Translating nutritional immunology into drug development for inflammatory bowel disease

Current Opinion in Gastroenterology

Volumn 32, Issue 6, 2016, Pages 443-449

  Leber, Andrew ^a   Hontecillas, Raquel ^a   Tubau Juni, Nuria ^a   Bassaganya Riera, Josep ^a  

^a VIRGINIA BIOINFORMATICS INSTITUTE   (United States)

Author keywords

Drug development; Immunoregulation; Inflammatory bowel disease; Lanthionine synthetase C like 2; Nutritional immunology

Indexed keywords

GASTROINTESTINAL AGENT;

DRUG DEVELOPMENT; DRUG RESEARCH; DRUG TARGETING; HUMAN; IMMUNOLOGY; IMMUNOSTIMULATION; INFLAMMATORY BOWEL DISEASE; INTESTINE FLORA; NERVE STIMULATION; NONHUMAN; NUTRITION; NUTRITIONAL IMMUNOLOGY; REVIEW; TRANSLATIONAL RESEARCH; MICROBIOLOGY; MOLECULARLY TARGETED THERAPY; PROCEDURES;

DRUG DISCOVERY; GASTROINTESTINAL AGENTS; GASTROINTESTINAL MICROBIOME; HUMANS; INFLAMMATORY BOWEL DISEASES; MOLECULAR TARGETED THERAPY; NUTRITIONAL PHYSIOLOGICAL PHENOMENA; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84988719241     PISSN: 02671379     EISSN: 15317056     Source Type: Journal    
DOI: 10.1097/MOG.0000000000000317     Document Type: Review

References (116)

