Chronic inflammation in the etiology of disease across the life span

Nature Medicine

Volumn 25, Issue 12, 2019, Pages 1822-1832

  Furman, David ^a,b,c,d   Campisi, Judith ^a,e   Verdin, Eric ^a   Carrera Bastos, Pedro ^f   Targ, Sasha ^d,g   Franceschi, Claudio ^h,i   Ferrucci, Luigi ^j   Gilroy, Derek W ^k   Fasano, Alessio ^l   Miller, Gary W ^m   Miller, Andrew H ⁿ   Mantovani, Alberto ^o,p,q   Weyand, Cornelia M ^b   Barzilai, Nir ^r   Goronzy, Jorg J ^b   Rando, Thomas A ^b,s   Effros, Rita B ^t   Lucia, Alejandro ^u,v   Kleinstreuer, Nicole ^w   Slavich, George M ^x  

^a BUCK INSTITUTE FOR RESEARCH ON AGING   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSIDAD AUSTRAL   (Argentina)

^d Iuve Inc   (United States)

^e LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

^f LUND UNIVERSITY   (Sweden)

^g UNIVERSITY OF CALIFORNIA   (United States)

^h IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA   (Italy)

ⁱ LOBACHEVSKY STATE UNIVERSITY OF NIZHNY NOVGOROD   (Russian Federation)

^j NATIONAL INSTITUTE ON AGING   (United States)

^k UNIVERSITY COLLEGE LONDON   (United Kingdom)

^l HARVARD MEDICAL SCHOOL   (United States)

^m NewYork Presbyterian Hospital   (United States)

ⁿ EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^o HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^p HUMANITAS UNIVERSITY   (Italy)

^q QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^r ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^s VA PALO ALTO HEALTH CARE SYSTEM   (United States)

^t UNIVERSITY OF CALIFORNIA   (United States)

^u UNIVERSIDAD EUROPEA DE MADRID   (Spain)

^v HOSPITAL UNIVERSITARIO 12 DE OCTUBRE   (Spain)

^w NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

^x UNIVERSITY OF CALIFORNIA   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; INDUSTRIAL TOXIC SUBSTANCE;

ARTICLE; CHRONIC DISEASE; CHRONIC INFLAMMATION; CULTURAL ANTHROPOLOGY; DIET; DISEASE ASSOCIATION; DISEASE PREDISPOSITION; DYSBIOSIS; ENVIRONMENT; HEALTH HAZARD; HUMAN; IMMUNE RESPONSE; INDUSTRY AND INDUSTRIAL PHENOMENA; INFECTION; INFLAMMATION; LIFE EXPECTANCY; LIFESPAN; LIFESTYLE; MENTAL STRESS; MICROBIOME; NON COMMUNICABLE DISEASE; NONHUMAN; PHENOTYPE; PHYSICAL ACTIVITY; PHYSICAL INACTIVITY; POLLUTANT; PRIORITY JOURNAL; RISK FACTOR; SOCIAL ASPECT; SYSTEMIC DISEASE; AUTOIMMUNE DISEASE; CARDIOVASCULAR DISEASE; CHRONIC KIDNEY FAILURE; COMPLICATION; DEGENERATIVE DISEASE; DIABETES MELLITUS; GENETICS; LONGEVITY; NEOPLASM; NONALCOHOLIC FATTY LIVER; PATHOPHYSIOLOGY; PHYSIOLOGY;

AUTOIMMUNE DISEASES; CARDIOVASCULAR DISEASES; CHRONIC DISEASE; DIABETES MELLITUS; HUMANS; INFLAMMATION; LIFE STYLE; LONGEVITY; NEOPLASMS; NEURODEGENERATIVE DISEASES; NON-ALCOHOLIC FATTY LIVER DISEASE; RENAL INSUFFICIENCY, CHRONIC; RISK FACTORS;

EID: 85076175435     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/s41591-019-0675-0     Document Type: Article

References (179)

