Skip to main content
Download PDF
Download ePub

Effect of probiotics on cognitive function and cardiovascular risk factors in mild cognitive impairment and Alzheimer’s disease: an umbrella meta-analysis

Journal of Health, Population and Nutrition volume 44, Article number: 109 (2025) Cite this article

Abstract

Background

This umbrella meta-analysis evaluates the effects of probiotics on cognitive function and metabolic health in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) by synthesizing findings from meta-analyses of randomized controlled trials (RCTs), as existing evidence remains inconclusive.

Methods

A systematic search was conducted in PubMed, Web of Science, and Scopus to identify meta-analyses of RCTs investigating the impact of probiotic supplementation on cognitive function and metabolic biomarkers. The random-effects model was used. Heterogeneity and publication bias were assessed.

Results

Thirteen meta-analyses, comprising 3910 patients, were included. Probiotics significantly improved cognitive function in AD (SMD = 0.78, 95% CI: 0.33 to 1.23) and MCI (SMD = 0.43, 95% CI: 0.15 to 0.70). Probiotics also increased total antioxidant capacity (SMD = 0.40, 95% CI: 0.11 to 0.70) and reduced MDA (SMD =  − 0.35, 95% CI: − 0.62 to − 0.09) and hs-CRP (SMD =  − 0.59, 95% CI: − 0.87 to − 0.30). Insulin resistance improved, as reflected by decreased HOMA-IR (SMD =  − 0.34, 95% CI: − 0.43 to − 0.26). No significant effects were observed on glutathione, nitric oxide, or lipid profiles.

Conclusion

Probiotic supplementation appears to enhance cognitive function and metabolic parameters in individuals with MCI and AD, likely through mechanisms involving inflammation reduction, oxidative stress modulation, and improved insulin sensitivity. Further high-quality RCTs are required to validate these findings and determine optimal probiotic formulations.

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide, accounting for nearly 80% of cases [1]. It is characterized by cognitive decline, memory impairment, and functional deterioration, significantly reducing patients’ quality of life [2]. The underlying pathophysiology of AD involves protein misfolding, abnormal amyloid-beta (Aβ) accumulation, tau hyperphosphorylation, oxidative stress, and neuroinflammation [3, 4]. Mild cognitive impairment (MCI) represents an intermediate stage between normal aging and AD, where individuals experience noticeable cognitive deficits without significant impairment in daily activities [5]. Approximately 5% to 10% of MCI cases progress to AD annually [6]. Given the increasing global prevalence of AD and MCI, along with the lack of effective curative treatments, there is an urgent need for alternative strategies to prevent or slow cognitive decline [7].

The gut microbiota has emerged as a key modulator of brain health through the gut-brain axis, influencing neuroinflammation, oxidative stress, and neurotransmitter signaling [8]. Dysbiosis, or gut microbiota imbalance, has been linked to cognitive impairment and neurodegeneration [9]. Probiotics, defined as live microorganisms that confer health benefits when administered in adequate amounts, have been proposed as a potential intervention for improving cognitive function [10]. They may exert neuroprotective effects by modulating gut microbiota composition, enhancing the production of neuroactive compounds, reducing systemic inflammation, and mitigating oxidative stress [11, 12].

Studies have demonstrated that probiotics can alter gut microbiota composition, potentially reducing inflammation, oxidative stress, and metabolic parameters, and improving cognitive function in MCI and AD [7, 12, 13]. Despite the promising findings, the current body of evidence is contradictory, characterized by variability in sample size, dose and duration of treatment, and outcome measures, leading to challenges in drawing definitive conclusions. The results of meta-analysis of randomized clinical trials (RCT) are also inconsistent [10, 11, 14, 15].

This umbrella meta-analysis aims to systematically review and synthesize the existing evidence on the effects of probiotics on cognitive function and metabolic outcomes in individuals with MCI and AD. By consolidating data from multiple studies, we seek to clarify the potential role of these interventions in the management of cognitive decline, providing a comprehensive overview that may inform clinical practice and future research directions.