1. Zhou YJ, Gao J, Yang HM, et al. The role of the lactadherin in promoting intestinal DCs development in vivo and vitro. Clin Dev Immunol 2010; 2010:357541.
2. Field CJ, Thomson CA, Van Aerde JE, et al. 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 2000; 31:291-299.
3. Richard C, Lewis ED, Goruk S, et al. The content of docosahexaenoic acid in the suckling and the weaning diet beneficially modulates the ability of immune cells to response to stimuli. J Nutr Biochem 2016; 35:22-29.
4. Schmitz G, Ecker J. The opposing effects of n-3 and n-6 fatty acids. Prog Lipid Res 2008; 47:147-155.
5. Sela DA, Chapman J, Adeuya A, et al. The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations formilk utilization within the infant microbiome. Proc Natl Acad Sci U S A 2008; 105:18964-18969.
6. Rikimaru T, Taniguchi K, Yartey JE, et al. Humoral and cell-mediated immunity in malnourished children in Ghana. Eur J Clin Nutr 1998; 52:344-350.
7. Nassar MF, El-Batrawy SR, Nagy NM. CD95 expression in white blood cells of malnourished infants during hospitalization and catch-up growth. East Mediterr Health J 2009; 15:574-583.
8. Hughes SM, Amadi B, Mwiya M, et al. Dendritic cell anergy results from endotoxemia in severe malnutrition. J Immunol 2009; 183:2818-2826.
9. Costa TB, Morais NG, Pedrosa AL, et al. Neonatal malnutrition programs the oxidant function of macrophages in response to Candida albicans. Microb Pathog 2016; 95:68-76.
10. deMoraisNG, daCostaTB, Pedrosa AL, et al. Effect of neonatalmalnutrition on expression of nitric oxide synthase enzyme, production of free radicals and in vitro viability of alveolar macrophages infected with methicillin-sensitive and methicillin-resistant Staphylococcus aureus. Eur J Nutr 2016; 55:403-411.
11. Philipson CW, Bassaganya-Riera J, Viladomiu M, et al. The role of peroxisome proliferator-activated receptor gamma in immune responses to enteroaggregative Escherichia coli infection. PLoS One 2013; 8:e57812.
12. Bolick DT, Kolling GL, Moore JH, 2nd, et al. Zinc deficiency alters host response and pathogen virulence in a mouse model of enteroaggregative Escherichia coli-induced diarrhea. Gut Microbes 2014; 5:618-627.
13. Kahlert S, Junnikkala S, Renner L, et al. Physiological Concentration of Exogenous Lactate Reduces Antimycin A Triggered Oxidative Stress in Intestinal Epithelial Cell Line IPEC-1 and IPEC-J2 In Vitro. PLoS One 2016; 11:e0153135.
14. Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013; 341:569-573.
15. Nish S, Medzhitov R. Host defense pathways: role of redundancy and compensation in infectious disease phenotypes. Immunity 2011; 34:629-636.
16. Yurist-Doutsch S, Arrieta MC, Tupin A, et al. Nutrient Deprivation Affects Salmonella Invasion and Its Interaction with the Gastrointestinal Microbiota. PLoS One 2016; 11:e0159676.
17. Buffie CG, Bucci V, Stein RR, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 2015; 517:205-208.
18. Foster JA, McVey Neufeld KA. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 2013; 36:305-312.
19. Lyte M. Microbial endocrinology in the microbiome-gut-brain axis: how bacterial production and utilization of neurochemicals influence behavior. PLoS Pathog 2013; 9:e1003726.
20. Willemze RA, Luyer MD, Buurman WA, et al. Neural reflex pathways in intestinal inflammation: hypotheses to viable therapy. Nat Rev Gastroenterol Hepatol 2015; 12:353-362.
21. Luyer MD, Greve JW, Hadfoune M, et al. Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve. J Exp Med 2005; 202:1023-1029.
22. de Jonge WJ, van der Zanden EP, The FO, et al. Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol 2005; 6:844-851.
23. Pavlov VA, Wang H, Czura CJ, et al. The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med 2003; 9:125-134.
24. Singh UP, Singh NP, Guan H, et al. The emerging role of leptin antagonist as potential therapeutic option for inflammatory bowel disease. Int Rev Immunol 2014; 33:23-33.
