Abstract
The chapter focuses on the key aspects of nutritional immunology that help accelerate the path to safer and more effective treatments. We review the complex network of interactions between diet, immune system, gut microbiome, and metabolism. We exemplify how advanced computational technologies such as artificial intelligence (AI) and machine learning methods combined with preclinical and translational models aid the discovery of novel immunoregulatory pathways. Further, we highlight nutritional immunology concepts translated to the development of novel therapeutics in immune mediated diseases such as IBD. Finally, we show how advancements in the field of nutritional immunology can be used to enable the development of predictive, preventive, and personalized path to safer and more effective drugs.
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References
Abedi V, Lu P, Hontecillas R, Meghna V, Vess GA et al (2016) Phase III placebo-controlled, randomized clinical trial with synthetic crohn’s disease patients to evaluate treatment response. In: Arabnia H, Qe NT (eds) Emerging trends in applications and infrastructures for computational biology, bioinformatics, and systems biology. Elsevier Inc., Cambridge, MA, pp 411–427. https://doi.org/10.1016/B978-0-12-804203-8.00028-6
Afacan NJ, Fjell CD, Hancock RE (2012) A systems biology approach to nutritional immunology–focus on innate immunity. Mol Asp Med 33:14–25
Allen IC et al (2011) NLRX1 protein attenuates inflammatory responses to infection by interfering with the RIG-I-MAVS and TRAF6-NF-κB signaling pathways. Immunity 34:854–865
Allison DB et al (2015) Goals in nutrition science 2015–2020. Front Nut 2:26
Bassaganya-Riera J, Hontecillas R (2006) CLA and n-3 PUFA differentially modulate clinical activity and colonic PPAR-responsive gene expression in a pig model of experimental IBD. Clin Nutr 25:454–465
Bassaganya-Riera J, Hontecillas R (2010) Dietary conjugated linoleic acid and n-3 polyunsaturated fatty acids in inflammatory bowel disease. Curr Opin Clin Nutr Metab Care 13:569–573. https://doi.org/10.1097/MCO.0b013e32833b648e
Bassaganya-Riera J et al (2004) Activation of PPAR γ and δ by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Gastroenterology 127:777–791
Bassaganya-Riera J et al (2011a) Activation of PPARγ and δ by dietary punicic acid ameliorates intestinal inflammation in mice. Br J Nutr 106:878–886
Bassaganya-Riera J et al (2011b) Soluble fibers and resistant starch ameliorate disease activity in interleukin-10–deficient mice with inflammatory bowel disease. J Nutr 141:1318–1325
Bassaganya-Riera J, Guri AJ, Hontecillas R (2011c) Treatment of obesity-related complications with novel classes of naturally occurring PPAR agonists. J Obes 2011:897894. https://doi.org/10.1155/2011/897894
Bassaganya-Riera J et al (2011d) Abscisic acid regulates inflammation via ligand-binding domain-independent activation of peroxisome proliferator-activated receptor γ. J Biol Chem 286:2504–2516
Bassaganya-Riera J et al (2012a) Helicobacter pylori colonization ameliorates glucose homeostasis in mice through a PPAR gamma-dependent mechanism. PLoS One 7:e50069. https://doi.org/10.1371/journal.pone.0050069
Bassaganya-Riera J, Hontecillas R, Horne WT, Sandridge M, Herfarth HH, Bloomfeld R, Isaacs KL (2012b) Conjugated linoleic acid modulates immune responses in patients with mild to moderately active Crohn's disease. Clin Nutr 31:721–727
Bassaganya-Riera J et al (2012c) Probiotic bacteria produce conjugated linoleic acid locally in the gut that targets macrophage PPAR γ to suppress colitis. PLoS One 7:e31238
Bassaganya-Riera J, Viladomiu M, Pedragosa M, De Simone C, Hontecillas R (2012d) Immunoregulatory mechanisms underlying prevention of colitis-associated colorectal cancer by probiotic bacteria. PLoS One 7:e34676
Basson A, Trotter A, Rodriguez-Palacios A, Cominelli F (2016) Mucosal interactions between genetics, diet, and microbiome in inflammatory bowel disease. Front Immunol 7:290. https://doi.org/10.3389/fimmu.2016.00290
