Treatment of active Crohn's Disease with an ordinary food-based diet that replicates exclusive enteral nutrition

Vaios Svolos; Richard Hansen; Ben Nichols; Christopher Quince; Umer Z. Ijaz; Rodanthi T. Papadopoulou; Christine A. Edwards; David Watson; Adel Alghamdi; Asker Brejnrod; Cecilia Ansalone; Hazel Duncan; Lisa Gervais; Rachel Tayler; Jonathan Salmond; Daniele Bolognini; Robert Klopfleisch; Daniel R. Gaya; Simon Milling; Richard K. Russell; Konstantinos Gerasimidis

doi:10.1053/j.gastro.2018.12.002

Treatment of active Crohn's Disease with an ordinary food-based diet that replicates exclusive enteral nutrition

Vaios Svolos, Richard Hansen, Ben Nichols, Christopher Quince, Umer Z. Ijaz, Rodanthi T. Papadopoulou, Christine A. Edwards, David Watson, Adel Alghamdi, Asker Brejnrod, Cecilia Ansalone, Hazel Duncan, Lisa Gervais, Rachel Tayler, Jonathan Salmond, Daniele Bolognini, Robert Klopfleisch, Daniel R. Gaya, Simon Milling, Richard K. RussellKonstantinos Gerasimidis

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Abstract

Background & Aims: Exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn's disease (CD), but its acceptability is limited. There is a need for novel dietary treatments for CD.

Methods: We evaluated the effects of an individualized food-based diet (CD-TREAT), with similar composition to EEN, on the gut microbiome, inflammation, and clinical response in a rat model, healthy adults, and children with relapsing CD. Twenty-five healthy adults randomly received EEN or CD-TREAT for 7 days, followed by a 14-day washout period, followed by the alternate diet. Fecal microbiome and metabolome were assessed before and after each diet. HLA-B7 and HLA-B27 transgenic rats with gut inflammation received EEN, CD-TREAT, or standard chow for 4 weeks. Fecal, luminal, and tissue microbiome, fecal metabolites, and gut inflammation were assessed. Five children with active CD activity received CD-TREAT and their clinical activity and calprotectin were evaluated after 8 weeks of treatment.

Results: For healthy adults, CD-TREAT was easier to comply with and more acceptable than EEN. CD-TREAT induced similar effects to EEN (EEN vs CD-TREAT) on fecal microbiome composition, metabolome, mean total sulfide (increase 133.0 ± 80.5 vs 54.3 ± 47.0 nmol/g), pH (increase 1.3 ± 0.5 vs 0.9 ± 0.6), and the short-chain fatty acids (μmol/g) acetate (decrease 27.4 ± 22.6 vs 21.6 ± 20.4), propionate (decrease 5.7 ± 7.8 vs 5.2 ± 7.9), and butyrate (decrease 7.0 ± 7.4 vs 10.2 ± 8.5). In the rat model, CD-TREAT and EEN produced similar changes in bacterial load (decrease 0.3 ± 0.3 log ₁₀ 16S rRNA gene copies per gram), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score decreases of 1.25 for EEN [P =.015] and 1.0 for CD-TREAT [P =.044] vs chow). In children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent decreases in fecal calprotectin (mean decrease 918 ± 555 mg/kg; P =.002).

Conclusion: CD-TREAT replicates EEN changes in the microbiome, decreases gut inflammation, is well tolerated, and is potentially effective in patients with active CD. ClinicalTrials.gov, numbers NCT02426567 and NCT03171246.

