exacerbate hyperglycemia, promote the generation of AGEs and inflammatory cytokines in the internal environment; on the other hand, dysbacteriosis in the gut will dramatically increase the production of endotoxin and decrease the level of SCFAs. Both dysbacteriosis and internal environment disorder will lead to the intestinal barrier and BBB dysfunction, facilitate harmful substance (e.g., AGEs, endotoxin, pathogens etc.) to access to neurons, and thus contribute to the development of DCI. ACTH, adrenocorticotrophin hormone; AGEs, advanced glycation end products; BBB, blood brain barrier; CRF, corticotropin releasing factor; GABA, γ-aminobutyric acid; ROS, reactive oxygen species; SCFAs, short chain fatty acids.