Gut microbiota mediates cognitive impairment in young mice after multiple neonatal exposures to sevoflurane

Abstract

Multiple exposures to anesthesia may increase the risk of cognitive impairment in young children. However, the mechanisms underlying this neurodevelopmental disorder remain elusive. In this study, we investigated alteration of the gut microbiota after multiple neonatal exposures to the anesthetic sevoflurane and the potential role of microbiota alteration on cognitive impairment using a young mice model. Multiple neonatal sevoflurane exposures resulted in obvious cognitive impairment symptoms and altered gut microbiota composition. Fecal transplantation experiments confirmed that alteration of the microbiota was responsible for the cognitive disorders in young mice. Microbiota profiling analysis identified microbial taxa that showed consistent differential abundance before and after fecal microbiota transplantation. Several of the differentially abundant taxa are associated with memory and/or health of the host, such as species of Streptococcus, Lachnospiraceae, and Pseudoflavonifractor. The results reveal that abnormal composition of the gut microbiota is a risk factor for cognitive impairment in young mice after multiple neonatal exposures to sevoflurane and provide insight into a potential therapeutic strategy for sevoflurane-related neurotoxicity.

Anesthesia and developing brain: What have we learned from recent studies

“…When exposed to isoflurane, the activity of GPX4 is inhibited, and accumulated lipid peroxides and ROS might lead to disruption in mitochondrial membrane potential and cell death (ferroptosis) ( Xia et al, 2018 ). In addition, exposure to isoflurane might increase the activity of the mitochondrial electron transport chain ( Liu et al, 2021 ). These processes can be attenuated by administering selective ferroptosis inhibitor ferrostatin-1 and mitochondria activator dimethyl fumarate ( Xia et al, 2018 ; Liu et al, 2021 ).…”

“…In addition, exposure to isoflurane might increase the activity of the mitochondrial electron transport chain ( Liu et al, 2021 ). These processes can be attenuated by administering selective ferroptosis inhibitor ferrostatin-1 and mitochondria activator dimethyl fumarate ( Xia et al, 2018 ; Liu et al, 2021 ).…”

“…Microbiota profiling analysis showed that some differentially abundant taxa are related to memory. Studies of gut microbiota dysregulation might provide a therapeutic strategy with novel insights ( Liu et al, 2021 ).…”

Research progress on molecular mechanisms of general anesthetic-induced neurotoxicity and cognitive impairment in the developing brain

“…However, it is unknown whether the Akt signaling pathway is affected by the down-regulation of BDNF. It has been shown that differential abundances of cognition related microbial taxa were found in the gut of young rats exposed to sevoflurane for several times ( 90 ). The abnormal composition of these gut microbiota may be a risk factor for common general anesthetics induced neurotoxicity and cognitive impairment in the developing brain, but there are currently few studies on the causal relationship between gut microbiota and general anesthetics induced neurotoxicity and cognitive impairment in the developing brain, and whether it can mediate such neurotoxicity by inhibiting Akt related signaling pathways remains undefined and requires further investigation.…”

A Non-Randomized Trial Investigating the Impact of Brown Rice Consumption on Gut Microbiota, Attention, and Short-Term Working Memory in Thai School-Aged Children

“…Fiber-rich brown rice has been shown to improve cognitive function in elderly populations receiving 6-month [ 20 ] and 24-month [ 21 ] interventions. Cognitive function impacts have been found as a result of microbiota transplantations in animal models [ 22 , 23 , 24 ] as well as with some intervention studies of probiotics/prebiotics [ 25 ]. However, a link between dietary intervention, gut microbiota, and cognitive function has only been elucidated in older adults [ 26 , 27 ].…”