The bowel and beyond: the enteric nervous system in neurological disorders

• Published in: Nature reviews. Gastroenterology & hepatology Vol. 13; no. 9; pp. 517 - 528
• Main Authors: Rao, Meenakshi, Gershon, Michael D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2016; Nature Publishing Group
• Subjects: 692/4020/2741; 692/53/2421; 692/698/1688/1315/1951; 692/699/375; Alzheimer's disease; Amyotrophic lateral sclerosis; Animals; Autism; Autonomic nervous system; Biomedicine; Central nervous system; Central nervous system diseases; Central Nervous System Diseases - complications; Central Nervous System Diseases - etiology; Complications and side effects; Digestive system; Disease; Enteric nervous system; Enteric Nervous System - physiology; Gastroenterology; Gastrointestinal diseases; Gastrointestinal Diseases - etiology; Gastrointestinal tract; Hepatology; Humans; Immune system; Latency; Medicine & Public Health; Meningitis; Movement disorders; Nervous system; Nervous System Diseases - complications; Nervous System Diseases - etiology; Neurodegenerative diseases; Neurological diseases; Neurological disorders; Neurotransmitters; Parkinson's disease; review-article; Risk factors; Signal transduction; Transmissible spongiform encephalopathy; Varicella
• ISSN: 1759-5045; 1759-5053
• DOI: 10.1038/nrgastro.2016.107

Key Points The enteric nervous system (ENS) is the largest component of the autonomic nervous system and is uniquely equipped with intrinsic microcircuits that enable it to orchestrate gastrointestinal function independently of central nervous system (CNS) input Because many neurotransmitters, signalling pathways and anatomical properties are common to the ENS and CNS, pathophysiological processes that underlie CNS disease often have enteric manifestations Neuronal connections and the immune system might provide conduits that allow diseases acquired in the gut to spread to the brain Transmissible spongiform encephalopathies, autistic spectrum disorders, Parkinson disease, Alzheimer disease, amyotrophic lateral sclerosis, and varicella zoster virus (VZV) infection are examples of disorders with both gastrointestinal and neurological consequences VZV reactivations from latency in enteric and other autonomic neurons that lack cutaneous projections are occult causes of zoster without rash that lead to gastrointestinal disease, meningitis and strokes Research on the gut–brain axis of disease is reasonably new, concepts are changing rapidly, and further investigation is much needed The enteric nervous system is vital for life, and its dysfunction participates not only in digestive disorders, but also in diseases of the central nervous system (CNS). Here, Rao and Gershon discuss the gastrointestinal consequences of neurological disorders, the acquisition of CNS disease in the gut and the spread of pathology along the gut–brain axis. The enteric nervous system (ENS) is large, complex and uniquely able to orchestrate gastrointestinal behaviour independently of the central nervous system (CNS). An intact ENS is essential for life and ENS dysfunction is often linked to digestive disorders. The part the ENS plays in neurological disorders, as a portal or participant, has also become increasingly evident. ENS structure and neurochemistry resemble that of the CNS, therefore pathogenic mechanisms that give rise to CNS disorders might also lead to ENS dysfunction, and nerves that interconnect the ENS and CNS can be conduits for disease spread. We review evidence for ENS dysfunction in the aetiopathogenesis of autism spectrum disorder, amyotrophic lateral sclerosis, transmissible spongiform encephalopathies, Parkinson disease and Alzheimer disease. Animal models suggest that common pathophysiological mechanisms account for the frequency of gastrointestinal comorbidity in these conditions. Moreover, the neurotropic pathogen, varicella zoster virus (VZV), unexpectedly establishes latency in enteric and other autonomic neurons that do not innervate skin. VZV reactivation in these neurons produces no rash and is therefore a clandestine cause of gastrointestinal disease, meningitis and strokes. The gut–brain alliance has raised consciousness as a contributor to health, but a gut–brain axis that contributes to disease merits equal attention.