Ferulic acid and feruloylated oligosaccharides alleviate anxiety and depression symptom via regulating gut microbiome and microbial metabolism

Incidence of anxiety and depression has been surging in recent years, causing unignorable mental health crisis across the globe. Mounting studies demonstrated that overgrowth of detrimental gut microbes is driving the development of anxiety and depression. Our previous studies suggested that ferulic acid (FA) and feruloylated oligosaccharides (FOs) were potent in regulating gut microbiome and microbial metabolism in a variety of disease settings, including neuroinflammation. Given the increasing evidence solidifying the role of gut-brain axis in neurological disorders, we here investigated the therapeutic potential of FA and FOs in anxiety and depression. In present study we found that FA and FOs effectively alleviated anxiety and depression-like behavior in mice, while increasing the abundance of Firmicutes, Solibacillus, Acinetobacter and Arthrobacter, and decreasing the abundance of Parabacteroides, Oscollospira and Rummeliibacillus. In addition, FA and FOs were efficacious in enhancing phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine and caffeine metabolism in mice having depression. Our results validated FA and FOs as effective nutrition to prevent anxiety and depression, as well as provided mechanistic insight into their anti-anxiety and anti-depression function. We suggested that FOs mitigated the symptom of depression in mice potentially via changing gut microbiome structure and microbial metabolism.