Enterale Ernährungstherapien beim pädiatrischen M.
                    Crohn Anwendungen und Wirkweise

André Hörning; Anjona Schmidt-Choudhury

doi:10.1055/a-2062-9552

Aktuelle Ernährungsmedizin, Table of Contents

Aktuelle Ernährungsmedizin 2023; 48(03): 183-194
DOI: 10.1055/a-2062-9552

Übersicht

Enterale Ernährungstherapien beim pädiatrischen M. Crohn Anwendungen und Wirkweise

Enteral Nutrition Therapies in Children with Crohn’s Disease – Current Strategies and Possible Modes of Action

André Hörning

¹Pädiatrische Gastroenterologie, Hepatologie und Endoskopie, Klinik für Kinder- und Jugendmedizin, Universitätsklinik Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg

,

Anjona Schmidt-Choudhury

²Pädiatrische Gastroenterologie und Hepatologie, Klinik für Kinder- und Jugendmedizin, Katholisches Klinikum Bochum, Universitätsklinikum der Ruhr-Universität Bochum

› Author Affiliations

Abstract

Zusammenfassung

Die Inzidenz chronisch-entzündlicher Darmerkrankungen (CED), insbesondere des Morbus Crohn, nimmt weltweit deutlich zu. Externe Umweltfaktoren, einschließlich der alltäglichen westlich-industrialisierten Ernährung, welche sich u. a. durch einen hohen Anteil prozessierter industriell hergestellter Lebensmittel auszeichnet, spielen eine Schlüsselrolle im Pathomechanismus der Krankheit.

Ernährungsspezifische Maßnahmen nehmen seit jeher eine zentrale Rolle bei der Behandlung der CED ein. Der erfolgreiche Einsatz der exklusiven enteralen Ernährung (EET), die als Induktionstherapie der ersten Wahl bei pädiatrischem Morbus Crohn (MC) gilt, spricht deutlich für einen Zusammenhang zwischen Ernährung und CED. Die EET wird alleinig oder im Verlauf der Erkrankung und auch beim hochaktiven MC in Kombination mit Immunmodulatoren eingesetzt. Einziger Nachteil dieser hocheffizienten Ernährungstherapie ist die Geschmacksmonotonie, die eine reduzierte Therapieadhärenz mit sich bringt. Die intestinale Mikrobiota und deren Stoffwechselaktivität (Mikrobiom) scheinen ebenso eine wichtige Rolle für die Pathogenese zu spielen, da Kinder und Jugendliche mit Morbus Crohn oder Colitis ulcerosa diesbezüglich häufig ausgeprägte Veränderungen aufweisen. Es ist bekannt, dass die Zusammensetzung der intestinalen Mikrobiota stark von der Ernährung beeinflusst wird. Auch die EET kann durch Ausschluss potenziell schädlicher Nahrungsbestandteile die Darmmikrobiota modifizieren und zur mukosalen Heilung führen.

Diätetische Interventionen könnten demnach eine sehr nebenwirkungsarme Möglichkeit darstellen, den MC zu behandeln und der Manifestation bei genetisch prädisponierten Individuen möglicherweise sogar vorzubeugen. Auf der Grundlage der Nährstoffzusammensetzung der EET hat daher die Suche nach einer geschmacklich verbesserten und gleichzeitig wirksamen Diät begonnen, die Ergebnisse dieser alternativen Ernährungsstrategien erscheinen vielversprechend.

Dieser Übersichtsartikel soll den Wirkmechanismus der exklusiven enteralen Eliminationsdiät und moderner ernährungsmedizinischer Therapiestrategien aufzeigen sowie den aktuellen Stand der wissenschaftlichen Erkenntnisse, die deren Wirksamkeit bei der Behandlung des pädiatrischen MC belegen, zusammenfassen. Insbesondere sollen dabei die möglichen pathophysiologischen Mechanismen, die der Remissionsinduktion und -erhaltung zugrunde liegen, auch im Hinblick auf Veränderungen des Darmmikrobioms beleuchtet werden.

