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

Vaios Svolos; Richard Hansen; Ben Nichols; Chrisopher 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, Chrisopher 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

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

235 Citations (Scopus)

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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 received CD-TREAT with clinical activity and fecal calprotectin evaluated after 8-week treatment.
Results Among 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), 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 log10 16S rRNA gene copies/g), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score reductions 1.25 for EEN (P=.015) and 1.0 for CD-TREAT (P=.044) vs chow). Among the children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent reductions in fecal calprotectin (mean decrease 918±555 mg/kg, (P=.002)).
Conclusion CD-TREAT replicates EEN changes in the microbiome, reduces gut inflammation, is well-tolerated and is potentially effective in patients with active CD.

Original language	English
Pages (from-to)	1354-1367
Number of pages	20
Journal	Gastroenterology
Volume	156
Issue number	5
Early online date	11 Dec 2018
DOIs	https://doi.org/10.1053/j.gastro.2018.12.002
Publication status	Published - 30 Apr 2019

Keywords

IBD
microbiota
pediatric trial
carbohydrate

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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. https://doi.org/10.1053/j.gastro.2018.12.002

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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{\textquoteright}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 received CD-TREAT with clinical activity and fecal calprotectin evaluated after 8-week treatment. Results Among 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), 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 log10 16S rRNA gene copies/g), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score reductions 1.25 for EEN (P=.015) and 1.0 for CD-TREAT (P=.044) vs chow). Among the children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent reductions in fecal calprotectin (mean decrease 918±555 mg/kg, (P=.002)). Conclusion CD-TREAT replicates EEN changes in the microbiome, reduces gut inflammation, is well-tolerated and is potentially effective in patients with active CD.",

keywords = "IBD, microbiota, pediatric trial, carbohydrate",

author = "Vaios Svolos and Richard Hansen and Ben Nichols and Chrisopher 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",

year = "2019",

month = apr,

day = "30",

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

language = "English",

volume = "156",

pages = "1354--1367",

journal = "Gastroenterology",

issn = "0016-5085",

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. 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, Chrisopher

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

PY - 2019/4/30

Y1 - 2019/4/30

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 received CD-TREAT with clinical activity and fecal calprotectin evaluated after 8-week treatment. Results Among 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), 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 log10 16S rRNA gene copies/g), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score reductions 1.25 for EEN (P=.015) and 1.0 for CD-TREAT (P=.044) vs chow). Among the children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent reductions in fecal calprotectin (mean decrease 918±555 mg/kg, (P=.002)). Conclusion CD-TREAT replicates EEN changes in the microbiome, reduces gut inflammation, is well-tolerated and is potentially effective in patients with active CD.

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 received CD-TREAT with clinical activity and fecal calprotectin evaluated after 8-week treatment. Results Among 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), 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 log10 16S rRNA gene copies/g), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score reductions 1.25 for EEN (P=.015) and 1.0 for CD-TREAT (P=.044) vs chow). Among the children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent reductions in fecal calprotectin (mean decrease 918±555 mg/kg, (P=.002)). Conclusion CD-TREAT replicates EEN changes in the microbiome, reduces gut inflammation, is well-tolerated and is potentially effective in patients with active CD.

KW - IBD

KW - microbiota

KW - pediatric trial

KW - carbohydrate

U2 - 10.1053/j.gastro.2018.12.002

DO - 10.1053/j.gastro.2018.12.002

M3 - Article

SN - 0016-5085

VL - 156

SP - 1354

EP - 1367

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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