Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Viruses. 2021 Oct 18;13(10):2101. doi: 10.3390/v13102101.
Hepatitis A virus (HAV) causes transient acute infection, and little is known of viral shedding via the duodenum and into the intestinal environment, including the gut microbiome, from the period of infection until after the recovery of symptoms. Therefore, in this study, we aimed to comprehensively observe the amount of virus excreted into the intestinal tract, the changes in the intestinal microbiome, and the level of inflammation during the healing process. We used blood and stool specimens from patients with human immunodeficiency virus who were infected with HAV during the HAV outbreak in Japan in 2018. Moreover, we observed changes in fecal HAV RNA and quantified the plasma cytokine level and gut microbiome by 16S rRNA analysis from clinical onset to at least 6 months after healing. HAV was detected from clinical onset up to a period of more than 150 days. Immediately after infection, many pro-inflammatory cytokines were elicited, and some cytokines showed different behaviors. The intestinal microbiome changed significantly after infection (dysbiosis), and the dysbiosis continued for a long time after healing. These observations suggest that the immunocompromised state is associated with prolonged viral shedding into the intestinal tract and delayed recovery of the intestinal environment.
甲型肝炎病毒（HAV）引起短暂的急性感染，人们对感染期间直至症状恢复后通过十二指肠排入肠道环境（包括肠道微生物组）的病毒脱落知之甚少。因此，在这项研究中，我们旨在全面观察肠道中排出的病毒量、肠道微生物组的变化以及愈合过程中的炎症水平。我们使用了 2018 年日本甲型肝炎爆发期间感染 HAV 的人类免疫缺陷病毒患者的血液和粪便标本。此外，我们观察了粪便 HAV RNA 的变化，并通过 16S rRNA 分析定量了血浆细胞因子水平和肠道微生物组，从临床发病到愈合后至少 6 个月。从临床发病到超过 150 天的时间都可以检测到 HAV。感染后立即引发了许多促炎细胞因子，其中一些细胞因子表现出不同的行为。感染后肠道微生物组发生了显著变化（生态失调），并且在愈合后很长一段时间内仍持续失调。这些观察结果表明，免疫功能低下与肠道内病毒持续脱落和肠道环境恢复延迟有关。