Abstract

Nutrition has an essential effect on the occurence and course of disease in inflammatory bowel disease.

Several factors as for example breast feeding, fiber intake from fruit as well as the so called „mediterranian diet“ have been identified as being protective with regard to developing IBD. On the other hand, intake of high levels of sugar, raw meat or ultraprocessed food is associated with a higher risk for a manifestation of IBD in genetically predisposed children. Nevertheless, the underlying mechanisms how exclusion diets alone or in combination with medication modulate intestinal microbiota lead to mucosal healing still have to be elucidated. Since there already exists knowledge on the influence of nutrition on treating or preventing IBD this should be implicated in therapeutic and prevention strategies.

Schlüsselwörter

Chronisch-entzündliche Darmerkrankungen - EET - CDED - Mikrobiota

Key words

IBD - nutrition - EET - CDED - microbiota

Full Text

References

Literatur
1 Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn’s disease. Lancet 2017; 389: 1741-1755
2 Ghione S, Sarter H, Fumery M. et al. Dramatic Increase in Incidence of Ulcerative Colitis and Crohn’s Disease (1988-2011): A Population-Based Study of French Adolescents. Am J Gastroenterol 2018; 113: 265-272
3 Roberts SE, Thorne K, Thapar N. et al. A Systematic Review and Meta-analysis of Paediatric Inflammatory Bowel Disease Incidence and Prevalence Across Europe. J Crohns Colitis 2020; 14: 1119-1148
4 Benchimol EI, Manuel DG, Guttmann A. et al. Changing age demographics of inflammatory bowel disease in Ontario, Canada: a population-based cohort study of epidemiology trends. Inflamm Bowel Dis 2014; 20: 1761-1769
5 Jostins L, Ripke S, Weersma RK. et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491: 119-124
6 McGovern DP, Kugathasan S, Cho JH. Genetics of Inflammatory Bowel Diseases. Gastroenterology 2015; 149: 116376 e2
7 Duricova D, Burisch J, Jess T. et al. Age-related differences in presentation and course of inflammatory bowel disease: an update on the population-based literature. J Crohns Colitis 2014; 8: 1351-1361
8 Van Limbergen J, Russell RK, Drummond HE. et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology 2008; 135: 1114-1122
9 Jakobsen C, Bartek J, Wewer V. et al. Differences in phenotype and disease course in adult and paediatric inflammatory bowel disease – a population-based study. Aliment Pharmacol Ther 2011; 34: 1217-1224
10 Kelsen J, Baldassano RN. Inflammatory bowel disease: the difference between children and adults. Inflamm Bowel Dis 2008; 14: S9-S11
11 Borrelli O, Cordischi L, Cirulli M. et al. Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn’s disease: a randomized controlled open-label trial. Clin Gastroenterol Hepatol 2006; 4: 744-753
12 Pigneur B, Lepage P, Mondot S. et al. Mucosal Healing and Bacterial Composition in Response to Enteral Nutrition Vs Steroid-based Induction Therapy-A Randomised Prospective Clinical Trial in Children With Crohn’s Disease. J Crohns Colitis 2019; 13: 846-855
13 van Rheenen PF, Aloi M, Assa A. et al. The Medical Management of Paediatric Crohn’s Disease: an ECCO-ESPGHAN Guideline Update. J Crohns Colitis. 2020
14 Levine A, Sigall Boneh R, Wine E. Evolving role of diet in the pathogenesis and treatment of inflammatory bowel diseases. Gut 2018; 67: 1726-1738
15 Lewis JD, Abreu MT. Diet as a Trigger or Therapy for Inflammatory Bowel Diseases. Gastroenterology 2017; 152: 398-414 e6
