Obesity and inflammatory bowel disease

Česká verzia

Authors: V. Teplan ^{1 3} ; Lukáš M. ¹
Authors place of work: Klinické a výzkumné centrum pro střevní záněty, Klinické centrum ISCARE a. s. a 1. LF UK v Praze ¹; Subkatedra nefrologie, IPVZ, Pra-ha ²; Katedra interních oborů, Interní klinika LF OU a FN Ostrava ³
Published in the journal: Gastroent Hepatol 2021; 75(1): 20-28
Category: IBD: Review Article
doi: https://doi.org/10.48095/ccgh202120

Summary

The incidence and prevalence of overweight and obesity has dramatically increased in the last decades and is generally considered to be global pandemics. The incidence of inflammatory bowel disease (IBD) is rising parallel with overweight and obesity. Contrary to a conventional believe, about 15–40% patients with IBD are obese, which can contribute to the development and course of IBD, especially in Crohn’s disease. Although the findings of some cohort studies are still conflicting, recent results indicate a special role of visceral adipose tissue and particularly mesenteric adipose tissue known as creeping fat, leading to intestinal inflammation. The involvement of altered adipocyte function and deregulated production of adipokines such as leptin and adiponectin has been suggested in the pathogenesis of IBD. The emerging role of Western diet and microbiota can also open new possibilities in IBD management. The effect of obesity on the IBD-related therapy remains to be studied. The finding that obesity results in suboptimal response to the therapy, potentially promoting rapid clearance of biologic agents and thus leading to their low concentrations, has a great importance. Obesity also makes IBD colorectal surgery technically challenging and might increase a risk of perioperative complications.

Keywords:

obesity – IBD – visceral fat – Adipokines – colorectal surgery

Zdroje

1. Ng M, Fleming T, Robinson M et al. Global, regional and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the global burden of disease study 2013. Lancet 2014; 384(9945): 766–781. doi: 10.1016/ S0140-6736(14)60460-8.

2. Ng SC, Zeng Z, Niewiadomski O et al. Early course of inﬂammatory bowel disease in a population-based inception cohort study from 8 countries in Asia and Australia. Gastroenterology 2016; 150(1): 86–95. doi: 10.1053/ j.gastro.2015.09.005.

3. Molodecky NA, Soon IS, Rabi DM et al. Increasing incidence and prevalence of the inﬂammatory bowel diseases with time, based on systematic review. Gastroenterology 2012; 142(1): 46–54. doi: 10.1053/ j.gastro.2011.10.001.

4. Ananthakrishnan AN. Environmental risk factors for inﬂammatory bowel diseases: a review. Dig Dis Sci 2015; 60(2): 290–298. doi: 10.1007/ s10620-014-3350-9.

5. Singh S, Dulai PS, Zarrinpar A et al. Obesity in IBD: epidemiology, pathogenesis, disease course and tratment outcomes. Nat Rev Gastroenterol Hepatol 2017; 14(2): 110–121. doi: 10.1038/ nrgastro.2016.181.

6. Suibhne TN, Raftery TC, McMahon O et al. High prevalence of overweight and obesity in adults with Crohn’s disease: associations with disease and lifestyle factors. J Crohns Colitis 2013; 7(7): e241–e248. doi: 10.1016/ j.crohns.2012.09.009.

7. Lynn AM, Harmsen WS, Aniwan S et al. Prevalence of obesity and influence on phenotype within a population-based cohort of inflammatory bowel disease patients. Gastroenterology 2018; 154(Suppl 6): S608.

8. Lynn AM, Harmsen WS, Tremaine WJ et al. Trends in the prevalence of overweight and obesity at the time of inflammatory bowel disease diagnosis: a population-based study. Gastroenterology 2018; 154(Suppl 6): S614–S615.

9. Snekvik I, Smith CH, Nilsen TIL et al. Obesity, waist circumference, weight change, and risk of incident psoriasis: prospective data from the HUNT study. J Invest Dermatol 2017; 137(12): 2484–2490. doi: 10.1016/ j.jid.2017.07.822.

10. Qin B, Yang M, Fu et al. Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis. Arthritis Res Ther 2015; 17(1): 86. doi: 10.1186/ s13 075-015-0601-x.

11. Maas F, Arends S, van der Veer E et al. Obesity is common in axial spondyloarthritis and is associated with poor clinical outcome. J Rheumatol 2016; 43(2): 383–387. 10.3899/ jrheum.150648.

