No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Biological Reviews of the Cambridge Philosophical Society
Douglas B Kell, Etheresia Pretorius


Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, pre-eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially 'external' causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress-induced iron dysregulation, and (ii) its ability to awaken dormant, non-replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic ...Continue Reading


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Jun 19, 2013·Cell Host & Microbe·Nadia R CohenJames J Collins
Jun 19, 2013·Cell Host & Microbe·Emily S C RittershausChristopher M Sassetti
Jun 21, 2013·Frontiers in Immunology·Martin KongsbakMarina Rode von Essen
Jun 27, 2013·Transfusion Medicine and Hemotherapy : Offizielles Organ Der Deutschen Gesellschaft Fur̈ Transfusionsmedizin Und Immunham̈atologie·Florian LangMichael Föller
Jul 3, 2013·Therapeutic Advances in Gastroenterology·Caitriona M Guinane, Paul D Cotter
Jul 3, 2013·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Chafic KaramStephen Scelsa
Jul 3, 2013·Antimicrobial Agents and Chemotherapy·Mehmet A Orman, Mark P Brynildsen
Jul 23, 2013·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Shoaib AfzalBørge G Nordestgaard
Aug 3, 2013·Cold Spring Harbor Perspectives in Medicine·Houchaima Ben-TekayaChristoph Dehio
Aug 3, 2013·Frontiers in Aging Neuroscience·Barry B Muhoberac, Ruben Vidal
Aug 6, 2013·Nutrients·Katharina KienreichStefan Pilz
Sep 3, 2013·Fertility and Sterility·Dongsheng HouChen Xu
Sep 11, 2013·Nature Reviews. Microbiology·Nathalie Q BalabanJohn D McKinney
Sep 17, 2013·Applied and Environmental Microbiology·Thomas K WoodBrian W Kwan
Oct 1, 2013·Atherosclerosis·Marta SerranoJosé Manuel Fernández-Real
Oct 2, 2013·Journal of Parkinson's Disease·Amie L PetersonJoseph F Quinn
Oct 2, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·G Thomas BrownThomas M McIntyre
Oct 10, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Yan Chun LiRavi Thadhani
Oct 11, 2013·Frontiers in Integrative Neuroscience·Augusto J Montiel-CastroGustavo Pacheco-López
Oct 12, 2013·Journal of Clinical Periodontology·Wijnand J TeeuwBruno G Loos
Oct 22, 2013·British Journal of Pharmacology·A AnzovinoDes R Richardson
Nov 6, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Pawel PludowskiJacek Michalkiewicz
Nov 7, 2013·Frontiers in Human Neuroscience·Boguslaw Lipinski, Etheresia Pretorius
Nov 10, 2013·Journal of the American Society of Nephrology : JASN·Justine BacchettaMartin Hewison
Nov 19, 2013·PLoS Computational Biology·Simon Mitchell, Pedro Mendes
Nov 20, 2013·Digestive Diseases·Stanislas MondotPatricia Lepage
Nov 28, 2013·Veterinary Pathology·T MurakamiK Higuchi
Dec 4, 2013·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Rosi BissingerFlorian Lang
Dec 4, 2013·Circulation·Eva KassiAthanasios G Papavassiliou
Dec 18, 2013·Critical Reviews in Biochemistry and Molecular Biology·Jemila C Kester, Sarah M Fortune
Dec 18, 2013·Seminars in Dialysis·Julie H Ishida, Kirsten L Johansen
Dec 18, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Aziza Jamal-AllialKatherine L Tucker
Dec 19, 2013·Nature Chemical Biology·Scott J Dixon, Brent R Stockwell
Dec 19, 2013·PLoS Pathogens·Migla MiskinyteIsabel Gordo
Dec 20, 2013·Clinical Reviews in Allergy & Immunology·Yu LiuQianjin Lu