Original language	English
Pages (from-to)	1354-1367.e6
Number of pages	20
Journal	Gastroenterology
Volume	156
Issue number	5
DOIs	https://doi.org/10.1053/j.gastro.2018.12.002
Publication status	Published - Apr 2019

Keywords

Carbohydrate
Inflammatory Bowel Disease
Microbiota
Pediatric Trial

ASJC Scopus subject areas

Hepatology
Gastroenterology

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10.1053/j.gastro.2018.12.002Licence: CC BY

Final Published VersionFinal published version, 4.31 MBLicence: CC BY

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Svolos, V., Hansen, R., Nichols, B., Quince, C., Ijaz, U. Z., Papadopoulou, R. T., Edwards, C. A., Watson, D., Alghamdi, A., Brejnrod, A., Ansalone, C., Duncan, H., Gervais, L., Tayler, R., Salmond, J., Bolognini, D., Klopfleisch, R., Gaya, D. R., Milling, S., ... Gerasimidis, K. (2019). Treatment of active Crohn's Disease with an ordinary food-based diet that replicates exclusive enteral nutrition. Gastroenterology, 156(5), 1354-1367.e6. https://doi.org/10.1053/j.gastro.2018.12.002

@article{3defa06b30e24b2bacce135874617b7c,

title = "Treatment of active Crohn's Disease with an ordinary food-based diet that replicates exclusive enteral nutrition",

abstract = " Background & Aims: Exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn's disease (CD), but its acceptability is limited. There is a need for novel dietary treatments for CD. Methods: We evaluated the effects of an individualized food-based diet (CD-TREAT), with similar composition to EEN, on the gut microbiome, inflammation, and clinical response in a rat model, healthy adults, and children with relapsing CD. Twenty-five healthy adults randomly received EEN or CD-TREAT for 7 days, followed by a 14-day washout period, followed by the alternate diet. Fecal microbiome and metabolome were assessed before and after each diet. HLA-B7 and HLA-B27 transgenic rats with gut inflammation received EEN, CD-TREAT, or standard chow for 4 weeks. Fecal, luminal, and tissue microbiome, fecal metabolites, and gut inflammation were assessed. Five children with active CD activity received CD-TREAT and their clinical activity and calprotectin were evaluated after 8 weeks of treatment. Results: For healthy adults, CD-TREAT was easier to comply with and more acceptable than EEN. CD-TREAT induced similar effects to EEN (EEN vs CD-TREAT) on fecal microbiome composition, metabolome, mean total sulfide (increase 133.0 ± 80.5 vs 54.3 ± 47.0 nmol/g), pH (increase 1.3 ± 0.5 vs 0.9 ± 0.6), and the short-chain fatty acids (μmol/g) acetate (decrease 27.4 ± 22.6 vs 21.6 ± 20.4), propionate (decrease 5.7 ± 7.8 vs 5.2 ± 7.9), and butyrate (decrease 7.0 ± 7.4 vs 10.2 ± 8.5). In the rat model, CD-TREAT and EEN produced similar changes in bacterial load (decrease 0.3 ± 0.3 log 10 16S rRNA gene copies per gram), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score decreases of 1.25 for EEN [P =.015] and 1.0 for CD-TREAT [P =.044] vs chow). In children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent decreases in fecal calprotectin (mean decrease 918 ± 555 mg/kg; P =.002). Conclusion: CD-TREAT replicates EEN changes in the microbiome, decreases gut inflammation, is well tolerated, and is potentially effective in patients with active CD. ClinicalTrials.gov, numbers NCT02426567 and NCT03171246.",

keywords = "Carbohydrate, Inflammatory Bowel Disease, Microbiota, Pediatric Trial",

author = "Vaios Svolos and Richard Hansen and Ben Nichols and Christopher Quince and Ijaz, {Umer Z.} and Papadopoulou, {Rodanthi T.} and Edwards, {Christine A.} and David Watson and Adel Alghamdi and Asker Brejnrod and Cecilia Ansalone and Hazel Duncan and Lisa Gervais and Rachel Tayler and Jonathan Salmond and Daniele Bolognini and Robert Klopfleisch and Gaya, {Daniel R.} and Simon Milling and Russell, {Richard K.} and Konstantinos Gerasimidis",