25. Singh UP, Singh NP, Guan H, et al. Leptin antagonist ameliorates chronic colitis in IL-10(-)/(-) mice. Immunobiology 2013; 218:1439-1451.
26. Al-Hassi HO, Bernardo D, Murugananthan AU, et al. A mechanistic role for leptin in human dendritic cell migration: differences between ileum and colon in health and Crohn's disease. Mucosal Immunol 2013; 6:751-761.
27. Bassaganya-Riera J, Dominguez-BelloMG, Kronsteiner B, et al. Helicobacter pylori colonization ameliorates glucose homeostasis in mice through a PPAR gamma-dependent mechanism. PLoS One 2012; 7:e50069.
28. Peterson LW, Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol 2014; 14:141-153.
29. Chaudhry KK, Shukla PK, Mir H, et al. Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice. J Nutr Biochem 2016; 27:16-26.
30. Wang B, Wu Z, Ji Y, et al. L-Glutamine Enhances Tight Junction Integrity by Activating CaMK Kinase 2-AMP-Activated Protein Kinase Signaling in Intestinal Porcine Epithelial Cells. J Nutr 2016; 146:501-508.
31. Kong J, Zhang Z, Musch MW, et al. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol 2008; 294:G208-G216.
32. Wong JM, de Souza R, Kendall CW, et al. Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 2006; 40:235-243.
33. Feng Y, Ralls MW, Xiao W, et al. Loss of enteral nutrition in a mouse model results in intestinal epithelial barrier dysfunction. Ann N Y Acad Sci 2012; 1258:71-77.
34. Soderholm JD, Oman H, Blomquist L, et al. Reversible increase in tight junction permeability to macromolecules in rat ileal mucosa in vitro by sodium caprate, a constituent of milk fat. Dig Dis Sci 1998; 43:1547-1552.
35. Lammers KM, Lu R, Brownley J, et al. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology 2008; 135:194-204; e3.
36. ScarpaM, Kessler S, Sadler T, et al. The epithelial danger signal IL-1alpha is a potent activator of fibroblasts and reactivator of intestinal inflammation. Am J Pathol 2015; 185:1624-1637.
37. Zhang H, Kovacs-Nolan J, Kodera T, et al. gamma-Glutamyl cysteine and gamma-glutamyl valine inhibit TNF-alpha signaling in intestinal epithelial cells and reduce inflammation in a mouse model of colitis via allosteric activation of the calcium-sensing receptor. Biochim Biophys Acta 2015; 1852:792-804.
38. Reinecker HC, Loh EY, Ringler DJ, et al.Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa. Gastroenterology 1995; 108:40-50.
39. Bansal T, Alaniz RC, Wood TK, et al. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc Natl Acad Sci U S A 2010; 107:228-233.
40. Prietl B, Treiber G, Mader JK, et al. High-dose cholecalciferol supplementation significantly increases peripheral CD4(+) Tregs in healthy adults without negatively affecting the frequency of other immune cells. Eur J Nutr 2014; 53:751-759.
41. Rosenkranz E, Metz CH, Maywald M, et al. Zinc supplementation induces regulatory T cells by inhibition of Sirt-1 deacetylase in mixed lymphocyte cultures. Mol Nutr Food Res 2016; 60:661-671.
42. Yao J, Wei C, Wang JY, et al. Effect of resveratrol on Treg/Th17 signaling and ulcerative colitis treatment in mice. World J Gastroenterol 2015; 21:6572-6581.
43. Mora JR, von Andrian UH. Role of retinoic acid in the imprinting of gut-homing IgA-secreting cells. Semin Immunol 2009; 21:28-35.
44. Hall JA, Grainger JR, Spencer SP, et al. The role of retinoic acid in tolerance and immunity. Immunity 2011; 35:13-22.
45. van de Pavert SA, Ferreira M, Domingues RG, et al. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity. Nature 2014; 508:123-127.
46. Kirchgessner TG, Sleph P, Ostrowski J, et al. Beneficial and Adverse Effects of an LXR Agonist on Human Lipid and Lipoprotein Metabolism and Circulating Neutrophils. Cell Metab 2016; 24:223-233.
47. Uderhardt S, Kronke G. 12/15-lipoxygenase during the regulation of inflammation, immunity, and self-tolerance. J Mol Med (Berl) 2012; 90:1247-1256.
