## 6 The Microbiome-Gut-Brain Axis
Fecal microbiota transplantation (FMT), pre- and probiotic treatments have shown positive results in smaller cohorts of patients with depressive symptoms [86], and in mouse models of obsessive-compulsive disorder (OCD) [87]. In addition, abnormal alterations in gut flora have been reported in a number of psychiatric disorders and neurodevelopmental disorders, such as bipolar disorder, schizophrenia, autism (ASD) and attention deficit hyperactivity disorder (ADHD) [88]. According to recent studies, the microbiome influences the efficacy of cancer immunotherapy. Antigens of commensals can pass the intestinal barrier and result in T-cell priming, along with the stimulation of cytokine and interferon production, promoting an anti-tumor immune response on the basis of molecular mimicry [89]. Intestinal fungal species may interact with bacterial growth or can direct immune cell trafficking, especially inflammatory or tolerant immune responses that can emerge or evolve [90; 91; 92]. A beneficial effect of Bacteroid in the immunostimulation associated with immune-checkpoint blockade was shown in recent studies [93; 94], whereas [PERSON] and colleagues showed that Bifidobacterium's oral administration had a similar effect as PD-L1-specific antibody therapy in experimental mouse models [95]. Another group described an association between the composition of the gut microbiome and immunotherapy efficacy on a sizable patient cohort of malignant melanoma [96]. Nonetheless, the prospect of the gut microbiome as a prognostic, and in the future, a potential therapeutic factor is immense and not negligible anymore. Despite the fact that FMT still has many limitations and risks, altering the human microbiome for therapeutic purposes cannot be rendered as an 'unicentific' or inceptive approach to fight diseases in the long term. Several hypotheses have been proposed to describe the relationship between the aforementioned conditions and the microbiome, the most important of which are the 'old friend' hypothesis and the 'leaky gut theory'. The former, also known as the 'early immune challenge' hypothesis, is a key element in the tens of thousands of years of coevolution between our gut and elements of the commensal flora [97]. Substantial changes in our modern society (health, lifestyle, nutrition) have reduced our contact with our 'old friends' and thus altered immunological maturation processes. Indirectly, this leads to an increased incidence of allergic and autoimmune diseases and chronic inflammatory processes [98]. The leaky gut theory is associated with a reduction in the function of the barriers (BBB, epithelial barrier of the gut), as the altered microbiome causes the tight junctions to loosen and changes in intestinal permeability. Thus, the potential for bacterial translocation increases, circulating lipopolysaccharide and immunoglobulin levels arise, where cyclic macromolecules cross the BBB, generating neuroinflammation-lammatory processes [99]. Although each theory has a slightly different focus, they all recognize immunological dysfunction and the underlying changes in the gut-brain axis as a central background. The gut microbiome plays an exceptional role in gut physiology. Being the largest contact area with the outer world lined by living cells it is continuously bombarded by immunological stimuli. We have already a plethora of circumstantial evidence of the fact that commensal microbiota effect the central nervous system and consequently, mental health. However, the identification of a direct link between the two networks supported by rigorous evidence has not been presented yet.