Constantinescu Cris S., Arsenescu Razvan I., Arsenescu Violeta (Eds.). Neuro-Immuno-Gastroenterology

Springer, 2016. — 345 p. — ISBN: 978-3-319-28607-5.The multidirectional interaction between the immune system, the gut and the brain has only become subject of more intense research interest in the last few years. Much work has been done in neuroimmunology and in the immunology and immunopathogenesis of the gastrointestinal tract, and the infl uence of the nervous system on both immune functions (neuroimmunomodulation and nerve-driven immunity) and on gastrointestinal processes has been studied in detail. However, to date, no dedicated forum exists, either in the form of a scientifi c journal or in the form of a book, which addresses issues at the interface between the three biological disciplines, and in which the dialogue on specifi c common issues between neuroimmunologists and immuno-gastroenterologists can take place.
Recent discoveries in fundamental immunology require an intensifi cation of this dialogue, so that understanding by scientists of one discipline of processes belonging to the other discipline is possible. For example, the fact that the gut has a critical function in shaping systemic immune responses, through innate lymphoid cells and mucosa-associated lymphoid tissues, means that scientists and physicians studying immune-mediated neurological disease need to gain insight into the immunology of the gastrointestinal system. Also, as it has recently become clear that the gut microbiota has a profound infl uence on the shaping of the immune response, as well as other processes such as metabolism, not only in the gastrointestinal system but also in the nervous system, scientists and clinicians in these fi elds require knowledge of the microbiology of the gastrointestinal tract. Fascinatingly, manipulation of the microbiota and of the intestinal immune responses can be used to modulate neurological and other immune-mediated infl ammatory diseases.
Conversely, the nervous system and the psyche have signifi cant effects on the functioning of the gastrointestinal tract.
Collaboration and communication between neuroscientists, gastrointestinal researchers, microbiologists and systematic biologists is essential for the advancement of this important fi eld.
This book, an editorial collaboration between a neuroimmunologist and an immuno-gastroenterologist and nutrition scientist couple, is a fi rst attempt at such a collaboration and communication. While not being an exhaustive, comprehensive textbook on the subject, it is a collection of relevant topics that address many important issues regarding the interaction between the nervous system, the immune system and the digestive system in health and disease.
Introductory chapters into the immunology, the nervous system (enteric nervous system) and the microbiology of the gastrointestinal system, each written by experts in their research fi elds, provide necessary fundamentals of knowledge in these areas.
The immunology chapter is written by gastroenterologists (Y Mahida and colleagues) with close attention to relevant disease entities. While not intended as a comprehensive review of the increasingly complicated landscape of the gut immune system, it provides essential information on this to allow the reader to put it in the context of immune-mediated infl ammatory diseases. The chapter on the enteric nervous system, by a pathologist, M Constantinescu, in addition to a review of the anatomy of the nervous system of the gut, provides very useful information on the anatomic pathology of the enteric nervous system.
Important neurotransmitters, such as substance P (J Vilisaar and R Arsenescu) and vasoactive intestinal polypeptide (VIP, Ganea and colleagues), are discussed in
particular with regard to their effect on the gut immune system and also their role in gut inflammation.
The role of stress in the gut-brain connection is expertly reviewed in a thorough, dedicated chapter by B Bonaz.
