Gough Ethan K, Bourke Claire D, Berejena Chipo, Shonhai Annie, Bwakura-Dangarembizi Mutsa, Prendergast Andrew J, Manges Amee R
Department of International Health, Division of Human Nutrition, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD, USA.
Blizard Institute, Queen Mary University of London , London, UK.
Gut Microbes. 2020 Jul 3;11(4):1104-1115. doi: 10.1080/19490976.2020.1717299. Epub 2020 Feb 5.
Antimicrobials have become a mainstay of healthcare in the past century due to their activity against pathogens. More recently, it has become clear that they can also affect health via their impact on the microbiota and inflammation. This may explain some of their clinical benefits despite global increases in antimicrobial resistance (AMR) and reduced antimicrobial effectiveness. We showed in a randomized controlled trial of stopping versus continuing cotrimoxazole prophylaxis among HIV-positive Zimbabwean children taking antiretroviral therapy (ART), that continuation of cotrimoxazole persistently suppressed gut-resident viridans group streptococcal species (VGS) that were associated with intestinal inflammation. In this addendum, we provide a broader overview of how antibiotics can shape the microbiota and use high read-depth whole metagenome sequencing data from our published study to investigate whether (i) the impact of cotrimoxazole on gut VGS and (ii) VGS associated inflammation, is attributable to strain-level variability. We focus on , the VGS species that was most prevalent in the cohort and for which there was sufficient genome coverage to differentiate strains. We demonstrate that suppression of by cotrimoxazole is not strain specific, nor did stool concentration of the pro-inflammatory mediator myeloperoxidase vary by strain. We also show that gut-resident strains present in this study population are distinct from common oral strains. This is the first analysis of how cotrimoxazole prophylaxis used according to international treatment guidelines for children living with HIV influences the gut microbiome at the strain-level. We also provide a detailed review of the literature on the mechanisms by which suppression of VGS may act synergistically with cotrimoxazole's anti-inflammatory effects to reduce gut inflammation. A greater understanding of the sub-clinical effects of antibiotics offers new insights into their responsible clinical use.
在过去的一个世纪里，抗菌药物因其对病原体的活性而成为医疗保健的支柱。最近，很明显它们还可以通过对微生物群和炎症的影响来影响健康。这可能解释了尽管全球抗菌药物耐药性（AMR）增加且抗菌效果降低，但它们仍具有一些临床益处的原因。我们在一项针对接受抗逆转录病毒治疗（ART）的HIV阳性津巴布韦儿童停止或继续服用复方新诺明预防治疗的随机对照试验中表明，继续服用复方新诺明可持续抑制与肠道炎症相关的肠道常驻草绿色链球菌属物种（VGS）。在本附录中，我们更全面地概述了抗生素如何塑造微生物群，并使用我们已发表研究中的高深度全宏基因组测序数据来研究：（i）复方新诺明对肠道VGS的影响以及（ii）VGS相关炎症是否归因于菌株水平的变异性。我们重点关注该队列中最普遍且有足够基因组覆盖度以区分菌株的VGS物种。我们证明复方新诺明对该物种的抑制作用不是菌株特异性的，促炎介质髓过氧化物酶的粪便浓度也不会因该物种的菌株而异。我们还表明，本研究人群中存在的肠道常驻该物种菌株与常见口腔菌株不同。这是首次分析按照国际治疗指南对HIV感染儿童使用复方新诺明预防治疗如何在菌株水平上影响肠道微生物群。我们还详细综述了关于VGS抑制可能与复方新诺明的抗炎作用协同发挥作用以减轻肠道炎症的机制的文献。对抗生素亚临床效应的更深入了解为其合理临床应用提供了新的见解。