Methods

This umbrella meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [16].

Study design and search strategy

A comprehensive literature search was performed in PubMed, Web of Science, and Scopus to identify meta-analyses of randomized controlled trials (RCTs) evaluating the effects of probiotics supplementation on cognitive function and metabolic biomarkers in individuals with MCI or AD. The search strategy included a combination of Medical Subject Headings (MeSH) terms and relevant keywords: (“Probiotics”[Majr] OR “Synbiotics”[Majr] OR “Prebiotics”[Majr] OR Probiotic*[Title/Abstract] OR Synbiotic*[Title/Abstract] OR Prebiotic*[Title/Abstract]) AND (“Alzheimer Disease”[Mesh] OR “Cognitive Dysfunction”[Majr] OR Alzheimer’s disease[Title/Abstract] OR cognitive dysfunction[Title/Abstract] OR cognitive impairment[Title/Abstract] OR cognitive decline[Title/Abstract]) AND (meta-analysis[Title/Abstract] OR meta-analysis[Title/Abstract] OR systematic review[Title/Abstract]). No restrictions on publication date or language were applied. The reference lists of included studies were also screened to identify additional relevant articles. All search results were managed and screened using the EndNote reference manager. Two independent reviewers initially assessed titles and abstracts for relevance, and full-text articles were obtained for studies meeting the inclusion criteria. Any discrepancies were resolved through discussion or consultation with a third reviewer.

Eligibility criteria

Studies were included if they met the following criteria: Population; Adults diagnosed with MCI or AD. Intervention; Oral probiotics supplementation. Comparator; Placebo or standard care. Outcomes; Primary outcome—cognitive function; Secondary outcomes—inflammatory and oxidative biomarkers, glycemic indices, and lipid profile. Study Type; Meta-analyses of RCTs.

Studies without quantitative analysis, non-human studies, reviews, editorials, letters, protocols, case reports, and those focusing on unrelated interventions were excluded.

Data extraction and quality assessment

Two independent reviewers extracted the following data from eligible studies: authors, publication year, number of included RCTs, total sample size, risk of bias (RoB) assessment, intervention details (probiotic strains, dosage, duration), cognitive assessment tools, and effect sizes for reported outcomes. Any discrepancies were resolved through discussion or consultation with a third reviewer.

The methodological quality of included meta-analyses was assessed using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) [17]. This tool evaluates 16 key domains related to study design, risk of bias, and reporting transparency, classifying studies as high, moderate, low, or critically low quality.

Statistical analysis

The standardized mean difference (SMD) or the weighted mean difference (WMD) with a 95% confidence interval (CI) was employed as the effect size measure to examine the impact of the intervention on the outcomes. Inter-study heterogeneity was assessed using chi-square statistics and I2 statistics. High heterogeneity among the studies was deemed present if P < 0.1 or I2 exceeded 50%. Data were pooled using a random effects model [18]. To identify the sources of heterogeneity, subgroup analyses were performed based on health conditions, sample size, and duration of supplementation. Sensitivity analyses were conducted to assess the robustness of the results using the leave-one-out method. Publication bias was examined using Egger’s test and funnel plots, which were only used for cognitive function [19]. All statistical analyses were performed using Stata 16 software.

Results

Out of the 252 records initially retrieved from electronic databases, 56 studies were identified as duplicates and excluded, while 176 publications were removed after reviewing their titles and abstracts. The remaining 20 studies underwent full-text screening, resulting in the exclusion of 7 studies based on the criteria outlined in the PRISMA flowchart (Fig. 1). Ultimately, 13 studies with 26 effect sizes, comprising 3910 patients, met the eligibility criteria and were included in the umbrella meta-analysis. The included studies were published between 2020 and 2024, with sample sizes ranging from 48 to 998 participants. The follow-up durations varied from 2 to 24 weeks, with most studies implementing a 12-week intervention. All studies assessed cognition as a primary outcome, and several also examined oxidative stress and inflammatory biomarkers such as MDA, hs-CRP, GSH, TAC, NO, TG, TC, and HOMA-IR. The included meta-analyses comprised RCTs that enrolled patients with AD, MCI, or both. Specifically, five studies assessed combined AD and MCI, six focused exclusively on AD, and seven examined MCI alone. The studies were conducted in China (9 studies) [1, 7, 11,12,13,14,15, 20, 21], Brazil (1 study) [10], Spain (1 study) [8], Iran (1 study) [22], and India (1 study) [23]. Detailed evaluations are presented in Table 1.

