The effect of single dose albendazole (400 mg) treatment on the human gut microbiome of hookworm-infected Ghanaian individuals.
The effect of single dose albendazole (400 mg) treatment on the human gut microbiome of hookworm-infected Ghanaian individuals.
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单剂量阿苯达唑（400 mg）治疗对钩虫感染的加纳个体的人类肠道微生物组的影响。
DOI：
10.1038/s41598-023-38376-3
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发表时间：
2023-07-12
影响因子：
4.6
通讯作者：
Wilson, Michael D.
中科院分区：
文献类型：
--
作者：
Appiah-Twum, Francis;Akorli, Jewelna;Okyere, Lydia;Sagoe, Kate;Osabutey, Dickson;Cappello, Michael;Wilson, Michael D.
微生物在人体肠道稳态、代谢、免疫和生理病理学中起着关键作用。2018-2021年在加纳Kintampo North Municipality进行的一项纵向研究表明，在一些社区使用单剂量400 mg阿苯达唑治疗后，钩虫感染治愈率较低。为了研究钩虫感染与肠道微生物组之间的关联，我们检查了来自同意的参与者的粪便样本，这些参与者在治疗后治愈或仍然感染。在每个时间点，收集阿苯达唑治疗前和治疗后10-14天的粪便。我们使用从粪便样本中提取的DNA的16 S rRNA扩增子测序来研究肠道微生物群的组成和多样性，并确定与治疗结果相关的潜在微生物生物标志物。钩虫感染与物种丰富度增加相关（p = 0.0093）。在接受治疗的个体中，在单剂量阿苯达唑治疗后10-14天，微生物群组成也有显着变化。与治疗前状态相比，治疗后治愈钩虫感染的个体显示微生物群组成显著减少（ANOSIM; p = 0.02），而未能清除感染的个体显示微生物群组成没有变化（ANOSIM; p = 0.35）。未感染者和成功治疗者的微生物组成和结构相似。我们还发现，丰富的梭菌属。在治疗前或治疗后的感染个体中增加。预测性功能分析揭示了两种丙酮酸铁氧还蛋白氧化还原酶亚基途径在治疗后仍被感染的个体中的富集（p < 0.05），暗示严格厌氧的肠道细菌如梭菌属（Clostridia spp.）这项研究表明人类肠道微生物群落生态失调与钩虫感染的阿苯达唑治疗结果之间的关系。未来的研究将进一步表征本研究中确定的特定生物标志物，以确定其评估驱虫治疗药理学反应的潜力，并探索使用益生菌补充剂作为辅助治疗以增加阿苯达唑对钩虫有效性的可能性。
Microbes play a key role in human gut homeostasis, metabolic, immunologic and physiopathology of the body. A longitudinal study conducted during 2018–2021 in the Kintampo North Municipality in Ghana demonstrated low hookworm infection cure rates following treatment with a single dose of 400 mg albendazole in some communities. To investigate associations between hookworm infection and the gut microbiome, we examined stool samples from consented participants who were either cured or remained infected after treatment. At each time point, stool was collected prior to and 10–14 days after albendazole treatment. We used 16S rRNA amplicon sequencing of DNA extracted from stool samples to investigate the composition and diversity of the gut microbiota and to identify potential microbial biomarkers associated with treatment outcomes. Hookworm infection was associated with increased species richness (p = 0.0093). Among treated individuals, there was also a significant variation in microbiota composition at 10–14 days following single-dose albendazole treatment. Individuals cured of hookworm infection after treatment showed a significant reduction in microbiota composition when compared to their pre-treatment state (ANOSIM; p = 0.02), whilst individuals who failed to clear the infection showed no change in microbiota composition (ANOSIM; p = 0.35). Uninfected individuals and those who were successfully treated were similar in their microbial composition and structure. We also found that the abundance of Clostridia spp. was increased in infected individuals pre- or post-treatment. Predictive functional profiling revealed the enrichment of two pyruvate ferredoxin oxidoreductase subunit pathways in individuals who remained infected after treatment (p < 0.05), alluding to an upturn of strictly anaerobic commensal bacteria such as Clostridia spp. This study suggests a relationship between human gut microbiome dysbiosis and albendazole therapy outcomes of hookworm infection. Future studies will further characterize specific biomarkers identified within this study to establish their potential for assessment of pharmacological responses to anthelminthic therapies, as well as explore the possibility of using probiotic supplementation as an adjunct treatment to increase albendazole effectiveness against hookworm.
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