Dialister-driven succinate accumulation is associated with disease activity and postoperative recurrence in Crohn’s disease

Table 1 Demographic characteristics and clinical data, n (%)

	Non-IBD	Inactive CD	Active CD
n	13	8	10
Age, mean ± SD	45.00 ± 10.70	51.62 ± 13.42	39.20 ± 22.19
Gender (male/female)	6/7	3/5	4/6
BMI, kg/m2, mean ± SD	23.96 ± 3.25	27.02 ± 4.80	23.15 ± 3.64
Smoking status
Current smoker	4 (30.8)	0 (0.0)	3 (30.0)
Ex-smoker	3 (23.1)	4 (50.0)	4 (40.0)
Never smoker	6 (46.2)	4 (50.0)	3 (30.0)
Years of evolution, mean ± SD	NA	17.38 ± 6.32	5.90 ± 7.32a
Surgical resection	NA	1 (12.5)	1 (10)
Corticosteroids	NA	3 (37.5)	0 (0.0)
Thiopurines	NA	3 (37.5)	3 (30)
Anti-TNF treatment	NA	2 (25)	1 (10)
Other biologics	NA	0 (0.0)	0 (0.0)
Antibiotic	NA	0 (0.0)	0 (0.0)
Probiotic	NA	0 (0.0)	0 (0.0)
Age at diagnosis
A1	NA	2 (25)	2 (20)
A2	NA	3 (37.5)	5 (50)
A3	NA	3 (37.5)	3 (30)
Location
L1	NA	0	2 (20)
L2	NA	6 (75)	5 (50)
L3	NA	2 (25)	3 (30)
Behaviour
B1	NA	7 (87.5)	6 (60)
B2	NA	0	0
B3	NA	1 (12.5)	4 (40)
Harvey-Bradshaw index (IQR)	NA	0.00 (0.00, 0.25)	4.50 (3.25, 8.25)a
C-reactive protein (IQR), mg/dL	NA	0.40 (0.40, 0.48)	1.20 (0.72, 1.80)a
Calprotectin (IQR), μg/g	NA	35.75 (27.00, 45.45)	464.90 (215.95, 667.50)a
SES-CD, mean ± SD	NA	0.80 ± 1.79	12.22 ± 6.59a
Succinate, μM, mean ± SD	104.38 ± 10.72	124.76 ± 39.19a	156.71 ± 28.94a,b

^aP < 0.01, significant differences compared with non-inflammatory bowel disease.

^bP < 0.05, significant differences compared with inactive disease.

Age at diagnosis: A1 < 16 years; A2 17-40 years; A3 > 40 years; location: L1 = ileal; L2 = colonic; L3 = ileocolonic; behavior: B1 = non-stenotic, non-fistulizing Crohn’s disease; B2 = stenotic Crohn’s disease; B3 = fistulizing Crohn’s disease. IBD: Inflammatory bowel disease; CD: Crohn’s disease; BMI: Body mass index; TNF: Tumor necrosis factor; IQR: Interquartile range; SES-CD: Simple Endoscopic Score for Crohn’s disease; NA: Not available.

Table 2 Significant bacterial species identified as succinate producers or consumers in the study cohort

Non-IBD vs inactive CD	P value	Non-IBD vs active CD	P value	Active vs inactive CD	P value
Succinate-producers
Paraprevotella clara	6.09E-06	Prevotella buccae	1.18E-10	Prevotella buccae	5.76E-07
Bacteroides intestinalis	3.95E-03	Roseburia hominis	6.15E-09	Prevotella copri	2.01E-06
Escherichia coli	3.01E-02	Fusobacterium nucleatum	8.20E-09	Fusobacterium nucleatum	7.22E-06
Parabacteroides johnsonii	3.37E-02	Campylobacter concisus	2.29E-07	Campylobacter concisus	2.50E-05
Faecalibacterium prausnitzii	4.38E-02	Escherichia coli	4.32E-04	Escherichia coli	6.09E-03
		Paraprevotella clara	6.91E-07	Bacteroides vulgatus	9.25E-03
		Bifidobacterium adolescentis	1.58E-06	Citrobacter freundii	9.26E-03
		Prevotella copri	5.58E-05	Parabacteroides johnsonii	9.89E-03
		Faecalibacterium prausnitzii	7.51E-04
		Citrobacter freundii	1.89E-03
Succinate-consumers
Phascolarctobacterium faecium	4.46E-03	Dialister pneumosintes	6.72E-09	Dialister pneumosintes	6.25E-06
Dialister invisus	2.80E-02			Phascolarctobacterium faecium	1.73E-03

CD: Crohn’s disease; IBD: Inflammatory bowel disease.