Effect of long-term azithromycin treatment on gut microbial diversity in children and adolescents with HIV-associated chronic lung disease.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-08-01 Epub Date: 2025-07-05 DOI:10.1016/j.ebiom.2025.105832

Trym Thune Flygel, Ahmed Bargheet, Regina Esinam Abotsi, Shantelle Claassen-Weitz, Victoria Simms, Erik Hjerde, Kilaza Samson Mwaikono, Grace Mchugh, Dan Hameiri-Bowen, Veronika Kuchařová Pettersen, Rashida Abbas Ferrand, Mark Nicol, Jorunn Pauline Cavanagh, Trond Flaegstad, Evgeniya Sovershaeva

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引用次数: 0

Abstract

Background: HIV-associated chronic lung disease (HCLD) is common in children and adolescents growing up with HIV. The use of azithromycin (AZM) reduces the rate of acute respiratory exacerbations in this population, however, impact of this treatment on the gut microbiota and associations with blood-derived inflammatory markers have not been studied.

Methods: Children and adolescents with HCLD in Harare, Zimbabwe and Blantyre, Malawi were recruited in a double-blind, placebo-controlled trial of once-weekly AZM or placebo for 48 weeks (BREATHE trial, NCT02426112). Rectal swabs were collected at inclusion (N = 346), 48 weeks (treatment end, N = 313), and 72 weeks (six months after treatment cessation, N = 244). The bacterial composition of fecal swabs was determined using 16S rRNA gene sequencing. Plasma biomarkers at inclusion and 48 weeks were measured using Luminex multiplex bead assay.

Findings: At 48 weeks, bacterial α-diversity was significantly lower in the AZM group, with 27 bacterial genera showing differential abundance between the study groups. The placebo group exhibited higher interconnectivity between bacterial genera at 48 weeks compared to the AZM group. Correlations between the top seven differentially abundant genera and biomarkers observed at inclusion were no longer significant at 48 weeks in both groups. Depletion of Campylobacter persisted for six months after cessation of AZM treatment.

Interpretation: Long-term AZM treatment in HCLD patients affects their gut bacterial composition at least 6 months after its cessation. The consequences of reduced bacterial diversity, such as altered interaction with the immune system and risk of resistance, need further investigation to understand how to optimise gut health during long-term antibiotic treatments.

Funding: The study was funded by the Norwegian Research Council and Helse Nord (HNF 1387-17).

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长期阿奇霉素治疗对艾滋病毒相关慢性肺病儿童和青少年肠道微生物多样性的影响

背景：HIV相关的慢性肺部疾病（HCLD）在感染HIV的儿童和青少年中很常见。阿奇霉素（AZM）的使用降低了这一人群急性呼吸恶化的发生率，然而，这种治疗对肠道微生物群的影响以及与血源性炎症标志物的关联尚未研究。方法：在津巴布韦哈拉雷和马拉维布兰太尔招募患有HCLD的儿童和青少年，进行双盲、安慰剂对照试验，每周服用一次AZM或安慰剂，持续48周（BREATHE试验，NCT02426112）。在入组（N = 346）、48周（治疗结束，N = 313）和72周（停止治疗6个月，N = 244）时收集直肠拭子。采用16S rRNA基因测序法测定粪便拭子细菌组成。采用Luminex多重头测定法测定纳入和48周时的血浆生物标志物。结果：在48周时，细菌α-多样性在AZM组显著降低，27个细菌属在研究组之间表现出丰度差异。与AZM组相比，安慰剂组在48周时表现出更高的细菌属之间的连通性。在两组中，在48周时，前7个差异丰富的属与纳入时观察到的生物标志物之间的相关性不再显著。在停止AZM治疗后，弯曲杆菌的消失持续了6个月。解释：长期AZM治疗HCLD患者在停药后至少6个月影响其肠道细菌组成。细菌多样性减少的后果，如与免疫系统的相互作用改变和耐药风险，需要进一步研究，以了解如何在长期抗生素治疗期间优化肠道健康。资助：本研究由挪威研究委员会和Helse Nord （HNF 1387-17）资助。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.