Review highlights advances on the role of gut microbiota and the immune system on the functioning of the enteric nervous system

immune-system

Human gut microbes function like an organ within the gastrointestinal tract, and homeostasis of the individual in the external environment seems to be highly influenced by the dynamic balance between microbial communities and the immune system. Although research is expanding what is known about gut microbiota’s influence on the gut-brain axis, the mechanisms of enteric nervous system (ENS)-microbe communication need to be further elucidated.

A recent review, led by Dr. Vassilis Pachnis from the Francis Crick Institute in London (United Kingdom), discusses recent advances on the role of gut microbiota and the immune system on the development of the ENS.

The lining of the gastrointestinal (GI) tract constitutes the largest and most vulnerable surface that faces the external environment in the body and features a gut sensory system that can detect nutrients, non-nutrient components of food, physicochemical conditions, toxins, pathogens and commensal microorganisms. The ENS is composed of enteric neurons (in humans, about 500 million neurons) and glial cells, and controls most aspects of gastrointestinal physiology; in addition, neural control of GI physiology is exerted via extrinsic nerves.

Although the cellular blueprint of the ENS is mostly in place by birth, its functional maturation is completed within the microenvironment of the postnatal gut, under the influence of gut microbiota and the mucosal immune system (commonly described by the acronym MALT, mucosa associated lymphoid tissue). Molecular interactions among gut microbiota, enteric neurons and immune cells have been described as essential for GI homeostasis, which is mainly studied in animal models. Besides this, the mechanisms underlying microbiota-gut-brain axis communication involve the endocrine system, neural pathways via the vagus nerve and perhaps the microbiota-dependent modulation of the central nervous system. Mechanisms of ENS-microbe communication involve, among others, Toll-like receptors (TLRs)/microbiota pathways, enteric neurogenesis and modulation of the blood brain barrier’s integrity by microbiota-derived short-chain fatty acids (SCFAs) and gut microbiota conversion of primary bile acids into secondary bile acids that activate receptors expressed by enteroendocrine cells and enteric neurons.

In addition to its role in GI physiology, the ENS has been linked to the pathogenesis of GI disorders (including dysmotility) and neurodegenerative disorders. For instance, irritable bowel syndrome may be associated with deficits of gut-brain communication, either afferent or efferent or both. Also, an emerging hypothesis implicates ENS deficits in the pathogenesis of neurodegenerative disorders, such as Parkinson’s disease (PD). A high percentage of PD patients show abnormal GI motility and constipation and it has been suggested that the ENS is an initial site in which neuron aggregations occur, and that these changes could precede the development of motor symptoms by several years. Thus, intestinal PD pathology could be a potentially useful biomarker for this condition.

To sum up, the function of the ENS is under partial control of gut microbes and the host immune system. Understanding of molecular mechanisms of gut microbiota-ENS interactions could open new therapeutic strategies not only for GI disorders, but also for neurodegenerative diseases associated with deficits in bidirectional gut-brain communication.

 

 

Reference:

Obata Y, Pachnis V. The effect of microbiota and the immune system on the development and organization of the enteric nervous system. Gastroenterology. 2016. doi: 10.10153/j.gastro.2016.07.044.

 

Paul Enck
Paul Enck
Prof. Dr. Paul Enck, Director of Research, Dept. of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Germany. His main interests are gut functions in health and disease, including functional and inflammatory bowel disorders, the role of the gut microbiota, regulation of eating and food intake and its disorders, of nausea, vomiting and motion sickness, and the psychophysiology and neurobiology of the placebo response, with specific emphasis on age and gender contributions. He has published more than 170 original data paper in scientific, peer-reviewed journals, and more than 250 book chapters and review articles. He is board member/treasurer of the European Society of Neurogastroenterology and Motility and of the German Society of Neurogastroenterology and Motility, and has served as reviewer for many international journals and grant agencies.