Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration

Abstract

There is a growing realisation that the gut-brain axis and its regulation by the microbiota may play a key role in the biological and physiological basis of neurodevelopmental, age-related and neurodegenerative disorders. The routes of communication between the microbiota and brain are being unravelled and include the vagus nerve, gut hormone signalling, the immune system, tryptophan metabolism or by way of microbial metabolites such as short chain fatty acids. The importance of early life gut microbiota in shaping future health outcomes is also emerging. Disturbances of this composition by way of antibiotic exposure, lack of breastfeeding, infection, stress and the environmental influences coupled with the influence of host genetics can result in long-term effects on physiology and behaviour, at least in animal models. It is also worth noting that mode of delivery at birth influences microbiota composition with those born by Caesarean section having a distinctly different microbiota in early life to those born per vaginum. At the other extreme of life, ageing is associated with a narrowing in microbial diversity and healthy ageing correlates with a diverse microbiome. Recently, the gut microbiota has been implicated in a variety of conditions including depression, autism, schizophrenia and Parkinson's disease. There is still considerable debate as to whether or not the gut microbiota changes are core to the pathophysiology of such conditions or are merely epiphenomenal. It is plausible that such neuropsychiatric disorders might be treated in the future by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics.

Keywords: ageing; gut-brain axis; stress.

Figure 1. We are living in a microbial world throughout our lifespan

A growing body of evidence suggests that gut microbiota is essential to human health and is a key player in the bidirectional communication across the gut–brain axis. The microbiota dynamically changes across the lifespan, establishing its relationship with the host at critical windows during infancy, adolescence and ageing. At these time windows, there is an increased vulnerability to external insults, which may result in enhanced susceptibility to brain disorders. Early life disturbance of the developing gut microbiota has the potential to significantly impact on neurodevelopment and potentially lead to adverse mental health outcomes later in life. Similarly, the microbiota may contribute to the ageing process and the trajectory of neurodegenerative disorders.