Fig. 1
figure 1

PRISMA flow diagram

Full size image
Table 1 Characteristics of studies included in umbrella meta-analysis
Full size table

Quality of studies

The methodological quality assessment classified seven studies as high quality [7, 10, 11, 15, 20, 22, 23], and six as moderate quality [1, 8, 12,13,14, 21]. High-quality studies demonstrated rigorous methodologies, while moderate- and low-quality studies had limitations such as incomplete reporting or insufficient sensitivity analyses. Detailed evaluations are presented in Supplementary Table 1.

Probiotics on cognitive function

SMD

Twelve studies (24 effect sizes) evaluated the impact of probiotics on cognitive function [7, 8, 10, 11, 13,14,15, 20,21,22,23]. The meta-analyses showed a significant improvement in cognitive function after probiotic consumption (SMD = 0.42; 95% CI: 0.25 to 0.59, I2 = 71.7%,P < 0.001) (Fig. 2). However, no significant improvement was found in MCI (SMD = 0.28; 95% CI: − 0.02 to 0.57) in the subgroup analysis (Table 2). Based on Begg test and funnel plot (Supplementary Fig. 1), indicated no evidence of publication bias. Additionally, the sensitivity analysis, conducted by sequentially excluding individual studies, showed no significant impact on the overall results, suggesting the robustness of the findings.

Fig. 2
figure 2

Mean difference and 95% CIs presented in forest plot of the studies on the effects of probiotics on cognitive function

Full size image
Table 2 Overall and subgroup analyses for the effect of probiotics on various outcomes in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI)
Full size table

WMD

One study with two arms using WMD was included, and the results were found to be statistically significant (WMD = 1.87; 95% CI: 0.46 to 3.28, I2 = 0.0%,P = 0.451) (Fig. 2) [1].

Probiotics on oxidative stress and inflammation

GSH

The pooled effect size for the four studies that showed no effect of probiotics on glutathion (SMD = 0.29; 95% CI: − 0.69 to 0.1.26, I2 = 86.2%, P < 0.001) (Fig. 3A) [7, 12, 13, 22].

Fig. 3
figure 3

Mean difference and 95% CIs presented in forest plot of the studies on the effects of probiotics on GSH (A), and MDA (B)

Full size image

MDA

The pooled analysis from five studies revealed a significant reduction in MDA levels with a pooled SMD of − 0.40 (95% CI: − 0.67 to − 0.12, I2 = 80.2%, P < 0.001) (Fig. 3B), indicating a meaningful decrease in MDA after probiotic supplementation [7, 10, 12, 13, 22]. However, one study that used WMD reported no significant effect (WMD = − 0.50; 95% CI: − 1.10 to 0.10) (Fig. 3B) [1].

NO

The pooled effect size for the three studies that showed no effect of probiotics on NO was (SMD = − 0.16; 95% CI: − 0.38 to 0.06, I2 = 0.0%, P = 0.427) (Fig. 4A) [7, 12, 22].

Fig. 4
figure 4figure 4

Mean difference and 95% CIs presented in forest plot of the studies on the effects of probiotics on NO (A), TAC (B), and hs-CRP (C)

Full size image

TAC

The pooled effect size for the four studies that showed a significant increase in TAC due to probiotics was (SMD = 4.81; 95% CI: 0.71 to 8.91, I2 = 95.5%, P < 0.001) (Fig. 4B) [7, 12, 13, 22].

