Study authors question results suggesting prebiotic diet out-performs synbiotic approach

By Nikki Hancocks

- Last updated on GMT

Getty | ChrisChrisW
Getty | ChrisChrisW

Related tags Cognitive health microbiome gut-brain axis Prebiotics Probiotics Gut health

Researchers have called for further studies after their RCT concluded a high-prebiotic diet could improve mood, anxiety, stress, and sleep, while synbiotic or probiotic supplements did not have a beneficial effect.

The RCT, conducted at The Melbourne Clinic, Australia, was the first to examine the effects of a high-prebiotic dietary intervention and probiotic supplements on the mental health of adults with moderate psychological distress.

For the “Gut Feelings” trial, the researchers developed a high-prebiotic diet and administered it in comparison with a multi-strain probiotic, and a synbiotic combination of both.

Their primary aim was to establish whether dietary intake of prebiotics and/or probiotic supplementation would improve mood in adults with symptoms of psychological distress and low prebiotic food intake, relative to placebo. Secondary aims were to measure treatment effects on depression, anxiety, stress, wellbeing, health-related quality of life (fatigue and wellbeing factors), bowel health, and sleep, and whether treatment response was moderated by intervention adherence.

They hypothesised that the synbiotic treatment would outperform all others in improving mood, while both prebiotic and probiotic treatments would be superior to placebo, and that this pattern would remain consistent across measures.

The 8-week, 2 × 2 factorial RCT of 119 adults with moderate psychological distress and low prebiotic food intake revealed the prebiotic diet reduced total mood disturbances (TMD) compared to placebo at 8 weeks, but, to the team's surprise, garnered no evidence of symptom improvement from probiotic or synbiotic treatments.

For the probiotic supplement, an improvement in wellbeing was noted, although the authors say this result should be considered preliminary as there was little evidence of benefit for probiotics on the primary outcome of TMD.

The report states: "An unexpected finding of our study was that the observed mood benefits of a high-prebiotic diet were not apparent when combined with a probiotic supplement. This means that we should be cautious in interpreting our findings as evidence that the prebiotic diet was the driver of the improved outcomes observed in the prebiotic intervention group."

The gut-brain axis

Research in humans suggests depression is linked with an altered gut microbiota​, though there is little consistency regarding specific differences between depressed and healthy individuals. 

Probiotics that have a beneficial effect on mental health, including those from the Lactobacillus​ and Bifidobacterium​ genera, have been termed “psychobiotics”. Probiotic-induced improvements in psychological symptoms, predominantly in clinical populations, have been reported in several meta-analyses​. 

Dietary interventions involving an increase in fibre intake and overall diet quality have been reported​ to reduce depressive symptoms in individuals with clinical depression and elevated depressive symptoms​.

The study

Eligible participants had moderate levels of psychological distress [K10 score of 16–26], prebiotic fibre intake of less than 3 g/day (ensuring sufficient scope for dietary improvement), and were aged 18–65 years.

There were four treatment arms: probiotic supplement and diet-as-usual (probiotic group); high-prebiotic diet and placebo supplement (prebiotic group); probiotic supplement and high-prebiotic diet (synbiotic group); and placebo supplement and diet-as-usual.

Participants were instructed to take capsules twice-daily for eight weeks. The probiotic formulation, provided by BioCeuticals, delivered 12 billion colony forming units (CFU) per capsule, containing: Bifidobacterium bifidum​ (Bb-06): 2 billion CFU; Bifidobacterium animalis​ subsp. lactis​ (HN019): 1 billion CFU; Bifidobacterium longum​ (R0175): 1 billion CFU; Lactobacillus acidophilus​ (La-14): 2 billion CFU; Lactobacillus helveticus​ (R0052): 2 billion CFU; Lactobacillus casei​ (Lc-11): 2 billion CFU; Lactobacillus plantarum​ (Lp-115): 1 billion CFU; Lactobacillus rhamnosus​ (HN001): 1 billion CFU. Participants were instructed to store the product below 25°C to ensure stability. 

The high-prebiotic diet developed for the study was adapted from the Monash University Department of Gastroenterology High Fibre, High-Prebiotic Diet. Participants were required to ingest seven or more serves per day of prebiotic-rich foods, drawn from a variety of food groups.

Dietary intake was measured by the Monash University Comprehensive Nutrition Assessment Questionnaire2​ (CNAQ), with reporting timeframe altered to “past month.” 

After baseline, assessment of the primary outcome was undertaken at each follow-up time point (weeks 2, 4, 6, 8, and 20), while secondary outcomes were reassessed at week 8 only. Safety monitoring was undertaken via a phone call at week 1, and assessments at weeks 2, 4, 6, and 8.

The primary outcome was total mood disturbance (TMD) score on the Profile of Mood States Adult Short Form, 2nd edition (POMS 2-SF). The POMS 2-SF provides a self-report measure of psychological distress experienced over the past week. 

Secondary outcomes included self-report measures of anxiety on the Beck Anxiety Inventory (BAI), depression on the Beck Depression Inventory-II (BDI), stress on the Perceived Stress Scale (PSS), wellbeing on the WHO-5 Wellbeing Index (WHO-5), sleep on the Leeds Sleep Evaluation Questionnaire (LSEQ), and the wellbeing and fatigue subscales of the Short Form Survey-36 (SF-36).

Bowels impacted mood?

Discussing their findings, the authors say it is unknown why the synbiotic did not appear to result in beneficial effects, as synbiotics have been reported to stimulate the gut microbiota and SCFA productio more than probiotics or prebiotics alone.

They state: "Synbiotics have been shown to improve psychological outcomes, reduce inflammatory markers CRP and tumour necrosis factor-α, decrease oxidative stress, and increase levels of serum brain-derived neurotrophic factor. Though random chance cannot be ruled out as an explanation for the differing apparent efficacy of the prebiotic and synbiotic treatments, other explanations may be proposed.

"It may be possible that the ingested probiotic bacteria competed with endogenous microbiota for prebiotic dietary substrates, potentially resulting in less substrate availability for endogenous bacteria such as butyrate-producing species, which may have led to outcomes such as lowered butyrate production.

"Second, a possible consequence of enhanced stimulation of the gut microbiota via synbiotics may be an increase in bowel symptoms; in such a scenario, treatment benefits may be somewhat diminished by bowel-related discomfort such as bloating.

"The potential interaction of a high-prebiotic diet and probiotic formula should be evaluated in a larger, future trial, and it is recommended that such studies employ a measure of bowel symptoms to elucidate whether symptoms may mediate any mental health changes."


Discussing limitations of the study, the authors note participants and investigators were not blinded to dietary intervention allocation, which may have influenced how participants perceived and/or reported symptoms.

Second, the contrast of the prebiotic dietary intervention to the placebo supplement may not represent a truly “placebo-controlled” comparison as participants may have had greater levels of expectancy about the dietary intervention than the probiotic supplements.

Third, only relatively small sample sizes were available for treatment comparisons.

And finally, the sample was largely female, and females appear to reap greater mental health benefits from dietary interventions than male​s.

Source: Frontiers in Neuroscience

doi: 10.3389/fnins.2022.1097278

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

Freijy TM, Cribb L, Oliver G, Metri NJ, Opie RS, Jacka FN, Hawrelak JA, Rucklidge JJ, Ng CH, Sarris J.

Related topics Research

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