The gut microbiome plays a vital role in numerous aspects of physiology, including functions related to metabolism, the immune system, behaviour, brain structure and function. Furthermore, it is now becoming increasingly clear that alterations in microbial composition or diversity are implicated in several disease states, including anxiety, depression, autism spectrum disorder (ASD), Alzheimer's disease (AD), Parkinson's disease (PD), obesity, and diabetes. Therefore, therapeutic targeting of the gut microbiota has the potential to be useful in the treatment of both stress-related disorders and metabolic diseases. An important method by which the gut microbiome can influence the gut-brain axis is through microbial production of psychoactive metabolites. Several bacteria have been shown to produce metabolites which can impact host health, such as short-chain fatty acids, conjugated linoleic acid, antimicrobials, exopolysaccharides, and vitamins. Furthermore, several molecules with neuroactive functions, including serotonin, gamma-aminobutyric acid, catecholamines, and acetylcholine, have been isolated from bacteria within the human gut. This review aims to explore the psychoactive metabolites reported to be produced by gut bacteria, particularly those of relevance to stress-related disorders. Screening methods for psychoactive metabolite production, as well as the challenges and limitations of this research, will also be addressed. Finally, the implications of metabolite production for neuropsychiatric disorders such as depression, anxiety, and stress, behavioural disorders such as ASD, and neurodegenerative disorders such as AD and PD will be discussed.
The gut-brain axis is a bidirectional communication system which allows the central nervous system and gastrointestinal tract to interact with and respond to each other rapidly and effectively. It is becoming increasingly clear that major players in this complex system are gut bacteria. The mechanisms of signal transmission from bacteria to the brain are complex and not fully elucidated, but include neural, endocrine, immune, and metabolic pathways. It was initially demonstrated in a rodent model of depression that the gut microbiota was altered. This observation has been replicated in patients with major depression who show decreased microbial diversity. Furthermore, when rodents receive a microbiota transplant from a depressed patient their behaviour alters, as does their tryptophan metabolism and immune status. Several studies of psychobiotics (bacteria with a potential mental health benefit) have been conducted in healthy populations and in patients with depression. While some psychobiotics have shown efficacy in treating depression, other bacteria have yielded negative findings. Larger-scale, well-designed studies are required. EU-funded guidelines recommend that patients with depression or vulnerability to depression should be encouraged to enhance a plant-based diet with a high content of grains/fibres, fermented foods, and fish. A significant impact of such a diet is likely mediated through the gut microbiota.
The human gut microbiome plays a key role in host physiology in health and disease. There is a growing emphasis on the bidirectional interaction between various medications and the gut microbiome. Here, we will first review how drugs can affect microbiome composition and how the microbiome can alter the pharmacodynamics and potentially pharmacokinetics of psychotropic medications. We will take into consideration different classes of psychotropics, including antipsychotics, antidepressants, antianxiety drugs, anticonvulsants/mood stabilisers, opioid analgesics, drugs of abuse, alcohol, nicotine, and xanthines. The varying effects of these widely used medications on microorganisms are becoming apparent from in vivo and in vitro studies. This has important implications for future drug discovery in psychiatry which will need to consider the host microbiome as a major potential target.
The dynamic population of microbes that reside in the gastrointestinal tract plays a pivotal role in orchestrating several aspects of host physiology and health, including but not limited to nutrient extraction and metabolism, as well as the regulation of intestinal epithelial barrier integrity. Gut microbes interact with the host in a bi-directional manner as the microbiota can support the development and education of the innate and adaptive immune systems, thereby conferring protection against pathogens and harmful stimuli while training the host to maintain a homeostatic tolerance towards commensal symbiotics. Recent advances in the field have highlighted the importance of the host-microbiota relationship in neurodevelopment and behaviour, with relevant implications for the onset and progression of brain disorders of inflammatory origin. Microbial modulation of brain function is achieved throughout complex neuro-immune-endocrine pathways of the microbiome-gut-brain axis. Changes in the composition of the gut microbiota or perturbation in microbial-derived metabolites and neuroactive compounds are sensed by the afferent branches of the sympathetic and vagal innervation and transmitted to the central nervous system, which in turn produces behavioural responses. Here, we focus on how the crosstalk between the gut microbiota and the immune system modulates the development and function of the peripheral and central nervous systems. Specific attention is afforded to the involvement of host-microbe neuroimmune interactions in the pathogenesis of neuro-psychiatric and neuroinflammatory disorders such as autism spectrum disorders, anxiety, and depression, as well as Parkinson's and Alzheimer's diseases.
There is currently enormous interest in the impact of the intestinal microbiota on the development and function of the brain via activity of the microbiota-gut-brain axis. It has long been recognised that symbiotic microorganisms influence host behaviour, but in recent years evidence has accumulated that this can, in fact, be beneficial to the host. Indeed, substantial research has now demonstrated an influence of the intestinal microbiota on a wide range of mammalian behaviours. Here, we review what is currently known about the influence of intestinal microbiota on learning and memory, olfaction, social behaviours, and circadian processes. While work in animal models is compelling, further work is required to elucidate mechanisms whereby bacterial influence is occurring, as well as to determine the extent to which gut microbiota can influence similar phenotypes in humans.