16 Khalili H, Hakansson N, Chan SS. et al. Adherence to a Mediterranean diet is associated with a lower risk of later-onset Crohn’s disease: results from two large prospective cohort studies. Gut 2020; 69: 1637-1644
17 Devkota S, Wang Y, Musch MW. et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/-mice. Nature 2012; 487: 104-108
18 Celiberto LS, Graef FA, Healey GR. et al. Inflammatory bowel disease and immunonutrition: novel therapeutic approaches through modulation of diet and the gut microbiome. Immunology 2018; 155: 36-52
19 Rosen MJ, Dhawan A, Saeed SA. Inflammatory Bowel Disease in Children and Adolescents. JAMA Pediatr 2015; 169: 1053-1060
20 Peloquin JM, Goel G, Villablanca EJ, Xavier RJ. Mechanisms of Pediatric Inflammatory Bowel Disease. Annu Rev Immunol 2016; 34: 31-64
21 McCole DF. IBD candidate genes and intestinal barrier regulation. Inflamm Bowel Dis 2014; 20: 1829-1849
22 Kleessen B, Kroesen AJ, Buhr HJ, Blaut M. Mucosal and invading bacteria in patients with inflammatory bowel disease compared with controls. Scand J Gastroenterol 2002; 37: 1034-1041
23 Zaidi D, Bording-Jorgensen M, Huynh HQ. et al. Increased Epithelial Gap Density in the Noninflamed Duodenum of Children With Inflammatory Bowel Diseases. J Pediatr Gastroenterol Nutr 2016; 63: 644-650
24 Zaidi D, Huynh HQ, Carroll MW. et al. Gut Microenvironment and Bacterial Invasion in Paediatric Inflammatory Bowel Diseases. J Pediatr Gastroenterol Nutr 2020; 71: 624-632
25 Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2021; 18: 56-66
26 De Filippo C, Di Paola M, Ramazzotti M. et al. Diet, Environments, and Gut Microbiota. A Preliminary Investigation in Children Living in Rural and Urban Burkina Faso and Italy. Front Microbiol 2017; 8: 1979
27 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 U S A 2010; 107: 14691-14696
28 Li T, Qiu Y, Yang HS. et al. Systematic review and meta-analysis: Association of a pre-illness Western dietary pattern with the risk of developing inflammatory bowel disease. J Dig Dis 2020; 21: 362-371
29 Huang H, Fang M, Jostins L. et al. Fine-mapping inflammatory bowel disease loci to single-variant resolution. Nature 2017; 547: 173-178
30 de Lange KM, Moutsianas L, Lee JC. et al. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet 2017; 49: 256-261
31 Turpin W, Goethel A, Bedrani L, Croitoru Mdcm K. Determinants of IBD Heritability: Genes, Bugs, and More. Inflamm Bowel Dis 2018; 24: 1133-1148
32 Bevins CL, Salzman NH. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 2011; 9: 356-368
33 Salzman NH, Bevins CL. Dysbiosis – a consequence of Paneth cell dysfunction. Semin Immunol 2013; 25: 334-341
34 Khalili H, Chan SSM, Lochhead P. et al. The role of diet in the aetiopathogenesis of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2018; 15: 525-535
35 Statovci D, Aguilera M, MacSharry J, Melgar S. The Impact of Western Diet and Nutrients on the Microbiota and Immune Response at Mucosal Interfaces. Front Immunol 2017; 8: 838
36 D’Souza S, Levy E, Mack D. et al. Dietary patterns and risk for Crohn’s disease in children. Inflamm Bowel Dis 2008; 14: 367-373
37 Jakobsen C, Paerregaard A, Munkholm P, Wewer V. Environmental factors and risk of developing paediatric inflammatory bowel disease – a population based study 2007-2009. J Crohns Colitis 2013; 7: 79-88
38 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: 563-573
39 Wark G, Samocha-Bonet D, Ghaly S, Danta M. The Role of Diet in the Pathogenesis and Management of Inflammatory Bowel Disease: A Review. Nutrients 2020; 13