Dec 25, 2013·Annual Review of Public Health·Lisa M Gargano, James M Hughes
Jan 7, 2014·Archives de pédiatrie : organe officiel de la Sociéte française de pédiatrie·C L LiuZ Y Sun
Jan 18, 2014·Circulation Research·P E Norman, J T Powell
Jan 25, 2014·Current Rheumatology Reports·Joanna KozielJan Potempa
Jan 31, 2014·Journal of Clinical Laboratory Analysis·Fernando OliveiraRúben Fernandes
Feb 14, 2014·Acta Physiologica·J B HansenT Mandrup-Poulsen
Feb 20, 2014·Metallomics : Integrated Biometal Science·Douglas B Kell, Etheresia Pretorius
Mar 5, 2014·Journal of Cardiovascular Translational Research·Travis Sharkey-ToppenSubha V Raman
Mar 25, 2014·Clinical Rheumatology·Antonio VitaleLuca Cantarini
Mar 29, 2014·Journal of Lipid Research·Tamer SallamCynthia Hong
Mar 29, 2014·Journal of Vascular Surgery·Marshall W WinnerSubha V Raman
Apr 4, 2014·The Journal of Clinical Endocrinology and Metabolism·Bruno VergèsRémy Burcelin
Apr 8, 2014·The Lancet. Diabetes & Endocrinology·Shoaib AfzalBørge G Nordestgaard
Apr 10, 2014·Integrative Biology : Quantitative Biosciences From Nano to Macro·Etheresia Pretorius, Douglas B Kell
Apr 11, 2014·Journal of Neurochemistry·Michelle Muller, Blair R Leavitt
Apr 18, 2014·Journal of Stroke·Jaydip Ray ChaudhuriVcs Srinivasarao Bandaru
Apr 22, 2014·Microbial Pathogenesis·Fengyi Tang, Milton H Saier
May 9, 2014·Future Microbiology·Frances Valencia-Shelton, Michael Loeffelholz
May 14, 2014·Prion·Fozia SaleemDavid S Wishart
May 14, 2014·The Journal of Experimental Medicine·Hyung Jin AhnSidney Strickland
May 23, 2014·Frontiers in Pharmacology·Francesca VinchiViktória Jeney
May 23, 2014·Frontiers in Pharmacology·Sonia Levi, Dario Finazzi
May 23, 2014·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Zheng LvSheng Bi
May 24, 2014·Nature Reviews. Molecular Cell Biology·Tuomas P J KnowlesChristopher M Dobson
Jun 6, 2014·Movement Disorders : Official Journal of the Movement Disorder Society·Leo P KellyJeffrey H Kordower
Jun 12, 2014·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Alexandr A NikonorovAnatoly V Skalny
Jun 12, 2014·British Journal of Cancer·N Keum, E Giovannucci
Jun 16, 2014·Seminars in Ultrasound, CT, and MR·Loizos SiakallisGeorgiades S Christos
Jun 16, 2014·Neurobiology of Aging·James M StankiewiczAntonia Ceccarelli
Jun 21, 2014·Immunity·Alison N ThorburnCharles R Mackay
Jun 24, 2014·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Petr DusekJan Aaseth
Jun 30, 2014·The Lancet. Diabetes & Endocrinology·Karani S VimaleswaranElina Hyppönen
Jul 1, 2014·Molecular Nutrition & Food Research·Jussi RyynänenCarsten Carlberg
Jul 2, 2014·Proceedings of the National Academy of Sciences of the United States of America·Joel C WattsStanley B Prusiner
Jul 6, 2014·Advances in Experimental Medicine and Biology·Carmen AlonsoJavier Santos
Jul 8, 2014·Oxidative Medicine and Cellular Longevity·Antonio AyalaSandro Argüelles
Jul 9, 2014·Nature Reviews. Neurology·Erin StephensonV Wee Yong
Jul 9, 2014·Pediatric Research·Carine TaraziKwang Sik Kim
Jul 12, 2014·The ISME Journal·Gangsheng WangWilfred M Post
Jul 23, 2014·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Meg ManginKelly Fincher
Jul 30, 2014·Chemical Research in Toxicology·Katrina M WatersThomas J Weber
Aug 7, 2014·Journal of Clinical & Translational Endocrinology·Susu M ZughaierVin Tangpricha
