A systematic review and meta-analysis of basal microbiota and cognitive function in Alzheimer's disease: A potential target for treatment or a contributor to disease progression?

Abstract

A systematic review and meta-analysis examined the impact of gut microbiota in Alzheimer's disease (AD) pathogenesis. Dysbiosis may influence neurodegeneration by affecting gut permeability and neurotrophic factors, leading to cognitive decline. The study analyzed microbiome differences between patients with AD and healthy individuals, as well as the impact of various interventions in both preclinical and clinical studies. Of 60 studies reviewed, 12 were excluded from the meta-analysis due to unsuitable data or lack of control groups. Meta-analyses revealed significant cognitive impairment in AD patients and animal models, with specific tests identifying these deficits. Notably, Bacteroides levels were higher in patients with AD, whereas probiotics improved Prevotella levels. Natural treatments increased Bacteroidetes and reduced Firmicutes in animal models. The findings emphasize the need for standardized methods to develop therapies targeting the gut microbiota to restore cognition in AD. Understanding individual dysbiosis could further clarify the cognitive effects of the gut-brain axis.

Highlights: Dysbiosis in the gut microbiota is linked to cognitive decline in Alzheimer's disease (AD).Patients with AD show significant differences in Bacteroides levels compared to healthy individuals.Probiotic treatments increase Prevotella levels in AD animal models.Natural agents boost Bacteroidetes and reduce Firmicutes in AD animal models.Human studies show no consistent effects of gut microbiota interventions on cognitive function in AD.

Keywords: Alzheimer´s disease; cognition; dysbiosis; gut microbiome; therapy.

FIGURE 1

PRISMA flow chart of selection of publications for inclusion in review. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta‐Analysis.

FIGURE 2

Meta‐analysis using a random‐effects model of selected studies for the Bacteroides changes in the human microbiota when comparing AD versus healthy subjects. The plot shows the effect estimates and corresponding CIs for each study included in the meta‐analysis. The relative weight or contribution of each study to the overall effect estimate is also included in percentages. The overall weighted effect is indicated by a diamond at the bottom of the figure. The figure was generated with R software version 4.3.1. AD, Alzheimer's disease; CI, confidence interval.

FIGURE 3

Meta‐analysis using a random‐effects model of selected studies for the Prevotella changes in the animal microbiota after a treatment with natural therapeutic agents. The plot shows the effect estimates and corresponding CIs for each study included in the meta‐analysis. The relative weight or contribution of each study to the overall effect estimate is also included in percentages. The overall weighted effect is indicated by a diamond at the bottom of the figure. The figure was generated with R software version 4.3.1. CI, confidence interval.

FIGURE 4

Meta‐analysis using a random‐effects model of selected studies for the Firmicutes (A) and Bacteroidetes (B) changes in the animal microbiota after a treatment with natural therapeutic agents. The plot shows the effect estimates and corresponding CIs for each study included in the meta‐analysis. The relative weight or contribution of each study to the overall effect estimate is also included in percentages. The overall weighted effect is indicated by a diamond at the bottom of the figure. The figure was generated with R software version 4.3.1. The number indicated silymarin‐administrated group (1) and silibinin‐administrated group (2) in Shen et al., and medium (1) and high (2) doses of defatted walnut powder in Xu et al. CI, confidence interval.