12. Steed H, Walsh S, Reynolds N. A brief report of the epidemiology of obesity in the inﬂammatory bowel disease population of Tayside, Scotland. Obes Facts 2009; 2(6): 370–372. doi: 10.1159/ 000262276.

13. Long MD, Crandall WV, Leibowitz IH et al. Prevalence and epidemiology of overweight and obesity in children with inﬂammatory bowel disease. Inﬂamm Bowel Dis 2011; 17(10): 2162–2168. doi: 10.1002/ ibd.21585.

14. Khalili H, Ananthakrishnan AN, Konijeti GG et al. Measures of obesity and risk of Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis 2015; 21(2): 361–368. doi: 10.1097/ MIB.0000000000000283.

15. Mendall M, Harpsøe MC, Kumar D et al. Relation of body mass index to risk of developing inflammatory bowel disease amongst women in the Danish National Birth Cohort. PLoS One 2018; 13(1): e0190600. doi: 10.1371/ journal.pone.0190600.

16. Harpsøe MC, Basit S, Andersson M et al. Body mass index and risk of autoimmune diseases: a study within the Danish National Birth Cohort. Int J Epidemiol 2014; 43(3): 843–855. doi: 10.1093/ ije/ dyu045.

17. Chan SS, Luben R, Olsen A et al. Body mass index and the risk for Crohn’s disease and ulcerative colitis: data from a European Prospective Cohort Study (The IBD in EPIC Study). Am J Gastroenterol 2013; 108(4): 575–582. doi: 10.1038/ ajg.2012.453.

18. Jensen CB, Ängquist LH, Mendall MA et al. Childhood body mass indexand risk of inflammatory bowel disease in adulthood: a population-based cohort study. Am J Gastroenterol 2018; 113(5): 694–701. doi: 10.1038/ s4139 5-018-0031-x.

19. Melinder C, Hiyoshi A, Hussein O et al. Physical fitness in adolescence and subsequent inflammatory bowel disease risk. Clin Transl Gastroenterol 2015; 6(11): e121. doi: 10.1038/ ctg.2015.49.

20. Mendall MA, Gunasekera AV, John BJ et al. Is obesity a risk factor for Crohn’s disease? Dig Dis Sci 2011; 56(3): 837–844. doi: 10.1007/ s10620-010-1541-6.

21. Hemminki K, Li X, Sundquist J et al. Risk of asthma and autoimmune diseases and related conditions in patients hospitalized for obesity. Ann Med 2012; 44(3): 289–295. doi: 10.3109/ 07853890.2010.547515.

22. Rahmani J, Kord-Varkaneh H, Hekmatdoost Aet al. Body mass index and risk of inflammatory bowel disease: a systematic review and dose-response meta-analysis of cohort studies of over a million participants. Obes Rev 2019; 20(9): 1312–1320. doi: 10.1111/ obr.12875.

23. Uko V, Vortia E, Achkar JP et al. Impact of abdominal visceral adipose tissue on disease outcome in pediatric Crohn’s disease. Inflamm Bowel Dis 2014; 20(12): 2286–2291. doi: 10.1097/ MIB.0000000000000200.

24. Kredel L, Batra A, Siegmund B et al. Role of fat and adipokines in intestinal inflammation. Curr Opin Gastroenterol 2014; 30(6): 559–565. doi: 10.1097/ MOG.0000000000000116.

25. Kredel LI, Siegmund B. Adipose-tissue and intestinal inflammation - visceral obesity and creeping fat. Front Immunol 2014; 5: 462. doi: 10.3389/ fimmu.2014.00462.

26. Blain A, Cattan S, Beaugerie L et al. Crohn’s disease clinical course abd severity in obese pateinets. Clin Nutr 2002; 21(1): 51–57. doi: 10.1054/ clnu.2001.0503.

27. Hass DJ, Brensinger CM, Lewis JD et al. The impact of increased body mass index on the clinical course of Crohn’s disease. Clin Gastroenterol Hepatol 2006; 4(4): 482–488. doi: 10.1016/ j.cgh.2005.12.015.

28. Long MD, Crandall WV, Leibowitz IH et al.Prevalence and epidemiology of overweight and obesity in children with inflammatory boweldisease. Inflamm Bowel Dis 2011; 17(10): 2162–2168. doi: 10.1002/ ibd.21585.