1. Furman, D. et al. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Nat. Med. 23, 174–184 (2017).
2. Netea, M. G. et al. A guiding map for inflammation. Nat. Immunol. 18, 826–831 (2017).
3. Slavich, G. M. Understanding inflammation, its regulation, and relevance for health: a top scientific and public priority. Brain Behav. Immun. 45, 13–14 (2015).
4. Bennett, J. M., Reeves, G., Billman, G. E. & Sturmberg, J. P. Inflammation–nature’s way to efficiently respond to all types of challenges: implications for understanding and managing “the epidemic” of chronic diseases. Front. Med. 5, 316 (2018).
5. GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1736–1788 (2018).
6. Miller, G. E., Chen, E. & Parker, K. J. Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving toward a model of behavioral and biological mechanisms. Psychol. Bull. 137, 959–997 (2011).
7. Fleming, T. P. et al. Origins of lifetime health around the time of conception: causes and consequences. Lancet 391, 1842–1852 (2018).
8. Renz, H. et al. An exposome perspective: early-life events and immune development in a changing world. J. Allergy Clin. Immunol. 140, 24–40 (2017).
9. Kotas, M. E. & Medzhitov, R. Homeostasis, inflammation, and disease susceptibility. Cell 160, 816–827 (2015).
10. Straub, R. H., Cutolo, M., Buttgereit, F. & Pongratz, G. Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J. Intern. Med. 267, 543–560 (2010).
11. Straub, R. H., Cutolo, M. & Pacifici, R. Evolutionary medicine and bone loss in chronic inflammatory diseases—a theory of inflammation-related osteopenia. Semin. Arthritis Rheum. 45, 220–228 (2015).
12. Straub, R. H. & Schradin, C. Chronic inflammatory systemic diseases: an evolutionary trade-off between acutely beneficial but chronically harmful programs. Evol. Med. Public Health 2016, 37–51 (2016).
13. Straub, R. H. The brain and immune system prompt energy shortage in chronic inflammation and ageing. Nat. Rev. Rheumatol. 13, 743–751 (2017).
14. Slavich, G. M. Psychoneuroimmunology of stress and mental health. in The Oxford Handbook of Stress and Mental Health (eds K. Harkness & E. P. Hayden) (Oxford University Press, in the press).
15. Fullerton, J. N. & Gilroy, D. W. Resolution of inflammation: a new therapeutic frontier. Nat. Rev. Drug Discov. 15, 551–567 (2016).
16. Calder, P. C. et al. A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies. Br. J. Nutr. 109, S1–S34 (2013).
17. Taniguchi, K. & Karin, M. NF-κB, inflammation, immunity and cancer: coming of age. Nat. Rev. Immunol. 18, 309–324 (2018).
18. Gisterå, A. & Hansson, G. K. The immunology of atherosclerosis. Nat Rev. Nephrol. 13, 368–380 (2017).
19. Ferrucci, L. & Fabbri, E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat. Rev. Cardiol. 15, 505–522 (2018).
20. Heneka, M. T., Kummer, M. P. & Latz, E. Innate immune activation in neurodegenerative disease. Nat. Rev. Immunol. 14, 463–477 (2014).
21. Miller, A. H. & Raison, C. L. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat. Rev. Immunol. 16, 22–34 (2016).
22. Shen-Orr, S. S. et al. Defective signaling in the JAK-STAT pathway tracks with chronic inflammation and cardiovascular risk in aging humans. Cell Syst. 3, 374–384.e4 (2016).
23. Verschoor, C. P. et al. Serum C-reactive protein and congestive heart failure as significant predictors of herpes zoster vaccine response in elderly nursing home residents. J. Infect. Dis. 216, 191–197 (2017).
24. Fourati, S. et al. Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination. Nat. Commun. 7, 10369 (2016).
25. McDade, T. W., Adair, L., Feranil, A. B. & Kuzawa, C. Positive antibody response to vaccination in adolescence predicts lower C-reactive protein concentration in young adulthood in the Philippines. Am. J. Hum. Biol. 23, 313–318 (2011).
26. Singer, K. & Lumeng, C. N. The initiation of metabolic inflammation in childhood obesity. J. Clin. Invest. 127, 65–73 (2017).
