Malham Mikkel, Vestergaard Marie V, Bataillon Thomas, Villesen Palle, Dempfle Astrid, Bang Corinna, Engsbro Anne Line, Jakobsen Christian, Franke Andre, Wewer Vibeke, Thingholm Louise B, Petersen Andreas M
Department of Pediatric and Adolescent Medicine, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents, and Adults, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
Inflamm Bowel Dis. 2025 Feb 10;31(2):501-513. doi: 10.1093/ibd/izae179.
Pediatric-onset ulcerative colitis (pUC) represents a more aggressive disease phenotype compared with adult-onset UC. We hypothesized that this difference can, in part, be explained by the composition of the microbiota.
In a prospective, longitudinal study, we included pediatric (N = 30) and adult (N = 30) patients with newly or previously (>1 year) diagnosed UC. We analyzed the microbiota composition in the mucosa-adherent microbiota at baseline, using 16S rRNA gene sequencing, and the fecal microbiota at baseline and at 3-month intervals, using shotgun metagenomics.
For fecal samples, the bacterial composition differed between pUC and aUC in newly diagnosed patients (β-diversity, Bray Curtis: R2 = 0.08, P = .02). In colon biopsies, microbial diversity was higher in aUC compared with pUC (α-diversity, Shannon: estimated difference 0.54, P = .006). In the mucosa-adherent microbiota, Alistipes finegoldii was negatively associated with disease activity in pUC while being positively associated in aUC (estimate: -0.255 and 0.098, P = .003 and P = .02 in pUC and aUC, respectively). Finally, we showed reduced stability of the fecal microbiota in pediatric patients, evidenced by a different composition of the fecal microbiota in newly and previously diagnosed pUC, a pattern not found in adults.
Our results indicate that pediatric UC patients have a more unstable fecal microbiota and a lower α diversity than adult patients and that the microbiota composition differs between aUC and pUC patients. These findings offer some explanation for the observed differences between pUC and aUC and indicate that individualized approaches are needed if microbiota modifications are to be used in the future treatment of UC.
与成人起病的溃疡性结肠炎(UC)相比,儿童起病的溃疡性结肠炎(pUC)代表一种更具侵袭性的疾病表型。我们推测这种差异部分可由微生物群的组成来解释。
在一项前瞻性纵向研究中,我们纳入了新诊断或既往(>1年)诊断为UC的儿科患者(N = 30)和成人患者(N = 30)。我们使用16S rRNA基因测序分析基线时黏膜附着微生物群中的微生物群组成,并使用鸟枪法宏基因组学分析基线时以及每隔3个月的粪便微生物群。
对于粪便样本,新诊断患者中pUC和成人起病的UC(aUC)之间的细菌组成存在差异(β多样性,Bray Curtis:R2 = 0.08,P = 0.02)。在结肠活检中,aUC的微生物多样性高于pUC(α多样性,Shannon:估计差异0.54,P = 0.006)。在黏膜附着微生物群中,纤细阿利斯杆菌与pUC中的疾病活动呈负相关,而在aUC中呈正相关(估计值:分别在pUC和aUC中为-0.255和0.098,P = 0.003和P = 0.02)。最后,我们发现儿科患者粪便微生物群的稳定性降低,新诊断和既往诊断的pUC中粪便微生物群组成不同可证明这一点,而成人未发现这种模式。
我们的结果表明,儿科UC患者的粪便微生物群比成人患者更不稳定,α多样性更低,并且aUC和pUC患者之间的微生物群组成不同。这些发现为pUC和aUC之间观察到的差异提供了一些解释,并表明如果未来要在UC治疗中使用微生物群修饰,需要采取个体化方法。