Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus-Exposed, Uninfected Infants.
Cotrimoxazole Prophylaxis Increases Resistance Gene Prevalence and α-Diversity but Decreases β-Diversity in the Gut Microbiome of Human Immunodeficiency Virus-Exposed, Uninfected Infants.
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DOI：
10.1093/cid/ciz1186
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发表时间：
2020-12-31
期刊：
影响因子：
--
通讯作者：
Dantas G
中科院分区：
文献类型：
--
作者：
D'Souza AW;Moodley-Govender E;Berla B;Kelkar T;Wang B;Sun X;Daniels B;Coutsoudis A;Trehan I;Dantas G
建议对暴露于人类免疫缺陷病毒 (HIV) 且未感染 (HEU) 的婴儿进行预防性复方新诺明治疗，但这种治疗对 HEU 婴儿肠道微生物群和耐药组发育的影响在很大程度上尚不清楚。我们分析了 163 个纵向收集的粪便样本的全宏基因组测序数据，这些样本来自 63 名 HEU 婴儿，这些婴儿随机接受（n = 34；CTX-T）或不接受（n = 29；CTX-N）预防性复方新诺明治疗。我们为每个样本生成了分类学、功能途径和耐药基因图谱，并比较了 CTX-T 和 CTX-N 婴儿之间的微生物组特征。宏基因组分析没有揭示 CTX-T 和 CTX-N 婴儿之间分类学或功能途径 α 多样性的显着差异。相反，CTX-T 婴儿中的抗性基因患病率 (P = .00719) 和 α-多样性 (P = .0045) 增加。对于通过对数归一化丰度（4 个月平均值，0.71 [95% 置信区间 {CI}，0.2–1.2] 和 6 个月平均值，0.85 [95% CI，0.1–1.7]）和 α 多样性（P = .0045）衡量的抗性基因流行率，这些差异随着时间的推移而增加。与 α 多样性不同，个体间肠道微生物组分类学（平均值，-0.11 [95% CI，-.15 至 -.077]）、功能分类学（平均值，-0.050 [95% CI，-.084 至 -.017]）和耐药基因（平均值，-0.13 [95% CI，-.17 至 -.099]）的 β 多样性在CTX-T 婴儿与 CTX-N 婴儿进行比较。这些结果与持续的抗生素选择压力一致。 HEU 婴儿中的复方新诺明预防降低了肠道微生物组 β 多样性，并增加了抗生素耐药性基因 α 多样性和患病率。抗生素耐药性是一个日益严重的威胁，特别是在低收入和中等收入国家，这些国家围产期艾滋病毒暴露率较高，导致需要复方新诺明进行预防。了解当前 HEU 婴儿抗生素预防指南的影响将为指南修订和减少不断增加的抗生素耐药性的努力提供信息。对暴露于 HIV 的未感染 (HEU) 婴儿进行复方新诺明治疗会增加耐药基因的患病率和 α 多样性，并降低微生物分类、功能途径和耐药基因 β 多样性。鉴于全球抗生素耐药性不断上升，未来的 HEU 婴儿预防建议应考虑这些发现。
Prophylactic cotrimoxazole treatment is recommended in human immunodeficiency virus (HIV)–exposed, uninfected (HEU) infants, but the effects of this treatment on developing HEU infant gut microbiotas and resistomes are largely undefined. We analyzed whole-metagenome sequencing data from 163 longitudinally collected stool samples from 63 HEU infants randomized to receive (n = 34; CTX-T) or to not receive (n = 29; CTX-N) prophylactic cotrimoxazole treatment. We generated taxonomic, functional pathway, and resistance gene profiles for each sample and compared microbiome signatures between the CTX-T and CTX-N infants. Metagenomic analysis did not reveal significant differences in taxonomic or functional pathway α-diversity between CTX-T and CTX-N infants. In contrast, resistance gene prevalence (P = .00719) and α-diversity (P = .0045) increased in CTX-T infants. These differences increased over time for both resistance gene prevalence measured by log-normalized abundance (4-month mean, 0.71 [95% confidence interval {CI}, .2–1.2] and 6-month mean, 0.85 [95% CI, .1–1.7]) and α-diversity (P = .0045). Unlike α-diversity, interindividual gut microbiome taxonomic (mean, −0.11 [95% CI, −.15 to −.077]), functional taxonomic (mean, −0.050 [95% CI, −.084 to −.017]), and resistance gene (mean, −0.13 [95% CI, −.17 to −.099]) β-diversity decreased in CTX-T infants compared with CTX-N infants. These results are consistent with persistent antibiotic selection pressure. Cotrimoxazole prophylaxis in HEU infants decreased gut microbiome β-diversity and increased antibiotic resistance gene α-diversity and prevalence. Antibiotic resistance is a growing threat, especially in low- and middle-income countries where the higher perinatal HIV exposure rates result in cotrimoxazole prophylaxis. Understanding effects from current HEU infant antibiotic prophylaxis guidelines will inform guideline revisions and efforts to reduce increasing antibiotic resistance. Cotrimoxazole treatment in HIV-exposed, uninfected (HEU) infants increases resistance gene prevalence and α-diversity, and decreases microbial taxonomic, functional pathway, and resistance gene β-diversity. Future HEU infant prophylaxis recommendations should consider these findings given rising global antibiotic resistance.
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影响因子：
28.3
作者：
Gibson, Molly K.;Wang, Bin;Ahmadi, Sara;Burnham, Carey-Ann D.;Tarr, Phillip I.;Warner, Barbara B.;Dantas, Gautam
通讯作者：
Dantas, Gautam
影响因子：
4.8
作者：
Clark, JS
通讯作者：
Clark, JS
影响因子：
17.1
作者：
Bourke, Claire D.;Gough, Ethan K.;Prendergast, Andrew J.
通讯作者：
Prendergast, Andrew J.
影响因子：
2.9
作者：
Coutsoudis, Anna;Daniels, Brodie;Ramjee, Gita
通讯作者：
Ramjee, Gita
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y