27. Olvera Alvarez, H. A., Kubzansky, L. D., Campen, M. J. & Slavich, G. M. Early life stress, air pollution, inflammation, and disease: an integrative review and immunologic model of social-environmental adversity and lifespan health. Neurosci. Biobehav. Rev. 92, 226–242 (2018).
28. Serhan, C. N. Pro-resolving lipid mediators are leads for resolution physiology. Nature 510, 92–101 (2014).
29. Serhan, C. N. & Levy, B. D. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. J. Clin. Invest. 128, 2657–2669 (2018).
30. Franceschi, C., Garagnani, P., Vitale, G., Capri, M. & Salvioli, S. Inflammaging and ‘garb-aging’. Trends Endocrinol. Metab. 28, 199–212 (2017).
31. Liston, A. & Masters, S. L. Homeostasis-altering molecular processes as mechanisms of inflammasome activation. Nat. Rev. Immunol. 17, 208–214 (2017).
32. Frank, D. & Vince, J. E. Pyroptosis versus necroptosis: similarities, differences, and crosstalk. Cell Death Differ. 26, 99–114 (2019).
33. Jin, C., Henao-Mejia, J. & Flavell, R. A. Innate immune receptors: key regulators of metabolic disease progression. Cell Metab. 17, 873–882 (2013).
34. Hotamisligil, G. S. Inflammation, metaflammation and immunometabolic disorders. Nature 542, 177–185 (2017).
35. Kazankov, K. et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Nat. Rev. Gastroenterol. Hepatol. 16, 145–159 (2019).
36. Redlich, K. & Smolen, J. S. Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat. Rev. Drug Discov. 11, 234–250 (2012).
37. Zhang, J. et al. The risk of metabolic syndrome in patients with rheumatoid arthritis: a meta-analysis of observational studies. PLoS One 8, e78151 (2013).
38. Armstrong, A. W., Harskamp, C. T. & Armstrong, E. J. Psoriasis and the risk of diabetes mellitus: a systematic review and meta-analysis. JAMA Dermatol. 149, 84–91 (2013).
39. Dregan, A., Charlton, J., Chowienczyk, P. & Gulliford, M. C. Chronic inflammatory disorders and risk of type 2 diabetes mellitus, coronary heart disease, and stroke: a population-based cohort study. Circulation 130, 837–844 (2014).
40. Ridker, P. M. A test in context: high-sensitivity C-reactive protein. J. Am. Coll. Cardiol. 67, 712–723 (2016).
41. Emerging Risk Factors Collaboration. et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 375, 132–140 (2010).
42. Burska, A. N., Sakthiswary, R. & Sattar, N. Effects of tumour necrosis factor antagonists on insulin sensitivity/resistance in rheumatoid arthritis: a systematic review and meta-analysis. PLoS One 10, e0128889 (2015).
43. Chou, R. et al. Treatment for rheumatoid arthritis and risk of Alzheimer’s disease: a nested case-control analysis. CNS Drugs 30, 1111–1120 (2016).
44. Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017).
45. Proctor, M. J. et al. Systemic inflammation predicts all-cause mortality: a Glasgow inflammation outcome study. PLoS One 10, e0116206 (2015).
46. Arai, Y. et al. Inflammation, but not telomere length, predicts successful ageing at extreme old age: a longitudinal study of semi-supercentenarians. EBioMedicine 2, 1549–1558 (2015).
47. Roubenoff, R. et al. Monocyte cytokine production in an elderly population: effect of age and inflammation. J. Gerontol. A Biol. Sci. Med. Sci. 53, M20–M26 (1998).
48. Ahluwalia, N. et al. Cytokine production by stimulated mononuclear cells did not change with aging in apparently healthy, well-nourished women. Mech. Ageing Dev. 122, 1269–1279 (2001).
49. Beharka, A. A. et al. Interleukin-6 production does not increase with age. J. Gerontol. A Biol. Sci. Med. Sci. 56, B81–B8 (2001).
50. Elisia, I. et al. Effect of age on chronic inflammation and responsiveness to bacterial and viral challenges. PLoS One 12, e0188881 (2017).
51. Morrisette-Thomas, V. et al. Inflamm-aging does not simply reflect increases in pro-inflammatory markers. Mech. Ageing Dev. 139, 49–57 (2014).
52. Alpert, A. et al. A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring. Nat. Med. 25, 487–495 (2019).