40 Narula N, Wong ECL, Dehghan M. et al. Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study. BMJ 2021; 374: n1554
41 Ng SC, Shi HY, Hamidi N. et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2017; 390: 2769-2778
42 Kaplan GG, Ng SC. Understanding and Preventing the Global Increase of Inflammatory Bowel Disease. Gastroenterology 2017; 152: 313-21 e2
43 Misra R, Faiz O, Munkholm P. et al. Epidemiology of inflammatory bowel disease in racial and ethnic migrant groups. World J Gastroenterol 2018; 24: 424-437
44 Shoda R, Matsueda K, Yamato S, Umeda N. 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: 741-745
45 Amre DK, D’Souza S, Morgan K. et al. Imbalances in dietary consumption of fatty acids, vegetables, and fruits are associated with risk for Crohn’s disease in children. Am J Gastroenterol 2007; 102: 2016-2025
46 Ananthakrishnan AN, Khalili H, Konijeti GG. et al. Long-term intake of dietary fat and risk of ulcerative colitis and Crohn’s disease. Gut 2014; 63: 776-784
47 Li X, Wei X, Sun Y. et al. High-fat diet promotes experimental colitis by inducing oxidative stress in the colon. Am J Physiol Gastrointest Liver Physiol 2019; 317: G453-G462
48 Ananthakrishnan AN, Khalili H, Konijeti GG. et al. A prospective study of long-term intake of dietary fiber and risk of Crohn’s disease and ulcerative colitis. Gastroenterology 2013; 145: 970-977
49 Canani RB, Costanzo MD, Leone L. et al. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol 2011; 17: 1519-1528
50 Stoeva MK, Garcia-So J, Justice N. et al. Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease. Gut Microbes 2021; 13: 1-28
51 Li J, Butcher J, Mack D, Stintzi A. Functional impacts of the intestinal microbiome in the pathogenesis of inflammatory bowel disease. Inflamm Bowel Dis 2015; 21: 139-153
52 Bischoff SC, Escher J, Hebuterne X. et al. ESPEN practical guideline: Clinical Nutrition in inflammatory bowel disease. Clin Nutr 2020; 39: 632-653
53 Tilg H, Moschen AR. Food, immunity, and the microbiome. Gastroenterology 2015; 148: 1107-1119
54 Desai MS, Seekatz AM, Koropatkin NM. et al. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell 2016; 167: 1339-53 e21
55 Martinez-Medina M, Denizot J, Dreux N. et al. Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation. Gut 2014; 63: 116-124
56 Yue B, Yu ZL, Lv C. et al. Regulation of the intestinal microbiota: An emerging therapeutic strategy for inflammatory bowel disease. World J Gastroenterol 2020; 26: 4378-4393
57 Critch J, Day AS, Otley A. et al. Use of enteral nutrition for the control of intestinal inflammation in pediatric Crohn disease. J Pediatr Gastroenterol Nutr 2012; 54: 298-305
58 Day AS, Lopez RN. Exclusive enteral nutrition in children with Crohn’s disease. World J Gastroenterol 2015; 21: 6809-6816
59 Caio G, Lungaro L, Caputo F. et al. Nutritional Treatment in Crohn’s Disease. Nutrients 2021; 13
60 Scarallo L, Lionetti P. Dietary Management in Pediatric Patients with Crohn’s Disease. Nutrients 2021; 13
61 Cucinotta U, Romano C, Dipasquale V. Diet and Nutrition in Pediatric Inflammatory Bowel Diseases. Nutrients 2021; 13
62 Green N, Miller T, Suskind D, Lee D. A Review of Dietary Therapy for IBD and a Vision for the Future. Nutrients 2019; 11
63 Verburgt CM, Ghiboub M, Benninga MA. et al. Nutritional Therapy Strategies in Pediatric Crohn’s Disease. Nutrients 2021; 13
64 Levine A, Wine E, Assa A. et al. Crohn’s Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial. Gastroenterology 2019; 157: 440-50 e8