29. Malik TA, Manne A, Oster RA et al. Obesity is associated with poor surgical outcome in Crohn’s disease. Gastroenterology Res 2013; 6(3): 85–90. doi: 10.4021/ gr553w.

30. Singla MB, Eickhoff C, Betteridge J. Extraintestinal manifestations are common in obese patients withCrohn’s disease. Inflamm Bowel Dis 2017; 23(9): 1637–1642. doi: 10.1097/ MIB.0000000000001187.

31. Pavelock N, Masood U, Minchenberg S et al. Effects of obesity on the course of inflammatory bowel disease. Proc (Bayl Univ Med Cent) 2019; 32(1): 14–17. doi: 10.1080/ 08998 280.2018.1542887.

32. Seminerio JL, Koutroubakis IE, Ramos-Rivers C et al. Impact of obesity on the management and clinical course of patients with inflammatory bowel disease. Inflamm Bowel Dis 2015; 21(12): 2857–2863. doi: 10.1097/ MIB.000000 0000000560.

33. Flores A, Burstein E, Cipher DJ et al. Obesity in inflammatory bowel disease: a marker of less severe disease. Dig Dis Sci 2015; 60(8): 2436–2445. doi: 10.1007/ s10620-015-3629-5.

34. Pringle PL, Stewart KO, Peloquin JM et al. Body mass index, genetic susceptibility, and risk of complications among individuals with Crohn’s disease. Inflamm Bowel Dis 2015; 21(10): 2304–2310. doi: 10.1097/ MIB.00 00000000000498.

35. Stabroth-Akil D, Leifeld L, Pfützer R et al. The effect of body weight on the severity and clinical course of ulcerative colitis. Int J Colorectal Dis 2015; 30(2): 237–242. doi: 10.1007/ s00384-014-2051-3.

36. Hu Q, Ren J, Li G et al. The impact of obesity on the clinical course of inflammatory bowel disease: a meta-analysis. Med Sci Monit 2017; 23: 2599–2606. doi: 10.12659/ msm.901969.

37. Randall CW, Vizuete JA, Martinez N et al. From historical pespectives to modern therapy: a review of current and future biologial treatment for Crohn’s disease. Therap Adv Gastroenterol 2015; 8(3): 143–159. doi: 10.1177/ 1756283X15576462.

38. Harper JW, Zisman TL. Interaction of obesity and inflammatory bowel disease. World J Gastroenterol 2016; 22(35): 7868–7881. doi: 10.3748/ wjg.v22.i35.7868.

39. Erhayiem B, Dhingsa R, Hawkey CJ et al. Ratio of visceral to subcutaneous fat area is a biomarker of complicated Crohn’s disease. Clin Gastroenterol Hepatol 2011; 9(8): 684–687. doi: 10.1016/ j.cgh.2011.05.005.

40. Li Y, Zhu W, Gong J et al. Visceral fat area is associatedwith a high risk for early postoperative recurrence in Crohn’s disease. Colorectal Dis 2015; 17(3): 225–234. doi: 10.1111/ codi.12798.

41. Bryant RV, Schultz CG, Ooi S et al. Visceral adipose tissue is associated with stricturing Crohn’s disease behavior, fecal calprotectin, and quality of life. Bowel Dis 2019; 25(3): 592–600. doi: 10.1093/ ibd/ izy278.

42. Connelly TM, Juza RM, Sangster W et al. Volumetric fat ratio and not body mass index is predictive of ileocolectomy outcomes in Crohn’s disease patients. Dig Surg 2014; 31(3): 219–224. doi: 10.1159/ 000365359.

43. Holt DQ, Moore GT, Strauss BJG et al. Visceral adiposity predicts post-operative Crohn’s disease recurrence. Aliment Pharmacol Ther 2017; 45(9): 1255–1264. doi: 10.1111/ apt.14018.

44.Van der Sloot KW, Joshi AD, Bellavance DR et al. Visceral adiposity, genetic susceptibility, and risk of complications among individuals with Crohn’s disease. Inflamm Bowel Dis 2016; 23(1): 82–88. doi: 10.1097/ MIB.0000000000000978.

45.Bryant RV, Schultz CG, Ooi S et al. Obesity in inflammatory bowel disease: gains in adiposity despite high prevalence of myopenia and osteopenia. Nutrients 2018; 10(9): 1192. doi: 10.3390/ nu10091192.