48. Verma M, Hontecillas R, Abedi V, et al. Modeling-Enabled Systems Nutritional Immunology. Front Nutr 2016; 3:5.
49. Ng KM, Ferreyra JA, Higginbottom SK, et al. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 2013; 502:96-99.
50. Neuman MG. Immune dysfunction in inflammatory bowel disease. Transl Res 2007; 149:173-186.
51. Zhang YZ, Li YY. Inflammatory bowel disease: pathogenesis. World J Gastroenterol 2014; 20:91-99.
52. Basson A, Trotter A, Rodriguez-Palacios A, et al. Mucosal Interactions between Genetics, Diet, and Microbiome in Inflammatory Bowel Disease. Front Immunol 2016; 7:290.
53. Strober W, Fuss IJ, Blumberg RS. The immunology of mucosal models of inflammation. Annu Rev Immunol 2002; 20:495-549.
54. Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol 2014; 14:329-342.
55. Ruemmele FM. Role of Diet in Inflammatory Bowel Disease. Ann Nutr Metab 2016; 68 (Suppl 1):33-41.
56. Ananthakrishnan AN, KhaliliH, Konijeti GG, et al. Long-term intake of dietary fat and risk of ulcerative colitis and Crohn's disease. Gut 2014; 63:776-784.
57. Ananthakrishnan AN, Khalili H, Konijeti GG, et al. A prospective study of longterm intake of dietary fiber and risk of Crohn's disease and ulcerative colitis. Gastroenterology 2013; 145:970-977.
58. Cheng L, Jin H, Qiang Y, et al. High fat diet exacerbates dextran sulfate sodium induced colitis through disturbing mucosal dendritic cell homeostasis. Int Immunopharmacol 2016; 40:1-10.
59. Hart AR, Luben R, Olsen A, et al. Diet in the aetiology of ulcerative colitis: a European prospective cohort study. Digestion 2008; 77:57-64.
60. John S, Luben R, Shrestha SS, et al. Dietary n-3 polyunsaturated fatty acids and the aetiology of ulcerative colitis: a UK prospective cohort study. Eur J Gastroenterol Hepatol 2010; 22:602-606.
61. Bassaganya-Riera J, Reynolds K, Martino-Catt S, et al. Activation of PPAR gamma and delta by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Gastroenterology 2004; 127:777-791.
62. Bassaganya-Riera J, Viladomiu M, Pedragosa M, et al. Immunoregulatory mechanisms underlying prevention of colitis-associated colorectal cancer by probiotic bacteria. PLoS One 2012; 7:e34676.
63. Evans NP, Misyak SA, Schmelz EM, et al. Conjugated linoleic acid ameliorates inflammation-induced colorectal cancer in mice through activation of PPARgamma. J Nutr 2010; 140:515-521.
64. Bassaganya-Riera J, Hontecillas R. CLA and n-3 PUFA differentially modulate clinical activity and colonic PPAR-responsive gene expression in a pig model of experimental IBD. Clin Nutr 2006; 25:454-465.
65. Bassaganya-Riera J, Viladomiu M, Pedragosa M, et al. Probiotic bacteria produce conjugated linoleic acid locally in the gut that targets macrophage PPAR gamma to suppress colitis. PLoS One 2012; 7:e31238.
66. Agostini L, Mazzi P, Cavaliere A. Multiple primary malignant tumours: gemistocytic astrocytoma with leptomeningeal spreading and papillary thyroid carcinoma. A case report. Acta Neurol (Napoli) 1990; 12:305-310.
67. Chang CH, Curtis JD, Maggi LB Jr, et al. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 2013; 153:1239-1251.
68. Michalek RD, Gerriets VA, Jacobs SR, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol 2011; 186:3299-3303.
69. Xu Y, Chaudhury A, Zhang M, et al. Glycolysis determines dichotomous regulation of T cell subsets in hypoxia. J Clin Invest 2016; 126:2678-2688.
70. Newton R, Priyadharshini B, Turka LA. Immunometabolism of regulatory T cells. Nat Immunol 2016; 17:618-625.
71. Haxhinasto S, Mathis D, Benoist C. The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells. J Exp Med 2008; 205:565-574.
72. Lu P, Hontecillas R, Horne WT, et al. Computational modeling-based discovery of novel classes of anti-inflammatory drugs that target lanthionine synthetase C-like protein 2. PLoS One 2012; 7:e34643.