65 Svolos V, Hansen R, Nichols B. et al. Treatment of Active Crohn’s Disease With an Ordinary Food-based Diet That Replicates Exclusive Enteral Nutrition. Gastroenterology 2019; 156: 1354-1367 e6
66 Akobeng AK, Miller V, Stanton J. et al. Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn’s disease. J Pediatr Gastroenterol Nutr 2000; 30: 78-84
67 Sakurai T, Matsui T, Yao T. et al. Short-term efficacy of enteral nutrition in the treatment of active Crohn’s disease: a randomized, controlled trial comparing nutrient formulas. JPEN J Parenter Enteral Nutr 2002; 26: 98-103
68 Rubio A, Pigneur B, Garnier-Lengline H. et al. The efficacy of exclusive nutritional therapy in paediatric Crohn’s disease, comparing fractionated oral vs. continuous enteral feeding. Aliment Pharmacol Ther 2011; 33: 1332-1339
69 Connors J, Basseri S, Grant A. et al. Exclusive Enteral Nutrition Therapy in Paediatric Crohn’s Disease Results in Long-term Avoidance of Corticosteroids: Results of a Propensity-score Matched Cohort Analysis. J Crohns Colitis 2017; 11: 1063-1070
70 Adamji M, Day AS. An overview of the role of exclusive enteral nutrition for complicated Crohn’s disease. Intest Res 2019; 17: 171-176
71 Belli DC, Seidman E, Bouthillier L. et al. Chronic intermittent elemental diet improves growth failure in children with Crohn’s disease. Gastroenterology 1988; 94: 603-610
72 Johnson T, Macdonald S, Hill SM. et al. Treatment of active Crohn’s disease in children using partial enteral nutrition with liquid formula: a randomised controlled trial. Gut 2006; 55: 356-361
73 Lee D, Baldassano RN, Otley AR. et al. Comparative Effectiveness of Nutritional and Biological Therapy in North American Children with Active Crohn’s Disease. Inflamm Bowel Dis 2015; 21: 1786-1793
74 Logan M, Clark CM, Ijaz UZ. et al. The reduction of faecal calprotectin during exclusive enteral nutrition is lost rapidly after food re-introduction. Aliment Pharmacol Ther 2019; 50: 664-674
75 Urlep D, Benedik E, Brecelj J, Orel R. Partial enteral nutrition induces clinical and endoscopic remission in active pediatric Crohn’s disease: results of a prospective cohort study. Eur J Pediatr 2020; 179: 431-438
76 Sigall Boneh R, Sarbagili Shabat C, Yanai H. et al. Dietary Therapy With the Crohn’s Disease Exclusion Diet is a Successful Strategy for Induction of Remission in Children and Adults Failing Biological Therapy. J Crohns Colitis 2017; 11: 1205-1212
77 Sigall-Boneh R, Pfeffer-Gik T, Segal I. et al. Partial enteral nutrition with a Crohn’s disease exclusion diet is effective for induction of remission in children and young adults with Crohn’s disease. Inflamm Bowel Dis 2014; 20: 1353-1360
78 Yanai H, Levine A, Hirsch A. et al. The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol 2022; 7: 49-59
79 Sabino J, Lewis JD, Colombel JF. Treating Inflammatory Bowel Disease With Diet: A Taste Test. Gastroenterology 2019; 157: 295-297
80 Olendzki BC, Silverstein TD, Persuitte GM. et al. An anti-inflammatory diet as treatment for inflammatory bowel disease: a case series report. Nutr J 2014; 13: 5
81 Sasson AN, Ananthakrishnan AN, Raman M. Diet in Treatment of Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol 2021; 19: 425-435 e3
82 de Laffolie J, Schwerd T, Simon A. et al. Crohn’s Disease Exclusion Diet – an alternative to exlusive enteral nutritional therapy in children and adolescents with Crohn’s disease? Statement of the GPGE working groups CEDATA and Nutrition/Nutrition Medicine]. Z Gastroenterol 2020; 58: 890-894