53. Coppé, J.-P., Desprez, P.-Y., Krtolica, A. & Campisi, J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99–118 (2010).
54. Zhu, Y., Armstrong, J. L., Tchkonia, T. & Kirkland, J. L. Cellular senescence and the senescent secretory phenotype in age-related chronic diseases. Curr. Opin. Clin. Nutr. Metab. Care 17, 324–328 (2014).
55. Kennedy, B. K. et al. Geroscience: linking aging to chronic disease. Cell 159, 709–713 (2014).
56. Campisi, J. Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 75, 685–705 (2013).
57. Effros, R. B. The silent war of CMV in aging and HIV infection. Mech. Ageing Dev. 158, 46–52 (2016).
58. Stout, M. B., Justice, J. N., Nicklas, B. J. & Kirkland, J. L. Physiological aging: links among adipose tissue dysfunction, diabetes, and frailty. Physiology (Bethesda) 32, 9–19 (2017).
59. Franceschi, C., Garagnani, P., Parini, P., Giuliani, C. & Santoro, A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat. Rev. Endocrinol. 159, 1–15 (2018).
60. Zitvogel, L., Pietrocola, F. & Kroemer, G. Nutrition, inflammation and cancer. Nat. Immunol. 18, 843–850 (2017).
61. Razzoli, M. et al. Social stress shortens lifespan in mice. Aging Cell 17, e12778 (2018).
62. Carroll, J. E. et al. Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans. Brain Behav. Immun. 51, 223–229 (2016).
63. Yuan, J. et al. Long-term persistent organic pollutants exposure induced telomere dysfunction and senescence-associated secretary phenotype. J. Gerontol. A Biol. Sci. Med. Sci. 73, 1027–1035 (2018).
64. Shen-Orr, S. S. & Furman, D. Variability in the immune system: of vaccine responses and immune states. Curr. Opin. Immunol. 25, 542–547 (2013).
65. McDade, T. W. Early environments and the ecology of inflammation. Proc. Natl Acad. Sci. USA 109, 17281–17288 (2012).
66. Carrera-Bastos, P., Fontes-Villalba, M., O’Keefe, J. H., Lindeberg, S. & Cordain, L. The western diet and lifestyle and diseases of civilization. Res. Rep. Clin. Cardiol. 2, 15–35 (2011).
67. Raichlen, D. A. et al. Physical activity patterns and biomarkers of cardiovascular disease risk in hunter-gatherers. Am. J. Hum. Biol. 29, e22919 (2017).
68. Kaplan, H. et al. Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study. Lancet 389, 1730–1739 (2017).
69. Lindeberg, S. & Lundh, B. Apparent absence of stroke and ischaemic heart disease in a traditional Melanesian island: a clinical study in Kitava. J. Intern. Med. 233, 269–275 (1993).
70. Lindeberg, S., Berntorp, E., Nilsson-Ehle, P., Terént, A. & Vessby, B. Age relations of cardiovascular risk factors in a traditional Melanesian society: the Kitava Study. Am. J. Clin. Nutr. 66, 845–852 (1997).
71. Lindeberg, S., Eliasson, M., Lindahl, B. & Ahrén, B. Low serum insulin in traditional Pacific Islanders—the Kitava Study. Metabolism 48, 1216–1219 (1999).
72. Brodin, P. et al. Variation in the human immune system is largely driven by non-heritable influences. Cell 160, 37–47 (2015).
73. Niedzwiecki, M. M. et al. The exposome: molecules to populations. Annu. Rev. Pharmacol. Toxicol. 59, 107–127 (2019).
74. Virgin, H. W., Wherry, E. J. & Ahmed, R. Redefining chronic viral infection. Cell 138, 30–50 (2009).
75. Wang, C. et al. Effects of aging, cytomegalovirus infection, and EBV infection on human B cell repertoires. J. Immunol. 192, 603–611 (2014).
76. Petta, S. et al. Hepatitis C virus infection is associated with increased cardiovascular mortality: a meta-analysis of observational studies. Gastroenterology 150, 145–155.e4 (2016).
77. Root-Bernstein, R. & Fairweather, D. Complexities in the relationship between infection and autoimmunity. Curr. Allergy Asthma Rep. 14, 407 (2014).
78. Furman, D. et al. Cytomegalovirus infection enhances the immune response to influenza. Sci. Transl. Med. 7, 281ra43 (2015).
79. Pawelec, G. et al. Human immunosenescence: is it infectious? Immunol. Rev. 205, 257–268 (2005).
80. Chou, J. P., Ramirez, C. M., Wu, J. E. & Effros, R. B. Accelerated aging in HIV/AIDS: novel biomarkers of senescent human CD8+ T cells. PLoS One 8, e64702 (2013).