Blümer N, Pfefferle PI, Renz H (2007) Development of mucosal immune function in the intrauterine and early postnatal environment. Curr Opin Gastroenterol 23:655–660. https://doi.org/10.1097/MOG.0b013e3282eeb428
Bolick DT et al (2014) Zinc deficiency alters host response and pathogen virulence in a mouse model of enteroaggregative Escherichia coli-induced diarrhea. Gut Microbes 5:618–627. https://doi.org/10.4161/19490976.2014.969642
Bruzzone S et al (2012) The plant hormone abscisic acid increases in human plasma after hyperglycemia and stimulates glucose consumption by adipocytes and myoblasts. FASEB J 26:1251–1260. https://doi.org/10.1096/fj.11-190140
Buffie CG et al (2015) Precision microbiome restoration of bile acid-mediated resistance to Clostridium difficile. Nature 517:205–208. https://doi.org/10.1038/nature13828
Carbo A et al (2013a) Predictive computational modeling of the mucosal immune responses during helicobacter pylori infection. PLoS One 8:e73365
Carbo A et al (2013b) Systems modeling of molecular mechanisms controlling cytokine-driven CD4+ T cell differentiation and phenotype plasticity. PLoS Comput Biol 9:e1003027
Carbo A et al (2014) Systems modeling of the role of interleukin-21 in the maintenance of effector CD4+ T cell responses during chronic Helicobacter pylori infection. MBio 5:e01243–e01214
Chang C-H et al (2013) Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153:1239–1251
Cipolletta D et al (2012) PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature 486:549–553
Evans NP, Misyak SA, Schmelz EM, Guri AJ, Hontecillas R, Bassaganya-Riera J (2010) Conjugated linoleic acid ameliorates inflammation-induced colorectal cancer in mice through activation of PPARγ. J Nutr 140:515–521
Everts B et al (2014) TLR-driven early glycolytic reprogramming via the kinases TBK1-IKK [epsiv] supports the anabolic demands of dendritic cell activation. Nat Immunol 15:323–332
Field CJ, Thomson CA, Van Aerde JE, Parrott A, Lien E, Clandinin MT (2000) Lower proportion of CD45R0+ cells and deficient interleukin-10 production by formula-fed infants, compared with human-fed, is corrected with supplementation of long-chain polyunsaturated fatty acids. J Pediatr Gastroenterol Nutr 31:291–299
Foster JA, McVey Neufeld KA (2013) Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 36:305–312. https://doi.org/10.1016/j.tins.2013.01.005
Gardy JL, Lynn DJ, Brinkman FS, Hancock RE (2009) Enabling a systems biology approach to immunology: focus on innate immunity. Trends Immunol 30:249–262
Guri AJ, Hontecillas R, Bassaganya-Riera J (2010a) Abscisic acid ameliorates experimental IBD by downregulating cellular adhesion molecule expression and suppressing immune cell infiltration. Clin Nutr 29:824–831
Guri AJ, Hontecillas R, Bassaganya-Riera J (2010b) Abscisic acid synergizes with rosiglitazone to improve glucose tolerance and down-modulate macrophage accumulation in adipose tissue: possible action of the cAMP/PKA/PPAR γ axis. Clin Nutr 29:646–653
Haxhinasto S, Mathis D, Benoist C (2008) The AKT–mTOR axis regulates de novo differentiation of CD4(+)Foxp3(+) cells. J Exp Med 205:565–574. https://doi.org/10.1084/jem.20071477
Hontecillas R, O’Shea M, Einerhand A, Diguardo M, Bassaganya-Riera J (2009) Activation of PPAR γ and α by punicic acid ameliorates glucose tolerance and suppresses obesity-related inflammation. J Am Coll Nutr 28:184–195
Hontecillas R et al (2011) Immunoregulatory mechanisms of macrophage PPAR-gamma in mice with experimental inflammatory bowel disease. Mucosal Immunol 4:304–313. https://doi.org/10.1038/mi.2010.75
John S, Luben R, Shrestha SS, Welch A, Khaw KT, Hart AR (2010) Dietary n-3 polyunsaturated fatty acids and the aetiology of ulcerative colitis: a UK prospective cohort study. Eur J Gastroenterol Hepatol 22:602–606. https://doi.org/10.1097/MEG.0b013e3283352d05
Johnson AR et al (2016) Metabolic reprogramming through fatty acid transport protein 1 (FATP1) regulates macrophage inflammatory potential and adipose inflammation. Mol Metab 5:506–526. https://doi.org/10.1016/j.molmet.2016.04.005