Hs-CRP

The pooled analysis from three studies revealed a significant reduction in hs-CRP levels with a pooled SMD of − 0.58 (95% CI: − 0.83 to − 0.32, I2 = 0.0%, P = 0.983) (Fig. 4C) [7, 12, 22]. However, one study that used WMD reported no significant effect (WMD = − 1.31; 95% CI: − 3.31 to 0.69) (Fig. 4C) [1].

Probiotics on glycemic indices and lipid profile

HOMA-IR

The pooled analysis from two studies revealed a significant reduction in HOMA-IR levels with a pooled SMD of − 0.35 (95% CI: − 0.52 to − 0.18, I2 = 0.0%, P  = 0.544) (Fig. 5A) [10, 12]. Additionally, one study that used WMD also reported a significant reduction (WMD = − 0.34; 95% CI: − 0.44 to − 0.24) (Fig. 5A) [1].

Fig. 5
figure 5figure 5figure 5

Mean difference and 95% CIs presented in forest plot of the studies on the effects of probiotics on HOMA-IR (A), QUICKI (B), TG (C), TC (D) and VLDL (E)

Full size image

QUICKI

The pooled analysis from two studies revealed no significant effect on QUICKI levels with a pooled SMD of 0.13 (95% CI: − 0.19 to 0.46, I2 = 70.1%, P = 0.067) (Fig. 5B) [10, 12]. Similarly, one study that used WMD also reported no significant effect (WMD = 0.01; 95% CI: − 0.00 to 0.01) (Fig. 5B) [1].

TG

The pooled analysis from three studies revealed a significant reduction in TG levels with a pooled SMD of − 4.95 (95% CI: − 17.03 to − 7.13, I2 = 84.1%, P = 0.002) (Fig. 5C)[10, 12, 22]. However, one study that used WMD reported no significant effect (WMD = − 15.65; 95% CI: − 27.47 to − 3.82) (Fig. 5C) [1].

TC

The pooled analysis from two studies showed no significant effect on TC levels, with a pooled SMD of − 1.66 (95% CI: − 5.53 to 2.22, I2 = 73.8%, P = 0.051) [12, 22], and a WMD of 0.05 (95% CI: − 0.29 to 0.39) (Fig. 5D) [1].

VLDL

The pooled analysis from two studies showed a non-significant effect on VLDL levels with a pooled SMD of − 1.61 (95% CI: − 4.45 to 1.23, I2 = 79.8%, P = 0.026) (Fig. 5E) [10, 12]. However, the WMD analysis revealed a significant reduction in VLDL with a WMD of − 3.71 (95% CI: − 6.11 to − 1.32) (Fig. 5E) [1].

Discussion

This umbrella meta-analysis provides a comprehensive synthesis of the existing evidence regarding the effects of probiotics on cognitive function and metabolic parameters in individuals with MCI and AD. Our findings suggest that probiotic supplementation significantly improves cognitive function in both AD and MCI populations while also exerting beneficial effects on oxidative stress, inflammation, and insulin resistance. These results underscore the potential role of probiotics as an adjunctive intervention for neurodegenerative disorders.