81. Sochocka, M., Zwolińska, K. & Leszek, J. The infectious etiology of Alzheimer’s disease. Curr. Neuropharmacol. 15, 996–1009 (2017).
82. Rook, G., Bäckhed, F., Levin, B. R., McFall-Ngai, M. J. & McLean, A. R. Evolution, human-microbe interactions, and life history plasticity. Lancet 390, 521–530 (2017).
83. McDade, T. W. et al. Analysis of variability of high sensitivity C-reactive protein in lowland Ecuador reveals no evidence of chronic low-grade inflammation. Am. J. Hum. Biol. 24, 675–681 (2012).
84. Liebert, M. A. et al. Implications of market integration for cardiovascular and metabolic health among an indigenous Amazonian Ecuadorian population. Ann. Hum. Biol. 40, 228–242 (2013).
85. Eriksson, U. K., van Bodegom, D., May, L., Boef, A. G. C. & Westendorp, R. G. J. Low C-reactive protein levels in a traditional West-African population living in a malaria endemic area. PLoS One 8, e70076 (2013).
86. Agmon-Levin, N. et al. Antitreponemal antibodies leading to autoantibody production and protection from atherosclerosis in Kitavans from Papua New Guinea. Ann. N. Y. Acad. Sci. 1173, 675–682 (2009).
87. Gurven, M., Jaeggi, A. V., Kaplan, H. & Cummings, D. Physical activity and modernization among Bolivian Amerindians. PLoS One 8, e55679 (2013).
88. Cordain, L. et al. Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets. Am. J. Clin. Nutr. 71, 682–692 (2000).
89. Kuipers, R. S., Joordens, J. C. A. & Muskiet, F. A. J. A multidisciplinary reconstruction of Palaeolithic nutrition that holds promise for the prevention and treatment of diseases of civilisation. Nutr. Res. Rev. 25, 96–129 (2012).
90. De la Iglesia, H. O. et al. Ancestral sleep. Curr. Biol. 26, R271–R272 (2016).
91. Slavich, G. M. & Cole, S. W. The emerging field of human social genomics. Clin. Psychol. Sci. 1, 331–348 (2013).
92. Chakravarthy, M. V. & Booth, F. W. Eating, exercise, and ‘thrifty’ genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases. J. Appl. Physiol. 96, 3–10 (2004).
93. Hallal, P. C. et al. Global physical activity levels: surveillance progress, pitfalls, and prospects. Lancet 380, 247–257 (2012).
94. Katzmarzyk, P. T., Lee, I.-M., Martin, C. K. & Blair, S. N. Epidemiology of physical activity and exercise training in the United States. Prog. Cardiovasc. Dis. 60, 3–10 (2017).
95. Fiuza-Luces, C. et al. Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors. Nat. Rev. Cardiol. 15, 731–743 (2018).
96. Breen, L. et al. Two weeks of reduced activity decreases leg lean mass and induces ‘anabolic resistance’ of myofibrillar protein synthesis in healthy elderly. J. Clin. Endocrinol. Metab. 98, 2604–2612 (2013).
97. Fedewa, M. V., Hathaway, E. D. & Ward-Ritacco, C. L. Effect of exercise training on C reactive protein: a systematic review and meta-analysis of randomised and non-randomised controlled trials. Br. J. Sports Med. 51, 670–676 (2017).
98. Meneses-Echávez, J. F. et al. The effect of exercise training on mediators of inflammation in breast cancer survivors: a systematic review with meta-analysis. Cancer Epidemiol. Biomarkers Prev. 25, 1009–1017 (2016).
99. Hayashino, Y. et al. Effects of exercise on C-reactive protein, inflammatory cytokine and adipokine in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Metab. Clin. Exp. 63, 431–440 (2014).
100. Booth, F. W., Roberts, C. K. & Laye, M. J. Lack of exercise is a major cause of chronic diseases. Compr. Physiol. 2, 1143–1211 (2012).
101. Wahid, A. et al. Quantifying the association between physical activity and cardiovascular disease and diabetes: a systematic review and meta-analysis. J. Am. Heart Assoc. 5, e002495 (2016).
102. Moore, S. C. et al. Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults. JAMA Intern. Med. 176, 816–825 (2016).
103. Santos-Lozano, A. et al. Physical activity and Alzheimer disease: a protective association. Mayo. Clin. Proc. 91, 999–1020 (2016).
