## 6 The Microbiome-Gut-Brain Axis  
The human body has more bacterial cells than eukaryotic. The skin, the respiratory tract, the urogenital tract and the intestine provide the largest and most diverse habitat for these microorganisms that live in commensal relationships with us, and which in turn influence the developmental and maturational processes of the alimentary tract together with its function. In many cases, the intestinal tract and its microbial flora perform digestion together and the molecular milieu that they produce provides a common input for higher immune, neuroendocrine and neurotransmitter capabilities. We call this unified structure the gut-brain axis, or, extendedly, the microbiome-gut-brain axis, which is based on the neuroimmunological interactions between the enteric nervous system and immune microenvironment of the gut. In a broader sense, the neuroendocrine and neuroimmune systems, such as the hypothalamic-pituitary-adrenal axis (HPA axis); the sympathetic and parasympathetic branches of the autonomic nervous system also contribute to this vast network. The first experiments suggesting the existence of a gut-brain axis connection were carried out by [PERSON], who found that certain sensory signals, such as the smell and sight of food, triggers the secretory function of the stomach and pancreas even before the food enters the oral cavity [74]. Interest in this research field was sparked by a 2004 study, which showed that mice kept in a germ-free environment showed an increased HPA response to stress [23]. The role of the microbiome in the gut-brain axis has been demonstrated in various experimental animals and a number of neuroactive substances produced by gut flora have been described. The role of gut flora composition in patients with various psychiatric and neurological conditions and the effects of probiotics began to be generally accepted [75]. However, it is still not fully understood whether changes in gut flora are a consequence, a cause, or both, of disease, through certain feedbacks mediated by the gut-brain axis [76; 77]. Multiple bacterial species are identified as exogenic neurotransmitter producers. Lactobacillus and Bifidobacterium species secrete GABA; they can influence the social behavior of the host and thus contribute to alleviating symptoms of anxiety, stress and depression in humans by restoring the disrupted oxytocin balance [78]. The gut-brain axis not only plays an important role in providing local functions, but we are also starting to understand its wider implications. The late prenatal and early postnatal development of the human brain, mental development and changes in the microbiome coincide in time [79]. However, the correlation is not only apparent: in germ-free mice, not only brain structure abnormalities, but also abnormal mental development have been described [80], which may even be due to alterations in fetal microglia populations [81]. Environmental influences that disrupt the normal gut flora (e.g., maternal stress, prenatal infections, antibiotic use) increase the risk of neurodevelopmental and mental disorders [82]. Thus, as surprising and neglected as it may seem, gut flora is a critical player in the development of normal behavioral patterns [83]. Germ-free mice were shown to be more sensitive to visceral pain, but after fecal transplantation with wild-type mice, this sensitization was abolished. A similar situation was observed in response to antibiotic treatment or infection, a condition that was also restored by probiotic treatment [84]. Not only the neuroendocrine, immune and nervous systems are responsible for the stress response, but the composition of the commensal flora may also be affected. Some research suggests that a normal bacterial composition helps our resilience to stress [83; 85]  
The microbiome, which acts through the gut-brain axis, is becoming an increasingly important therapeutic target because of its presumptive link with mental and neurological disorders.