Over the past few decades, extensive research has focused on creating effective pharmaceutical solutions for managing MCI and AD. However, no treatment has yet proven fully satisfactory. Our findings reinforce the evidence that altering gut microbiota is pivotal in addressing cognitive decline. This aligns with an increasing body of research emphasizing the importance of lifestyle and dietary modifications as key elements in dementia care strategies [24]. The positive effects of probiotics on cognitive function observed in this study are consistent with prior meta-analyses of RCTs [25]. Previous systematic reviews have reported that probiotics can modulate gut microbiota composition, leading to reduced systemic inflammation and oxidative stress, which are key contributors to neurodegeneration [25]. The biological mechanisms affecting cognition operate through multiple interconnected pathways, including the gut-brain axis, neurotransmitter production, amyloid-β and tau-related biomarkers, as well as inflammation and oxidative stress [14, 15, 26]. The gut-brain axis is a two-way communication system connecting the gastrointestinal tract with the central nervous system (CNS). Probiotics impact this connection by modifying the gut microbiota, which subsequently influences brain function and behavior [14]. Probiotics can boost the production of neurotransmitters like serotonin and gamma-aminobutyric acid (GABA), which are essential for regulating mood and supporting cognitive functions [27]. Impairments in memory and cognition are linked to dysfunctions in the serotonergic (5-HT) and GABAergic systems [28]. Probiotics might activate the vagus nerve, a crucial channel for communication among neurons that influence behavior, memory, and learning, potentially enhancing cognitive abilities [29, 30].

Chronic inflammation is a significant contributor to cognitive decline in AD and MCI [14]. Furthermore, studies have shown that diet, particularly probiotics, play a role in reducing inflammation and CRP levels [31, 32]. The study found that probiotic consumption was linked to reduced levels of systemic inflammation and oxidative stress markers, including hs-CRP and MDA. By decreasing MDA levels, probiotics mitigate lipid peroxidation, a process that can harm cell membranes and cause neuronal death, ultimately promoting cognitive health [33, 34]. Also, our study demonstrated that the consumption of probiotics leads to an increase in TAC in the body, which helps combat oxidative damage by neutralizing free radicals. These findings indicate that probiotics may have neuroprotective effects by reducing both inflammation and oxidative damage, which are key contributors to the development of cognitive dysfunction and neurodegenerative diseases. Additionally, prior research has indicated that probiotic treatment results in a reduction of oxidative stress and inflammation-related gene expression in the hippocampus of AD models [35]. The hippocampus plays a key role in cognition and can be affected by gut-brain axis. Multiple studies have demonstrated that probiotic use significantly elevates the protein expression of brain-derived neurotrophic factor (BDNF) while decreasing apoptosis in the hippocampus [36]. BDNF is a crucial neurotrophin involved in neuronal growth, survival, and plasticity, the last of which is especially significant for cognitive functions [37]. Research indicates that probiotic supplementation could help reduce proteinopathy by decreasing amyloid-β and tau-related biomarkers [15]. This discovery supports the attenuation of AD as described by the amyloid-beta and hyperphosphorylated tau hypotheses. Probiotics can affect the release of gut hormones such as glucagon-like peptide-1 (GLP-1), which is involved in glucose metabolism and insulin sensitivity [38]. Insulin resistance has been implicated in the pathogenesis of AD. Our analysis revealed a significant reduction in homeostatic model assessment for insulin resistance (HOMA-IR) and an improvement in the quantitative insulin sensitivity check index (QUICKI), indicating that probiotics may enhance insulin sensitivity and glucose metabolism. Given the growing recognition of AD as a “type 3 diabetes,” these metabolic benefits could have direct implications for cognitive health [1, 39, 40].

Despite the promising findings, several limitations must be acknowledged. The included studies exhibited significant heterogeneity in terms of probiotic strains, dosages, and treatment durations, which may have influenced the observed effects. Furthermore, many studies had relatively short follow-up periods (ranging from 2 to 24 weeks), making it difficult to determine the long-term impact of probiotic supplementation on cognitive function and metabolic parameters. Additionally, the potential for publication bias cannot be entirely ruled out, as studies with negative results may be less likely to be published.

Future research should focus on addressing these limitations by conducting large-scale, high-quality randomized controlled trials with standardized probiotic formulations and extended follow-up durations. It is also essential to explore the individual variability in response to probiotics, particularly concerning baseline gut microbiota composition. Investigating the potential synergistic effects of probiotics with other dietary and pharmacological interventions may further elucidate their role in cognitive health. Moreover, mechanistic studies are needed to clarify the precise pathways through which probiotics influence neurodegeneration and metabolic function.

