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肠道微生物群与坏死性胰腺炎后的动态关系:来自多阶段16S rRNA测序研究的见解

Dynamic relationship between gut microbiota and post-necrotizing pancreatitis: insights from a multi-stage 16S rRNA sequencing study.

作者信息

Lu Jiongdi, Wang Zhe, Cao Feng, Li Jia, Ji Guofeng, Li Fei

机构信息

Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, China.

出版信息

Front Pharmacol. 2025 May 22;16:1577558. doi: 10.3389/fphar.2025.1577558. eCollection 2025.

Abstract

BACKGROUND

Acute pancreatitis (AP) is a common digestive disorder, with necrotizing pancreatitis (NP) occurring in 20% of cases. Long-term complications can include pancreatic exocrine and endocrine insufficiency, with gut microbiota (GM) playing a significant role in pancreatic diseases. Although previous studies have established a connection between gut microbiota dysbiosis and the onset of necrotizing pancreatitis, the composition of GM in patients who have experienced post-NP post-necrotizing pancreatitis remains largely unexamined.

METHODS

We conducted a single-center, prospective, long-term follow-up study of 88 participants, including 68 NP patients and 20 healthy controls. NP patients were divided into NP (onset-NP) and PNP groups based on disease progression. Gut microbial diversity and composition were assessed using 16S rRNA sequencing, followed by bioinformatic analyses such as Alpha and Beta diversity metrics, linear discriminant analysis effect size (LEfSe), and functional pathway predictions. Clinical data were correlated with GM profiles to evaluate associations.

RESULTS

29.5% and 19.1% of NP patients progressed to pancreatic endocrine and exocrine insufficiency, respectively. Alpha and Beta diversity analyses revealed significantly lower microbial diversity in NP and PNP groups. Dysbiosis was characterized by a reduction in beneficial bacteria such as and , and an increase in opportunistic pathogens such as and . Functional prediction suggested disruptions in cellular processes, including apoptosis and necroptosis, and links to pathways associated with inflammatory and metabolic diseases. Correlation analyses demonstrated significant associations between GM alterations and clinical markers of inflammation, such as IL-6, C-reactive protein (CRP), and Procalcitonin (PCT).

CONCLUSION

Our findings highlight distinct GM profiles in NP and PNP patients compared to healthy controls, with partial recovery of beneficial flora in PNP patients. The study underscores the role of GM dysbiosis in NP progression and long-term outcomes, offering insights into potential therapeutic targets and strategies to improve patient management and quality of life. Future studies should explore multicenter validations and the mechanisms linking GM alterations to clinical outcomes.

摘要

背景

急性胰腺炎(AP)是一种常见的消化系统疾病,其中20%的病例会发展为坏死性胰腺炎(NP)。长期并发症可能包括胰腺外分泌和内分泌功能不全,肠道微生物群(GM)在胰腺疾病中起着重要作用。尽管先前的研究已经建立了肠道微生物群失调与坏死性胰腺炎发病之间的联系,但NP后(坏死性胰腺炎后)患者的GM组成在很大程度上仍未得到研究。

方法

我们对88名参与者进行了一项单中心、前瞻性、长期随访研究,其中包括68名NP患者和20名健康对照。NP患者根据疾病进展分为NP(发病-NP)组和PNP组。使用16S rRNA测序评估肠道微生物多样性和组成,随后进行生物信息学分析,如Alpha和Beta多样性指标、线性判别分析效应大小(LEfSe)以及功能途径预测。将临床数据与GM谱相关联以评估相关性。

结果

分别有29.5%和19.1%的NP患者进展为胰腺内分泌和外分泌功能不全。Alpha和Beta多样性分析显示,NP组和PNP组的微生物多样性显著降低。微生物群失调的特征是有益菌如[具体有益菌名称1]和[具体有益菌名称2]减少,以及机会致病菌如[具体机会致病菌名称1]和[具体机会致病菌名称2]增加。功能预测表明细胞过程受到干扰,包括凋亡和坏死性凋亡,并与炎症和代谢性疾病相关的途径存在联系。相关性分析表明,GM改变与炎症的临床标志物如白细胞介素-6(IL-6)、C反应蛋白(CRP)和降钙素原(PCT)之间存在显著关联。

结论

我们的研究结果突出了NP患者和PNP患者与健康对照相比不同的GM谱,PNP患者中有益菌群有部分恢复。该研究强调了GM失调在NP进展和长期预后中的作用,为潜在的治疗靶点和改善患者管理及生活质量的策略提供了见解。未来的研究应探索多中心验证以及GM改变与临床结局之间的联系机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96db/12137087/466b12ad42ca/fphar-16-1577558-g001.jpg

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