104. Pérez, L. M. et al. ‘Adipaging’: ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue. J. Physiol. 594, 3187–3207 (2016).
105. Schipper, H. S., Prakken, B., Kalkhoven, E. & Boes, M. Adipose tissue-resident immune cells: key players in immunometabolism. Trends Endocrinol. Metabol. 23, 407–415 (2012).
106. Tchernof, A. & Després, J.-P. Pathophysiology of human visceral obesity: an update. Physiol. Rev. 93, 359–404 (2013).
107. Pellegrinelli, V., Carobbio, S. & Vidal-Puig, A. Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia 59, 1075–1088 (2016).
108. Frasca, D., Blomberg, B. B. & Paganelli, R. Aging, obesity, and inflammatory age-related diseases. Front. Immunol. 8, 1745 (2017).
109. Grant, R. W. & Dixit, V. D. Adipose tissue as an immunological organ. Obesity (Silver Spring) 23, 512–518 (2015).
110. Versini, M., Jeandel, P.-Y., Rosenthal, E. & Shoenfeld, Y. Obesity in autoimmune diseases: not a passive bystander. Autoimm. Rev. 13, 981–1000 (2014).
111. Himbert, C. et al. Signals from the adipose microenvironment and the obesity-cancer link–a systematic review. Cancer Prev. Res. (Phila.) 10, 494–506 (2017).
112. van Dijk, G. et al. Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration. Front. Neurosci. 9, 173 (2015).
113. NCD Risk Factor Collaboration (NCD-RisC). et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet 390, 2627–2642 (2017).
114. Cani, P. D. & Jordan, B. F. Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer. Nat. Rev. Gastroenterol. Hepatol. 15, 671–682 (2018).
115. Le Chatelier, E. et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541–546 (2013).
116. Aron-Wisnewsky, J. et al. Major microbiota dysbiosis in severe obesity: fate after bariatric surgery. Gut 68, 70–82 (2019).
117. Sturgeon, C. & Fasano, A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers 4, e1251384 (2016).
118. Jayashree, B. et al. Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes. Mol. Cell. Biochem. 388, 203–210 (2014).
119. Küme, T. et al. The relationship between serum zonulin level and clinical and laboratory parameters of childhood obesity. J. Clin. Res. Pediatr. Endocrinol. 9, 31–38 (2017).
120. Qi, Y. et al. Intestinal permeability biomarker zonulin is elevated in healthy aging. J. Am. Med. Direc. Assoc. 18, 810.e1–810.e4 (2017).
121. Le Bastard, Q. et al. Systematic review: human gut dysbiosis induced by non-antibiotic prescription medications. Aliment. Pharmacol. Ther. 47, 332–345 (2018).
122. Bjarnason, I. et al. Mechanisms of damage to the gastrointestinal tract from nonsteroidal anti-inflammatory drugs. Gastroenterology 154, 500–514 (2018).
123. Sonnenburg, E. D. & Sonnenburg, J. L. The ancestral and industrialized gut microbiota and implications for human health. Nat. Rev. Microbiol. 17, 383–390 (2019).
124. Bentley, J. U.S. trends in food availability and a dietary assessment of loss-adjusted food availability, 1970-2014. EIB-166, U.S. Department of Agriculture, Economic Research Service (2017).
125. Martínez Steele, E. et al. Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study. BMJ Open 6, e009892 (2016).
126. Grant, B. F. et al. Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the United States, 2001–2002 to 2012–2013: results from the national epidemiologic survey on alcohol and related conditions. JAMA. Psychiatry 74, 911–923 (2017).
127. Chassaing, B., Van de Wiele, T., De Bodt, J., Marzorati, M. & Gewirtz, A. T. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut 66, 1414–1427 (2017).
128. Zmora, N., Bashiardes, S., Levy, M. & Elinav, E. The role of the immune system in metabolic health and disease. Cell Metab. 25, 506–521 (2017).
129. Richards, J. L., Yap, Y. A., McLeod, K. H., Mackay, C. R. & Mariño, E. Dietary metabolites and the gut microbiota: an alternative approach to control inflammatory and autoimmune diseases. Clin. Trans. Immunol. 5, e82 (2016).
130. Bishehsari, F. et al. Alcohol and gut-derived inflammation. Alcohol Res. 38, 163–171 (2017).