One of the key strengths of this umbrella meta-analysis is the comprehensive evaluation of probiotic effects across multiple health parameters in AD and MCI. By synthesizing data from several meta-analyses, our study provides a robust and holistic overview of the current evidence. Additionally, our inclusion of metabolic and inflammatory biomarkers strengthens the understanding of potential mechanisms linking probiotics to cognitive function. The rigorous methodological assessment of included studies further enhances the reliability of our findings.

Conclusion

In conclusion, this umbrella meta-analysis suggests that probiotic supplementation has a beneficial impact on cognitive function, oxidative stress, inflammation, and metabolic parameters in individuals with MCI and AD. These findings support the growing evidence for the gut-brain connection and highlight the potential of microbiome-targeted interventions in neurodegenerative disorders. Further research is warranted to establish optimal probiotic regimens and elucidate their long-term effects on cognitive health.

Availability of data and materials

The original data used during the current study can be obtained by contacting the corresponding author.

References

  1. Li X, Lv C, Song J, Li J. Effect of probiotic supplementation on cognitive function and metabolic status in mild cognitive impairment and Alzheimer’s disease: a meta-analysis. Front Nutr. 2021;8: 757673.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Migliore L, Coppedè F. Genetics, environmental factors and the emerging role of epigenetics in neurodegenerative diseases. Mutat Res/Fundam Mol Mech Mutagen. 2009;667(1–2):82–97.

    Article  CAS  Google Scholar 

  3. Adav SS, Sze SK. Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling. Mol Brain. 2016;9:1–22.

    Article  Google Scholar 

  4. Tran L, Ha-Duong T. Exploring the Alzheimer amyloid-β peptide conformational ensemble: a review of molecular dynamics approaches. Peptides. 2015;69:86–91.

    Article  CAS  PubMed  Google Scholar 

  5. Maitre Y, Mahalli R, Micheneau P, Delpierre A, Amador G, Denis F. Evidence and therapeutic perspectives in the relationship between the oral microbiome and Alzheimer’s disease: a systematic review. Int J Environ Res Public Health. 2021;18(21):11157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Petersen RC, Negash S. Mild cognitive impairment: an overview. CNS Spectr. 2008;13(1):45–53.

    Article  PubMed  Google Scholar 

  7. Den H, Dong X, Chen M, Zou Z. Efficacy of probiotics on cognition, and biomarkers of inflammation and oxidative stress in adults with Alzheimer’s disease or mild cognitive impairment—a meta-analysis of randomized controlled trials. Aging (Albany NY). 2020;12(4):4010.

    Article  PubMed  Google Scholar 

  8. Ruiz-Gonzalez C, Roman P, Rueda-Ruzafa L, Rodriguez-Arrastia M, Cardona D. Effects of probiotics supplementation on dementia and cognitive impairment: a systematic review and meta-analysis of preclinical and clinical studies. Prog Neuropsychopharmacol Biol Psychiatry. 2021;108: 110189.

    Article  PubMed  Google Scholar 

  9. Liu S, Gao J, Zhu M, Liu K, Zhang H-L. Gut microbiota and dysbiosis in Alzheimer’s disease: implications for pathogenesis and treatment. Mol Neurobiol. 2020;57:5026–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Krüger JF, Hillesheim E, Pereira AC, Camargo CQ, Rabito EI. Probiotics for dementia: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2021;79(2):160–70.

    Article  PubMed  Google Scholar 

  11. Zhu G, Zhao J, Zhang H, Chen W, Wang G. Probiotics for mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis. Foods. 2021;10(7):1672.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xiang S, Ji J-L, Li S, Cao X-P, Xu W, Tan L, et al. Efficacy and safety of probiotics for the treatment of Alzheimer’s disease, mild cognitive impairment, and Parkinson’s disease: a systematic review and meta-analysis. Frontiers in aging neuroscience. 2022;14: 730036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kou J, Kang H, Hu L, Wang D, Wang S, Wang Q, et al. Evaluation of improvement of cognitive impairment in older adults with probiotic supplementation: a systematic review and meta-analysis. Geriatr Nurs. 2023;54:155–62.

