Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour

• Published in: Nature reviews. Neuroscience Vol. 13; no. 10; pp. 701 - 712
• Main Authors: Cryan, John F., Dinan, Timothy G.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2012; Nature Publishing Group
• Subjects: 42; 631/443/376; 692/698/2741/2135; 692/699/375/1367; Animal Genetics and Genomics; Animals; Anxiety; Bacterial infections; Behavioral Sciences; Biological and medical sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Brain; Brain - microbiology; Brain - physiology; Brain research; Care and treatment; Cognition - physiology; Disease; Fundamental and applied biological sciences. Psychology; Gastrointestinal Tract - microbiology; Gastrointestinal Tract - physiology; General aspects. Models. Methods; Humans; Hypothalamic-pituitary-adrenal axis; Influence; Irritable bowel syndrome; Medical sciences; Metabolic diseases; Metagenome - physiology; Microbiota; Microbiota (Symbiotic organisms); Microorganisms; Motility; Nervous system; Neurobiology; Neurosciences; Obesity; Physiological aspects; review-article; Signal Transduction - physiology; Stress (Psychology); Stress, Psychological - microbiology; Stress, Psychological - psychology; University colleges; Vertebrates: nervous system and sense organs; United Kingdom; Ireland; Affect affectivity; Obesity; Composition; Digestive system; Nutrition disorder; Gut; Central nervous system; Cognition; Encephalon; Infection; Pain; Mood; Modulation; Bacteriosis; Bacteria; Strategy; Anxiety; Physiology; Nutritional status
• ISSN: 1471-003X; 1471-0048; 1469-3178
• DOI: 10.1038/nrn3346

Key Points There is a growing appreciation that the gut microbiota plays a key role in maintaining homeostasis and that a disruption in its composition contributes to various disease states, including CNS disorders. The concept of a microbiota–gut–brain axis, although debated, is emerging to capture the importance that the microbiota has on regulating bidirectional gut–brain communication pathways. It is clear that stress, including stress in early life, can alter microbiota composition and this can have marked consequences on physiology in adulthood. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Although not as conceptually or empirically developed, the gut microbiota has also been implicated in obesity, autism and multiple sclerosis. Mechanisms as to how the microbiota are affecting gut–brain signalling are only now being unravelled. These mechanisms may include alterations in microbial composition, immune activation, vagus nerve signalling, alterations in tryptophan metabolism, production of specific microbial neuroactive metabolites and bacterial cell wall sugars. Harnessing such mechanisms may pave the way for microbial-based therapeutics for various CNS disorders. Gut microbiota are increasingly being recognized as influencing many aspects of human health. In this Review, Cryan and Dinan discuss rapidly emerging evidence that the gut microbiota also influence brain and behaviour and may have a role in anxiety, mood, cognition and pain. Recent years have witnessed the rise of the gut microbiota as a major topic of research interest in biology. Studies are revealing how variations and changes in the composition of the gut microbiota influence normal physiology and contribute to diseases ranging from inflammation to obesity. Accumulating data now indicate that the gut microbiota also communicates with the CNS — possibly through neural, endocrine and immune pathways — and thereby influences brain function and behaviour. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota–gut–brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.