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Anxiolytic effects of a galacto-oligosaccharides prebiotic in healthy females (18-25 years) with corresponding changes in gut bacterial composition.

ABSTRACT: Current research implicates pre- and probiotic supplementation as a potential tool for improving symptomology in physical and mental ailments, which makes it an attractive concept for clinicians and consumers alike. Here we focus on the transitional period of late adolescence and early adulthood during which effective interventions, such as nutritional supplementation to influence the gut microbiota, have the potential to offset health-related costs in later life. We examined multiple indices of mood and well-being in 64 healthy females in a 4-week double blind, placebo controlled galacto-oligosaccharides (GOS) prebiotic supplement intervention and obtained stool samples at baseline and follow-up for gut microbiota sequencing and analyses. We report effects of the GOS intervention on self-reported high trait anxiety, attentional bias, and bacterial abundance, suggesting that dietary supplementation with a GOS prebiotic may improve indices of pre-clinical anxiety. Gut microbiota research has captured the imagination of the scientific and lay community alike, yet we are now at a stage where this early enthusiasm will need to be met with rigorous research in humans. Our work makes an important contribution to this effort by combining a psychobiotic intervention in a human sample with comprehensive behavioural and gut microbiota measures.

SUBMITTER: Johnstone N

PROVIDER: S-EPMC8050281 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPrebiotic galacto-oligosaccharides (GOS) have an extensively demonstrated beneficial impact on intestinal health. In this study, we determined the impact of GOS diets on hallmarks of gut aging: microbiome dysbiosis, inflammation, and intestinal barrier defects ("leaky gut"). We also evaluated if short-term GOS feeding influenced how the aging gut responded to antibiotic challenges in a mouse model of Clostridioides difficile infection. Finally, we assessed if colonic organoids could reproduce the GOS responder-non-responder phenotypes observed in vivo.ResultsOld animals had a distinct microbiome characterized by increased ratios of non-saccharolytic versus saccharolytic bacteria and, correspondingly, a lower abundance of β-galactosidases compared to young animals. GOS reduced the overall diversity, increased the abundance of specific saccharolytic bacteria (species of Bacteroides and Lactobacillus), increased the abundance of β-galactosidases in young and old animals, and increased the non-saccharolytic organisms; however, a robust, homogeneous bifidogenic effect was not observed. GOS reduced age-associated increased intestinal permeability and increased MUC2 expression and mucus thickness in old mice. Clyndamicin reduced the abundance Bifidobacterium while increasing Akkermansia, Clostridium, Coprococcus, Bacillus, Bacteroides, and Ruminococcus in old mice. The antibiotics were more impactful than GOS on modulating serum markers of inflammation. Higher serum levels of IL-17 and IL-6 were observed in control and GOS diets in the antibiotic groups, and within those groups, levels of IL-6 were higher in the GOS groups, regardless of age, and higher in the old compared to young animals in the control diet groups. RTqPCR revealed significantly increased gene expression of TNFα in distal colon tissue of old mice, which was decreased by the GOS diet. Colon transcriptomics analysis of mice fed GOS showed increased expression of genes involved in small-molecule metabolic processes and specifically the respirasome in old animals, which could indicate an increased oxidative metabolism and energetic efficiency. In young mice, GOS induced the expression of binding-related genes. The galectin gene Lgals1, a β-galactosyl-binding lectin that bridges molecules by their sugar moieties and is an important modulator of the immune response, and the PI3K-Akt and ECM-receptor interaction pathways were also induced in young mice. Stools from mice exhibiting variable bifidogenic response to GOS injected into colon organoids in the presence of prebiotics reproduced the response and non-response phenotypes observed in vivo suggesting that the composition and functionality of the microbiota are the main contributors to the phenotype.ConclusionsDietary GOS modulated homeostasis of the aging gut by promoting changes in microbiome composition and host gene expression, which was translated into decreased intestinal permeability and increased mucus production. Age was a determining factor on how prebiotics impacted the microbiome and expression of intestinal epithelial cells, especially apparent from the induction of galectin-1 in young but not old mice. Video abstract.