    Article  PubMed  Google Scholar 

  14. Lv T, Ye M, Luo F, Hu B, Wang A, Chen J, et al. Probiotics treatment improves cognitive impairment in patients and animals: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2021;120:159–72.

    Article  CAS  PubMed  Google Scholar 

  15. Meng HYH, Mak CCH, Mak WY, Zuo T, Ko H, Chan FKL. Probiotic supplementation demonstrates therapeutic potential in treating gut dysbiosis and improving neurocognitive function in age-related dementia. Euro J Nutr. 2022. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00394-021-02760-4.

    Article  Google Scholar 

  16. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021. https://doiorg.publicaciones.saludcastillayleon.es/10.1136/bmj.n71.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Perry R, Whitmarsh A, Leach V, Davies P. A comparison of two assessment tools used in overviews of systematic reviews: ROBIS versus AMSTAR-2. Syst Rev. 2021;10:1–20.

    Article  Google Scholar 

  18. Lin L. Comparison of four heterogeneity measures for meta-analysis. J Eval Clin Pract. 2020;26(1):376–84.

    Article  PubMed  Google Scholar 

  19. Song F, Khan KS, Dinnes J, Sutton AJ. Asymmetric funnel plots and publication bias in meta-analyses of diagnostic accuracy. Int J Epidemiol. 2002;31(1):88–95.

    Article  PubMed  Google Scholar 

  20. Liu N, Yang D, Sun J, Li Y. Probiotic supplements are effective in people with cognitive impairment: a meta-analysis of randomized controlled trials. Nutr Rev. 2023;81(9):1091–104.

    Article  PubMed  Google Scholar 

  21. Mo R, Jiang M, Xu H, Jia R. Effect of probiotics on cognitive function in adults with mild cognitive impairment or Alzheimer’s disease: a meta-analysis of randomized controlled trials. Medicina Clínica (English Edition). 2024;162(12):565–73.

    Article  CAS  Google Scholar 

  22. Tahmasbi F, Mirghafourvand M, Shamekh A, Mahmoodpoor A, Sanaie S. Effects of probiotic supplementation on cognitive function in elderly: a systematic review and meta-analysis. Aging Ment Health. 2022;26(9):1778–86.

    Article  PubMed  Google Scholar 

  23. Tripathi S, Kaushik M, Dwivedi R, Tiwari P, Tripathi M, Dada R. The effect of probiotics on select cognitive domains in mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimer’s Dis Rep. 2024;8(1):1422–33.

    Article  Google Scholar 

  24. Morris MC, et al. MIND diet slows cognitive decline with aging. Alzheimer’s Demen. 2015;11:1015–22.

    Article  Google Scholar 

  25. Ojha S, Patil N, Jain M, Kole C, Kaushik P. Probiotics for neurodegenerative diseases: a systemic review. Microorganisms. 2023;11(4):1083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13(10):701–12.

    Article  CAS  PubMed  Google Scholar 

  27. Eastwood J, van Hemert S, Poveda C, Elmore S, Williams C, Lamport D, et al. The effect of probiotic bacteria on composition and metabolite production of faecal microbiota using in vitro batch cultures. Nutrients. 2023;15(11):2563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Castellani RJ, Lee H-G, Zhu X, Perry G, Smith MA. Alzheimer disease pathology as a host response. J Neuropathol Experim Neurol. 2008;67(6):523–31.

    Article  CAS  Google Scholar 

  29. Wood JD. Enteric neuroimmunophysiology and pathophysiology. Gastroenterology. 2004;127(2):635–57.

    Article  CAS  PubMed  Google Scholar 

  30. Yan L, Li H, Qian Y, Zhang J, Cong S, Zhang X, et al. Transcutaneous vagus nerve stimulation: A new strategy for Alzheimer’s disease intervention through the brain-gut-microbiota axis? Front Aging Neurosci. 2024;16:1334887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pam P, Behrooz M, Jamali M, Ghorbani H, Hiradfar A, Rezamand A, et al. The relationships between dietary inflammatory and antioxidant index with inflammatory markers in children with acute lymphocytic leukemia. Nutr Food Sci. 2025;55(1):205–21.

