FIGURE 2.

The dysbiosis of gut microbes in aging process. Aging is accompanied by significant changes in lifestyle, such as biological age, nutritional changes, decreased locomotion, antibiotic use, and chronic stress, which may cause an alteration of microbes’ composition and exacerbate the dysbiosis of gut microbiota in frail elderly people. Microbes dysbiosis in aging shows a severe decrease of beneficial bacteria, such as SCFA-producing bacteria, and increased pathogenic bacteria, such as Enterobacteriaceae, affecting gut physiology and leading to reduced intestinal motility, gut-barrier dysfunction, and increased intestinal permeability. Furthermore, the dysbiosis of microbiota could influence the brain function through various routes including: (1) promote the release of pro-inflammatory cytokines and bacterial toxins to the circulatory system, such as LPS, causing systemic inflammation via neuroimmune pathway; (2) inhibit the transmission of neural signal from enteric nervous system (ENS) to central nervous system (CNS) mainly via vagus nerve; (3) suppress the production and release of microbial neurotransmitters and hormones to circulatory system and subsequently to brain through neuroendocrine pathway. All these factors cause a chain of detrimental events to the brain that enhancing the risk of developing aging-related pathologies. (This figure was created with BioRender.com).