83 Amenyogbe N, Kollmann TR, Ben-Othman R. Early-Life Host-Microbiome Interphase: The Key Frontier for Immune Development. Front Pediatr 2017; 5: 111
84 Agrawal M, Sabino J, Frias-Gomes C. et al. Early life exposures and the risk of inflammatory bowel disease: Systematic review and meta-analyses. EClinicalMedicine 2021; 36: 100884
85 Xu L, Lochhead P, Ko Y. et al. Systematic review with meta-analysis: breastfeeding and the risk of Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther 2017; 46: 780-789
86 Coker MO, Hoen AG, Dade E. et al. Specific class of intrapartum antibiotics relates to maturation of the infant gut microbiota: a prospective cohort study. BJOG 2020; 127: 217-227
87 Fitzgerald RS, Sanderson IR, Claesson MJ. Paediatric Inflammatory Bowel Disease and its Relationship with the Microbiome. Microb Ecol 2021; 82: 833-844
88 Hill CJ, Lynch DB, Murphy K. et al. Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort. Microbiome 2017; 5: 4
89 Kashtanova DA, Popenko AS, Tkacheva ON. et al. Association between the gut microbiota and diet: Fetal life, early childhood, and further life. Nutrition 2016; 32: 620-627
90 Madan JC, Hoen AG, Lundgren SN. et al. Association of Cesarean Delivery and Formula Supplementation With the Intestinal Microbiome of 6-Week-Old Infants. JAMA Pediatr 2016; 170: 212-219
91 Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009; 9: 799-809
92 de Souza HS, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol 2016; 13: 13-27
93 Kamada N, Seo SU, Chen GY, Nunez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol 2013; 13: 321-335
94 Purchiaroni F, Tortora A, Gabrielli M. et al. The role of intestinal microbiota and the immune system. Eur Rev Med Pharmacol Sci 2013; 17: 323-333
95 Merga Y, Campbell BJ, Rhodes JM. Mucosal barrier, bacteria and inflammatory bowel disease: possibilities for therapy. Dig Dis 2014; 32: 475-483
96 Vindigni SM, Zisman TL, Suskind DL, Damman CJ. The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions. Therap Adv Gastroenterol 2016; 9: 606-625
97 Kellermayer R, Zilbauer M. The Gut Microbiome and the Triple Environmental Hit Concept of Inflammatory Bowel Disease Pathogenesis. J Pediatr Gastroenterol Nutr 2020; 71: 589-595
98 Sheehan D, Moran C, Shanahan F. The microbiota in inflammatory bowel disease. J Gastroenterol 2015; 50: 495-507
99 Gevers D, Kugathasan S, Denson LA. et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 2014; 15: 382-392
100 Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology 2014; 146: 1489-1499
101 Pascal V, Pozuelo M, Borruel N. et al. A microbial signature for Crohn’s disease. Gut 2017; 66: 813-822
102 Schwiertz A, Jacobi M, Frick JS. et al. Microbiota in pediatric inflammatory bowel disease. J Pediatr 2010; 157: 240-244 e1
103 Manichanh C, Rigottier-Gois L, Bonnaud E. et al. Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 2006; 55: 205-211
104 Pittayanon R, Lau JT, Leontiadis GI. et al. Differences in Gut Microbiota in Patients With vs Without Inflammatory Bowel Diseases: A Systematic Review. Gastroenterology 2020; 158: 930-946 e1
105 Liu S, Zhao W, Lan P, Mou X. The microbiome in inflammatory bowel diseases: from pathogenesis to therapy. Protein Cell 2021; 12: 331-345
106 Nishida A, Inoue R, Inatomi O. et al. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin J Gastroenterol 2018; 11: 1-10
107 Schwerd T, Frivolt K, Clavel T. et al. Exclusive enteral nutrition in active pediatric Crohn disease: Effects on intestinal microbiota and immune regulation. J Allergy Clin Immunol 2016; 138: 592-596
