The pathogenesis of irritable bowel syndrome (IBS)-a disorder of gut-brain interaction that affects up to 10% of the world's population-remains uncertain. It is puzzling that a disorder so prevalent and archetypal among humans can be explained by disparate theories, respond to treatments with vastly different mechanisms of action, and present with a dazzling array of comorbidities. It is reasonable to question whether there is a unifying factor that binds these divergent theories and observations, and if so, what that factor might be. This article offers a testable hypothesis that seeks to accommodate the manifold theories, clinical symptoms, somatic comorbidities, neuropsychological features, and treatment outcomes of IBS by describing the syndrome in relation to a principal force of human evolution: gravity. In short, the hypothesis proposed here is that IBS may result from ineffective anatomical, physiological, and neuropsychological gravity management systems designed to optimize gastrointestinal form and function, protect somatic and visceral integrity, and maximize survival in a gravity-bound world. To explain this unconventional hypothesis of IBS pathogenesis, referred to herein as the gravity hypothesis, this article reviews the influence of gravity on human evolution; discusses how Homo sapiens imperfectly evolved to manage this universal force of attraction; and explores the mechanical, microbial, and neuropsychological consequences of gravity intolerance with a focus on explaining IBS. This article concludes by considering the diagnostic and therapeutic implications of this new hypothesis and proposes experiments to support or reject this line of inquiry. It is hoped that the ideas in this thought experiment may also help encourage new or different ways of thinking about this common disorder.
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.