Pre-Diagnosis Diet Predicts Response to Exclusive Enteral Nutrition and Correlates with Microbiome in Pediatric Crohn Disease

Author:

Dijk Stephanie1ORCID,Jarman Megan2,Zhang Zhengxiao34ORCID,Lawley Morgan5,Ahmad Muzammil5,Suarez Ricardo5,Rossi Laura6,Chen Min7,Wu Jessica7,Carroll Matthew W.5ORCID,Otley Anthony8,Sherlock Mary9,Mack David R.10,Jacobson Kevan11ORCID,deBruyn Jennifer C.12,El-Matary Wael13ORCID,Deslandres Colette14,Rashid Mohsin8,Church Peter C.15,Walters Thomas D.15,Huynh Hien Q.5,Surette Michael G.616,Griffiths Anne M.15ORCID,Wine Eytan15ORCID

Affiliation:

1. Department of Physiology, University of Alberta, Edmonton, AB T6G 1C9, Canada

2. Department of Agriculture, Life, & Environmental Science, University of Alberta, Edmonton, AB T6G 2R3, Canada

3. Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada

4. College of Food and Biological Engineering, Jimei University, Xiamen 361000, China

5. Division of Pediatric Gastroenterology, Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, Canada

6. Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada

7. Nutrition Services (Child Health), Alberta Health Services, Edmonton, AB T5J 3E4, Canada

8. Division of Gastroenterology & Nutrition, Department of Pediatrics, Dalhousie University, Halifax, NS B3H 4R2, Canada

9. Division of Gastroenterology and Nutrition, Department of Pediatrics, McMaster University, Hamilton, ON L8S 4L8, Canada

10. CHEO IBD Center, Department of Pediatrics, University of Ottawa, Ottawa, ON K1N 6N5, Canada

11. Division of Gastroenterology, Hepatology and Nutrition, B.C. Children’s Hospital, British Columbia Children’s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada

12. Section of Pediatric Gastroenterology, Department of Pediatrics, University of Calgary, Calgary, AB T2N 1N4, Canada

13. Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada

14. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, CHU Sainte-Justine Hospital, Université de Montréal, Montréal, QC H3T 1J4, Canada

15. Division of Pediatric Gastroenterology, IBD Center, Hospital for Sick Children, University of Toronto, Toronto, ON M5S 1C6, Canada

16. Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4L8, Canada

Abstract

Exclusive enteral nutrition (EEN) is effective in inducing remission in pediatric Crohn disease (CD). EEN alters the intestinal microbiome, but precise mechanisms are unknown. We hypothesized that pre-diagnosis diet establishes a baseline gut microbiome, which then mediates response to EEN. We analyzed prospectively recorded food frequency questionnaires (FFQs) for pre-diagnosis dietary patterns. Fecal microbiota were sequenced (16SrRNA) at baseline and through an 18-month follow-up period. Dietary patterns, Mediterranean diet adherence, and stool microbiota were associated with EEN treatment outcomes, disease flare, need for anti-tumor necrosis factor (TNF)-α therapy, and long-term clinical outcomes. Ninety-eight patients were included. Baseline disease severity and microbiota were associated with diet. Four dietary patterns were identified by FFQs; a “mature diet” high in fruits, vegetables, and fish was linked to increased baseline microbial diversity, which was associated with fewer disease flares (p < 0.05) and a trend towards a delayed need for anti-TNF therapy (p = 0.086). Baseline stool microbial taxa were increased (Blautia and Faecalibacterium) or decreased (Ruminococcus gnavus group) with the mature diet compared to other diets. Surprisingly, a “pre-packaged” dietary pattern (rich in processed foods) was associated with delayed flares in males (p < 0.05). Long-term pre-diagnosis diet was associated with outcomes of EEN therapy in pediatric CD; diet–microbiota and microbiota–outcome associations may mediate this relationship.

Funder

Canadian Institutes of Health Research

Children with Intestinal and Liver Disorders (CH.I.L.D.) foundation

Women & Children’s Health Research Institute

IMAGINE Chronic Disease Network

Publisher

MDPI AG

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