Aug 8, 2014·Neurology·Thomas J LittlejohnsDavid J Llewellyn
Aug 8, 2014·Scientifica·Anna K CoussensRobert J Wilkinson
Aug 21, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shaoping ZhangGarth J S Cooper
Aug 22, 2014·Current Opinion in Cardiology·Arthur R MenezesJames J DiNicolantonio
Sep 4, 2014·Journal of Alzheimer's Disease : JAD·Priya Maheshwari, Guy D Eslick
Sep 6, 2014·Frontiers in Pharmacology·Joanna F Collingwood, Mark R Davidson
Sep 7, 2014·Microbes and Infection·Christoph Gradmann
Sep 19, 2014·Journal of Biological Rhythms·Miguel A Gutierrez-MonrealSean-Patrick Scott
Sep 27, 2014·Nutrients·Taifeng ZhuangZhenyu Yang
Sep 30, 2014·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Jean D SipePer Westermark
Sep 30, 2014·Gastroenterology·Michael B WallaceJörg-Dieter Schulzke
Oct 1, 2014·JAMA : the Journal of the American Medical Association·Thomas L HollandVance G Fowler
Oct 22, 2014·The American Journal of the Medical Sciences·Malcolm D KearnsVin Tangpricha
Oct 22, 2014·Integrative Biology : Quantitative Biosciences From Nano to Macro·Douglas B Kell, Etheresia Pretorius
Nov 21, 2014·Aging·Etheresia PretoriusDouglas B Kell
Dec 3, 2014·Virus Research·Paula Saá, Larisa Cervenakova
Dec 3, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Noora SaksaCarsten Carlberg
Dec 3, 2014·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·M D WithamF Khan
Dec 7, 2014·Advances in Experimental Medicine and Biology·Julia ChifmanSuzy V Torti
Dec 11, 2014·The Journal of Obstetrics and Gynaecology Research·Ranmalee AmarasekaraVajira H W Dissanayake
Dec 17, 2014·Biochemical and Biophysical Research Communications·P PrabhakarR Christopher
Dec 17, 2014·Science·Andrew E Armitage, Hal Drakesmith
Dec 19, 2014·Reviews in Endocrine & Metabolic Disorders·Xinhui WangFudi Wang
Dec 20, 2014·Handbook of Experimental Pharmacology·Angela PirilloGiuseppe Danilo Norata
Dec 30, 2014·Current Opinion in Structural Biology·Beat H Meier, Anja Böckmann
Dec 31, 2014·Cellular and Molecular Life Sciences : CMLS·Adam SanMiguel, Elizabeth A Grice
Jan 3, 2015·Science·David W Holden
Jan 6, 2015·American Journal of Obstetrics and Gynecology·Kathleen M AntonyKjersti M Aagaard
Jan 13, 2015·Virus Research·Rodrigo MoralesClaudio Soto
Feb 1, 2015·Seminars in Cell & Developmental Biology·Elisabeth Lang, Florian Lang
Feb 2, 2015·Microbes and Infection·David Ribet, Pascale Cossart
Feb 14, 2015·Metallomics : Integrated Biometal Science·Sargurunathan Subashchandrabose, Harry L T Mobley
Mar 10, 2015·PloS One·Christian DamgaardClaus Henrik Nielsen
Mar 27, 2015·Journal of Human Hypertension·V MajumdarR Christopher
Mar 27, 2015·Journal of Natural Science, Biology, and Medicine·Gaffar Sarwar Zaman, Fawzia Zaman
Mar 31, 2015·Cell·Sathish SubramanianJeffrey I Gordon
Mar 31, 2015·Virus Research·Christopher J SilvaJesús R Requena
Apr 3, 2015·Advances in Experimental Medicine and Biology·Russell W ChesneyXiaobin Han
Apr 4, 2015·Tissue Barriers·J LuettigJ D Schulzke
Apr 8, 2015·Acta Crystallographica. Section D, Biological Crystallography·Annette E LangkildeBente Vestergaard
Apr 9, 2015·Nature Reviews. Microbiology·Ana L Flores-MirelesScott J Hultgren
Apr 15, 2015·Research in Microbiology·Reet MändarJaak Truu
Apr 17, 2015·Mediators of Inflammation·C LehmannB Holbein
