A Mediterranean Diet Pattern Improves Intestinal Inflammation Concomitant with Reshaping of the Bacteriome in Ulcerative Colitis: A Randomised Controlled Trial.

Natasha Haskey, Mehrbod Estaki, Jiayu Ye, Rachel K Shim, Sunny Singh, Levinus A Dieleman, Kevan Jacobson, Deanna L Gibson

Journal: Journal of Crohn's & colitis 2023;17(10):1569-1578

PMID: 37095601

Plain Language Summary

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Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with debilitating symptoms. Patients live with considerable symptom burden, increased risk of disability, and lower quality of life despite medical treatment. The aim of this study was to investigate the efficacy of the Mediterranean Diet Pattern (MDP) compared with a Canadian Habitual Diet Pattern (CHD) on UC disease activity, inflammation, and the gut microbiome. This study was a randomised controlled trial where participants were randomly assigned to follow the MDP or CHD for 12 weeks. Results showed that: - the MDP reduces clinical symptoms and reduces inflammation. - the MDP promotes faecal secretory immunoglobulin A [the principal weapon protecting us from pathogens and toxins that might otherwise penetrate mucosal surfaces. - the MDP is positively associated with microbes that produce potentially beneficial metabolites. - the MDP is negatively associated with microbes predicted to carry pathobiont traits. - the MDP increases faecal short-chain fatty acids production. Authors conclude that the MDP is well tolerated and is a reasonable, healthy eating pattern that practitioners can recommend to patients with UC in remission to prevent relapses, in addition to their standard medical therapy.

Expert Review

Reviewer: Wilma Kirsten and Gail Brady
18th Jul 2024
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Conflict of interest

None

Take home message

A Mediterranean Diet Pattern may be beneficial as a support therapy for maintaining remission from ulcerative colitis.

Evidence category

A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)

Summary review

Introduction

The management of ulcerative colitis (UC) may be influenced by diet through its effects on gut microbial composition and levels of inflammation. The aim of this randomised controlled trial (RCT) was to compare the efficacy of a Mediterranean Diet Pattern (MDP) with a Canadian Habitual Diet Pattern (CHD) (usual diet) for the management of UC disease activity.

Methods

This trial included 28 mild-moderate diseased UC patients in remission - inclusive of participants who were on a stable dose of UC therapy. Participants were randomised to either MDP (n=15) or CHD (n=13). MDP participants received one-on-one dietary coaching from a dietician whilst the CHD group continued with their regular diet. Health markers included nutrition and medical history, blood work, and stool analysis at baseline and week 12 with disease activity assessed using the Simple Clinical Colitis Activity Index (SCCAI) and Partial Mayo Scores for the two intervals. Biomarkers included:

  • Complete Blood Count
  • C-reactive protein
  • Albumin
  • Vitamin B12
  • Vitamin D
  • Short-chain Fatty Acids (SCFA)
  • Faecal secretory Immunoglobulin A (SigA)
  • Faecal DNA
  • Faecal Calprotectin (FC)

Results

Difference in scores between baseline and week 12, per group:

  • Clinically significant reduction in the primary outcome of SCCAI>1.5: MDP 4/15 (27%); CHD 3/13 (23%)
  • Change in secondary outcome of FC: MDP no change (p=0.375); CHD increase in FC (p=0.0488)
  • Change in SigA: MDP increase (p=0.0040); CHD unchanged (p=0.0803)
  • Change in SCFA: MDP increase in total SCFA (p=0.0129); CHD decrease of Acetic acid (p=0.0398) and Valeric acid (p=0.0215) only
  • Change in Bacteriome: Using the BIRDMAn tool the study showed notable changes in microbiome variation for both positively and negatively associated outcomes between the two groups (p=0.00018).