Kverka M et al (2011) Oral administration of Parabacteroides distasonis antigens attenuates experimental murine colitis through modulation of immunity and microbiota composition. Clin Exp Immunol 163:250–259
Leber A et al (2015) Systems modeling of interactions between mucosal immunity and the gut microbiome during clostridium difficile infection. PLoS One 10:e0134849
Leber A et al (2016) Modeling the role of lanthionine synthetase C-like 2 (LANCL2) in the modulation of immune responses to helicobacter pylori infection. PLoS One 11:e0167440
Leber A, Hontecillas R, Abedi V, Tubau-Juni N, Zoccoli-Rodriguez V, Stewart C, Bassaganya-Riera J (2017a) Modeling new immunoregulatory therapeutics as antimicrobial alternatives for treating Clostridium difficile infection. Artif Intell Med 78:1–13. https://doi.org/10.1016/j.artmed.2017.05.003
Leber A et al (2017b) NLRX1 regulates effector and metabolic functions of CD4+ T cells. J Immunol 198:2260–2268. https://doi.org/10.4049/jimmunol.1601547
Lee YS et al (2013) The fractalkine/CX3CR1 system regulates β cell function and insulin secretion. Cell 153:413–425
Lu P, Bevan DR, Lewis SN, Hontecillas R, Bassaganya-Riera J (2011) Molecular modeling of lanthionine synthetase component C-like protein 2: a potential target for the discovery of novel type 2 diabetes prophylactics and therapeutics. J Mol Model 17:543–553. https://doi.org/10.1007/s00894-010-0748-y
Lu P et al (2012) Computational modeling-based discovery of novel classes of anti-inflammatory drugs that target Lanthionine Synthetase C-like protein 2. PLoS One 7:e34643. https://doi.org/10.1371/journal.pone.0034643
Lu P et al (2015) Modeling-enabled characterization of novel NLRX1 ligands. PLoS One 10:e0145420. https://doi.org/10.1371/journal.pone.0145420
Luyer MD, Greve JW, Hadfoune M, Jacobs JA, Dejong CH, Buurman WA (2005) Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve. J Exp Med 202:1023–1029. https://doi.org/10.1084/jem.20042397
Lyte M (2013) Microbial endocrinology in the microbiome-gut-brain axis: how bacterial production and utilization of neurochemicals influence behavior. PLoS Pathog 9:e1003726. https://doi.org/10.1371/journal.ppat.1003726
McDonald D, Glusman G, Price ND (2016) Personalized nutrition through big data. Nat Biotechnol 34:152–154. https://doi.org/10.1038/nbt.3476
Mei Y et al (2014) ENISI MSM: a novel multi-scale modeling platform for computational immunology. In: 2014 IEEE international conference on Bioinformatics and Biomedicine (BIBM). IEEE, pp 391–396
Michalek RD et al (2011) Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol 186:3299–3303
Neuman MG (2007) Immune dysfunction in inflammatory bowel disease. Transl Res 149:173–186. https://doi.org/10.1016/j.trsl.2006.11.009
Neurath MF (2014) Cytokines in inflammatory bowel disease. Nat Rev Immunol 14:329–342. https://doi.org/10.1038/nri3661
Newton R, Priyadharshini B, Turka LA (2016) Immunometabolism of regulatory T cells. Nat Immunol 17:618–625
O’Neill LAJ, Kishton RJ, Rathmell J (2016) A guide to immunometabolism for immunologists. Nat Rev Immunol 16:553–565. https://doi.org/10.1038/nri.2016.70
Penders J et al (2006) Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 118:511–521. https://doi.org/10.1542/peds.2005-2824
Philipson CW, Bassaganya-Riera J, Viladomiu M, Pedragosa M, Guerrant RL, Roche JK, Hontecillas R (2013) The role of peroxisome proliferator-activated receptor gamma in immune responses to enteroaggregative Escherichia Coli infection. PLoS One 8:e57812. https://doi.org/10.1371/journal.pone.0057812
Philipson CW et al (2015) Modeling the regulatory mechanisms by which NLRX1 modulates innate immune responses to Helicobacter pylori infection. PLoS One 10:e0137839. https://doi.org/10.1371/journal.pone.0137839
Picard F, Auwerx J (2002) PPAR(gamma) and glucose homeostasis. Annu Rev Nutr 22:167–197. https://doi.org/10.1146/annurev.nutr.22.010402.102808