May 6, 2015·FEMS Microbiology Reviews·Marnie PotgieterEtheresia Pretorius
May 20, 2015·Nature Communications·Scott AytonAlzheimer's Disease Neuroimaging Initiative
May 27, 2015·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Anya TuretskyNils Henninger
Jun 2, 2015·Frontiers in Immunology·Karin de Punder, Leo Pruimboom
Jun 10, 2015·Nature Reviews. Neurology·Heather Wood
Jun 18, 2015·Immunity·Paul M GalloÇagla Tükel
Jun 20, 2015·BioMed Research International·Benoit StijlemansPatrick De Baetselier
Jul 3, 2015·Atherosclerosis·Luiz Sergio F Carvalho, Andrei C Sposito
Jul 11, 2015·PLoS Pathogens·Robert P Dickson, Gary B Huffnagle
Jul 11, 2015·BMC Genetics·Tessel E GaleslootSita H Vermeulen
Jul 11, 2015·Cell Host & Microbe·Caitlin N SpauldingScott J Hultgren
Jul 11, 2015·Nature Reviews. Immunology·Tomas Ganz, Elizabeta Nemeth
Jul 18, 2015·Cerebrovascular Diseases·Kwang-Yeol ParkOh-Sang Kwon
Jul 21, 2015·Nature Reviews. Microbiology·Peter LiehlMaria M Mota
Jul 25, 2015·Science·Mohamed S Donia, Michael A Fischbach
Aug 19, 2015·Journal of Dermatological Science·Sarah L Edmonds-WilsonMichael Wilson
Aug 19, 2015·Current Biology : CB·Alexander Sturm, Jonathan Dworkin
Aug 20, 2015·Proceedings of the National Academy of Sciences of the United States of America·Amanda L WoermanStanley B Prusiner
Aug 21, 2015·PLoS Pathogens·Kathryn MichelsBorna Mehrad
Aug 25, 2015·Autoimmunity Reviews·Maximiliano Javier Jiménez-DalmaroniIannis E Adamopoulos
Sep 1, 2015·Parkinsonism & Related Disorders·Susanne A Schneider
Sep 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Stanley B PrusinerKurt Giles
Sep 15, 2015·JAMA Neurology·Joshua W MillerCharles DeCarli
Sep 22, 2015·Chembiochem : a European Journal of Chemical Biology·Ting DongXiaoguang Lei
Sep 29, 2015·Brazilian Journal of Microbiology : [publication of the Brazilian Society for Microbiology]·Amani M Alnimr
Jan 1, 2014·Dermato-endocrinology·John J CannellMichael F Holick
Oct 13, 2015·Trends in Cell Biology·Adriano Aguzzi, Asvin K K Lakkaraju
Oct 16, 2015·Behavioral and Brain Functions : BBF·Danielle N DollJames W Simpkins
Oct 27, 2015·Frontiers in Microbiology·Derrick R SamuelsonJudd E Shellito
Oct 29, 2015·Journal of Neurochemistry·Myles R MinterPeter J Crack
Nov 4, 2015·Annual Review of Physiology·Robert P DicksonGary B Huffnagle
Nov 8, 2015·Journal of Neurochemistry·Abdel A Belaidi, Ashley I Bush
Dec 15, 2015·Trends in Cell Biology·Wan Seok Yang, Brent R Stockwell
Dec 31, 2015·Journal of Physiology and Biochemistry·Mei LvFeng-shuang An
Jan 8, 2016·International Journal of Molecular Sciences·Raymond Shim, Connie H Y Wong
Jan 14, 2016·Current Opinion in Gastroenterology·Eamonn M M Quigley
Jan 15, 2016·International Journal of Stroke : Official Journal of the International Stroke Society·Suzanne E JuddOrlando M Gutiérrez
Jan 15, 2016·International Journal of Stroke : Official Journal of the International Stroke Society·Julia PetrovaBorislav Marinov
Jan 19, 2016·The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases·Suprabhat MukherjeeSanti Prasad Sinha Babu
Jan 23, 2016·Cytokine & Growth Factor Reviews·Mieke De BuckJo Van Damme
Jan 28, 2016·Science·Allyson L Byrd, Julia A Segre
Feb 7, 2016·Progress in Histochemistry and Cytochemistry·A S M HungD T Yew
Mar 10, 2016·Oral Diseases·T A van der MeulenA Vissink
Mar 10, 2016·Angewandte Chemie·Karthikeyan AnnamalaiMarcus Fändrich