Important conceptual developments, especially the concepts of allostasis and allostatic load 4, continue to provide a more refined psychoneurobiological framework to explain the mechanisms and clinical implications of chronic stress and stress-related conditions. Seventy years after Selye’s account and at the end of the “Decade of the Brain”, the September 2015 issue of Nature Neuroscience provided state-of-the-art reviews of stress research summarizing the remarkable progress in our understanding of mechanisms involved in central processes and their clinical implications for multiple diseases and health conditions, ranging from psychiatric to cardiovascular and immune-related diseases. Ulcers are no longer a major focus of stress research in gastroenterology, but, given the detection of Helicobacter pylori and its involvement in ulcer formation, stress research in gastroenterology continues to thrive. This promoted the idea that central stress causes or contributes to many peripheral diseases-a concept that ever since has been discussed in gastroenterology, much earlier than in other core medical areas and subspecialties. Yet it was GI physiology and the search for pathways and their neuroendocrine mediators, including those involved in “stress ulcers” in the gut, that subsequently received the most attention: UCLA’s Center for Ulcer Research and Education 3, founded in 1974, was the Mecca for stress research outside its hub in Montreal, Canada.
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Ten years later, Selye published a full account of his experimental findings, entitled “The general adaptation syndrome and diseases of adaptation” 2, that may mark the true beginning of the GAS/stress theory, again remarkable for different reasons: for the fact that this paper was published simultaneously in several journals ( Journal of Allergy, Annales d’Endocrinologie, Manpower, Piersol’s Cyclopedia of Medicine, Surgery and Specialties, and Bulletin de Biologie et de Médecine Expérimental de l’U.R.S.S.), which is entirely impossible to think of nowadays, and for the frequently reproduced figure illustrating the-at that time-unknown pathways connecting the brain to peripheral bodily systems, including the GI tract. It also contained no reference that this concept may be of any special relevance to the GI tract, except that Selye noted that “the formation of acute erosions in the digestive tract, particular in the stomach, small intestine and appendix” of the animals (rats) following exposure to noxious agents occurred 1. Although it described the major principle, a global and homogenous three-phase bodily response to a variety of different noxious stimuli, the term “stress” was not mentioned. This short note entitled “A syndrome produced by diverse nocuous agents” 1 was about twice the size of an abstract nowadays, yet the syndrome would later become known as the stress concept, also known as “general adaptation syndrome” (GAS). at Johns Hopkins University and immigrating to Montreal, published his first (!) paper. In the July issue of the journal Nature in 1936, 29-year-old Hans Selye, a Vienna-born Austrian-Hungarian who studied medicine and chemistry in Prague, Paris, and Rome before completing his Ph.D. Future directions of research should include not only the genetics of the stress response and resilience but also epigenetic contributions. We demonstrate that neurobiological stress research continues to be a driving force for scientific progress in gastroenterology and related clinical areas, inspiring translational research from animal models to clinical applications, while highlighting some areas that remain incompletely understood, such as the roles of sex/gender and gut microbiota in health and disease.
More than eighty years after Hans Selye (1907–1982) first developed a concept describing how different types of environmental stressors affect physiological functions and promote disease development (called the “general adaptation syndrome”) in 1936, we herein review advances in theoretical, mechanistic, and clinical knowledge in stress research, especially in the area of gastroenterology, and summarize progress and future perspectives arising from an interdisciplinary psychoneurobiological framework in which genetics, epigenetics, and other advanced ( omics) technologies in the last decade continue to refine knowledge about how stress affects the brain-gut axis in health and gastrointestinal disease.
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