Effect of Anesthesia/Surgery on Gut Microbiota and Fecal Metabolites and Their Relationship With Cognitive Dysfunction

Abstract

Aims: Post-operative cognitive dysfunction (POCD) is the decline in cognitive function of the central nervous system (CNS) after anesthesia/surgery. The present study explored whether anesthesia/surgery altered gut microbiota and fecal metabolites, examining their associations with risk factors of cognitive dysfunction in aged mice.Methods: Sixteen-month-old C57BL/6 mice underwent abdominal surgery under isoflurane anesthesia to establish an animal model of POCD. The Morris water maze test (MWMT) was used as an indicator of memory after surgery. The effects of anesthesia/surgical interventions on gut microbiota, fecal metabolites, hippocampus, and serum levels of inflammatory factors were examined.Results: The anesthesia/surgery induced more serious POCD behavior, increasing brain interleukin (IL)-6, and IL-1β levels than sham control mice. The relative abundance of bacterial genera Bacteroidales_unclassified, Mucispirillum, and Clostridiales_unclassified declined, whereas that of Escherichia–Shigella, actinomyces, Ruminococcus_gnavus_group, and Lachnospiraceae_FCS020_group were enriched after anesthesia/surgery compared to the baseline controls. Liquid chromatography–mass spectrometry (LC–MS) showed that the metabolites differed between post-anesthesia+surgery (post_A + S) and baseline samples and were associated with the fecal metabolism of tryptophan, kynurenic acid, N-oleoyl γ-aminobutyric acid (GABA), 2-indolecarboxylic acid, and glutamic acid. Furthermore, the differential metabolites were associated with alterations in the abundance of specific bacteria. These results indicate that the POCD intervention may be achieved by targeting specific bacteria associated with neurotransmitter metabolism.Conclusions: A transient cognitive disturbance induced by anesthesia/surgery may be associated with unfavorable alterations in gut microbiota and fecal metabolites, thereby contributing to the POCD development.

A multi‐omics analysis for the prediction of neurocognitive disorders risk among the elderly in Macao

“…The increase of Desulfovibrio abundance coincided with abundant microglial accumulation at sites of amyloid deposition in the brain of AD mouse models, which was viewed as an inflammation‐related bacterial profile 30 . R. gnavus was also found to be enriched in post‐operative cognitive dysfunction 31 . These results suggested that the four specific species negatively influenced the cognitive function, and these enrichments accounted for the susceptibility of vulnerable group to NCDs partly.…”

“… 30 R. gnavus was also found to be enriched in post‐operative cognitive dysfunction. 31 These results suggested that the four specific species negatively influenced the cognitive function, and these enrichments accounted for the susceptibility of vulnerable group to NCDs partly.…”

Neuroinflammation as the Underlying Mechanism of Postoperative Cognitive Dysfunction and Therapeutic Strategies

“…Remarkably, dysregulation of gut microbiota promoted the progression of neurodegenerative diseases and the release of inflammatory markers such as IL-6 and TNF-α ( Yang et al, 2018 ; Dalton et al, 2019 ). In recent years, increasing numbers of animal experiments have confirmed that surgery and anesthesia could induce intestinal microflora imbalance and then affected brain cognitive function through certain mechanisms ( Zhan et al, 2019 ; Lian et al, 2021 ). These pathological mechanisms could be ameliorated by the increase of beneficial bacteria in the gut, such as Bifidobacterium , Lactobacillus , and Galactose oligosaccharide ( Jeong et al, 2015 ; Kobayashi et al, 2017 ; Yang et al, 2018 ).…”

Postoperative Delirium in Neurosurgical Patients: Recent Insights into the Pathogenesis

“…A novel study suggested that oxidative stress and mitochondrial damage in microglia driven by the gut microbiota are probably the results of the metabolite N6-carboxymethyllysine [ 123 ]. Furthermore, alterations in certain bacteria associated with differential fecal metabolism of tryptophan, kynurenic acid, GABA, 2-indolecarboxylic acid, and glutamic acid in POCD mice suggest that the gut microbiota might contribute to cognitive dysfunction after surgery through neurotransmitter metabolism [ 124 ]. Taking the above findings together, we hypothesized that gut microbiota dysregulation may promote POD through inflammation worsened by a broken intestinal barrier, oxidative stress, and neurotransmitter disorders.…”