免疫检查点抑制剂诱发的肠炎从发病到缓解期间肠道微生物群的变化:一份病例报告。

IF 4.3 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Yuki Hirata, Yoshiki Tanaka, Haruka Yokota, Hiroshi Ohno, Koji Nishida, Hikaru Shimizu, Noboru Mizuta, Kei Nakazawa, Ryoji Koshiba, Kazuki Kakimoto, Takako Miyazaki, Shiro Nakamura, Hiroki Nishikawa
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引用次数: 0

摘要

背景:免疫检查点抑制剂(ICIs)在癌症治疗中至关重要;然而,它们也存在免疫相关不良事件(irAEs)的风险,如肠炎:本研究调查了肠道微生物群在一名接受抗PD-1和抗CTLA-4治疗的IV期黑色素瘤患者肠炎的发生和缓解过程中的作用。在开始接受 ICI 治疗后,该患者出现了严重腹泻,被诊断为 3 级 irAE 肠炎。类固醇和益生菌治疗迅速缓解了症状并减轻了病情,粪便钙蛋白水平降低和胃肠道成像证实了这一点。通过 16S rRNA 基因测序进行的微生物群多样性分析发现,随着肠炎症状的改善,链球菌的感染率也有所下降。相反,镰刀菌属、粪杆菌属、乳杆菌属、普雷沃特氏菌属和双歧杆菌属在病情缓解后的代表性有所增加。这些菌属与抗炎特性和纤维基质降解有关,有助于肠道健康。免疫学评估显示,细胞因子的表达和成本刺激分子的调节出现波动,这与治疗干预和微生物群的改变相一致:我们的研究结果表明,irAE 肠炎患者的肠道微生物群与免疫反应之间存在明显的相关性。结论:我们的研究结果表明,irAE 肠炎患者的肠道微生物群与免疫反应之间存在明显的相关性,这凸显了微生物群分析在预测irAE发生和提供治疗策略方面的潜在作用,从而促进采用更全面的方法来管理 ICIs 的不良反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Gut microbiota shifts from onset to remission in immune checkpoint inhibitor-induced enterocolitis: a case report.

Background: Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment; however, they carry the risk of immune-related adverse events (irAEs), such as enteritis.

Case presentation: This study investigated the role of the gut microbiota during the onset and remission of irAE enteritis in a patient with stage IV melanoma undergoing anti-PD-1 and anti-CTLA-4 therapy. Following commencement of ICI treatment, the patient developed severe diarrhea and was diagnosed with grade 3 irAE enteritis. Steroid and probiotic treatments provided swift symptom relief and remission, as confirmed by reduced fecal calprotectin levels and gastrointestinal imaging. Microbiota diversity analysis conducted via 16S rRNA gene sequencing identified a decrease in Streptococcus prevalence with improvement in enteritis symptoms. Conversely, genera Fusobacterium, Faecalibacterium, Bacteroides, Prevotella, and Bifidobacterium showed increased representation after remission. These genera are associated with anti-inflammatory properties and fibrous substrate degradation, aiding gut health. Immunological assessment demonstrated fluctuations in cytokine expression and the modulation of costimulatory molecules, aligning with therapeutic interventions and microbiota alterations.

Conclusions: Our findings indicate a significant correlation between gut microbiota and immune responses in irAE enteritis. This underscores the potential utility of microbiome profiling in predicting irAE occurrence and in providing treatment strategies, thereby promoting a more comprehensive approach to managing the adverse effects of ICIs.

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来源期刊
Gut Pathogens
Gut Pathogens GASTROENTEROLOGY & HEPATOLOGY-MICROBIOLOGY
CiteScore
7.70
自引率
2.40%
发文量
43
期刊介绍: Gut Pathogens is a fast publishing, inclusive and prominent international journal which recognizes the need for a publishing platform uniquely tailored to reflect the full breadth of research in the biology and medicine of pathogens, commensals and functional microbiota of the gut. The journal publishes basic, clinical and cutting-edge research on all aspects of the above mentioned organisms including probiotic bacteria and yeasts and their products. The scope also covers the related ecology, molecular genetics, physiology and epidemiology of these microbes. The journal actively invites timely reports on the novel aspects of genomics, metagenomics, microbiota profiling and systems biology. Gut Pathogens will also consider, at the discretion of the editors, descriptive studies identifying a new genome sequence of a gut microbe or a series of related microbes (such as those obtained from new hosts, niches, settings, outbreaks and epidemics) and those obtained from single or multiple hosts at one or different time points (chronological evolution).
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