    Article  Google Scholar 

  32. Rahimlou M, Nematollahi S, Husain D, Banaei-Jahromi N, Majdinasab N, Hosseini SA. Probiotic supplementation and systemic inflammation in relapsing-remitting multiple sclerosis: a randomized, double-blind, placebo-controlled trial. Front Neurosci. 2022;16: 901846.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Grotto D, Maria LS, Valentini J, Paniz C, Schmitt G, Garcia SC, et al. Importance of the lipid peroxidation biomarkers and methodological aspects for malondialdehyde quantification. Quim Nova. 2009;32:169–74.

    Article  CAS  Google Scholar 

  34. Montine TJ, Neely MD, Quinn JF, Beal MF, Markesbery WR, Roberts LJ II, et al. Lipid peroxidation in aging brain and Alzheimer’s disease. Free Radical Biol Med. 2002;33(5):620–6.

    Article  CAS  Google Scholar 

  35. Kobayashi Y, Sugahara H, Shimada K, Mitsuyama E, Kuhara T, Yasuoka A, et al. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer’s disease. Sci Rep. 2017;7(1):13510.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Chunchai T, Thunapong W, Yasom S, Wanchai K, Eaimworawuthikul S, Metzler G, et al. Decreased microglial activation through gut-brain axis by prebiotics, probiotics, or synbiotics effectively restored cognitive function in obese-insulin resistant rats. J Neuroinflammation. 2018;15:1–15.

    Article  Google Scholar 

  37. Yoshii A, Constantine-Paton M. Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol. 2010;70(5):304–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Shyshkan-Shyshova K, Zinych O, Kushnareva N, Кovalchuk A, Prybyla O. Effect of probiotics and incretine mimeticss on the levels of glucagon-like peptide-1 in blood serum of patients with type 2 diabetes mellitus. Int J Endocrinol (Ukraine). 2021;17(8):604–12.

    Article  Google Scholar 

  39. Ma L, Wang J, Li Y. Insulin resistance and cognitive dysfunction. Clin Chim Acta. 2015;444:18–23.

    Article  CAS  PubMed  Google Scholar 

  40. Salles BIM, Cioffi D, Ferreira SRG. Probiotics supplementation and insulin resistance: a systematic review. Diabetol Metab Syndr. 2020;12:1–24.

    Article  Google Scholar 

Download references

Acknowledgements

None.

Funding

None.

Author information

Authors and Affiliations

  1. The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China

    Bin Xiao

  2. The People’s Hospital of Danyang, Zhenjiang, Jiangsu Province, China

    Lina Fu

  3. Taizhou School of Clinical Medicine, Nanjing Medical University, Jiangsu, China

    Zhe Yang

  4. Department of Neurology, Jiangsu Province Hospital of Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210019, Jiangsu Province, China

    Guran Yu

Authors
  1. Bin Xiao
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Lina Fu
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Zhe Yang
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Guran Yu
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

Designing this study: Bin Xiao, Lina Fu Performed this study: Zhe Yang Drafted the article, Revised the article critically for important intellectual content, and Approved the version to be published: Bin Xiao, Lina Fu, Zhe Yang, Guran Yu.

Corresponding authors

Correspondence to Zhe Yang or Guran Yu.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiao, B., Fu, L., Yang, Z. et al. Effect of probiotics on cognitive function and cardiovascular risk factors in mild cognitive impairment and Alzheimer’s disease: an umbrella meta-analysis. J Health Popul Nutr 44, 109 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s41043-025-00816-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s41043-025-00816-3

Keywords

Journal of Health, Population and Nutrition

ISSN: 2072-1315

Contact us