73. Allen IC, Moore CB, Schneider M, et al. NLRX1 protein attenuates inflammatory responses to infection by interfering with the RIG-I-MAVS and TRAF6-NF-kappaB signaling pathways. Immunity 2011; 34:854-865.
74. Carbo A, Hontecillas R, Kronsteiner B, et al. Systems modeling of molecular mechanisms controlling cytokine-driven CD4+ T cell differentiation and phenotype plasticity. PLoS Comput Biol 2013; 9:e1003027.
75. Cipolletta D, Feuerer M, Li A, et al. PPAR-gamma is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature 2012; 486:549-553.
76. Pearce EL, Walsh MC, Cejas PJ, et al. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 2009; 460:103-107.
77. Everts B, Amiel E, Huang SC, et al. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKvarepsilon supports the anabolic demands of dendritic cell activation. Nat Immunol 2014; 15:323-332.
78. Jha AK, Huang SC, Sergushichev A, et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 2015; 42:419-430.
79. Johnson AR, Qin Y, Cozzo AJ, et al. Metabolic reprogramming through fatty acid transport protein 1 (FATP1) regulates macrophage inflammatory potential and adipose inflammation. Mol Metab 2016; 5:506-526.
80. Lampropoulou V, Sergushichev A, Bambouskova M, et al. Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation. Cell Metab 2016; 24:158-166.
81. Lee YS, Morinaga H, Kim JJ, et al. The fractalkine/CX3CR1 system regulates beta cell function and insulin secretion. Cell 2013; 153:413-425.
82. Shah R, O'Neill SM, Hinkle C, et al. Metabolic Effects of CX3CR1 Deficiency in Diet-Induced Obese Mice. PLoS One 2015; 10:e0138317.
83. Feng X, Szulzewsky F, Yerevanian A, et al. Loss of CX3CR1 increases accumulation of inflammatory monocytes and promotes gliomagenesis. Oncotarget 2015; 6:15077-15094.
84. Medina-Contreras O, Geem D, Laur O, et al. CX3CR1 regulates intestinal macrophage homeostasis, bacterial translocation, and colitogenic Th17 responses in mice. J Clin Invest 2011; 121:4787-4795.
85. Schneider KM, Bieghs V, Heymann F, et al. CX3CR1 is a gatekeeper for intestinal barrier integrity in mice: Limiting steatohepatitis by maintaining intestinal homeostasis. Hepatology 2015; 62:1405-1416.
86. Hontecillas R, Horne WT, Climent M, et al. Immunoregulatory mechanisms of macrophage PPAR-gamma in mice with experimental inflammatory bowel disease. Mucosal Immunol 2011; 4:304-313.
87. Picard F, Auwerx J. PPAR(gamma) and glucose homeostasis. Annu Rev Nutr 2002; 22:167-197.
88. Bardot O, Aldridge TC, Latruffe N, et al. PPAR-RXR heterodimer activates a peroxisome proliferator response element upstream of the bifunctional enzyme gene. Biochem Biophys Res Commun 1993; 192:37-45.
89. Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 1996; 15:5336-5348.
90. Mayerson AB, Hundal RS, Dufour S, et al. The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes 2002; 51:797-802.
91. Remels AH, Langen RC, Gosker HR, et al. PPARgamma inhibits NF-kappaBdependent transcriptional activation in skeletal muscle. Am J Physiol Endocrinol Metab 2009; 297:E174-E183.
92. Bassaganya-Riera J, Hontecillas R, Horne WT, et al. Conjugated linoleic acid modulates immune responses in patients with mild to moderately active Crohn's disease. Clin Nutr 2012; 31:721-727.
93. Bassaganya-Riera J, DiGuardo M, Climent M, et al. Activation of PPARgamma and delta by dietary punicic acid ameliorates intestinal inflammation in mice. Br J Nutr 2011; 106:878-886.
94. Bassaganya-Riera J, Guri AJ, Lu P, et al. Abscisic acid regulates inflammation via ligand-binding domain-independent activation of peroxisome proliferatoractivated receptor gamma. J Biol Chem 2011; 286:2504-2516.
95. Sturla L, Fresia C, Guida L, et al. LANCL2 is necessary for abscisic acid binding and signaling in human granulocytes and in rat insulinoma cells. J Biol Chem 2009; 284:28045-28057.
96. Bruzzone S, Ameri P, Briatore L, et al. The plant hormone abscisic acid increases in human plasma after hyperglycemia and stimulates glucose consumption by adipocytes and myoblasts. FASEB J 2012; 26:1251-1260.