46. Scaldaferri F, Pizzoferrato M, Lopetuso LR et al. Nutrition and IBD: malnutrition and/ or sarcopenia? A practical guide. Gastroenterol Res Pract 2017; 2017: 8646495. doi: 10.1155/ 2017/ 8646495.

47. Bilski J, Mazur-Bialy A, Brzozowski B et al. Can exerise affect the course of inflammatory bowel disease ? Experimenal and clinical evidence. Pharmacol Rep 2016; 68(4): 827–836. doi: 10.1016/ j.pharep.2016.04.009.

48. Ellulu MS, Patimah I, Khaza’ai H et al. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci 2017; 13(4): 851–863. doi: 10.5114/ aoms.2016.58928.

49. Dandona P, Aljada A, Chaudhuri A et al. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 2005; 111(11): 1448–1454. doi: 10.1161/ 01.CIR.0000158483.13093.9D.

50. Weidinger C, Ziegler JF, Letizia M et al. Adipokines and their role in intestinal inflammation. Front Immunol 2018; 9: 1974. doi: 10.3389/ fimmu.2018.01974.

51. Lanthier N, Leclercq IA. Adipose tissues as endocrine target organs. Best Pract Res Clin Gastroenterol 2014; 28(4): 545–558. doi: 10.1016/ j.bpg.2014.07.002.

52. Rosenwald M, Wolfrum C. The origin and definition of brite versus white and classical brown adipocytes. Adipocyte 2014; 3(1): 4–9. doi: 10.4161/ adip.26232.

53. Tchkonia T, Thomou T, Zhu Y eet al. Mechanisms and metabolic implications of regional differences among fat depots. Cell Metab 2013; 17(5): 644–656. doi: 10.1016/ j.cmet.2013.03.008.

54. Karagiannides I, Pothoulakis C. Obesity, innate immunity and gut inflammation. Curr Opin Gastroenterol 2007; 23(6): 661–666. doi: 10.1097/ MOG.0b013e3282c8c8d3.

55. Nam SY. Obesity-related digestive diseases and their pathophysiology. Gut Liver 2017; 11(3): 323–334. doi: 10.5009/ gnl15557.

56. Genser L, Aguanno D, Soula HA et al. Increased jejunal permeability in human obesity is revealed by a lipid challenge and is linked to inflammation and type 2 diabetes. J Pathol 2018; 246(2): 217–230. doi: 10.1002/ path.5134.

57. Harper JW, Zisman TL. Interaction of obesity and inflammatory bowel disease. World J Gastroenterol 2016; 22(35): 7868–7881. doi: 10.3748/ wjg.v22.i35.7868.

57. Crohn BB, Ginzburg L, Oppenheimer GD. Regional ileitis: a pathologic and clinical entity. JAMA 1932; 99: 1323–1329.

58. Desreumaux P, Ernst O, Geboes K et al. Inflammatory alterations in mesenteric adipose tissue in Crohn’s disease. Gastroenterology1999; 117(1): 73–81. doi: 10.1016/ s0016-508 5(99)70552-4.

59. Sheehan AL, Warren BF, Gear MW et al. Fat-wrapping in Crohn’s disease: pathological basis and relevance to surgical practice. Br J Surg 1992; 79(9): 955–958. doi: 10.1002/ bjs.1800790934.

60. Peyrin-Biroulet L, Chamaillard M, Gonzalez F et al. Mesenteric fat in Crohn’s disease: a pathogenetic hallmark or an innocent bystander? Gut 2007; 56(4): 577–583. doi: 10.1136/ gut. 2005.082925.

61. Fink C, Karagiannides I, Bakirtzi K et al. Adipose tissue and inflammatory bowel disease pathogenesis. Inflamm Bowel Dis 2012; 18(8): 1550–1557. doi: 10.1002/ ibd.22893.

62. Peyrin-Biroulet L, Gonzalez F, Dubuquoy L et al. Mesenteric fat as a source of C reactive protein and as a target forbacterial translocation in Crohn’s disease. Gut 2012; 61(1): 78–85. doi: 10.1136/ gutjnl-2011-300370.

63. Kaser A, Tilg H. “Metabolic aspects” in inflammatory bowel diseases. Curr Drug Deliv 2012; 9(4): 326–332. doi: 10.2174/ 156720112801323044.

64. Mao R, Kurada S, Gordon IO et al. The mesenteric fat and intestinal muscle interface: creeping fat influencing stricture formation in Crohn’s disease. Inflamm Bowel Dis 2019; 25(3): 421–426. doi: 10.1093/ ibd/ izy331.

