Exploring the gut-brain axis in alzheimer's disease treatment via probiotics: evidence from animal studies-a systematic review and meta-analysis

Abstract

Introduction: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder in the elderly, causing cognitive impairment. Its pathogenesis is characterized by amyloid beta deposition, neurofibrillary tangles, and neuroinflammation. Recent research has identified the link between gut dysbiosis, an imbalance of intestinal microorganisms, to this pathogenesis via the gut-brain axis. This study aims to review the probiotics' therapeutic effect, targeting the gut-brain axis, for AD treatment in animals.

Methods: The method utilized in this study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Three reviewers searched articles through PubMed, Scopus, and Embase using advanced search strategy. Articles published between 2010 and 2023 that met the criteria were included.

Results: Of 2,273 articles, 21 animal studies measuring the effects of probiotics genera Lactobacillus and/or Bifidobacterium on AD via at least one of these four outcomes: AD pathology, cognitive function, neuroinflammation, and gut microbiota composition. The results demonstrated that probiotics could repair gut dysbiosis by decreasing pro-inflammatory bacteria and increasing anti-inflammatory bacteria. Repaired dysbiosis was found to be associated with less neuroinflammation as significant reductions in neuroinflammatory markers related to the pathogenesis of AD such as TNF-α (SMD = -2.08, P = 0.005), IL-6 (SMD = -2.98, P < 0.0005), and IL-1β (SMD = -2.49, P = 0.003) were observed. Reduced amyloid beta deposition (SMD = -1.17, P = 0.009) was reported, but reduction in tau hyperphosphorylation was found to be insignificant. For cognitive function, positive results were demonstrated for all three aspects of cognitive function including long-term memory (SMD = 2.55, P < 0.00001), short-term memory (SMD = 1.32, P = 0.003), and spatial recognition (SMD = -1.13, P < 0.00001).

Conclusions: Particular formulas of probiotics showed potential effectiveness in AD therapies with demonstrated association with the gut-brain axis. Future studies are required to investigate strain-specific results and optimal dosages and regimens.

Keywords: Alzheimer’s disease; Gut microbiota; Gut-brain axis; Probiotics.

Fig. 1

PRISMA flow chart

Fig. 2

Table of risk of bias assessment (+ reflects yes, x reflects no, and—reflects unclear)

Fig. 3

Forest plot showing the effects of probiotics treatment on amyloid beta deposition in AD induced animals (ng/mL)

Fig. 4

Forest plot showing the effects of probiotics treatment on tau hyperphosphorylation in AD induced animals (relative value)

Fig. 5

Forest plot showing the effects of probiotics treatment on short term memory of AD-induced animals (percent of alteration)

Fig. 6

Forest plot showing the effects of probiotics treatment on long term memory of AD-induced animals using the unit latency time (second)

Fig. 7

Forest plot showing the effects of probiotics treatment on spatial recognition of AD induced animals using the unit latency time (second). Combined probiotics A = L. reuteri, L. rhamnosus, and B. infantis. Combined probiotics B = L. acidophilus, L. fermentum, B. lactis, and B. longum. Combined probiotics C = L. acidophilus, B. bifidum and B. longum in capsulated form

Fig. 8

Forest plot showing the effects of probiotics treatment on TNF-α level (pg/mg)

Fig. 9

Forest plot showing the effects of probiotics treatment on IL-1β level (pg/mg)

Fig. 10

Forest plot showing the effects of probiotics treatment on IL-6 level (relative value)

Fig. 11

Forest plot showing the effects of probiotics treatment on Iba1 level (relative value)

Fig. 12

Forest plot showing the effects of probiotics treatment on GFAP level (relative value)

Fig. 13

Forest plot showing the effects of probiotics treatment on BDNF level (relative value)