131. Lerner, A. & Matthias, T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimm. Rev. 14, 479–489 (2015).
132. Vlassara, H. & Striker, G. E. AGE restriction in diabetes mellitus: a paradigm shift. Nat. Rev. Endocrinol. 7, 526–539 (2011).
133. Dickinson, S., Hancock, D. P., Petocz, P., Ceriello, A. & Brand-Miller, J. High-glycemic index carbohydrate increases nuclear factor-kappaB activation in mononuclear cells of young, lean healthy subjects. Am. J. Clin. Nutr. 87, 1188–1193 (2008).
134. Mozaffarian, D., Aro, A. & Willett, W. C. Health effects of trans-fatty acids: experimental and observational evidence. Eur. J. Clin. Nutr. 63, S5–S21 (2009).
135. Muller, D. N., Wilck, N., Haase, S., Kleinewietfeld, M. & Linker, R. A. Sodium in the microenvironment regulates immune responses and tissue homeostasis. Nat. Rev. Immunol. 19, 243–254 (2019).
136. Schnabel, L. et al. Association between ultraprocessed food consumption and risk of mortality among middle-aged adults in France. JAMA Intern. Med. 179, 490–498 (2019).
137. Bonaventura, P., Benedetti, G., Albarède, F. & Miossec, P. Zinc and its role in immunity and inflammation. Autoimm. Rev. 14, 277–285 (2015).
138. Nielsen, F. H. Effects of magnesium depletion on inflammation in chronic disease. Curr. Opin. Clin. Nutr. Metab. Care 17, 525–530 (2014).
139. Calder, P. C. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem. Soc. Trans. 45, 1105–1115 (2017).
140. Blasbalg, T. L., Hibbeln, J. R., Ramsden, C. E., Majchrzak, S. F. & Rawlings, R. R. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am. J. Clin. Nutr. 93, 950–962 (2011).
141. Calder, P. C. Very long-chain n-3 fatty acids and human health: fact, fiction and the future. Proc. Nutr. Soc. 77, 52–72 (2018).
142. Kiecolt-Glaser, J. K. et al. Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial. Brain Behav. Immun. 25, 1725–1734 (2011).
143. Kiecolt-Glaser, J. K. et al. Omega-3 supplementation lowers inflammation in healthy middle-aged and older adults: a randomized controlled trial. Brain Behav. Immun. 26, 988–995 (2012).
144. AbuMweis, S., Jew, S., Tayyem, R. & Agraib, L. Eicosapentaenoic acid and docosahexaenoic acid containing supplements modulate risk factors for cardiovascular disease: a meta-analysis of randomised placebo-control human clinical trials. J. Hum. Nutr. Diet. 31, 67–84 (2017).
145. Danaei, G. et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med. 6, e1000058 (2009).
146. GBD 2017 Diet Collaborators. Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 393, 1958–1972 (2019).
147. Hall, K. D. Did the food environment cause theobesity epidemic? Obesity (Silver Spring) 26, 11–13 (2018).
148. van Niekerk, G., Toit, du, A., Loos, B. & Engelbrecht, A.-M. Nutrient excess and autophagic deficiency: explaining metabolic diseases in obesity. Metab. Clin. Exp. 82, 14–21 (2018).
149. Slavich, G. M. & Irwin, M. R. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol. Bull. 140, 774–815 (2014).
150. Tobaldini, E. et al. Short sleep duration and cardiometabolic risk: from pathophysiology to clinical evidence. Nat. Rev. Cardiol. 16, 213–224 (2019).
151. Reutrakul, S. & Van Cauter, E. Sleep influences on obesity, insulin resistance, and risk of type 2 diabetes. Metab. Clin. Exp. 84, 56–66 (2018).
152. Valtorta, N. K., Kanaan, M., Gilbody, S., Ronzi, S. & Hanratty, B. Loneliness and social isolation as risk factors for coronary heart disease and stroke: systematic review and meta-analysis of longitudinal observational studies. Heart 102, 1009–1016 (2016).
153. Steptoe, A., Shankar, A., Demakakos, P. & Wardle, J. Social isolation, loneliness, and all-cause mortality in older men and women. Proc. Natl Acad. Sci. USA 110, 5797–5801 (2013).
154. Kivimaki, M. & Steptoe, A. Effects of stress on the development and progression of cardiovascular disease. Nat. Rev. Cardiol. 15, 215–229 (2018).