97. Zeng M, van der Donk WA, Chen J. Lanthionine synthetase C-like protein 2 (LanCL2) is a novel regulator of Akt. Mol Biol Cell 2014; 25:3954-3961.
98. Bassaganya-Riera J, Skoneczka J, Kingston DG, et al. Mechanisms of action and medicinal applications of abscisic Acid. CurrMed Chem 2010; 17:467-478.
99. Guri AJ, Hontecillas R, Bassaganya-Riera J. Abscisic acid ameliorates experimental IBD by downregulating cellular adhesion molecule expression and suppressing immune cell infiltration. Clin Nutr 2010; 29:824-831.
100. Guri AJ, Hontecillas R, Si H, et al. Dietary abscisic acid ameliorates glucose tolerance and obesity-related inflammation in db/db mice fed high-fat diets. Clin Nutr 2007; 26:107-116.
101. Hontecillas R, Roberts PC, Carbo A, et al. Dietary abscisic acid ameliorates influenza-virus-associated disease and pulmonary immunopathology through a PPARgamma-dependent mechanism. J Nutr Biochem 2013; 24:1019-1027.
102. Magnone M, Ameri P, Salis A, et al. Microgram amounts of abscisic acid in fruit extracts improve glucose tolerance and reduce insulinemia in rats and in humans. FASEB J 2015; 29:4783-4793.
103. Lu P, Hontecillas R, Philipson CW, et al. Lanthionine synthetase component C-like protein 2: a new drug target for inflammatory diseases and diabetes. Curr Drug Targets 2014; 15:565-572.
104. Yang CS, Kim JJ, Lee HM, et al. The AMPK-PPARGC1A pathway is required for antimicrobial host defense through activation of autophagy. Autophagy 2014; 10:785-802.
105. Staib F, Seibold M, L'Age M. Persistence of Cryptococcus neoformans in seminal fluid and urine under itraconazole treatment. The urogenital tract (prostate) as a niche for Cryptococcus neoformans. Mycoses 1990; 33:369-373.
106. Lu P, Hontecillas R, Abedi V, et al. Modeling-Enabled Characterization of Novel NLRX1 Ligands. PLoS One 2015; 10:e0145420.
107. Fukata M, Vamadevan AS, Abreu MT. Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in inflammatory disorders. Semin Immunol 2009; 21:242-253.
108. Saxena M, Yeretssian G. NOD-Like Receptors: Master Regulators of Inflammation and Cancer. Front Immunol 2014; 5:327.
109. Philipson CW, Bassaganya-Riera J, Viladomiu M, et al. Modeling the Regulatory Mechanisms by Which NLRX1 Modulates Innate Immune Responses to Helicobacter pylori Infection. PLoS One 2015; 10:e0137839.
110. Hontecillas R, O'Shea M, Einerhand A, et al. Activation of PPAR gamma and alpha by punicic acid ameliorates glucose tolerance and suppresses obesityrelated inflammation. J Am Coll Nutr 2009; 28:184-195.
111. Vroegrijk IO, van Diepen JA, van den Berg S, et al. Pomegranate seed oil, a rich source of punicic acid, prevents diet-induced obesity and insulin resistance in mice. Food Chem Toxicol 2011; 49:1426-1430.
112. Spisni E, Valerii MC, De Fazio L, et al. Cyclooxygenase-2 silencing for the treatment of colitis: a combined in vivo strategy based on RNA interference and engineered Escherichia coli. Mol Ther 2015; 23:278-289.
113. De Fazio L, Spisni E, Cavazza E, et al. Dietary Geraniol by Oral or Enema Administration Strongly Reduces Dysbiosis and Systemic Inflammation in Dextran Sulfate Sodium-Treated Mice. Front Pharmacol 2016; 7:38.
114. Zbakh H, Talero E, Avila J, et al. The Algal Meroterpene 11-Hydroxy-1'-OMethylamentadione Ameloriates Dextran Sulfate Sodium-Induced Colitis in Mice. Mar Drugs 2016; 14:149.
115. Bissel P, Boes K, Hinckley J, et al. Exploratory Studies With BT-11: A Proposed Orally Active Therapeutic for Crohn's Disease. Int J Toxicol 2016; 35:521-529.
116. Abedi V, Lu P, Hontecillas R, et al. Phase III placebo-controlled, randomized clinical trial with synthetic Crohn's disease patients to evaluate treatment response, in Emerging Trends in Applications and Infrastructure in Computational Biology, Bioinformatics and Systems Biology. In: Arabnia H, Tran Q, editors. Cambridge, MA: Elsevier; 2015. pp. 411-425.