HIV Pathogenesis Section, Laboratory of Immunoregulation, NIAID/NIH, Rockville, MD, USA; Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands.
Amsterdam University Medical Centers, University of Amsterdam, Infectious Diseases, Amsterdam, the Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands; Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands.
Cell Rep. 2023 Nov 28;42(11):113336. doi: 10.1016/j.celrep.2023.113336. Epub 2023 Nov 1.
Antiretroviral therapy (ART) has dramatically lengthened lifespan among people with HIV (PWH), but this population experiences heightened rates of inflammation-related comorbidities. HIV-associated inflammation is linked with an altered microbiome; whether such alterations precede inflammation-related comorbidities or occur as their consequence remains unknown. We find that ART-treated PWH exhibit depletion of gut-resident bacteria that produce short-chain fatty acids (SCFAs)-crucial microbial metabolites with anti-inflammatory properties. Prior reports establish that fecal SCFA concentrations are not depleted in PWH. We find that gut-microbiota-mediated SCFA production capacity is better reflected in serum than in feces and that PWH exhibit reduced serum SCFA, which associates with inflammatory markers. Leveraging stool and serum samples collected prior to comorbidity onset, we find that HIV-specific microbiome alterations precede morbidity and mortality in ART-treated PWH. Among these microbiome alterations, reduced microbiome-mediated conversion of lactate to propionate precedes mortality in PWH. Thus, gut microbial fiber/lactate conversion to SCFAs may modulate HIV-associated comorbidity risk.
抗逆转录病毒疗法 (ART) 极大地延长了艾滋病毒感染者 (PWH) 的寿命，但这一人群炎症相关合并症的发生率更高。与 HIV 相关的炎症与微生物组的改变有关；这种改变是先于炎症相关合并症发生，还是作为其后果发生，目前尚不清楚。我们发现，接受 ART 治疗的 PWH 表现出产生短链脂肪酸 (SCFA) 的肠道常驻细菌的消耗，这些细菌是具有抗炎特性的关键微生物代谢物。先前的报告表明，PWH 粪便中的 SCFA 浓度并没有耗尽。我们发现，血清比粪便更能反映肠道微生物群介导的 SCFA 产生能力，而 PWH 血清中的 SCFA 减少，与炎症标志物相关。利用在合并症发生之前收集的粪便和血清样本，我们发现 HIV 特异性微生物组的改变先于接受 ART 治疗的 PWH 的发病率和死亡率。在这些微生物组改变中，乳酸向丙酸盐转化的微生物组介导能力的降低先于 PWH 的死亡率。因此，肠道微生物纤维/乳酸向 SCFA 的转化可能调节与 HIV 相关的合并症风险。
