Effects of a high-prebiotic diet versus probiotic supplements versus synbiotics on adult mental health: The “Gut Feelings” randomised controlled trial

Frontiers in Neuroscience

Feb 2023

DOI: 10.3389/fnins.2022.1097278

Citations:45

Influential Citations:1

Interventional (Human) Studies

Enhanced Details

Methods

Design: 8-week, 2×2 factorial, randomized, placebo-controlled, superiority trial conducted in Melbourne, Australia. Participants: 119 non-clinical adult individuals with moderate psychological distress and low prebiotic intake. Blinding: supplement interventions double-blinded; dietary intervention not blinded.

Intervention

Probiotic capsules: multi-strain formulation delivering 12 billion CFU per capsule; take 2 capsules daily for 8 weeks with food. Placebo capsules: identical in appearance; take 2 capsules daily for 8 weeks with food.

Results

Primary outcome: high-prebiotic diet reduced mood disturbance at week 8 vs placebo (POMS 2-SF TMD MD −6.97; 95% CI −13.6 to −0.345; p=0.039; Cohen's d ≈ −0.60). Secondary outcomes: anxiety (BAI) reduced (OR 0.29; 95% CI 0.10–0.80; p=0.018), perceived stress (PSS) reduced (MD −3.20; 95% CI −5.82 to −0.575; p=0.017), and sleep improved (LSEQ MD 0.770; 95% CI 0.119–1.42; p=0.021). Probiotic treatment improved wellbeing on SF-36 (OR 2.90; 95% CI 1.10–7.77; p=0.032) and showed weak evidence for anxiety reduction (BAI; OR 0.394; 95% CI 0.142–1.07; p=0.069). Synbiotic showed no improvement. There was weak evidence of antagonistic interaction between prebiotic diet and probiotic on several outcomes. Mood benefits may be reversible after stopping the high-prebiotic diet (week-20 follow-up). Interpretation: A high-prebiotic diet for 8 weeks may improve mood, anxiety, and sleep in non-clinical adults with low baseline prebiotic intake; probiotic effects are inconsistent and the synbiotic combination did not provide added benefits; larger confirmatory trials are needed.

Limitations

Not blinded to dietary allocation; potential reporting bias due to non-blinded diet; diet–placebo contrast may reflect expectancy effects and is not a true placebo-controlled dietary comparison. Relatively small sample size for treatment comparisons and interactions. External validity limited to non-clinical, largely female, higher socioeconomic status adults. Not powered to reliably detect diet–probiotic interactions in a factorial design; 8-week duration with limited long-term data; reliance on self-reported outcomes.

Abstract

Background Preliminary evidence supports the use of dietary interventions and gut microbiota-targeted interventions such as probiotic or prebiotic supplementation for improving mental health. We report on the first randomised controlled trial (RCT) to examine the effects of a high-prebiotic dietary intervention and probiotic supplements on mental health. Methods “Gut Feelings” was an 8-week, 2 × 2 factorial RCT of 119 adults with moderate psychological distress and low prebiotic food intake. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). The primary outcome was assessment of total mood disturbance (TMD; Profile of Mood States Short Form) from baseline to 8 weeks. Secondary outcomes included anxiety, depression, stress, sleep, and wellbeing measures. Results A modified intention-to-treat analysis using linear mixed effects models revealed that the prebiotic diet reduced TMD relative to placebo at 8 weeks [Cohen’s d = −0.60, 95% confidence interval (CI) = −1.18, −0.03; p = 0.039]. There was no evidence of symptom improvement from the probiotic (d = −0.19, 95% CI = −0.75, 0.38; p = 0.51) or synbiotic treatments (d = −0.03, 95% CI = −0.59, 0.53; p = 0.92). Improved anxiety, stress, and sleep were noted in response to the prebiotic diet while the probiotic tentatively improved wellbeing, relative to placebo. No benefit was found in response to the synbiotic intervention. All treatments were well tolerated with few adverse events. Conclusion A high-prebiotic dietary intervention may improve mood, anxiety, stress, and sleep in adults with moderate psychological distress and low prebiotic intake. A synbiotic combination of high-prebiotic diet and probiotic supplement does not appear to have a beneficial effect on mental health outcomes, though further evidence is required. Results are limited by the relatively small sample size. Clinical trial registration https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372753, identifier ACTRN12617000795392. show less