Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients.

Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients.
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长期抗逆转录病毒治疗对HIV-1感染者肠道和口腔微生物群的影响。

DOI:
10.1038/s41598-020-80247-8
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发表时间:
2021-01-13
期刊:
影响因子:
4.6
通讯作者:
Iwatani Y
Iwatani Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Imahashi M;Ode H;Kobayashi A;Nemoto M;Matsuda M;Hashiba C;Hamano A;Nakata Y;Mori M;Seko K;Nakahata M;Kogure A;Tanaka Y;Sugiura W;Yokomaku Y;Iwatani Y

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在 HIV-1 感染患者中,抗逆转录病毒治疗 (ART) 是可能影响共生微生物群并导致出现副作用的关键因素。然而,目前尚不完全了解长期 ART 方案如何随着时间的推移对微生物组成产生不同的影响。在这里,我们对接受不同长期 ART 的患者的粪便和唾液微生物组进行了 16S 核糖体 RNA 基因测序。我们发现 ART,尤其是基于传统核苷酸/核苷逆转录酶抑制剂 (NRTI) 的 ART,对粪便微生物多样性具有显着影响:随着时间的推移,α 多样性减少,β 多样性增加。相反,没有观察到唾液微生物组的动态多样性变化。对细菌属组成的比较分析显示,随着时间的推移,ART 患者的肠道微生物群倾向于富含普雷沃氏菌和缺乏拟杆菌。此外,我们观察到在传统 ART 下拟杆菌逐渐减少,但琥珀弧菌和/或巨球菌急剧增加。这些结果表明,ART,特别是基于 NRTI 的 ART,对肠道微生物群组成和多样性的抑制作用比对口腔的影响更大,这可能导致患者肠道菌群失调。因此,保留 NRTI 的 ART,特别是含有整合酶链转移抑制剂 (INSTI) 和/或非核苷酸逆转录酶抑制剂 (NNRTI) 的治疗方案,可能会减轻长期 ART 下 HIV-1 感染患者肠道菌群失调的负担。
In HIV-1-infected patients, antiretroviral therapy (ART) is a key factor that may impact commensal microbiota and cause the emergence of side effects. However, it is not fully understood how long-term ART regimens have diverse impacts on the microbial compositions over time. Here, we performed 16S ribosomal RNA gene sequencing of the fecal and salivary microbiomes in patients under different long-term ART. We found that ART, especially conventional nucleotide/nucleoside reverse transcriptase inhibitor (NRTI)-based ART, has remarkable impacts on fecal microbial diversity: decreased α-diversity and increased ß-diversity over time. In contrast, dynamic diversity changes in the salivary microbiome were not observed. Comparative analysis of bacterial genus compositions showed a propensity for Prevotella-enriched and Bacteroides-poor gut microbiotas in patients with ART over time. In addition, we observed a gradual reduction in Bacteroides but drastic increases in Succinivibrio and/or Megasphaera under conventional ART. These results suggest that ART, especially NRTI-based ART, has more suppressive impacts on microbiota composition and diversity in the gut than in the mouth, which potentially causes intestinal dysbiosis in patients. Therefore, NRTI-sparing ART, especially integrase strand transfer inhibitor (INSTI)- and/or non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens, might alleviate the burden of intestinal dysbiosis in HIV-1-infected patients under long-term ART.
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