65. Westcott ED, Mattacks CA, Windsor ACJ et al. Perinodal adipose tissue and fatty acid composition of lymphoid tissues in patients with and without Crohn’s disease and their implications for the etiology and treatment of CD. Ann NY Acad Sci 2006; 1072: 395–400. doi: 10.1196/ annals.1326.034.

66. Bilski J, Mazur-Bialy A, Wojcik D et al. Role of obesity, mesenteric adipose tissue, and adipokies in inflammatory bowel diseases. Biomolecules 2019; 9(12): 780. doi: 10.3390/ biom9120780.

67. Kredel LI, Batra A, Stroh T et al. Adipokines from local fat cells shape the macrophage compartment of the creeping fat in Crohn’s disease. Gut 2013; 62(6): 852–862. doi: 10.1136/ gutjnl-2011-301424.

68. Tilg H, Kaser A. Gut microbiome, obesity, and metabolic dysfunction. J Clin Invest 2011; 121(6): 2126–2132. doi: 10.1172/ JCI58109.

69. Batra A, Heimesaat MM, Bereswill S et al. Mesenteric fat – control site for bacterial translocation in colitis? Mucosal Immunol 2012; 5(5): 580–591. doi: 10.1038/ mi.2012.33.

70. Batra A, Zeitz M, Siegmund B. Adipokine signaling in inflammatory bowel disease. Inflamm Bowel Dis 2009; 15(12): 1897–1905. doi: 10.1002/ ibd.20937.

71. Kruis T, Batra A, Siegmund B. Bacterial translocation – impact on the adipocyte compartment. Front Immunol 2014; 4: 510. doi: 10.3389/ fimmu.2013.00510.

72. Sideri A, Bakirtzi K, Shih DQ et al. Substance P mediates pro-inflammatory cytokine release form mesenteric adipocytes in inflammatory bowel disease patients. Cell Mol Gastroenterol Hepatol 2015; 1(4): 420–432. doi: 10.1016/ j.jcmgh.2015.03.003.

73. Drouet M, Dubuquoy L, Desreumaux P et al. Visceral fat and gut inflammation. Nutrition 2012; 28(2): 113–117. doi: 10.1016/ j.nut.2011.09.009.

74. Acedo SC, Gotardo EMF, Lacerda JM et al. Perinodal adipose tissue and mesenteric lymph node activation during reactivated TNBS-colitis in rats. Dig Dis Sci 2011; 56(9): 2545–2552. doi: 10.1007/ s10620-011-1644-8.

75. Gewirtz AT. Deciphering the role of mesenteric fat in inflammatory bowel disease. Cell Mol Gastroenterol Hepatol 2015; 1(4): 352–353. doi: 10.1016/ j.jcmgh.2015.05.004.

76. Vermeire S, Van Assche G, Rutgeerts P. The role of C-reactive protein as an inflammatory marker ingastrointestinal diseases. Nat Clin Pract Gastroenterol Hepatol 2005; 2(12): 580–586. doi: 10.1038/ ncpgasthep0359.

77. Zulian A, Cancello R, Micheletto G et al. Visceral adipocytes: old actors in obesity and new protagonists in Crohn’s disease? Gut 2012; 61(1): 86–94. doi: 10.1136/ gutjnl-2011-300391.

78. Zulian A, Cancello R, Ruocco C et al. Differences in visceral fat and fat bacterial colonization between ulcerative colitis and Crohn’sdisease. An in vivo and in vitro study. PLoS One 2013; 8(10): e78495. doi: 10.1371/ journal.pone.0078495.

79. Charrière G, Cousin B, Arnaud E et al. Preadipocyte conversion to macrophage. Evidence of plasticity. J Biol Chem 2003; 278(11): 9850–9855. doi: 10.1074/ jbc.M210811200.

80. Xu H, Barnes GT, Yang Q et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112(12): 1821–1830. doi: 10.1172/ JCI19451.

81. Morshedzadeh N, Rahimlou M, Asadzadeh AH et al. Association between adipokines levels with inflammatory bowel disease (IBD): systematic reviews. Dig Dis Sci 2017; 62(12): 3280–3286. doi: 10.1007/ s10620-017-4806-5.

82. Azamar-Llamas D, Hernández-Molina G, Ramos-Ávalos B et al. Adipokine contribution to the pathogenesis of osteoarthritis. Mediators Inflamm 2017; 2017: 5468023. doi: 10.1155/ 2017/ 5468023.