Five chapters deal with how gastrointestinal infections or commensal fl ora infl uence immune-mediated infl ammatory diseases of the ventral and peripheral nervous system, while a separate chapter deals with the role of nutrition and macrobiotics in the gut and brain infl ammation. In this context, the most widely discussed condition is the infl ammatory demyelinating disease of the central nervous system, multiple sclerosis (MS), which, almost from its fi rst clinicopathological descriptions by Charcot and his pupils, was postulated to have an infectious pathogenesis. Infections that potentially have a protective infl uence such as Helicobacter pylori (K Robinson, B Gran and colleagues) and intestinal parasites like Necator americanus (R Tanasescu) which is currently used in a phase II clinical trial of helminth immunotherapy in MS are thoroughly presented in separate chapters by established investigators in their respective areas, along with their potential immunomodulatory mechanisms in MS and its experimental model, experimental autoimmune encephalomyelitis (EAE). On the other hand, the negative infl uence of certain gut bacteria can be inferred from a thorough account of intestinal microbiota dysregulation in MS, with particular emphasis on Japanese MS (the epidemiology of which can be explained through major nutritional changes in Japan in the last decades), presented by a pioneering researcher in the fi eld, T Yamamura, and by a comment on the role of certain bacteria and bacterial toxins in MS and neuromyelitis optica (NMO) by I-J Chou and CS Constantinescu. Nutrition and nutritional interventions, discussed in a chapter by V Arsenescu, for example, in the form of macrobiotics, are increasingly being studied in the context of infl ammatory diseases of both the gastrointestinal and the nervous system. In the peripheral nervous system, N Shahrizaila and N Yuki use the best known example of molecular mimicry in autoimmunity, between Campylobacter and peripheral nerve glycolipids, to discuss the role of Campylobacter jejuni infection in the Guillain-Barré syndrome (GBS). The coexistence between immune-mediated (autoimmune) infl ammatory diseases of the nervous and the gastrointestinal system is another reason to support the development of neuro-immuno-gastroenterology. For example, MS is thought to coexist with infl ammatory bowel disease more often than just by chance. Although this has been challenged by studies suggesting this association is merely due to the increased susceptibility of women to both of these conditions, the association seems to be genuine even after correcting for gender in some studies, suggesting common mechanisms of immunopathogenesis. On the other hand, even if the association were purely by chance, the frequency of the conditions means that management issues need considerations when they coexist, and not only common but differing immunopathogenesis mechanisms are to be taken into account. Demyelinating disease during or following treatment with anti-TNF agents for infl ammatory bowel disease (and other immune-mediated diseases) is discussed in a chapter by SY Lim and CS Constantinescu. This is an unresolved issue, but the chapter provides a review of the information to date and balances the risk of coexistence of the conditions (with or without treatment) with that of “induction” of MS by anti-TNF treatment.
Cannabinoids are molecules involved in many biological functions, produced in large amounts in the central nervous system as endocannabinoids are fulfi lling the definition of neurotransmitters (albeit nonclassical). The plant-derived or synthetic cannabinoids are also drugs that affect the immune, nervous system and gut functions. A team of pharmacologists led by P Gershkovich discuss novel ways of exploiting their physicochemical properties (liposolubility) to improve delivery to the gut lymphoid tissue to achieve and/or enhance neuroimmunological effects.
The last four chapters are dedicated to established neurological disease entities where the immune system and the gut play essential parts.
Gluten intolerance is an immune-mediated condition that is widely known to gastroenterologists. However, its neurological manifestations are less explored. Knowledge of these manifestations is important for gastroenterologists, nutritionists and neurologists alike. This is discussed in detail in the chapter by M Hadjivassiliou and colleagues. A view of pernicious anaemia, with interesting historical details, although the condition is certainly not a disease of the past, and in which often autoimmune mechanisms are critical, is provided by L Edwards. The profound effects in which the immune-mediated central nervous system disease, MS, affects the gut are expertly discussed by D Levinthal and K Bielefeldt. Finally, R Bassil and C Ionete review the neurological manifestation in the complex immunopathogenesis of the primary gastrointestinal condition of Whipple’s disease.
The book does not aim to cover all aspects of neuro-immuno-gastroenterology. Functional neuro-gastroenterological disorders where infl ammation or infection has been implicated, including irritable bowel syndrome and other motility disorders, are not discussed in a dedicated chapter. The mucosal immunology of the gut is an ever-increasing fi eld as is the gut microbiota and its role in physiology and disease, so all very recent developments cannot be covered in a book like this.
However, the novelty of this book and the breadth of subjects covered offer a background of knowledge and an opening for the development of an important interdisciplinary scientifi c and clinical area of research. We, therefore, hope that it will appeal to neurologists, gastroenterologists, nutritionists and other scientists interested in the complex interaction of the digestive, nervous and immune systems.
The idea of this book originated from many discussions between the editors and their colleagues, where the need for a more formalised interdisciplinary approach was recognised. We are grateful to all our colleagues involved in these fruitful discussions. We are also grateful to the Multiple Sclerosis Society of the UK and Northern Ireland, the funder of a large trial of helminth therapy in MS (the Worms for Immune Regulation in MS, or WIRMS Trial), which generated a number of the theoretical and practical questions that led to the idea of this book. We also are grateful for the readiness of Springer to consider and accept this novel idea.
The process of preparing and editing the multiauthored book is always slower than one wishes and at times frustrating, but the professionality, patience and editorial skills of the Springer editorial team of Joanna Bolesworth and Michael Griffin are gratefully acknowledged.