155. Chandola, T., Brunner, E. & Marmot, M. Chronic stress at work and the metabolic syndrome: prospective study. BMJ 332, 521–525 (2006).
156. Cohen, S. et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc. Natl Acad. Sci. USA 109, 5995–5999 (2012).
157. Lunn, R. M. et al. Health consequences of electric lighting practices in the modern world: a report on the National Toxicology Program’s workshop on shift work at night, artificial light at night, and circadian disruption. Sci. Total Environ. 607–608, 1073–1084 (2017).
158. Hatori, M. et al. Global rise of potential health hazards caused by blue light-induced circadian disruption in modern aging societies. NPJ Aging Mech. Dis. 3, 9 (2017).
159. Touitou, Y., Reinberg, A. & Touitou, D. Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: health impacts and mechanisms of circadian disruption. Life Sci. 173, 94–106 (2017).
160. Leproult, R., Holmbäck, U. & Van Cauter, E. Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss. Diabetes 63, 1860–1869 (2014).
161. Jiang, C. et al. Dynamic human environmental exposome revealed by longitudinal personal monitoring. Cell 175, 277–291.e31 (2018).
162. Sly, P. D. et al. Health consequences of environmental exposures: causal thinking in global environmental epidemiology. Ann. Glob. Health 82, 3–9 (2016).
163. Collins, F. S., Gray, G. M. & Bucher, J. R. Toxicology. Transforming environmental health protection. Science 319, 906–907 (2008).
164. Kleinstreuer, N. C. et al. Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms. Nat. Biotechnol. 32, 583–591 (2014).
165. Thompson, P. A. et al. Environmental immune disruptors, inflammation and cancer risk. Carcinogenesis 36, S232–S253 (2015).
166. Floreani, A., Leung, P. S. C. & Gershwin, M. E. Environmental basis of autoimmunity. Clin. Rev. Allergy Immunol. 50, 287–300 (2016).
167. GBD 2015 Tobacco Collaborators. Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015: a systematic analysis from the Global Burden of Disease Study 2015. Lancet 389, 1885–1906 (2017).
168. McDade, T. W., Rutherford, J., Adair, L. & Kuzawa, C. W. Early origins of inflammation: microbial exposures in infancy predict lower levels of C-reactive protein in adulthood. Proc. Biol. Sci. 277, 1129–1137 (2010).
169. Fagundes, C. P., Glaser, R. & Kiecolt-Glaser, J. K. Stressful early life experiences and immune dysregulation across the lifespan. Brain Behav. Immun. 27, 8–12 (2013).
170. Slavich, G. M., Way, B. M., Eisenberger, N. I. & Taylor, S. E. Neural sensitivity to social rejection is associated with inflammatory responses to social stress. Proc. Natl Acad. Sci. USA 107, 14817–14822 (2010).
171. Macpherson, A. J., de Agüero, M. G. & Ganal-Vonarburg, S. C. How nutrition and the maternal microbiota shape the neonatal immune system. Nat. Rev. Immunol. 17, 508–517 (2017).
172. Blazkova, J. et al. Multicenter systems analysis of human blood reveals immature neutrophils in males and during pregnancy. J. Immunol. 198, 2479–2488 (2017).
173. Aghaeepour, N. et al. An immune clock of human pregnancy. Sci. Immunol. 2, eaan2946 (2017).
174. Simmen, F. A. & Simmen, R. C. M. The maternal womb: a novel target for cancer prevention in the era of the obesity pandemic? Eur. J. Cancer Prev. 20, 539–548 (2011).
175. Le Belle, J. E. et al. Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells. Stem Cell Reports 3, 725–734 (2014).
176. Su, L. F. et al. The promised land of human immunology. Cold Spring Harb. Symp. Quant. Biol. 78, 203–213 (2013).
177. Davis, M. M., Tato, C. M. & Furman, D. Systems immunology: just getting started. Nat. Immunol. 18, 725–732 (2017).
178. Schüssler-Fiorenza Rose, S. M. et al. A longitudinal big data approach for precision health. Nat. Med. 25, 792–804 (2019).
179. Slavich, G. M. & Sacher, J. Stress, sex hormones, inflammation, and major depressive disorder: extending social signal transduction theory of depression to account for sex differences in mood disorders. Psychopharmacology (Berl.) 236, 3063–3079 (2019).