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特发性药物性肝损伤与阿莫西林克拉维酸钾：关注患者的肠道微生物群、粪便代谢组和胆汁酸谱。

Idiosyncratic Drug-Induced Liver Injury and Amoxicillin-Clavulanate: Spotlight on Gut Microbiota, Fecal Metabolome and Bile Acid Profile in Patients.

机构信息

Instituto Universitario de Biomedicina (IBIOMED), Universidad de León, 24071 León, Spain.

Servicio de Aparato Digestivo, Complejo Asistencial Universitario de León, 24008 León, Spain.

出版信息

Int J Mol Sci. 2024 Jun 22;25(13):6863. doi: 10.3390/ijms25136863.

DOI:10.3390/ijms25136863
PMID:38999973
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11241776/
Abstract

Several hepatic disorders are influenced by gut microbiota, but its role in idiosyncratic drug-induced liver injury (iDILI), whose main causative agent is amoxicillin-clavulanate, remains unknown. This pioneering study aims to unravel particular patterns of gut microbiota composition and associated metabolites in iDILI and iDILI patients by amoxicillin-clavulanate (iDILI-AC). Thus, serum and fecal samples from 46 patients were divided into three study groups: healthy controls (n = 10), non-iDILI acute hepatitis (n = 12) and iDILI patients (n = 24). To evaluate the amoxicillin-clavulanate effect, iDILI patients were separated into two subgroups: iDILI non-caused by amoxicillin-clavulanate (iDILI-nonAC) (n = 18) and iDILI-AC patients (n = 6). Gut microbiota composition and fecal metabolome plus serum and fecal bile acid (BA) analyses were performed, along with correlation analyses. iDILI patients presented a particular microbiome profile associated with reduced fecal secondary BAs and fecal metabolites linked to lower inflammation, such as dodecanedioic acid and pyridoxamine. Moreover, certain taxa like , and spp. correlated with significant metabolites and BAs. Additionally, comparisons between iDILI-nonAC and iDILI-AC groups unraveled unique features associated with iDILI when caused by amoxicillin-clavulanate. In conclusion, specific gut microbiota profiles in iDILI and iDILI-AC patients were associated with particular metabolic and BA status, which could affect disease onset and progression.

摘要

几种肝脏疾病受肠道微生物群的影响，但肠道微生物群在阿莫西林克拉维酸引起的特发性药物性肝损伤（iDILI）中的作用尚不清楚，阿莫西林克拉维酸是其主要致病药物。这项开创性的研究旨在揭示 iDILI 和 iDILI 患者（由阿莫西林克拉维酸引起的 iDILI-AC）中肠道微生物群组成和相关代谢物的特定模式。因此，从 46 名患者中采集血清和粪便样本，分为三组：健康对照组（n = 10）、非 iDILI 急性肝炎组（n = 12）和 iDILI 患者组（n = 24）。为了评估阿莫西林克拉维酸的作用，将 iDILI 患者分为两组：非阿莫西林克拉维酸引起的 iDILI（iDILI-nonAC）（n = 18）和 iDILI-AC 患者（n = 6）。对肠道微生物群组成和粪便代谢组以及血清和粪便胆汁酸（BA）分析进行了分析，并进行了相关性分析。iDILI 患者呈现出与粪便次级 BA 减少和与炎症程度较低相关的粪便代谢物相关的特定微生物群特征，如十二烷二酸和吡哆醛。此外，某些分类群如 、 和 spp.与显著的代谢物和 BAs 相关。此外，iDILI-nonAC 和 iDILI-AC 组之间的比较揭示了与阿莫西林克拉维酸引起的 iDILI 相关的独特特征。总之，iDILI 和 iDILI-AC 患者的特定肠道微生物群特征与特定的代谢和 BA 状态相关，这可能影响疾病的发生和进展。

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