note = "Publisher Copyright: {\textcopyright} 2019 AGA Institute Vaios Svolos was funded by a PhD studentship from the Glasgow Children Hospital Charity. Rodanthi T. Papadopoulou and Hazel Duncan were funded by the Catherine McEwan Foundation. Ben Nichols was funded from an industrial partnership between the University of Glasgow and Nestle Health Science. Umer Z. Ijaz is funded by a NERC Independent Research Fellowship (NE/L011956/1). Richard Hansen is funded by a Career Researcher Fellowship by NHS Research Scotland. The proprietary feeds used in this study were a donation from Nestle Health Science. Animal experiments were funded by a grant from the Medical Research Council to Simon Milling (MR/N023625/1) and the running costs of the open-label trial were funded by the Cure Crohn{\textquoteright}s Colitis (C3) charity in Scotland. None of the study sponsors had a role in the study design, data collection, analysis, and interpretation or any aspects during the write up and publication of this work.",

year = "2019",

month = apr,

doi = "10.1053/j.gastro.2018.12.002",

language = "English",

volume = "156",

pages = "1354--1367.e6",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders",

number = "5",

}

Svolos, V, Hansen, R, Nichols, B, Quince, C, Ijaz, UZ, Papadopoulou, RT, Edwards, CA, Watson, D, Alghamdi, A, Brejnrod, A, Ansalone, C, Duncan, H, Gervais, L, Tayler, R, Salmond, J, Bolognini, D, Klopfleisch, R, Gaya, DR, Milling, S, Russell, RK & Gerasimidis, K 2019, 'Treatment of active Crohn's Disease with an ordinary food-based diet that replicates exclusive enteral nutrition', Gastroenterology, vol. 156, no. 5, pp. 1354-1367.e6. https://doi.org/10.1053/j.gastro.2018.12.002

TY - JOUR

T1 - Treatment of active Crohn's Disease with an ordinary food-based diet that replicates exclusive enteral nutrition

AU - Svolos, Vaios

AU - Hansen, Richard

AU - Nichols, Ben

AU - Quince, Christopher

AU - Ijaz, Umer Z.

AU - Papadopoulou, Rodanthi T.

AU - Edwards, Christine A.

AU - Watson, David

AU - Alghamdi, Adel

AU - Brejnrod, Asker

AU - Ansalone, Cecilia

AU - Duncan, Hazel

AU - Gervais, Lisa

AU - Tayler, Rachel

AU - Salmond, Jonathan

AU - Bolognini, Daniele

AU - Klopfleisch, Robert

AU - Gaya, Daniel R.

AU - Milling, Simon

AU - Russell, Richard K.

AU - Gerasimidis, Konstantinos

N1 - Publisher Copyright: © 2019 AGA Institute Vaios Svolos was funded by a PhD studentship from the Glasgow Children Hospital Charity. Rodanthi T. Papadopoulou and Hazel Duncan were funded by the Catherine McEwan Foundation. Ben Nichols was funded from an industrial partnership between the University of Glasgow and Nestle Health Science. Umer Z. Ijaz is funded by a NERC Independent Research Fellowship (NE/L011956/1). Richard Hansen is funded by a Career Researcher Fellowship by NHS Research Scotland. The proprietary feeds used in this study were a donation from Nestle Health Science. Animal experiments were funded by a grant from the Medical Research Council to Simon Milling (MR/N023625/1) and the running costs of the open-label trial were funded by the Cure Crohn’s Colitis (C3) charity in Scotland. None of the study sponsors had a role in the study design, data collection, analysis, and interpretation or any aspects during the write up and publication of this work.

