Reduction of butyric acid-producing bacteria in the ileal mucosa-associated microbiota is associated with the history of abdominal surgery in patients with Crohn’s disease

Figures & data

Table 1. The characteristics of healthy control and patients with Crohn’s disease.

		Healthy control	Patients with Crohn's disease	P-value
Number		23	32	-
Age (mean ± SD)		56.2 ± 12.5	39.5 ± 17.2	< 0.001 *
Female / Male		15/8	11/21	0.093 ^†
CDAI		-	100.5 ± 77.0	-
Types of CD (Number)
ileal type		-	6	-
ileocolonic type		-	22	-
colonic type		-	4	-
5-ASA		-	12	-
IM		-	5	-
Probiotics		-	11	-
Biologics		-	22	-
History of intestinal surgery		-	8	-
Presence of ileal stenosis		-	12	-

P-values were calculated using Welch’s t-test (*) or chi-squared test (†).

CDAI; Crohn’s disease activity index, 5-ASA; 5-aminosalicylic acid, IM; immunomodulator; CD, Crohn’s disease; SD, standard deviation.

Table 2. The difference of α-diversity index in ileal MAM between healthy control and patients with Crohn’s disease.

	Healthy control (n = 23)	Patients with Crohn's disease (n = 32)	P-value ^†
Observed features	132.22 ± 49.80	101.09 ± 46.18	0.023
Shannon	5.48 ± 0.76	4.75 ± 1.14	0.006
Chao1	176.36 ± 83.61	133.88 ± 76.01	0.060

Values mean relative abundance (% of total bacteria) and are shown as mean ± standard deviation.

Bold font shows statistically higher values among the two groups compared.

† P-values were calculated using Welch’s t-test

MAM, mucosa-associated microbiota

Figure 1. Difference of β-diversity index in MAM between healthy control and patients with Crohn’s disease, Principal coordinate analysis (PCoA) was based on Bray–Curtis dissimilarities in the composition of the ileal MAM. Red and blue dots denote individual samples of patients with Crohn’s disease and healthy controls, respectively. Ellipses indicate 95% confidence intervals. Statistical differences between groups were assessed using PERMANOVA with 9,999 permutations.

Table 3. Bacterial taxa showing significant difference in relative abundances in ileal MAM between healthy control and patients with Crohn’s disease.

Taxa	Healthy control (n = 23)	Patients with Crohn's disease (n = 32)	P-value ^†
g__Faecalibacterium *	7.94 ± 6.41	3.13 ± 4.93	0.004
f__Lachnospiraceae (unclassified genus)	7.39 ± 7.58	3.11 ± 3.42	0.017
g__Blautia *	5.66 ± 3.79	3.22 ± 3.38	0.018
g__Ruminococcus *	3.19 ± 3.10	1.03 ± 1.84	0.005
g__Coprococcus *	2.51 ± 1.99	0.93 ± 2.06	0.006
g__Roseburia *	2.48 ± 2.11	0.77 ± 1.62	0.002
g__Gemmiger *	2.15 ± 2.34	0.57 ± 1.57	0.008
g__Butyricicoccus *	0.63 ± 0.64	0.25 ± 0.49	0.021
g__Sutterella	0.57 ± 0.50	1.17 ± 1.47	0.038
g__Clostridium (Lachnospiraceae)	0.33 ± 0.36	1.23 ± 2.11	0.023

Values mean relative abundance (% of total bacteria) and are shown as mean ± standard deviation.

Bold font shows statistically higher values among the two groups compared.

* Genus including butyrate-producing species or isolate

† P-values were calculated using Welch’s t-test

MAM, mucosa-associated microbiota

Table 4. Bacterial taxa showing significant difference in the relative abundances in ileal MAM among types of Crohn’s disease.

Taxa	ileal type (n = 6)	ileocolonic type (n = 22)	colonic type (n = 4)	P-value ^†
g__Veillonella	3.85 ± 2.65	0.70 ± 0.99	3.53 ± 3.75	0.023
f__Gemellaceae (unclassified genus)	1.71 ± 2.35	0.30 ± 1.21	1.11 ± 2.13	0.019
f__Actinomycetaceae (unclassified genus)	0.01 ± 0.02	0.00 ± 0.01	0.00 ± 0.00	0.012
g__cc115 (Erysipelotrichaceae)	0.01 ± 0.02	0.01 ± 0.02	0.14 ± 0.15	0.024
f__Christensenellaceae (unclassified genus)	0.01 ± 0.02	ND ± ND	1.35 ± 2.67	0.005

Values mean relative abundance (% of total bacteria) and are shown as mean ± standard deviation.

† P-values were calculated using Kruskal–Wallis test

MAM, mucosa-associated microbiota

Table 5. Bacterial taxa showing significant difference in relative abundances in ileal MAM between patients with Crohn’s disease with or without stenosis.

Taxa	Stenosis (-) (n = 20)	Stenosis (+) (n = 12)	P-value ^†
o__Clostridiales (unclassified family/genus)	0.69 ± 0.91	0.14 ± 0.32	0.019

Values mean relative abundance (% of total bacteria) and are shown as mean ± standard deviation.

Bold font shows statistically higher values among the two groups compared.

† P-value was calculated using Welch’s t-test

MAM, mucosa-associated microbiota

Table 6. Bacterial taxa showing significant difference in relative abundances in ileal MAM between patients with Crohn’s disease with or without a history of surgery.

Taxa	Surgery (-) (n = 24)	Surgery (+) (n = 8)	P-value ^†
g__Faecalibacterium *	4.12 ± 5.35	0.14 ± 0.32	0.001
g__Dorea *	4.09 ± 5.07	0.96 ± 2.16	0.022
g__Blautia *	3.85 ± 3.58	1.32 ± 1.72	0.013
f__Lachnospiraceae (unclassified genus)	3.83 ± 3.64	0.96 ± 1.17	0.002
g__Coprococcus *	1.22 ± 2.32	0.06 ± 0.18	0.023
o__Clostridiales (unclassified family/genus)	0.67 ± 1.23	0.11 ± 0.29	0.047
g__Butyricicoccus *	0.33 ± 0.54	0.03 ± 0.06	0.013
g__Alistipes	0.28 ± 0.52	0.01 ± 0.03	0.018

Values mean relative abundance (% of total bacteria) and are shown as mean ± standard deviation.

Bold font shows statistically higher values among the two groups compared.

* Genus including butyrate-producing species or isolate

† P-values were calculated using Welch’s t-test

MAM, mucosa-associated microbiota

Figure 2. Function of butyric acid-producing bacteria, BA, butyric acid; BA, butyric acid-producing bacteria; ROS, reactive oxygen species.

Data availability statement

The data that support the findings of this study are available from the corresponding author, Osamu Handa, upon reasonable request.