Anesthesia and surgery induce cognitive dysfunction in elderly male mice: the role of gut microbiota

Abstract

It is well known that the incidence of postoperative cognitive dysfunction (POCD) is high in elderly patients. The pathogenesis and therapeutic mechanisms of POCD, however, have not yet been completely elucidated. The effects of gut microbiota, particularly in terms of regulating brain function, have gradually attracted increasing attention. In this study, we investigated the potential role of gut microbiota in POCD in aged male mice and attempted to determine whether alterations in gut microbiota would be helpful in the diagnosis of POCD. POCD and non-POCD mice were classified by hierarchical cluster analysis of behavioral results. Additionally, α- and β-diversity of gut microbiota showed a differential profile between the groups. In total, 24 gut bacteria were significantly altered in POCD mice compared with those in non-POCD mice, in which 13 gut bacteria were significantly correlated with escape latency in the Morris water maze test (MWMT). Remarkably, receiver operating characteristic curves revealed that the Dehalobacteriaceae family and Dehalobacterium genus are potentially important bacteria for the diagnosis of POCD. These findings indicate that alterations in the composition of gut microbiota are probably involved in the pathogenesis of POCD in aged mice. Novel therapeutic strategies regulating specific gut bacteria may be helpful for the prevention and treatment of POCD.

Spatial Memory and Gut Microbiota Alterations Are Already Present in Early Adulthood in a Pre-clinical Transgenic Model of Alzheimer’s Disease

“…Furthermore, the results of the LEfSe analysis in female and male 3xTg-AD mice at 3 and 5 months old in fecal samples, show bacteria with a statistically significant change in LDA scores such as Xanthomonadaceae , Oxalobacteraceae , Streptomycetaceae , Koribacteraceae , and Streptomycetaceae families, Gemella , Dehalobacterium , Clostridium , Allobaculum , Selenomonas , Veillonella , Lactococcus , Desulfovibrio , Bradyrhizobium , Campylobacter , Erythrobacter , Neisseria , Flexispira , Microbacterium , Collinsella , Atopobium , Pedobacter , and the S1 genera. These microorganisms have been associated with both pre-clinical models and patients who present AD mainly; however, other bacteria are related to aging, cognitive decline, cerebral damage, and inflammatory response in mice and humans ( Thomas et al, 2012 ; Wang et al, 2016 ; Bonfili et al, 2017 ; Harach et al, 2017 ; Morris et al, 2017 ; Vogt et al, 2017 ; Zhang et al, 2017 ; Aguayo et al, 2018 ; Alonso et al, 2018 ; Antonets et al, 2018 ; Bäuerl et al, 2018 ; Dong et al, 2018 ; Zhuang et al, 2018 ; Haran et al, 2019 ; Li et al, 2019 ; Zhan et al, 2019 ; Beydoun et al, 2020 ; Na et al, 2020 ; Westfall et al, 2020 ). These results suggest that bacteria families and genera are representative microorganisms of gut microbiota of disease that could be considered a useful tool for diagnostic as well as a progression biomarker of AD.…”

Abnormal gut microbiota composition contributes to cognitive dysfunction in streptozotocin-induced diabetic mice

“…The MWM is a commonly used task for assessing spatial learning and memory in models of neurodegenerative disorders [24]. In the present study, diabetic mice could be stratified into CD and Non-CD groups using the hierarchical cluster analysis of MWM performance indices [17]. Previous studies have reported CD in diabetic mice [20, 25]; however, in the present study, we excluded those without CD to distinctly reveal associations with specific diabetes-related changes (in this case, gut microbiota).…”

“…Our previous study has demonstrated that CD in SAMP8 mice was strongly associated with gut microbiota composition and relative abundance [16]. Further, we have observed a substantial difference in gut microbiota composition among aged mice with CD after surgery and anesthesia [17]. In the present study, we observed no significant difference in α-diversity (consisting of Shannon and Simpson indices) among the control, CD, and Non-CD groups, suggesting little change in bacterial numbers.…”

“…Our previous study has demonstrated a strong association between CD in SAMP8 mice and abnormal gut microbiota composition [16]. In addition, CD in aged mice following surgery and anesthesia may be associated with altered gut microbiota composition [17]. Furthermore, gut microbiota dysbiosis and increased intestinal permeability have been observed in patients with diabetes [18, 19].…”

Effect of dihydromyricetin on hepatic encephalopathy associated with acute hepatic failure in mice

“…Spatial learning and memory function were assessed using the Morris water maze test (Zhan et al 2019). Briefly, mice were trained four times each day for five consecutive days in a circular pool where each mouse was permitted 60 s to find the hidden platform, which was 10 cm in diameter and submerged 1 cm below the water surface in the target quadrant.…”