Gut microbiome changes after synbiotic treatment in adults with attention-deficit/hyperactivity disorder and/or borderline personality disorder

Gut microbiome changes after synbiotic treatment in adults with attention-deficit/hyperactivity disorder and/or borderline personality disorder

Background

Increasing evidence suggests that the gut microbiome may influence brain function and behaviour through the gut-brain axis. Synbiotics, a combination of beneficial microbes and growth-promoting fibres, have been proposed to modulate the gut microbiome and thereby regulate gut-brain communication pathways and behavioural outcomes. Prior work in the PROBIA randomised controlled trial demonstrated that synbiotic treatment reduced irritability and emotional dysregulation compared to placebo in adults with attention-deficit/hyperactivity disorder (ADHD) and/or borderline personality disorder [1]. However, it remains unclear whether these clinical effects were accompanied by measurable changes in the gut microbiome.

Aims

To determine whether synbiotic treatment alters gut microbiome diversity, taxonomic composition, and functional potential in adults with ADHD and/or BPD.

Methods

Our analysis included 131 participants from the PROBIA cohort, who underwent a 10-week synbiotic (n=65) or placebo (n=66) treatment. Stool samples were collected at baseline, week 5, and week 10 of treatment and underwent shotgun metagenomic sequencing. Species-level taxonomic profiles were generated with MetaPhlAn4 and functional profiling was done with HUMAnN3 against the MetaCyc pathway database. Alpha diversity (Shannon index) and species-level differential abundance was analysed using linear-mixed models with group-by-timepoint interaction. The interaction effects were evaluated with Type III ANOVA, and post-hoc pairwise comparisons were performed using estimated marginal means. Beta diversity (Aitchison distance) was analysed using repeated-measures and pairwise PERMANOVA (999 permutations, stratified by subject). All models were adjusted for age, sex, body mass index, and study site. P-values were corrected using the Benjamini-Hochberg false discovery rate.

Results

Synbiotic treatment did not affect taxonomic alpha diversity over time (group-by-timepoint: F(2, 175.90)=0.602, p=0.548). Changes in taxonomic beta diversity were observed in the synbiotic group between baseline and week 5 (F=0.606, R²=0.006, q=0.015) and baseline and week 10 (F=0.605, R²=0.007, q=0.006). There were no changes from week 5 to week 10 (F=0.319, R²=0.004, q=0.594), nor where there changes over time in the placebo group. Within the synbiotic group, the four administered probiotic species significantly increased in abundance over time: Lactiplantibacillus plantarum (q=1.84x10^-21), Lacticaseibacillus paracasei (q=3.49x10^-12), Pediococcus pentosaceus (q=7.29x10^-12), Leuconostoc mesenteroides (q=4.85x10^-05). These increases in species abundance were observed between baseline and week 5 and sustained at week 10. MetaCyc pathway analysis showed a similar pattern: there were changes in beta diversity in the synbiotic group from baseline to week 5 (F=1.563, R²=0.017, q=0.024) and baseline to week 10 (F=1.454, R=0.018, q=0.024), with no significant shifts from week 5 to week 10 (F=0.996, R²=0.012, q=0.246), nor in the placebo group.

Conclusions

Synbiotic treatment led to selective and sustained shifts in the gut microbiome, characterised by increased abundance of all four administered probiotic species and altered metabolic pathway profiles, while alpha diversity remained unaffected. These microbial and functional changes emerged within the first five weeks of treatment, after which the microbial profile stabilized. Future analyses will examine whether the observed changes are linked with clinical outcomes, with the aim to further explore gut-brain mechanisms underlying the effects of synbiotic treatment.

References

Arteaga-Henríquez, G., Ramos-Sayalero, C., Ibañez-Jimenez, P., Rosales-Ortiz, S.K., Kilencz, T., Schiweck, C., Schnorr, I., Siegl, A., Arias-Vasquez, A., Bitter, I., Fadeuilhe, C., Ferrer, M., Lavebratt, C., Matura, S., Reif, A., Réthelyi, J.M., Richarte, V., Rommelse, N., Ramos-Quiroga, J.A., 2024. Efficacy of a synbiotic in the management of adults with attention-deficit and hyperactivity disorder and/or borderline personality disorder and high levels of irritability: results from a multicenter, randomized, placebo-controlled, “basket” trial. Brain Behav. Immun. 120, 360–371.