Transcriptomics to study the effect of a Mediterranean-inspired diet on inflammation in Crohn's disease patients

Gareth Marlow, Stephanie Ellett, Isobel R Ferguson, Shuotun Zhu, Nishi Karunasinghe, Amalini C Jesuthasan, Dug Yeo Han, Alan G Fraser, Lynnette R Ferguson, Gareth Marlow, Stephanie Ellett, Isobel R Ferguson, Shuotun Zhu, Nishi Karunasinghe, Amalini C Jesuthasan, Dug Yeo Han, Alan G Fraser, Lynnette R Ferguson

Abstract

Background: Inflammation is an essential immune response; however, chronic inflammation results in disease including Crohn's disease. Therefore, reducing the inflammation can yield a significant health benefit, and one way to achieve this is through diet. We developed a Mediterranean-inspired anti-inflammatory diet and used this diet in a 6-week intervention in a Crohn's disease population. We examined changes in inflammation and also in the gut microbiota. We compared the results of established biomarkers, C-reactive protein and the micronuclei assay, of inflammation with results from a transcriptomic approach.

Results: Data showed that being on our diet for 6 weeks was able to reduce the established biomarkers of inflammation. However, using transcriptomics, we observed significant changes in gene expression. Although no single gene stood out, the cumulative effect of small changes in many genes combined to have a beneficial effect. Data also showed that our diet resulted in a trend of normalising the microbiota.

Conclusions: This study showed that our Mediterranean-inspired diet appeared to benefit the health of people with Crohn's disease. Our participants showed a trend for reduced markers of inflammation and normalising of the microbiota. The significant changes in gene expression after 6 weeks highlighted the increased sensitivity of using transcriptomics when compared to the established biomarkers and open up a new era of dietary intervention studies.

Figures

Figure 1
Figure 1
Mean (±SE) levels of C-reactive protein pre- and post-dietary intervention for each participant.
Figure 2
Figure 2
Mean (±SE) micronuclei scored in 1,100 cytokinesis-blocked cells for each participant pre- and post-dietary intervention.
Figure 3
Figure 3
Differential expression of top 100 genes (p < 0.002) pre- and post-dietary intervention. Based on analysis of the top differentially expressed transcripts, it is clear that transcription expression is changed over time, with expression being both increased (red) and decreased (green) significantly in just 6 weeks.
Figure 4
Figure 4
Generation of a biological network of genes related to the upstream regulator IRF2. Network was generated by IPA. Connections were applied based on known interactions within the Ingenuity Pathway Knowledge Base. Solid lines between genes represent direct interactions and the dashed lines indirect. Genes are represented by nodes, with the red and green colours indicating up- or down-regulated expression; the greater the colour intensity, the higher the level of differential expression.
Figure 5
Figure 5
Relative abundance of microbiota pre- and post-dietary intervention. Healthy samples (n = 2), CD pre-diet (n = 8) and CD post-diet (n = 8).

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