Project description:IntroductionGalacto-oligosaccharides (GOS) are well-substantiated prebiotic substrates. Multiple studies have demonstrated a positive impact of GOS on gut microbiota composition and activity, so-far mainly related to Bifidobacterium. However, data on the beneficial impact at lower dosages in a healthy female population are limited. The primary aim of the current study was to reveal the effect of low dosages (1.3 and 2.0 g) of GOS on fecal Bifidobacterium abundance in healthy women. Other outcomes included the effect of low dosage of GOS on overall fecal microbiota composition and on self-perceived GI comfort, sleep quality and mental wellbeing.MethodEighty-eight healthy women (42-70 years, BMI 18.7-30 kg/m2) were included in this randomized, parallel, double-blind study of 6 weeks. The participants were stratified for fiber intake, BMI and age and randomized to consume either 1.3 or 2.0 g of GOS per day for 3 weeks after a control period of 3 weeks without any intervention. Fecal samples were collected for shotgun metagenomics sequencing at the start (t = -3) and end (t = 0) of the control period and at the end of the intervention period (t = 3). Self-perceived gut comfort, sleep quality, and mental wellbeing were assessed weekly. Hierarchical clustering of principal components was applied to data collected from study participants.ResultsThe relative abundance of Bifidobacterium in feces increased significantly after 3 weeks of daily consumption of both 1.3 g (p < 0.01) and 2.0 g GOS (p < 0.01). This was accompanied by a significant shift in the overall microbiota composition for the dosage of 2.0 g GOS (p < 0.01). Participants that showed a larger increase in Bifidobacterium in the intervention period compared to the change in Bifidobacterium in the control period, defined as responders, showed a significant overall difference in initial fecal microbiota composition as compared to non-responders (p = 0.04) and a trend towards lower baseline levels of Bifidobacterium in responders (p = 0.10).ConclusionDaily consumption of a low dose of GOS can lead to an increase in the relative abundance of Bifidobacterium in feces of healthy women. Additionally, with 2.0 g GOS, the enrichment of Bifidobacterium is accompanied with a shift in the overall microbiota composition.Clinical trial registration: clinicaltrials.gov, identifier NCT05762965.

Project description:BackgroundGalacto-oligosaccharides (GOS) have been shown to modulate the intestinal microbiota of suckling piglets to exert beneficial effects on intestinal function. However, the modulation of intestinal microbiota and intestinal function by GOS in intestinal inflammation injury models has rarely been reported. In this study, we investigated the effects of GOS on the colonic mucosal microbiota composition, barrier function and inflammatory response of lipopolysaccharides (LPS)-challenged suckling piglets.MethodsA total of 18 newborn suckling piglets were divided into three groups, the CON group, the LPS-CON group and the LPS-GOS group. Piglets in the LPS-GOS group were orally fed with 1 g/kg body weight of GOS solution every day. On the d 14, piglets in the LPS-CON and LPS-GOS group were challenged intraperitoneally with LPS solution. All piglets were slaughtered 2 h after intraperitoneal injection and sampled.ResultsWe found that the colonic mucosa of LPS-challenged piglets was significantly injured and shedding, while the colonic mucosa of the LPS-GOS group piglets maintained its structure. Moreover, GOS significantly reduced the concentration of malondialdehyde (MDA) and the activity of reactive oxygen species (ROS) in the LPS-challenged suckling piglets, and significantly increased the activity of total antioxidant capacity (T-AOC). GOS significantly increased the relative abundance of norank_f__Muribaculaceae and Romboutsia, and significantly decreased the relative abundance of Alloprevotella, Campylobacter and Helicobacter in the colonic mucosa of LPS-challenged suckling piglets. In addition, GOS increased the concentrations of acetate, butyrate and total short chain fatty acids (SCFAs) in the colonic digesta of LPS-challenged suckling piglets. GOS significantly reduced the concentrations of interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and cluster of differentiation 14 (CD14), and the relative mRNA expression of Toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) in the LPS-challenged suckling piglets. In addition, GOS significantly reduced the relative mRNA expression of mucin2 (MUC2), and significantly increased the protein expression of Claudin-1 and zonula occluden-1 (ZO-1) in LPS-challenged suckling piglets.ConclusionsThese results suggested that GOS can modulate the colonic mucosa-associated microbiota composition and improve the intestinal function of LPS-challenged suckling piglets.

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Anxiolytic effects of a galacto-oligosaccharides prebiotic in healthy females (18-25 years) with corresponding changes in gut bacterial composition.

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