83. Graßmann S, Wirsching J, Eichelmann F et al. Association between peripheral adipokines and inflammation markers: a systematic review and meta-analysis. Obesity (Silver Spring) 2017; 25(10): 1176–1785. doi: 10.1002/ oby.21945.

84. Biesiada G, Czepiel J, Ptak-Belowska A et al. Expression and release of leptin and proinflammatory cytokines in patients with ulcerative colitis and infectious diarrhea. J Physiol Pharmacol 2012; 63(5): 471–481.

85. Tuzun A, Uygun A, Yesilova Z et al. Leptin levels in the acute stage of ulcerative colitis. J Gastroenterol Hepatol 2004; 19(4): 429–432. doi: 10.1111/ j.1440-1746.2003.03300.x.

86. Barbier M, Vidal H, Desreumaux P et al. Overexpression of leptin mRNA in mesenteric adipose tissue in inflammatory bowel diseases. Gastroenterol Clin Biol 2003; 27(11): 987–991.

87. Paul G, Schäffler A, Neumeier M et al. Profiling adipocytokine secretion from creeping fat in Crohn’s disease. Inflamm Bowel Dis 2006; 12(6): 471–477. doi: 10.1097/ 00054725-200606 000-00005.

88. Kahraman R, Calhan T, Sahin A et al. Are adipocytokines inflammatory or metabolic mediators in patients with inflammatory bowel disease? Ther Clin Risk Manag 2017; 13: 1295–1301. doi: 10.2147/ TCRM.S140618.

89. Valentini L, Wirth EK, Schweizer U et al. Circulating adipokines and the protective effects of hyperinsulinemia in inflammatory bowel disease. Nutrition 2009; 25(2): 172–181. doi: 10.1016/ j.nut.2008.07.020.

90. Karmiris K, Koutroubakis IE, Xidakis C et al. Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease. Inflamm Bowel Dis 2006; 12(2): 100–105. doi: 10.1097/ 01.MIB.0000200345.38837.46.

91. Yamamoto K, Kiyohara T, Murayama Y et al. Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn’s disease. Gut 2005; 54(6): 789–796. doi: 10.1136/ gut.2004.046516.

92. Al-Suhaimi EA, Shehzad A. Leptin, resistin and visfatin: the missing link between endocrine metabolic disorders and immunity. Eur J Med Res 2013; 18(1): 12. doi: 10.1186/ 2047-783X-18-12.

93. Karmiris K, Koutroubakis IE, Xidakis C et al. The effect of infliximab on circulating levels of leptin, adiponectin and resistin in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2007; 19(9): 789–794. doi: 10.1097/ MEG.0b013e3282202bca.

94. Han S, Wang G, Qiu S et al. Increased colonic apelin production in rodents with experimental colitis and in humans with IBD. Regul Pept 2007; 142(3): 131–137. doi: 10.1016/ j.regpep.2007.02.002.

95. Ge Y, Li Y, Chen Q et al. Adipokine apelin ameliorates chronic colitis in Il-10−/ −mice by promoting intestinal lymphatic functions. Biochem Pharmacol 2018; 148: 202–212. doi: 10.1016/ j.bcp.2018.01.011.

96. Weigert J, Obermeier F, Neumeier M et al. Circulating levels of chemerin and adiponectin are higher in ulcerative colitis and chemerin is elevated in Crohn’s disease. Inflamm Bowel Dis 2010; 16(4): 630–637. doi: 10.1002/ ibd.21091.

97. Terzoudis S, Malliaraki N, Damilakis J et al. Chemerin, visfatin, and vaspin serum levels in relation to bone mineral density in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2016; 28(7): 814–819. doi: 10.1097/ MEG.0000000000000617.

98. Waluga M, Hartleb M, Boryczka G et al. Serum adipokines in inflammatory bowel disease. World J Gastroenterol 2014; 20(22): 6912–6917. doi: 10.3748/ wjg.v20.i22.6912.

99. Dogan S, Guven K, Celikbilek M et al. Serum visfatin levels in ulcerative colitis. J Clin Lab Anal 2016; 30(5): 552–556. doi: 10.1002/ jcla.21901.

100. Moschen AR, Kaser A, Enrich B et al. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol 2007; 178(3): 1748–1758. doi: 10.4049/ jimmunol.178.3.1748.

