Intest Res.  2022 Jul;20(3):370-380. 10.5217/ir.2021.00054.

Relationship between the gut microbiota and bile acid composition in the ileal mucosa of Crohn’s disease

• Bamba S
• Inatomi O
• Nishida A
• Ohno M
• Imai T
• Takahashi K
• Naito Y
• Iwamoto J
• Honda A
• Inohara N
• Andoh A

• KMID: 2531991
• DOI: http://doi.org/10.5217/ir.2021.00054

Abstract

Background/Aims
Crosstalk between the gut microbiota and bile acid plays an important role in the pathogenesis of gastrointestinal disorders. We investigated the relationship between microbial structure and bile acid metabolism in the ileal mucosa of Crohn’s disease (CD).
Methods
Twelve non-CD controls and 38 CD patients in clinical remission were enrolled. Samples were collected from the distal ileum under balloon-assisted enteroscopy. Bile acid composition was analyzed by liquid chromatography-mass spectrometry. The gut microbiota was analyzed by 16S rRNA gene sequencing.
Results
The Shannon evenness index was significantly lower in endoscopically active lesions than in non-CD controls. β-Diversity, evaluated by the UniFrac metric, revealed a significant difference between the active lesions and non-CD controls (P=0.039). The relative abundance of Escherichia was significantly higher and that of Faecalibacterium and Roseburia was significantly lower in CD samples than in non-CD controls. The increased abundance of Escherichia was more prominent in active lesions than in inactive lesions. The proportion of conjugated bile acids was significantly higher in CD patients than in non-CD controls, but there was no difference in the proportion of primary or secondary bile acids. The genera Escherichia and Lactobacillus were positively correlated with the proportion of conjugated bile acids. On the other hand, Roseburia, Intestinibacter, and Faecalibacterium were negatively correlated with the proportion of conjugated bile acids.
Conclusions
Mucosa-associated dysbiosis and the alteration of bile acid composition were identified in the ileum of CD patients. These may play a role in the pathophysiology of ileal lesions in CD patients.

Keyword

Single-balloon enteroscopy; Crohn disease; Mucosa associated microbiota

Figure

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  Fig. 1. Comparative analysis of the gut microbial communities in non-CD controls (n=9) and inactive (n=18) and active lesions (n=9) of CD patients. (A) Observed species. (B) Chao1 index. (C) Shannon index. (D) β-Diversity estimated using the UniFrac metric and visualized using NMDS ordination. There was a significant difference between active lesions and non-CD samples (P=0.039, permutational multivariate analysis of variance). aP<0.05, Mann-Whitney U test. CD, Crohn’s disease; NMDS, non-metric multidimensional scaling; NS, not significant.

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  Fig. 2. Comparative analysis of the taxonomic composition of the microbial community at the phylum level in non-CD controls (n=9) and inactive (n=18) and active lesions (n=9) of CD patients. (A) Firmicutes. (B) Bacteroidetes. (C) Proteobacteria. (D) Fusobacteria. (E) Actinobacteria. aP<0.05, Mann-Whitney U test. CD, Crohn’s disease; NS, not significant.

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  Fig. 3. Comparative analysis of the taxonomic composition of the microbial community at the genus level using linear discriminant analysis effect size. (A) Comparison between non-CD (n=9) and CD samples (n=27). (B) Comparison between inactive (n=18) and active lesions (n=9) of CD patients. CD, Crohn’s disease.

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  Fig. 4. Bile acid composition in the ileum of non-CD controls (n=10) and inactive (n=25) and active CD patients (n=8). (A) Bile acid composition was visualized using NMDS ordination. There was a significant difference between active CD and non-CD controls (P=0.033, permutational multivariate analysis of variance). (B) Total bile acids. (C) Proportion of primary bile acids. (D) Proportion of secondary bile acids. (E) Proportion of conjugated bile acids. (F) Proportion of unconjugated bile acids. (G) Ratio of glycine-conjugated to taurine-conjugated bile acids. aP<0.05, Mann-Whitney U test. CD, Crohn’s disease; NMDS, non-metric multidimensional scaling; NS, not significant.

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