Effects of 4G-beta-D-Galactosylsucrose in patients with depression: A randomized, double-blinded, placebo-controlled, parallel-group comparative study

Advances in genetic research on microbiome have led to several trials on the effectiveness of synbiotics or probiotics in patients with depression; however, none have evaluated the efficacy of prebiotics. 4G-beta-D-Galactosylsucrose (Lactosucrose, LS) is selectively assimilated by Bifidobacterium as a prebiotic and improves microbiome diversity. However, as it is not clear if LS consumption can improve symptoms of depression, we investigated whether LS intake can improve depressive symptoms, quality of life (QOL), and self-efficacy by conducting a single cite, double-blinded, randomized controlled trial in 20 outpatients with depressive episodes (F32, ICD-10) for 24 weeks. Participants (age range, 36–72 years) were randomized to the LS (n = 9) or placebo groups (n = 11). Primary outcome was improvement in total Montgomery Asberg Depression Rating Scale (MADRS) score, and the secondary outcomes were MADRS subscores, global self-efficacy scale (GSES) score, World Health Organization QOL (WHO/QOL-26) score, and 16S rRNA analysis of the fecal microbiome. LS consumption did not significantly improve total MADRS scores (−2 (−16 to 16) vs 0 (−6 to 10), p = 0.552), but GSES tended to improve in the LS group (2.00 ± 4.24 vs −1.36 ± 4.15, p = 0.091) with a large effect size (Cohen's d = 0.802). Sequencing of 16S rRNA revealed individual-level differences in microbiome diversity changes due to the intervention. Thus, we show that LS intake can improve self-efficacy, but not depressive symptoms, even in a small sample. Additional studies that also regulate diet and ensure adherence may help determine a correlation between depression and the gut microbiome. •This study is the first clinical trial of intaking Galactosylsucrose for 6 months.•We performed 16S rRNA analysis of microbiome as well as the psychological tests.•Galactosylsucrose intake may improve self-efficacy for patients with depression.•The change of microbiome intaking Galactosylsucrose varied greatly among individuals.