Abstract
ObjectiveEmerging evidence links perturbations in the microbiome to neurodegeneration in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) and to surgical stress. In this study, we attempted to identify preoperative differences intestinal microbiota (IM) and barrier function between pAD [prodromal AD: Subjective cognitive decline (SCD) and aMCI] patients and normal neurocognition (NC) patients. Additionally, the potential associations between IM and barrier function, inflammation, and the clinical characteristics of pAD were evaluated.DesignEighty elderly patients scheduled to undergo orthopedic surgery were consecutively enrolled and grouped as NC, SCD, and aMCI following neuropsychological assessment. IM was determined by 16S rRNA MiSeq sequencing, and PICRUSt was used to predict functional shifts in IM. Furthermore, we investigated the association between IM and plasma claudin-1, occludin, LPS, systemic inflammatory cytokines, neuropsychological assessment, and clinical characteristics.ResultsThere was a lower Chao1 index in the SCD group (P = 0.004) and differences in beta diversity among the three groups (PCA: P = 0.026, PCoA: P= 0.004). The relative abundance of Bacteroidetes was higher in the SCD group (P = 0.016, P = 0.008), and Firmicutes were more enriched in the aMCI group than in the SCD group (P= 0.026). At the family level, the total abundance of Gram-negative bacteria was higher in the SCD group than in the aMCI group (P = 0.047), and the Christensenellaceae family was detected at lower levels in the SCD and aMCI groups than in the NC group (P= 0.039). At the genus level, the eleven short-chain fatty acid (SCFA)-producing bacteria exhibited differences among the three groups. PICRUSt analysis showed that the pathways involved in SCFA catabolism, biosynthesis, and adherent junctions were reduced in SCD patients, and lipid synthesis proteins were reduced in pAD patients. Meanwhile, elevated plasma LPS and CRP were observed in SCD patients, and higher plasma occludin in aMCI patients. The IM was correlated with plasma claudin-1, LPS, inflammatory factors, neuropsychological assessment, and clinical characteristics.ConclusionThe intestines of SCD and aMCI patients preoperatively exhibited IM dysbiosis and barrier dysfunction, and elevated plasma LPS and CRP were observed in SCD patients.
Highlights
Alzheimer’s disease (AD) typically progresses in three stages: the preclinical stage, the mild cognitive impairment (MCI) stage, and the dementia stage (Sperling et al, 2011)
Intestinal microbial dysbiosis has been observed in patients with pAD, including those suffering from MCI and amnestic MCI due to AD (Li B. et al, 2019; Liu P. et al, 2019)
We investigated the preoperative differences in IM, intestinal barrier dysfunction, and low-grade inflammation between pAD patients and patients with normal cognition, and we investigated the association between the gut microbiota, as reflected by preoperative fecal samples, and intestinal linker proteins, plasma LPS, systemic inflammatory cytokines, neuropsychological assessment, and clinical characteristics
Summary
AD typically progresses in three stages: the preclinical stage, the mild cognitive impairment (MCI) stage, and the dementia stage (Sperling et al, 2011). Intestinal microbial dysbiosis in AD and pAD patients is characterized by an increase in proinflammatory bacteria and a decrease in anti-inflammatory bacteria (Cattaneo et al, 2016). Gram-negative bacteria, such as Escherichia and Shigella, are associated with brain amyloidosis in patients with neurocognitive impairment (Cattaneo et al, 2016). Gramnegative bacteria may induce intestinal barrier dysfunction (Wang et al, 2019), resulting in the translocation of Gramnegative bacteria-derived LPS either into the blood or directly into the brain. Bacterial LPS may induce systemic inflammation, neuroinflammation, and pathological processes that are associated with amyloidosis and impaired neurocognitive function (Brown, 2019). Decreased levels of Gram-negative bacteria may slow the progression of AD by inhibiting systemic inflammation, which may reduce the accumulation of amyloid beta aggregates and brain damage (Bonfili et al, 2017)
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