Effects of probiotics on cognitive function in adults with mild cognitive impairment or minimal hepatic encephalopathy: an umbrella review of meta-analyses of randomized controlled trials

The effects of probiotics on the gut–brain axis have piqued interest in its potential role in improving cognition in adults with Mild Cognitive Impairment (MCI) or Minimal Hepatic Encephalopathy (MHE). MCI is characterized by cognitive decline with preserved independence in activities of daily living. MHE is characterized by clinically inapparent mild cognitive and motor dysfunction (1,2) . While early intervention for both conditions help to preserve cognition and prevent further decline, there are currently no effective treatment options (3,4) . Recently published systematic reviews with meta-analyses (SRMAs) have yielded conflicting results, contributing to the uncertainty surrounding the effects of probiotic supplements on both conditions. Therefore, this umbrella review aimed to assess the SRMAs’ consistency and synthesize the pooled effects of probiotic supplements on cognition in adults with either condition. MEDLINE, Embase, Cochrane and Scopus were searched from inception to 21 February 2025 (PROSPERO: CRD420251000238). Only English SRMAs of randomized controlled trials published since 2015 that investigated probiotics compared to placebo/no-intervention on cognitive function in adults with MCI or MHE were included. Methodological quality was assessed using AMSTAR2 and evidence certainty was evaluated using GRADE. The primary outcomes were differences in cognitive test scores between probiotics and control groups and MHE reversal. To address trial overlap per outcome, reviews with the highest AMSTAR2 rating, followed by largest number of studies or participants, were prioritized. Pooled effect sizes from unique trials were estimated if necessary. Of 6639 records screened, fifteen SRMAs (AMSTAR2 ‘critically low’ to ‘moderate’), published from 2015 to 2024, were included. Seven reviews (61–78y) compared the effects of probiotics supplements to placebo in MCI while eight reviews (36–65y) compared the effects of probiotics to placebo or no intervention in MHE. For MCI, probiotics did not significantly improve MMSE (5 reviews:3 unique trials (n = 167; 12–24w): SMD 0.79, 95% CI: −1.63, 3.22; GRADE: Very Low) or RBANS scores (2 reviews: 2 unique trials (n = 196; 12–16w): SMD −2.01, 95% CI: −5.56, 1.55; GRADE: Low). For MHE, probiotics significantly reversed MHE (8 reviews: 7 unique trials (n = 430; 4–12w): RR 1.54, 95% CI: 1.03, 2.32; GRADE: Low) and improved performance on MHE diagnostic tests (Number Connection Test: 2 reviews:2 unique trials (n = 104; 4w): SMD −0.87, 95% CI: −1.43, −0.31, GRADE: Moderate; Critical Flicker Frequency: 2 reviews:2 unique trials (n = 335; 8–12w): SMD 0.69, 95% CI: 0.41, 0.98, GRADE: Moderate; Digit Symbol Test: 2 reviews:2 unique trials (n = 108; 2–8w): SMD 0.39, 95% CI: 0.01, 0.78, GRADE: Very Low). Our findings suggest that probiotics supplements did not affect cognitive function scores related to MCI but improved those for MHE. More methodologically rigorous studies are required to draw definitive conclusions on the effectiveness of probiotic regimens for cognitive function.