Depression in Individuals Coinfected with HIV and HCV Is Associated with Systematic Differences in the Gut Microbiome and Metabolome,mSystems

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Depression in Individuals Coinfected with HIV and HCV Is Associated with Systematic Differences in the Gut Microbiome and Metabolome
mSystems ( IF 6.4 ) Pub Date : 2020-09-29 , DOI: 10.1128/msystems.00465-20
Bryn C Taylor ₁ , Kelly C Weldon _{2,

3} , Ronald J Ellis _{4,

5} , Donald Franklin ₆ , Tobin Groth ₇ , Emily C Gentry ₂ , Anupriya Tripathi _{2,

7,

8} , Daniel McDonald ₈ , Gregory Humphrey ₈ , MacKenzie Bryant ₈ , Julia Toronczak ₈ , Tara Schwartz ₈ , Michelli F Oliveira ₉ , Robert Heaton ₆ , Igor Grant ₆ , Sara Gianella ₁₀ , Scott Letendre _{9,

11} , Austin Swafford ₃ , Pieter C Dorrestein _{2,

3,

8} , Rob Knight _{8,

12,

13,

14}

Affiliation

Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA.
Department of Neuroscience, HIV Neurobehavioral Research Center, University of California San Diego, La Jolla, California, USA.
Department of Psychiatry, HIV Neurobehavioral Research Center, University of California San Diego, La Jolla, California, USA.
Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, California, USA.
Division of Biological Sciences, University of California San Diego, La Jolla, California, USA.
Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California, USA.
Department of Medicine, University of California San Diego, La Jolla, California, USA.
Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, California, USA.
Department of Psychiatry, University of California San Diego, La Jolla, California, USA.
Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, USA.
Department of Bioengineering, University of California San Diego, La Jolla, California, USA.

Depression is influenced by the structure, diversity, and composition of the gut microbiome. Although depression has been described previously in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) monoinfections, and to a lesser extent in HIV-HCV coinfection, research on the interplay between depression and the gut microbiome in these disease states is limited. Here, we characterized the gut microbiome using 16S rRNA amplicon sequencing of fecal samples from 373 participants who underwent a comprehensive neuropsychiatric assessment and the gut metabolome on a subset of these participants using untargeted metabolomics with liquid chromatography-mass spectrometry. We observed that the gut microbiome and metabolome were distinct between HIV-positive and -negative individuals. HCV infection had a large association with the microbiome that was not confounded by drug use. Therefore, we classified the participants by HIV and HCV infection status (HIV-monoinfected, HIV-HCV coinfected, or uninfected). The three groups significantly differed in their gut microbiome (unweighted UniFrac distances) and metabolome (Bray-Curtis distances). Coinfected individuals also had lower alpha diversity. Within each of the three groups, we evaluated lifetime major depressive disorder (MDD) and current Beck Depression Inventory-II. We found that the gut microbiome differed between depression states only in coinfected individuals. Coinfected individuals with a lifetime history of MDD were enriched in primary and secondary bile acids, as well as taxa previously identified in people with MDD. Collectively, we observe persistent signatures associated with depression only in coinfected individuals, suggesting that HCV itself, or interactions between HCV and HIV, may drive HIV-related neuropsychiatric differences.

中文翻译：

HIV 和 HCV 合并感染个体的抑郁与肠道微生物组和代谢组的系统差异有关

抑郁症受肠道微生物组的结构、多样性和组成的影响。尽管先前已经在人类免疫缺陷病毒 (HIV) 和丙型肝炎病毒 (HCV) 单一感染中描述了抑郁症，并且在较小程度上在 HIV-HCV 合并感染中描述了抑郁症，但对抑郁症与这些疾病状态下肠道微生物组之间相互作用的研究是有限的。在这里，我们使用来自 373 名参与者的粪便样本的 16S rRNA 扩增子测序来表征肠道微生物组，这些参与者接受了全面的神经精神病学评估，并使用非靶向代谢组学和液相色谱-质谱法对这些参与者的一部分进行了肠道代谢组学分析。我们观察到，HIV 阳性和阴性个体的肠道微生物组和代谢组是不同的。HCV 感染与未被药物使用混淆的微生物组有很大的关联。因此，我们根据 HIV 和 HCV 感染状态（HIV 单一感染、HIV-HCV 合并感染或未感染）对参与者进行分类。三组在肠道微生物组（未加权的 UniFrac 距离）和代谢组（Bray-Curtis 距离）方面存在显着差异。合并感染的个体也具有较低的 alpha 多样性。在三组中的每一组中，我们评估了终生重度抑郁症 (MDD) 和当前的贝克抑郁量表-II。我们发现，仅在合并感染的个体中，肠道微生物组在抑郁状态之间存在差异。具有终生 MDD 病史的合并感染个体富含初级和次级胆汁酸，以及先前在 MDD 患者中发现的分类群。总的来说，

更新日期：2020-09-29

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