Yokoyama Yoshihiro, Ichiki Tomoko, Yamakawa Tsukasa, Tsuji Yoshihisa, Kuronuma Koji, Takahashi Satoshi, Narimatsu Eichi, Nakase Hiroshi
Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of General Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Front Med (Lausanne). 2022 Aug 10;9:941422. doi: 10.3389/fmed.2022.941422. eCollection 2022.
Coronavirus disease 2019 (COVID-19) is still causing a global pandemic. But the mechanism of COVID-19 severity is not well elucidated.
We conducted two single-center observational studies of patients with COVID-19. In the first study, the enrolled patients were distinguished based on critical vs. non-critical COVID-19. We collected blood samples from the patients at admission to measure markers related to inflammation and thrombosis and stool samples to analyze the fecal microbiome, metabolome, and calprotectin level. In the second study, we collected ileum and colon tissue samples from patients with critical COVID-19 who required colonoscopy due to severe gastrointestinal symptoms and analyzed mucosal gene expression.
A total of 19 blood samples and 10 stool samples were collected. Interleukin (IL)-6 was the only serum inflammatory marker with significantly higher levels in the critical group than in the non-critical group. The fecal calprotectin level in the critical group was significantly higher than that in the non-critical group ( = 0.03), regardless of the presence of gastrointestinal symptoms. Stool metabolomic analysis showed that the level of indole-3-propionic acid, a ligand for aryl hydrocarbon receptor (AhR), was markedly decreased in the critical group compared to that in the non-critical group ( = 0.01). The expression of genes involved in tryptophan metabolism, including , , , and , was downregulated in the ileum of critical COVID-19 patients who required a colonoscopy.
Critical COVID-19 patients have gastrointestinal inflammation potentially caused by impaired tryptophan metabolism in the small intestine due to decreased expression of genes involved in tryptophan metabolism.
2019年冠状病毒病（COVID-19）仍在全球范围内引发大流行。但COVID-19严重程度的机制尚未完全阐明。
我们对COVID-19患者进行了两项单中心观察性研究。在第一项研究中，根据COVID-19病情严重程度将入组患者分为重症组和非重症组。我们在患者入院时采集血样以检测与炎症和血栓形成相关的标志物，并采集粪便样本以分析粪便微生物组、代谢组和钙卫蛋白水平。在第二项研究中，我们从因严重胃肠道症状需要进行结肠镜检查的重症COVID-19患者中采集回肠和结肠组织样本，并分析黏膜基因表达。
共采集了19份血样和10份粪便样本。白细胞介素（IL）-6是唯一在重症组中水平显著高于非重症组的血清炎症标志物。无论是否存在胃肠道症状，重症组的粪便钙卫蛋白水平均显著高于非重症组（P = 0.03）。粪便代谢组学分析显示，与非重症组相比，重症组中芳烃受体（AhR）的配体吲哚-3-丙酸水平显著降低（P = 0.01）。在需要进行结肠镜检查的重症COVID-19患者的回肠中，参与色氨酸代谢的基因，包括[具体基因名称未给出]、[具体基因名称未给出]、[具体基因名称未给出]和[具体基因名称未给出]的表达下调。
重症COVID-19患者存在胃肠道炎症，这可能是由于参与色氨酸代谢的基因表达降低，导致小肠色氨酸代谢受损所致。
