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

BAMBA Shigeki 40422901 0000-0002-4108-5894 INATOMI Osamu 70530351 0000-0002-5837-6575 NISHIDA Atsushi 90719915 0000-0002-1288-3272 OHNO Masashi 80845488 0000-0003-3505-7835 IMAI Takayuki 0000-0002-9170-4075 TAKAHASHI Kenichiro 20773493 0000-0002-3522-9740 NAITO Yuji 0000-0001-5443-788X IWAMOTO Junichi 0000-0002-5238-3272 HONDA Akira 0000-0003-0902-8272 INOHARA Naohiro 0000-0002-4215-9349 ANDOH Akira 90252395 0000-0001-8533-2669 滋賀医科大学

2022.07

概要

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.

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www.irjournal.org

https://doi.org/10.5217/ir.2021.00054 • Intest Res 2022;20(3):370-380

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

pages 370-380.

Supplementary Table 1. Background Characteristics of Crohn’s Disease

Characteristics

Inactive (n = 18)

Active (n = 9)

Sex (male/female)

14/4

7/2

Age (yr), median (IQR)

35.1 (31.9–47.0)

47.4 (35.3–60.7)

Body mass index (kg/m2), median (IQR)

21.2 (18.6–24.5)

21.7 (20.2–23.5)

Smoking status (never/previous/current)

12/3/3

7/2/0

History of intestinal resection (yes/no)

Disease duration (yr), median (IQR)

Disease location (L1/L2/L3)

Disease behavior (B1/B2/B3)

3/15

0/9

9.5 (6.6–14.5)

14.6 (1.6–33.0)

9/1/8

4/0/5

9/7/2

1/5/3

62.0 (46.5–83.7)

66.0 (48.0–96.0)

Crohn’s disease

18

Gastrointestinal bleeding

Intestinal neoplasia

Other

3 (16.7)

2 (22.2)

CDAI, median (IQR)

Disease

Medication, No. (%)

Proton pump inhibitors

Probiotics

6 (33.3)

4 (44.4)

5-ASA/SASP

11 (61.1)

7 (77.8)

Prednisolone

1 (5.6)

10 (55.6)

3 (33.3)

6 (33.3)

3 (33.3)

Immunomodulators

Biologics

IQR, interquartile range; L1, ileal; L2, colonic; L3, ileocolonic; B1, non-stricturing, non-penetrating; B2, stricturing; B3, penetrating; CDAI, Crohn’s disease

activity index; 5-ASA, 5-aminosalicylates; SASP, sulfasalazine.

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Shigeki Bamba, et al. • Ileal gut microbiota and bile acids in CD

Supplementary Table 2. Comparison of Bile Acid Fraction between Active and Inactive CD

Bile acids (%)

Median (IQR)

P -value

Inactive (n = 25)

Active (n = 8)

CA

11.10 (4.51–47.70)

12.10 (4.68–38.80)

0.983

GCA

33.0 (11.3–55.7)

40.9 (26.3–54.2)

0.883

TCA

2.890 (0.654–4.580)

2.090 (0.983–6.700)

0.412

CDCA

2.00 (0.71–5.63)

3.47 (1.28–18.00)

0.185

GCDCA

10.80 (4.33–18.60)

18.60 (8.18–26.30)

0.265

TCDCA

1.140 (0.287–4.030)

2.690 (0.692–4.580)

0.462

0.840 (0.158–1.490)

0.185

DCA

1.920 (0.267–7.270)

GDCA

0.46400 (0.04670–3.95000)

0.01680 (0.00399–0.23800)

0.046

TDCA

0.07270 (0.00815–0.31900)

0.01210 (0.00298–0.15200)

0.344

LCA

0.639 (0.212–4.400)

0.529 (0.304–1.810)

0.629

GLCA

0.00443 (0.00145–0.02680)

0.00217 (0.00169–0.00667)

0.159

TLCA

0.01000 (0.00217–0.07730)

0.00614 (0.00252–0.00887)

0.437

UDCA

0.531 (0.037–1.380)

0.387 (0.191–1.160)

0.850

GUDCA

0.331 (0.134–4.080)

1.710 (0.508–5.830)

0.185

TUDCA

0.0356 (0.0107–0.3360)

0.0225 (0.0116–0.3100)

0.659

CD, Crohn’s disease; IQR, interquartile range; CA, cholic acid; GCA, glycocholic acid; TCA, taurocholic acid; CDCA, chenodeoxycholic acid; GCDCA, glyco­

chenodeoxycholic acid; TCDCA, taurochenodeoxycholic acid; DCA, deoxycholic acid; GDCA, glycodeoxycholic acid; TDCA, taurodeoxycholic acid; LCA,

litho­cholic acid; GLCA, glycolithocholic acid; TLCA, taurolithocholic acid; UDCA, ursodeoxycholic acid; GUDCA, glycoursodeoxycholic acid; TUDCA, tauro­

ursodeoxycholic acid.

P-values were calculated using the Mann-Whitney U test.

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