Probiotics in Wellbeing

Overview

This study will investigate whether taking a probiotic supplement every day for 12 weeks can reduce low-level inflammation and improve wellbeing in generally healthy adults. Forty adults will be randomly assigned to receive either a probiotic capsule or a placebo capsule that looks the same but does not contain probiotic bacteria. Neither the participants nor the researchers involved in the study will know which treatment each participant receives until the study is completed. Participants will attend a study visit before starting the supplement and another visit after 12 weeks, with a remote check midway through the study. Blood samples will be collected to measure markers of inflammation and stress. Stool samples will be collected to assess the gut microbiota and substances produced by gut bacteria. Urine samples will also be collected to measure metabolites, which are small molecules produced by normal processes in the body and by interactions between the body, diet and gut microbiota. Participants will also complete questionnaires about wellbeing, mood, anxiety, quality of life and memory. The main aim of the study is to determine whether the probiotic reduces a combined measure of several markers of inflammation compared with placebo. The study will also explore whether changes in inflammation are associated with changes in wellbeing and memory, and whether these effects are accompanied by changes in the gut microbiota or in metabolic profiles measured in stool and urine. The results will help researchers understand how probiotics may influence communication between the gut, immune system and brain, and will provide information to help design a larger clinical trial.

The gut microbiota can influence host immune function through interactions with the intestinal barrier, microbial metabolites and systemic immune signalling. In turn, systemic inflammatory mediators have been associated with mood, wellbeing and cognitive function. This study will investigate a proposed gut-immune-brain pathway in which modulation of the gut environment by a probiotic intervention may alter systemic inflammatory signalling and thereby influence psychological wellbeing and cognitive function. This is a 12-week, randomised, double-blind, placebo-controlled, parallel-arm pilot study in 40 generally healthy adults. Following baseline assessments, participants will be randomly allocated to receive either a daily multi-strain probiotic supplement or a matched placebo for 12 weeks. Assessments will take place at baseline and at the end of the 12-week intervention, with a remote adherence and tolerability check approximately halfway through the intervention. The primary objective is to determine whether probiotic supplementation reduces systemic pro-inflammatory activity compared with placebo. The primary endpoint is the change from baseline to week 12 in a pre-specified pro-inflammatory composite comprising IL-6, TNF-α, IL-1β, IL-8, IFN-γ and high-sensitivity C-reactive protein (hsCRP). Each marker will be standardised relative to its baseline variability and combined into a direction-consistent composite in which higher values indicate greater inflammatory activity. Secondary assessments will include the anti-inflammatory cytokine IL-10, serum cortisol and validated questionnaires assessing quality of life, depressive symptoms, anxiety, wellbeing and prospective and retrospective memory. Exploratory mechanistic outcomes will include faecal short-chain fatty acids and related organic acids measured by gas chromatography-mass spectrometry, quantification of selected major bacterial groups using fluorescence in situ hybridisation coupled with flow cytometry, and descriptive 16S rRNA gene sequencing to characterise gut microbial community features. Urine samples collected at baseline and week 12 will undergo nuclear magnetic resonance (NMR) spectroscopy-based metabolomic profiling to assess changes in urinary metabolites associated with the intervention. These analyses will provide an additional measure of host-microbial metabolic activity and will be explored in relation to changes in the gut microbiota, inflammatory markers and wellbeing outcomes. The study will additionally examine whether within-person reductions in the pro-inflammatory composite are associated with improvements in wellbeing and cognitive measures, whether this relationship differs between the probiotic and placebo groups, and whether baseline inflammatory status modifies the response to the intervention. Exploratory mediation analyses will investigate whether changes in inflammatory activity may partly account for any observed effect of the intervention on wellbeing. By integrating measures of gut microbial composition and activity, faecal and urinary metabolite profiles, systemic immune signalling and psychological outcomes within a controlled intervention study, the trial aims to improve mechanistic understanding of communication along the gut-immune-brain axis and to provide effect-size and feasibility data for a future larger randomised controlled trial.