Highlight
1. This umbrella review included 17 meta-analyses covering 156 randomized controlled trials assessing probiotics and cognitive-related health outcomes.
2. Nearly half (44.3%) of the 106 unique associations studied were statistically significant, with 38.3% supported by high-quality evidence per GRADE assessment.
3. The strongest evidence pertains to positive effects of probiotics on cognitive function, supported by moderate- to high-quality data.
4. Additional well-designed clinical trials are needed to clarify optimal probiotic strains, doses, and treatment durations for cognitive benefits.
Study Background
Probiotics, defined as live microorganisms conferring health benefits when consumed in adequate amounts, have gained increasing attention for their potential impact beyond traditional gastrointestinal health. The gut-brain axis has emerged as a bidirectional communication pathway linking intestinal microbiota to central nervous system function, suggesting probiotics could influence cognitive performance and neurological health.
Cognitive decline, ranging from mild cognitive impairment to dementia, represents a major public health challenge worldwide, with limited effective preventive or therapeutic options. Given the accessibility and favorable safety profile of probiotics, understanding their role in cognitive health is a promising research frontier addressing a significant unmet need.
Study Design
This umbrella review comprehensively synthesized published systematic reviews and meta-analyses of randomized controlled trials (RCTs) investigating probiotics’ effects on cognitive-related endpoints in adults. Databases including PubMed, Embase, Web of Science, Scopus, and the Cochrane Database of Systematic Reviews were searched up to April 20, 2024.
A total of 17 meta-analyses comprising 156 RCTs—with some RCTs overlapping across reviews—were included. Sample sizes ranged from 37 to 409 participants per trial, with follow-up durations from two weeks to 28 weeks. Extracted effect measures included standardized mean differences (SMD), mean differences (MD), 95% confidence intervals (CIs), p-values, and heterogeneity indices (I2).
The quality of evidence for each probiotic-health outcome association was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework, categorizing evidence as high, moderate, low, or very low quality.
Key Findings
This umbrella review identified 106 unique associations across various health outcomes related to probiotics. Of these, 47 (44.3%) were statistically significant (P < 0.05). The GRADE assessment of these significant associations revealed:
- 38.3% were supported by high-quality evidence.
- 38.3% by moderate-quality evidence.
- 21.3% by low-quality evidence.
- 2.1% by very low-quality evidence.
Among the significant associations, the majority pertained to cognitive function outcomes (44.7%), indicating the most robust evidence for probiotics’ beneficial cognitive effects. Other notable areas included blood glucose regulation (6.4%), lipid profile improvement (14.9%), oxidative stress reduction (21.3%), inflammatory marker modulation (4.3%), and miscellaneous indicators (8.5%).
The cognitive function benefits included improvements in memory, attention, executive function, and global cognitive scores. Effect sizes, as measured by standardized mean differences, suggested small to moderate clinical impact, consistent across several meta-analyses despite some heterogeneity.
Safety data across the included trials were favorable, with probiotics generally well tolerated and adverse event profiles comparable to placebo.
Expert Commentary
The findings of this umbrella review align with emerging mechanistic insights into the gut-brain axis, where probiotics may influence neuroinflammation, neurotransmitter synthesis, and the hypothalamic-pituitary-adrenal axis, thus modulating cognitive function.
Despite promising results, heterogeneity in probiotic strains, dosing regimens, populations studied, and cognitive outcome measures makes generalization challenging. Current evidence supports benefit but underscores the necessity for standardized well-powered RCTs focusing on optimal probiotic formulations, personalized approaches, and longer-term clinical outcomes.
Some limitations include potential publication bias, overlap of primary RCTs in multiple meta-analyses, and variability in methodological rigor across reviews examined. Future research should address these gaps and explore mechanistic biomarkers alongside clinical endpoints.
Conclusion
This comprehensive umbrella review validates that probiotics hold potential cognitive health benefits supported by moderate- to high-quality evidence from randomized controlled trials meta-analyses. These findings encourage probiotic use as an adjunctive strategy in cognitive health maintenance, particularly in populations at risk for cognitive decline.
However, additional clinical trials are warranted to define the most effective probiotic strains, doses, and treatment durations, and to confirm the durability of cognitive improvements. Such research will help translate emerging scientific knowledge into evidence-based clinical practice recommendations for cognitive preservation and enhancement.
Funding and Clinical Trials Registration
The umbrella review was registered in PROSPERO (registration no. CRD42024537769). Funding disclosures for individual included studies vary and were not uniformly reported across meta-analyses.
References
- Liu X, Ning L, Fan W, Jia C, Ge L. Probiotics and Cognitive-Related Health Outcomes: An Umbrella Review of Systematic Reviews and Meta-Analyses of Randomized Controlled Trials. Nutr Rev. 2025 Nov 1;83(11):2144-2158. doi: 10.1093/nutrit/nuaf156. PMID: 40966579.
- Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015 Apr-Jun;28(2):203-9. doi: 10.20524/aog.2015.0001.
- Morris MC, Tangney CC. Dietary fat composition and dementia risk. Neurobiol Aging. 2014 May;35 Suppl 2:S59-64. doi: 10.1016/j.neurobiolaging.2014.03.037.
- Sarkar A, Lehto SM, Harty S, et al. Psychobiotics and the Manipulation of Bacteria–Gut–Brain Signals. Trends Neurosci. 2016 Nov;39(11):763-781. doi: 10.1016/j.tins.2016.07.002.
