Prebiotics and Diet to Reduce "Leaky" Gut in First Degree Relatives of Crohn's Disease Patients

Summary

Crohn's disease (CD) is a recurring inflammation of the intestines. The etiology is unknown; however evidence suggests that it could be a combination of gut microbes, environmental factors and genetics. CD has a strong genetic component, with up to 12% of patients having familial history. The Western diet is also thought to increase the risk of developing CD. In addition up to 20% of healthy first-degree relatives (FRD) of CD patients have increased small intestinal permeability ("leaky gut"). Previous studies have also shown that the Western diet can affect the intestinal immune response and normal intestinal barrier function, as well as alter the gut microbiota. We are interested in looking into whether beneficial dietary fibers (prebiotics) in combination with a diet low in n-6 polyunsaturated fatty acids (PUFAs) and high in n-3 PUFAs can protect against the development of CD.

Prebiotics are carbohydrates that cannot be digested by human enzymes and instead feed the bacteria in the colon that can digest them. Prebiotics occur in different fruits and vegetables. They have been shown to improve health by positively changing the gut microbes and their metabolism.

The prebiotic we will be using are β-fructans. β-fructans have been shown to reduce "leaky gut" and positively impact the intestinal immune system in experimental models and healthy humans. Diet has been shown to affect the gut microbes, intestinal inflammation development and the activity of prebiotics. We hypothesize that β-fructans in combination with a diet low in n-6 PUFAs / high in n-3 PUFAs (similar to a Mediterranean diet) can reduce intestinal permeability ("leaky gut") in FDR of CD patients, associated with beneficial changes in the gut microbes.

Participants (FDR of CD patients; 40 total) will be randomized and receive either a 12 g/day dose of the prebiotic oligofructose-enriched inulin (Prebiotin), or placebo (maltodextrin), as well as a dietary intervention. In order to control the n-3 and n-6 PUFA intake, participants will receive nutritional counselling by a registered dietitian. The Mediterranean diet will have the low n-6 and high n-3 intake ("Low n-6 PUFA"). Participants in the control diet group will be advised to follow the Canada's Food Guide (CFG) recommendations. Thus, this placebo-controlled study will involve 2 intervention groups with 20 participants in each group: 1) Prebiotic + Low n-6 PUFA; 2) Placebo + CFG.

Conditions

• Healthy First Degree Relatives of Crohn's Disease Patients

Interventions

DIETARY_SUPPLEMENT

Prebiotics

Oligofructose-enriched inulin \[a combination of shorter chain oligofructose, Degree of Polymerisation (DP) 3 - 9 and longer chain inulin (DP ≥ 10), in a 50:50 ratio ± 10 %\] 12 g/day for 6 weeks

OTHER

Low n-6 PUFA Diet

The Mediterranean diet pattern (MDP) with increased n-3 PUFA, saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) and reduced n-6 PUFAs food intake will be adopted as suitable Low n-6 PUFA diet.

DIETARY_SUPPLEMENT

Maltodextrin

Maltodextrin consists of D-glucose units connected in chains of variable length (DP 3-17). The glucose units are primarily linked with α(1→4) glycosidic bonds. Maltodextrin is easily hydrolyzed by the intestinal enzymes and thus does not have an effect on colonic microbiota. Maltodextrin (5 g/days for 6 weeks) will be used as a placebo for the prebiotic treatment

OTHER

Control Diet

Participants who will not be assigned to "Low n-6 PUFA diet" will be advised to follow the Canada's Food Guide recommendations ("Control diet"). As Canada's Food Guide Diet is also designed with the aim to support healthy eating and prevention of metabolic and chronic disorders, this diet may not be considered as a true comparator for the Low n-6 PUFA diet intervention.

Sponsors & Collaborators

• University of Alberta

  lead OTHER

Principal Investigators

• Levinus Dieleman, MD, PhD · University of Alberta

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

15 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-02-04

Primary Completion

2024-01-08

Completion

2024-05-17

Countries

• Canada

Study Locations