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      Inflammation–Nature's Way to Efficiently Respond to All Types of Challenges: Implications for Understanding and Managing “the Epidemic” of Chronic Diseases

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          Abstract

          Siloed or singular system approach to disease management is common practice, developing out of traditional medical school education. Textbooks of medicine describe a huge number of discrete diseases, usually in a systematic fashion following headings like etiology, pathology, investigations, differential diagnoses, and management. This approach suggests that the body has a multitude of ways to respond to harmful incidences. However, physiology and systems biology provide evidence that there is a simple mechanism behind this phenotypical variability. Regardless if an injury or change was caused by trauma, infection, non-communicable disease, autoimmune disorders, or stress, the typical physiological response is: an increase in blood supply to the area, an increase in white cells into the affected tissue, an increase in phagocytic activity to remove the offending agent, followed by a down-regulation of these mechanisms resulting in healing. The cascade of inflammation is the body‘s unique mechanism to maintain its integrity in response to macroscopic as well as microscopic injuries. We hypothesize that chronic disease development and progression are linked to uncontrolled or dysfunctional inflammation to injuries regardless of their nature, physical, environmental, or psychological. Thus, we aim to reframe the prevailing approach of management of individual diseases into a more integrated systemic approach of treating the “person as a whole,” enhancing the patient experience, ability to a make necessary changes, and maximize overall health and well-being. The first part of the paper reviews the local immune cascades of pro- and anti-inflammatory regulation and the interconnected feedback loops with neural and psychological pathways. The second part emphasizes one of nature's principles at work— system design and efficiency. Continually overwhelming this finely tuned system will result in systemic inflammation allowing chronic diseases to emerge; the pathways of several common conditions are described in detail. The final part of the paper considers the implications of these understandings for clinical care and explore how this lens could shape the physician-patient encounter and health system redesign. We conclude that healthcare professionals must advocate for an anti-inflammatory lifestyle at the patient level as well as at the local and national levels to enhance population health and well-being.

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          Most cited references276

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          Diagnostic and Statistical Manual of Mental Disorders

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            Diet rapidly and reproducibly alters the human gut microbiome

            Long-term diet influences the structure and activity of the trillions of microorganisms residing in the human gut 1–5 , but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here, we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale, and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals 2 , reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi, and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids, and the outgrowth of microorganisms capable of triggering inflammatory bowel disease 6 . In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
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              Pattern recognition receptors and inflammation.

              Infection of cells by microorganisms activates the inflammatory response. The initial sensing of infection is mediated by innate pattern recognition receptors (PRRs), which include Toll-like receptors, RIG-I-like receptors, NOD-like receptors, and C-type lectin receptors. The intracellular signaling cascades triggered by these PRRs lead to transcriptional expression of inflammatory mediators that coordinate the elimination of pathogens and infected cells. However, aberrant activation of this system leads to immunodeficiency, septic shock, or induction of autoimmunity. In this Review, we discuss the role of PRRs, their signaling pathways, and how they control inflammatory responses. 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                27 November 2018
                2018
                : 5
                : 316
                Affiliations
                [1] 1Department of Psychological Science, StressWAVES Biobehavioral Research Lab, The University of North Carolina at Charlotte , Charlotte, NC, United States
                [2] 2School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle , Newcastle, NSW, Australia
                [3] 3Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University , Columbus, OH, United States
                [4] 4School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle , Newcastle, NSW, Australia
                [5] 5Foundation President, International Society for Systems and Complexity Sciences for Health , Delaware, United States
                Author notes

                Edited by: Kai Johannes Lorenz, Universität Ulm, Germany

                Reviewed by: Robert Drury, ReThink Health, United States; Frode Forland, Norwegian Institute of Public Health, Norway

                *Correspondence: Jeanette M. Bennett jbenne70@ 123456uncc.edu

                This article was submitted to Family Medicine and Primary Care, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2018.00316
                6277637
                30538987
                5c7b9f7a-5466-4b41-b910-59ba7e76692a
                Copyright © 2018 Bennett, Reeves, Billman and Sturmberg.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 June 2018
                : 23 October 2018
                Page count
                Figures: 12, Tables: 3, Equations: 0, References: 257, Pages: 30, Words: 21399
                Categories
                Medicine
                Hypothesis and Theory

                chronic disease,inflammation,interdisciplinary,clinical care,stress,anti-inflammatory lifestyle,complex adaptive systems

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