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Multi-Omic and dietary analysis of Crohn’s disease identifies pathogenetic factors

Presented by
Dr Yael Haberman, Sheba Medical Center, Israel
Conference
ECCO 2022
Dietary differences between participants with Crohn’s disease (CD) at diagnosis and healthy controls were observed in an analysis of the Israelian Sheba cohort. The consumption of vitamin D, olive oil, and vegetables was reduced in participants with CD, whereas their sugar, starch, and nitrite intake was increased in this group. Moreover, integration between dietary and transcriptomics, metabolomics, and the microbiome revealed novel pathogenetic factors.

Dr Yael Haberman (Sheba Medical Center, Israel) and colleagues aimed to decipher dietary, environmental, and host factors that drive the increasing incidence of CD [1]. For this purpose, they collected dietary, transcriptomic, metabolomic, environmental, and microbial data from 25 participants with CD at CD diagnosis and 33 healthy controls.

The dietary analysis showed that vitamin D, olive oil, and vegetable intake was significantly lowerd in participants with CD compared with healthy controls. In contrast, sugar, starch, and nitrite consumption was higher. The environmental questionnaire did not reveal significant differences between the study groups.

Microbial data (feacal and mucosal biopsies) demonstrated significant differences between participants with CD and healthy controls, with increased levels of Enterobacteriaceae Ruminococcus gnavus in participants with CD and decreased levels of Ruminococceae Lachnospiraceae. In addition, it was shown that biopsy samples compared with stool samples were enriched with pathogenic bacteria like Veillonella, Fusobacterium, Neisseria, and Ruminococcus gnavus.

Furthermore, metabolite serum analysis revealed that oxalate, GABA, and serotonin serum levels were significantly higher in participants with CD, whereas decanoic and octanoic acid serum levels were lower compared with healthy controls. Dr Haberman added that participants with CD consume fewer vegetables than controls, have lower levels of Oxalobacter formigenes in their stool but display higher serum levels of oxalate than controls, suggesting that participants with CD may have less oxalate degradation in the gut.

Transcriptmics of the ileum demonstrated a reduction in epithelial genes and pathways, such as GUCA2B, SLC10A2, MT1A, and GSTA1. Also, an increase of DUOX2, CXCL9, CSF2, and DEFB4A was observed, which are innate epithelial pro-inflammatory genes and immune signatures linked to the extracellular matrix.

Subsequently, host transcriptomics were linked to dietary factors via co-expression models. According to Dr Haberman, these models may help to re-direct disease recommendations in individual patients with Crohn’s disease.

  1. Haberman Y, et al. Dietary and Multi-Omic characterization of new onset treatment naive Crohn Disease identifies factors that may contribute to disease pathogenesis. OP31, ECCO 2022, 16–19 February.

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