**6.1 Depression and anxiety**

Depression and anxiety are common psychological disorders that they are highly comorbid with each other, and are important public health problems. The efficacy of probiotics on depression and anxiety through meta-analysis studies over the course of 20 years (from 2000 to 2020) was reviewed comprehensively. Half of these studies showed that probiotics could improve the symptoms of these patients [159–162] while the other half reported, probiotic therapy for these mental disorders is not proven [163–166]. In a randomized, double-blind, placebo-controlled trial treatment of 65 multiple sclerosis patients with multi-strain probiotics, promoted mental health parameters [167]. Recent research found that two hypotheses may explain the potential positive effect of probiotics on mood and cognition; one theory is controlling important neurotransmitters and the other is regulating inflammatory markers by these probiotics [168]. Studies exhibit that cytokines increase by inflammatory factors, and subsequently, cytokines effect on synthesis, release, and absorption of neurotransmitters [169–171]. Ultimately, the increased levels of proinflammatory cytokines are associated with neurological disorders such as depression and anxiety. Probiotics improve mood and insomnia in depressed patients [172–174] by reducing inflammatory cytokines Interleukin-1 beta (IL-1β), [175, 176], Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) [172–174, 176].
