Prebiotics modulate the microbiota–gut–brain axis and ameliorate anxiety and depression-like behavior in HFD-fed mice

Scheme summarizing the mechanisms of action of FOS and GOS on diet-induced depression and anxiety in obese mice. FOS and GOS improve the intestinal microbiota, reducing the number of Faecalibaculum rodentium (blue rod) and increasing the count of Bacteroides dorei (brown rod), and Bacteroides acidifaciens (pink rod) which, in turn, produce acetate (blue square). Prebiotics can heighten the levels of tight junction proteins in the intestinal mucosa, decreasing leaky gut. The intestinal microbiota, in turn, may affect brain physiology, reducing cytokine levels such as IL-1β and TNF-α, inhibiting the enzymes IDO-1, KMO, and HAAO, allowing tryptophan (TRP) to be converted into serotonin (5-HT) in the HC and PFC. This prevents neuronal death and excitotoxicity. FOS and GOS restore the expression of the NMDA receptor (N-Methyl-D-Aspartate), which plays a pivotal role in synaptic plasticity. Prebiotics lead to increased BDNF expression and activation of the PI3K/AKT/CREB pathway through Tropomyosin receptor kinase B (TrkB) in HC and PFC. Additionally, prebiotics result in a decrease in the number of Iba+ and GFAP+ cells (not shown). The acetate produced by B. acidifaciens and B. dorei interacts with its G protein-coupled receptor 43 (GPR43) and can act as an immunoregulatory molecule, modulating neuroinflammation in HC and PFC. Altogether, this inhibits depression and anxiety in mice fed a high-fat diet. [Display omitted] •FOS and GOS reversed the symptoms of depression and anxiety in HFD-fed mice.•Prebiotic reshaped the imbalanced gut microbiota by raising Bacteroidetes.•FOS and GOS reduced intestinal inflammation and improved gut barrier.•Prebiotics reduced neuroinflammation, IDO signaling and, improved neuroplasticity.•FOS and GOS promoted elevated levels of acetate and GPR43 in the brain. Previous research has demonstrated that Prebiotics can influence the composition of the gut microbiota, consequently impacting mood regulation. This study aimed to assess the effects of Prebiotics, specifically Fructooligosaccharides (FOS) and Galactooligosaccharides (GOS) on neuroinflammation, depression, and anxiety-like behavior in a mouse model fed a high-fat diet (HFD). Initially, mice were divided into two groups: a control group on a standard diet (n = 15) and a group on an HFD for 18 weeks (n = 45). By the 13th week, the HFD group was further divided into experimental groups: Control (n = 15), HFD (n = 15), HFD receiving Prebiotics (n = 15), and HFD receiving Fluoxet