101. Starr AE, Deeke SA, Ning Z et al. Proteomic analysis of ascending colon biopsies from a paediatric inflammatory bowel disease inception cohort identifies protein biomarkers that differentiate Crohn’s disease from UC. Gut 2017; 66(9): 1573–1583. doi: 10.1136/ gutjnl-2015-310705.

102. DeClercq V, Langille MGI, Van Limbergen J. Differences in adiposity and diet quality among individuals with inflammatory bowel disease in Eastern Canada. PLoS One 2018; 13(7): e0200580. doi: 10.1371/ journal.pone.0200580.

103. González-Muniesa P, Mártinez-González MA, Hu FB et al. Obesity. Nat Rev Dis Primers 2017; 3: 17034. doi: 10.1038/ nrdp.2017.34.

104. Shoda R, Matsueda K, Yamato S et al. Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr 1996; 63(5): 741–745. doi: 10.1093/ ajcn/ 63.5.741.

105. Hou JK, Abraham B, El-Serag H. Dietary intake and risk of developing inflammatory bowel disease: A systematic review of the literature. Am J Gastroenterol 2011; 106(4): 563–573. doi: 10.1038/ ajg.2011.44.

106. Wright EK, Kamm MA, Teo SM et al. Recent advances in characterizing the gastrointestinal microbiome in Crohn’s disease: a systematic review. Inflamm Bowel Dis 2015; 21(6): 1219–1228. doi: 10.1097/ MIB.000000000000382.

107. Schaubeck M, Haller D. Reciprocal interaction of diet and microbiome in inflammatory bowel diseases. Curr Opin Gastroenterol 2015; 31(6): 464–470. doi: 10.1097/ MOG.000 000000000216.

108. De Filippo C, Cavalieri D, Di Paola M et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA 2010; 107(33): 14691–14696. doi: 10.1073/ pnas.1005963107.

109. Albenberg LG, Lewis JD, Wu GD. Food and the gut microbiota in inflammatory bowel diseases: a critical connection. Curr Opin Gastroenterol 2012; 28(4): 314–320. doi: 10.1097/ MOG. 0b013e328354586f.

110. Kim A. Dysbiosis: a review highlighting obesity and inflammatory bowel disease. J Clin Gastroenterol 2015; 49(Suppl 1): S20–S24. doi: 10.1097/ MCG.0000000000000356.

111. Ni J, Wu GD, Albenberg L et al. Gut microbiota and IBD: causation or correlation? Nat Rev Gastroenterol Hepatol 2017; 14(10): 573–584. doi: 10.1038/ nrgastro.2017.88.

112. DeGruttola AK, Low D, Mizoguchi A et al. Current understanding of dysbiosis in disease in human and animal models. Inflamm Bowel Dis 2016; 22(5): 1137–1150. doi: 10.1097/ MIB.000 0000000000750.

113. Schink M, Konturek PC, Tietz E et al. Microbial patterns in patients with histamine intolerance. J Physiol Pharmacol 2018; 69(4): 579–593. doi: 10.26402/ jpp.2018.4.09.

114. Pendyala S, Walker JM, Holt PR. A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology 2012; 142(5): 1100–1101. doi: 10.1053/ j.gastro.2012.01.034.

115. Ghanim H, Abuaysheh S, Sia CL et al. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care 2009; 32(12): 2281–2287. doi: 10.2337/ dc09-0979.

116. Maciejewska D, Skonieczna-Zydecka K, Lukomska A et al. The short chain fatty acids and lipopolysaccharides status in Sprague-Dawley rats fed with high-fat and high-cholesterol diet. J Physiol Pharmacol 2018; 69(2): 6. doi: 10.26402/ jpp.2018.2.05.

117. Singh S, Proudfoot J, Xu R et al. Obesity and response to infliximab in patients with inflammatory bowel diseases: pooled analysis of individual participant data from clinical trials. Am J Gastroenterol 2018; 113(6): 883–889. doi: 10.1038/ s41395-018-0104-x.

118. Bhalme M, Sharma A, Keld R et al. Does weight-adjusted anti-tumour necrosis factor treatment favour obese patients with Crohn’s disease? Eur J Gastroenterol Hepatol 2013; 25(5): 543–549. doi: 10.1097/ MEG.0b013e32835d1f15.

119. Dotan I, Ron Y, Yanai H et al. Patient factors that increase infliximab clearance and shorten half-life in inflammatory bowel disease: a population pharmacokinetic study. Inflamm Bowel Dis 2014; 20(12): 2247–2259. doi: 10.1097/ MIB.0000000000000212.