Redig AJ, Jänne PA (2015) Basket trials and the evolution of clinical trial design in an era of genomic medicine. J Clin Oncol 33:975–977
Richard C, Lewis ED, Goruk S, Field CJ (2016) A dietary supply of docosahexaenoic acid early in life is essential for immune development and the establishment of oral tolerance in female rat offspring. J Nutr 146:2398–2406. https://doi.org/10.3945/jn.116.237149
Ruemmele FM (2016) Role of diet in inflammatory bowel disease. Ann Nutr Metab 68(Suppl 1):33–41. https://doi.org/10.1159/000445392
Schuhmacher A, Gassmann O, Hinder M (2016) Changing R&D models in research-based pharmaceutical companies. J Transl Med 14(1):105
Shah R et al (2015) Metabolic effects of CX3CR1 deficiency in diet-induced obese mice. PLoS One 10:e0138317
Singh UP et al (2014) The emerging role of leptin antagonist as potential therapeutic option for inflammatory bowel disease. Int Rev Immunol 33:23–33. https://doi.org/10.3109/08830185.2013.809071
Smith PM et al (2013) The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341:569–573. https://doi.org/10.1126/science.1241165
Sturla L et al (2009) LANCL2 is necessary for abscisic acid binding and signaling in human granulocytes and in rat insulinoma cells. J Biol Chem 284:28045–28057. https://doi.org/10.1074/jbc.M109.035329
Verma M et al (2016) Modeling-enabled systems nutritional immunology. Front Nutr 3:5. https://doi.org/10.3389/fnut.2016.00005
Verma M et al (2017) Modeling the mechanisms by which HIV-associated immunosuppression influences HPV persistence at the oral mucosa. PLoS One 12:e0168133. https://doi.org/10.1371/journal.pone.0168133
Vodovotz Y et al (2016) Solving Immunology? Trends Immunol 38(2):116–127. https://doi.org/10.1016/j.it.2016.11.006
Vroegrijk IO et al (2011) Pomegranate seed oil, a rich source of punicic acid, prevents diet-induced obesity and insulin resistance in mice. Food Chem Toxicol 49:1426–1430. https://doi.org/10.1016/j.fct.2011.03.037
Wendelsdorf K, Bassaganya-Riera J, Hontecillas R, Eubank S (2010) Model of colonic inflammation: immune modulatory mechanisms in inflammatory bowel disease. J Theor Biol 264:1225–1239
Wendelsdorf KV et al (2012) ENteric Immunity SImulator: a tool for in silico study of gastroenteric infections. IEEE Trans Nanobioscience 11:273–288
Wooden B, Goossens N, Hoshida Y, Friedman SL (2017) Using big data to discover diagnostics and therapeutics for gastrointestinal and liver diseases. Gastroenterology 152:53–67000. https://doi.org/10.1053/j.gastro.2016.09.065
Xu Y et al (2016) Glycolysis determines dichotomous regulation of T cell subsets in hypoxia. J Clin Invest 126:2678–2688
Yurist-Doutsch S, Arrieta MC, Tupin A, Valdez Y, Antunes LC, Yen R, Finlay BB (2016) Nutrient deprivation affects salmonella invasion and its interaction with the gastrointestinal microbiota. PLoS One 11:e0159676. https://doi.org/10.1371/journal.pone.0159676
Zeevi D et al (2015) Personalized nutrition by prediction of glycemic responses. Cell 163:1079–1094. https://doi.org/10.1016/j.cell.2015.11.001
Zeng M, van der Donk WA, Chen J (2014) Lanthionine synthetase C-like protein 2 (LanCL2) is a novel regulator of Akt. Mol Biol Cell 25:3954–3961. https://doi.org/10.1091/mbc.E14-01-0004
Zhang YZ, Li YY (2014) Inflammatory bowel disease: pathogenesis. World J Gastroenterol 20:91–99. https://doi.org/10.3748/wjg.v20.i1.91
Zhou YJ, Gao J, Yang HM, Yuan XL, Chen TX, He ZJ (2010) The role of the lactadherin in promoting intestinal DCs development in vivo and vitro. Clin Dev Immunol 2010:357541. https://doi.org/10.1155/2010/357541
Zocchi E et al (2017) Abscisic acid: a novel nutraceutical for glycemic control. Front Nutr 4:24. https://doi.org/10.3389/fnut.2017.00024
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Verma, M. et al. (2018). From Nutritional Immunology to Drug Development. In: Bassaganya-Riera, J. (eds) Accelerated Path to Cures. Springer, Cham. https://doi.org/10.1007/978-3-319-73238-1_4
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