Fecal Microbiota Transplantation Derived from Mild Cognitive Impairment Individuals Impairs Cerebral Glucose Uptake and Cognitive Function in Wild-type Mice: and TXNIP-GLUT Signaling Pathway

Overview

Journal Gut Microbes

Specialties Gastroenterology
Microbiology

Date 2024 Sep 12

PMID 39262376

Authors

Tao Wang

Ling Hao

Kexin Yang

Wenjing Feng

Zhiting Guo

Miao Liu

Rong Xiao

Affiliations

Soon will be listed here.

Abstract

Gut microbiome dysbiosis has been widely implicated in cognitive impairment, but the identity of the specific bacterial taxa and mechanisms are not fully elucidated. Brain glucose hypometabolism coincides with the cognitive decline. This study explored the link among cognition, gut microbiota and glucose uptake based on the fecal microbiota transplantation from mild cognitive impairment individuals (MCI-FMT) and investigated whether similar mechanisms were involved in 27-hydroxycholesterol (27-OHC)-induced cognitive decline. Our results showed that the MCI-FMT mice exhibited learning and memory decline and morphological lesions in the brain and colon tissues. There were reduced F-fluorodeoxyglucose uptake, downregulated expression of glucose transporters (GLUT1,3,4) and upregulated negative regulator of glucose uptake (TXNIP) in the brain. MCI-FMT altered the bacterial composition and diversity of the recipient mice, and the microbial signatures highlighted by the increased abundance of recapitulated the negative effects of MCI bacterial colonization. However, inhibiting or TXNIP increased the expression of GLUT1 and GLUT4, significantly improving brain glucose uptake and cognitive performance in 27-OHC-treated mice. Our study verified that cognitive decline and abnormal cerebral glucose uptake were associated with gut microbiota dysbiosis; we also revealed the involvement of and molecular mechanisms of TXNIP-related glucose uptake in cognitive deficits caused by 27-OHC.

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