120. Sharma S, Eckert D, Hyams JS et al. Pharmacokinetics and exposure-efficacy relationship of adalimumab in pediatric patients with moderate to severe Crohn’s disease: results from a randomized, multicenter, phase-3 study. Inflamm Bowel Dis 2015; 21(4): 783–792. doi: 10.1097/ MIB.0000000000000327.

121. Colombel JF, Sandborn WJ, Allez M et al. Association between plasma concentrations of certolizumab pegol and endoscopic outcomes of patients with Crohn’s disease. Clin Gastroenterol Hepatol 2014; 12(3): 423–431. doi: 10.1016/ j.cgh.2013.10.025.

122. Xu ZH, Lee H, Vu T et al. Population pharmacokinetics of golimumab in patients with ankylosing spondylitis: impact of body weight and immunogenicity. Int J Clin Pharmacol Ther 2010; 48(9): 596–607. doi: 10.5414/ cpp48596.

123. Rosario M, Dirks NL, Gastonguay MR et al. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn’s disease. Aliment Pharmacol Ther 2015; 42(2): 188–202. doi: 10.1111/ apt.13243.

124. Swanson SM, Harper J, Zisman TL. Obesity and inflammatory bowel disease: diagnostic and therapeutic implications. Curr Opin Gastroenterol 2018; 34(2): 112–119. doi: 10.1097/ MOG.0000000000000422.

125. Harper JW, Sinanan MN, Zisman TL. Increased body mass index is associated with earlier time to loss of response to infliximab in patients with inflammatory bowel disease. Inflamm Bowel Dis 2013; 19(10): 2118–2124. doi: 10.1097/ MIB.0b013e31829cf401.

126. Bultman E, de Haar C, van Liere-Baron A et al. Predictors of dose escalation of adalimumab in a prospective cohort of Crohn’s disease patients. Aliment Pharmacol Ther 2012; 35(3): 335–341. doi: 10.1111/ j.1365-2036.2011.04946.x.

127. Klaasen R, Wijbrandts CA, Gerlag DM et al. Body mass index and clinical response to infliximab in rheumatoid arthritis. Arthritis Rheum 2011; 63(2): 359–364. doi: 10.1002/ art.30136.

128. Gremese E, Carletto A, Padovan M et al. Obesity and reduction of the response rate to anti-tumor necrosis factor á in rheumatoid arthritis: an approach to a personalized medicine. Arthritis Care Res (Hoboken) 2013; 65(1): 94–100. doi: 10.1002/ acr.21768.

129. Eder L, Thavaneswaran A, Chandran V et al. Obesity is associated with a lower probability of achieving sustained minimal disease activity state among patients with psoriatic arthritis. Ann Rheum Dis 2015; 74(5): 813–817. doi: 10.1136/ annrheumdis-2013-204448.

130. Poon SS, Asher R, Jackson R et al. Body mass index and smoking affect thioguanine nucleotide levels in inflammatory bowel disease. J Crohns Colitis 2015; 9(8): 640–646. doi: 10.1093/ ecco-jcc/ jjv084.

131. Makino T, Shukla PJ, Rubino F et al. The impact of obesity on perioperative outcomes after laparoscopic colorectal resection. Ann Surg 2012; 255(2): 228–236. doi: 10.1097/ SLA.0b013 e31823dcbf7.

132. Jain A, Limketkai BN, Hutfless S. The effect of obesity on post-surgical complications during hospitalizations for inflammatory bowel disease: a nationwide analysis. Gastroenterology 2014; 146(5): S595–S596.

133. Ding Z, Wu XR, Remer EM et al. Association between high visceral fat area and postoperative complications in patients with Crohn’s disease following primary surgery. Colorectal Dis 2016; 18(2): 163–172. doi: 10.1111/ codi.13128.

134. Colombo F, Rizzi A, Ferrari C et al. Bariatric surgery in patients with inflammatory bowel disease: an accessible path? Report of a case series and review of the literature. J Crohns Colitis 2015; 9(2): 185–190. doi: 10.1093/ ecco-jcc/ jju011.

135. Aminian A, Andalib A, Ver MR et al. Outcomes of bariatric surgery in patients with inflammatory bowel disease. Obes Surg 2016; 26(6): 1186–1190. doi: 10.1007/ s11695-015-1909-y.