Abstract
Cognitive function declines during the aging process, meanwhile, gut microbiota of the elderly changed significantly. Although previous studies have reported the effect of gut microbiota on learning and memory, all the reports were based on various artificial interventions to change the gut microbiota without involvement of aging biological characteristics. Here, we investigated the effect of aged gut microbiota on cognitive function by using fecal microbiota transplantation (FMT) from aged to young rats. Results showed that FMT impaired cognitive behavior in young recipient rats; decreased the regional homogeneity in medial prefrontal cortex and hippocampus; changed synaptic structures and decreased dendritic spines; reduced expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor NR1 subunit, and synaptophysin; increased expression of advanced glycation end products (AGEs) and receptor for AGEs (RAGE). All these behavioral, brain structural and functional alterations induced by FMT reflected cognitive decline. In addition, FMT increased levels of pro-inflammatory cytokines and oxidative stress in young rats, indicating that inflammation and oxidative stress may underlie gut-related cognitive decline in aging. This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function.
Highlights
Aging is characterized by a progressive functional decline that is inevitable in the life process [1]
Claesson et al have shown that the gut microbiota of the elderly is substantially different from the younger adults [5], and correlates with frailty measured by functional independence measure (FIM) [6]
Our results showed that the fecal microbiota transplantation (FMT) rats possessed a lower regional homogeneity (ReHo) in medial prefrontal cortex (mPFC) and hippocampus compared with the non-fecal microbiota transplantation (NFMT) rats, indicating that FMT decreased the functional activities in these two brain areas in the young recipient rats (Figure 6B)
Summary
Aging is characterized by a progressive functional decline that is inevitable in the life process [1]. The brain undergoes a myriad of alterations, including biological, psychological, neuroanatomical, and neurophysiological changes, which are closely tied to the decline in cognitive functions. The human gastrointestinal tract harbors a complex and dynamic population of some 1014 microorganisms, referred to as gut microbiota [2]. The gut microbiota is very important for the development and homeostasis of the body; it regulates intestinal motility and gastrointestinal barrier [3], host energy metabolism and mitochondrial function [4], as well as immune responses and the central nervous system [2]. The microbiota reaches a relative equilibrium, and does not significantly change under stable www.aging-us.com environmental and health conditions. Given our current inability to delineate the most significant effector mechanisms involved in the host-microbiota interactions over a lifetime, it is difficult to tease apart causality from correlation
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