Conclusion

Despite the small size of this study (note: no sample size calculation was reported), a 12-week MDP intervention appears to decrease disease activity with improved SCCAI scores. Inflammatory markers (e.g. FC) in the MDP cohort remained unchanged but increased in 75% of the control group. The CHD group had lower levels of beneficial SCFA that has been shown to be associated with opportunistic infection related microbes.

Clinical practice applications

  • A standard Western Style diet (typically low in fibre with increased animal protein and ultra-processed food) is associated with both onset and progression of Inflammatory Bowel Disease (IBD).
  • A Mediterranean diet that consists of legumes, whole grains, vegetables, fruit, nuts, seeds, olive oil, fish, poultry and dairy products is associated with reduced inflammation and improved gut microbiome diversity.
  • A Mediterranean diet may be effective as an adjunct therapy for maintaining clinical remission of UC by lowering faecal calprotectin, increasing faecal SIgA, improving the diversity and abundance of the microbiome, decreasing the abundance of pathogenic microbes and increasing total SCFAs.
  • However, given the established inflammatory nature of IBD it is advisable to introduce gut microbiome altering food options - in line with ongoing therapeutic intervention - slowly whilst constantly monitoring the patient.
  • Note that the conclusions were based on a very small, select cohort with associations between specific nutrients (e.g. catechins found in grapes that metabolise quercetin to produce butyrate) based on previous studies inclusive of murine models.

Considerations for future research

  • The background diet of two participants in the CHD cohort was similar to a Mediterranean type diet, which may have biased SCCAI scores and other biomarkers in this group due to the small sample size. Larger cohorts and longer trial periods are therefore needed to confirm tolerance, efficacy and safety of a MDP in IBD patients.
  • The effect of a MDP on patients with more severe symptomatology still needs to be assessed.
  • Future research should consider potential confounding factors and endoscopic (gold standard) analysis of mucosal healing.
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Abstract

BACKGROUND AND AIMS

Dietary patterns are important in managing ulcerative colitis [UC], given their influence on gut microbiome-host symbiosis and inflammation. We investigated whether the Mediterranean Diet Pattern [MDP] vs the Canadian Habitual Diet Pattern [CHD] would affect disease activity, inflammation, and the gut microbiome in patients with quiescent UC.

METHODS

We performed a prospective, randomised, controlled trial in adults [65% female; median age 47 years] with quiescent UC in an outpatient setting from 2017 to 2021. Participants were randomised to an MDP [n = 15] or CHD [n = 13] for 12 weeks. Disease activity [Simple Clinical Colitis Activity Index] and faecal calprotectin [FC] were measured at baseline and week 12. Stool samples were analysed by 16S rRNA gene amplicon sequencing.

RESULTS

The diet was well tolerated by the MDP group. At week 12, 75% [9/12] of participants in the CHD had an FC >100 μg/g, vs 20% [3/15] of participants in the MDP group. The MDP group had higher levels of total faecal short chain fatty acids [SCFAs] [p = 0.01], acetic acid [p = 0.03], and butyric acid [p = 0.03] compared with the CHD. Furthermore, the MDP induced alterations in microbial species associated with a protective role in colitis [Alistipes finegoldii and Flavonifractor plautii], as well as the production of SCFAs [Ruminococcus bromii].

CONCLUSIONS

An MDP induces gut microbiome alterations associated with the maintenance of clinical remission and reduced FC in patients with quiescent UC. The data support that the MDP is a sustainable diet pattern that could be recommended as a maintenance diet and adjunctive therapy for UC patients in clinical remission. ClinicalTrials.gov no: NCT0305371.

© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.

Address: Department of Biology, Irving K Barber Faculty of Science, University of British Columbia-Okanagan, Kelowna, BC, Canada.; Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Diabetes Center, University of California San Francisco, San Francisco, CA, USA.; Department of Public Health Sciences, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.; Division of Gastroenterology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.; Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.; Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition and British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.; Department of Medicine, Faculty of Medicine, University of British Columbia, BC, Canada.

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Clinical Imbalances

Laboratory Testing

Modifiable Lifestyle Factors

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