Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
PLoS Pathog. 2023 Oct 19;19(10):e1011661. doi: 10.1371/journal.ppat.1011661. eCollection 2023 Oct.
The pathophysiology of severe falciparum malaria involves a complex interaction between the host, parasite, and gut microbes. In this review, we focus on understanding parasite-induced intestinal injury and changes in the human intestinal microbiota composition in patients with Plasmodium falciparum malaria. During the blood stage of P. falciparum infection, infected red blood cells adhere to the vascular endothelium, leading to widespread microcirculatory obstruction in critical tissues, including the splanchnic vasculature. This process may cause intestinal injury and gut leakage. Epidemiological studies indicate higher rates of concurrent bacteraemia in severe malaria cases. Furthermore, severe malaria patients exhibit alterations in the composition and diversity of the intestinal microbiota, although the exact contribution to pathophysiology remains unclear. Mouse studies have demonstrated that the gut microbiota composition can impact susceptibility to Plasmodium infections. In patients with severe malaria, the microbiota shows an enrichment of pathobionts, including pathogens that are known to cause concomitant bloodstream infections. Microbial metabolites have also been detected in the plasma of severe malaria patients, potentially contributing to metabolic acidosis and other clinical complications. However, establishing causal relationships requires intervention studies targeting the gut microbiota.
严重疟疾的病理生理学涉及宿主、寄生虫和肠道微生物之间的复杂相互作用。在这篇综述中，我们专注于了解寄生虫诱导的肠道损伤以及恶性疟原虫感染患者肠道微生物群落组成的变化。在恶性疟原虫感染的血液阶段，受感染的红细胞黏附在内皮细胞上，导致包括内脏血管在内的关键组织中广泛的微循环阻塞。这一过程可能导致肠道损伤和肠道渗漏。流行病学研究表明，严重疟疾病例中并发菌血症的发生率更高。此外，严重疟疾患者的肠道微生物群落组成和多样性发生改变，尽管其对病理生理学的确切贡献仍不清楚。小鼠研究表明，肠道微生物群落组成可以影响对疟原虫感染的易感性。在严重疟疾患者中，微生物群落中存在病原体的富集，包括已知会引起并发血流感染的病原体。严重疟疾患者的血浆中也检测到微生物代谢物，可能导致代谢性酸中毒和其他临床并发症。然而，建立因果关系需要针对肠道微生物群的干预研究。