108 Yamamoto T, Nakahigashi M, Umegae S. et al. Impact of elemental diet on mucosal inflammation in patients with active Crohn’s disease: cytokine production and endoscopic and histological findings. Inflamm Bowel Dis 2005; 11: 580-588
109 de Jong NS, Leach ST, Day AS. Polymeric formula has direct anti-inflammatory effects on enterocytes in an in vitro model of intestinal inflammation. Dig Dis Sci 2007; 52: 2029-2036
110 Nahidi L, Day AS, Lemberg DA, Leach ST. Differential effects of nutritional and non-nutritional therapies on intestinal barrier function in an in vitro model. J Gastroenterol 2012; 47: 107-117
111 Wedrychowicz A, Kowalska-Duplaga K, Jedynak-Wasowicz U. et al. Serum concentrations of VEGF and TGF-beta1 during exclusive enteral nutrition in IBD. J Pediatr Gastroenterol Nutr 2011; 53: 150-155
112 Triantafillidis JK, Tzouvala M, Triantafyllidi E. Enteral Nutrition Supplemented with Transforming Growth Factor-beta, Colostrum, Probiotics, and Other Nutritional Compounds in the Treatment of Patients with Inflammatory Bowel Disease. Nutrients 2020; 12
113 Lewis JD, Chen EZ, Baldassano RN. et al. Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn’s Disease. Cell Host Microbe 2015; 18: 489-500
114 Lewis JD, Albenberg L, Lee D. et al. The Importance and Challenges of Dietary Intervention Trials for Inflammatory Bowel Disease. Inflamm Bowel Dis 2017; 23: 181-191
115 Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol 2015; 12: 205-217
116 Marion-Letellier R, Amamou A, Savoye G, Ghosh S. Inflammatory Bowel Diseases and Food Additives: To Add Fuel on the Flames!. Nutrients 2019; 11
117 Chassaing B, Koren O, Goodrich JK. et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 2015; 519: 92-96
118 Chassaing B, Compher C, Bonhomme B. et al. Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome. Gastroenterology. 2021
119 Borsani B, De Santis R, Perico V. et al. The Role of Carrageenan in Inflammatory Bowel Diseases and Allergic Reactions: Where Do We Stand?. Nutrients 2021; 13
120 Hart L, Verburgt CM, Wine E. et al. Nutritional Therapies and Their Influence on the Intestinal Microbiome in Pediatric Inflammatory Bowel Disease. Nutrients 2021; 14
121 Matuszczyk M, Kierkus J. Nutritional Therapy in Pediatric Crohn’s Disease-Are We Going to Change the Guidelines?. J Clin Med 2021; 10
122 Ruiz PA, Moron B, Becker HM. et al. Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome. Gut 2017; 66: 1216-1224
123 White JH. Vitamin D deficiency and the pathogenesis of Crohn’s disease. J Steroid Biochem Mol Biol 2018; 175: 23-28
124 Cantorna MT, Rogers CJ, Arora J. Aligning the Paradoxical Role of Vitamin D in Gastrointestinal Immunity. Trends Endocrinol Metab 2019; 30: 459-466
125 Fletcher J, Cooper SC, Ghosh S, Hewison M. The Role of Vitamin D in Inflammatory Bowel Disease: Mechanism to Management. Nutrients 2019; 11
126 Nielsen OH, Rejnmark L, Moss AC. Role of Vitamin D in the Natural History of Inflammatory Bowel Disease. J Crohns Colitis 2018; 12: 742-752
127 Hlavaty T, Krajcovicova A, Payer J. Vitamin D therapy in inflammatory bowel diseases: who, in what form, and how much?. J Crohns Colitis 2015; 9: 198-209
128 Mariamenatu AH, Abdu EM. Overconsumption of Omega-6 Polyunsaturated Fatty Acids (PUFAs) versus Deficiency of Omega-3 PUFAs in Modern-Day Diets: The Disturbing Factor for Their “Balanced Antagonistic Metabolic Functions” in the Human Body. J Lipids 2021; 2021: 8848161