PY - 2019/4

Y1 - 2019/4

N2 - Background & Aims: Exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn's disease (CD), but its acceptability is limited. There is a need for novel dietary treatments for CD. Methods: We evaluated the effects of an individualized food-based diet (CD-TREAT), with similar composition to EEN, on the gut microbiome, inflammation, and clinical response in a rat model, healthy adults, and children with relapsing CD. Twenty-five healthy adults randomly received EEN or CD-TREAT for 7 days, followed by a 14-day washout period, followed by the alternate diet. Fecal microbiome and metabolome were assessed before and after each diet. HLA-B7 and HLA-B27 transgenic rats with gut inflammation received EEN, CD-TREAT, or standard chow for 4 weeks. Fecal, luminal, and tissue microbiome, fecal metabolites, and gut inflammation were assessed. Five children with active CD activity received CD-TREAT and their clinical activity and calprotectin were evaluated after 8 weeks of treatment. Results: For healthy adults, CD-TREAT was easier to comply with and more acceptable than EEN. CD-TREAT induced similar effects to EEN (EEN vs CD-TREAT) on fecal microbiome composition, metabolome, mean total sulfide (increase 133.0 ± 80.5 vs 54.3 ± 47.0 nmol/g), pH (increase 1.3 ± 0.5 vs 0.9 ± 0.6), and the short-chain fatty acids (μmol/g) acetate (decrease 27.4 ± 22.6 vs 21.6 ± 20.4), propionate (decrease 5.7 ± 7.8 vs 5.2 ± 7.9), and butyrate (decrease 7.0 ± 7.4 vs 10.2 ± 8.5). In the rat model, CD-TREAT and EEN produced similar changes in bacterial load (decrease 0.3 ± 0.3 log 10 16S rRNA gene copies per gram), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score decreases of 1.25 for EEN [P =.015] and 1.0 for CD-TREAT [P =.044] vs chow). In children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent decreases in fecal calprotectin (mean decrease 918 ± 555 mg/kg; P =.002). Conclusion: CD-TREAT replicates EEN changes in the microbiome, decreases gut inflammation, is well tolerated, and is potentially effective in patients with active CD. ClinicalTrials.gov, numbers NCT02426567 and NCT03171246.

AB - Background & Aims: Exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn's disease (CD), but its acceptability is limited. There is a need for novel dietary treatments for CD. Methods: We evaluated the effects of an individualized food-based diet (CD-TREAT), with similar composition to EEN, on the gut microbiome, inflammation, and clinical response in a rat model, healthy adults, and children with relapsing CD. Twenty-five healthy adults randomly received EEN or CD-TREAT for 7 days, followed by a 14-day washout period, followed by the alternate diet. Fecal microbiome and metabolome were assessed before and after each diet. HLA-B7 and HLA-B27 transgenic rats with gut inflammation received EEN, CD-TREAT, or standard chow for 4 weeks. Fecal, luminal, and tissue microbiome, fecal metabolites, and gut inflammation were assessed. Five children with active CD activity received CD-TREAT and their clinical activity and calprotectin were evaluated after 8 weeks of treatment. Results: For healthy adults, CD-TREAT was easier to comply with and more acceptable than EEN. CD-TREAT induced similar effects to EEN (EEN vs CD-TREAT) on fecal microbiome composition, metabolome, mean total sulfide (increase 133.0 ± 80.5 vs 54.3 ± 47.0 nmol/g), pH (increase 1.3 ± 0.5 vs 0.9 ± 0.6), and the short-chain fatty acids (μmol/g) acetate (decrease 27.4 ± 22.6 vs 21.6 ± 20.4), propionate (decrease 5.7 ± 7.8 vs 5.2 ± 7.9), and butyrate (decrease 7.0 ± 7.4 vs 10.2 ± 8.5). In the rat model, CD-TREAT and EEN produced similar changes in bacterial load (decrease 0.3 ± 0.3 log 10 16S rRNA gene copies per gram), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score decreases of 1.25 for EEN [P =.015] and 1.0 for CD-TREAT [P =.044] vs chow). In children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent decreases in fecal calprotectin (mean decrease 918 ± 555 mg/kg; P =.002). Conclusion: CD-TREAT replicates EEN changes in the microbiome, decreases gut inflammation, is well tolerated, and is potentially effective in patients with active CD. ClinicalTrials.gov, numbers NCT02426567 and NCT03171246.

KW - Carbohydrate

KW - Inflammatory Bowel Disease

KW - Microbiota

KW - Pediatric Trial

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U2 - 10.1053/j.gastro.2018.12.002

DO - 10.1053/j.gastro.2018.12.002

M3 - Article

C2 - 30550821

AN - SCOPUS:85063389989

SN - 0016-5085

VL - 156

SP - 1354-1367.e6

JO - Gastroenterology

JF - Gastroenterology

IS - 5

ER -

Treatment of active Crohn's Disease with an ordinary food-based diet that replicates exclusive enteral nutrition

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