Integrated microbiome and metabolome analysis reveals the potential therapeutic mechanism of Qing-Fei-Pai-Du decoction in mice with coronavirus-induced pneumonia

Abstract

Current studies have shown that gut microbiota may be closely related to the severity of coronavirus disease 2019 (COVID-19) by regulating the host immune response. Qing-Fei-Pai-Du decoction (QFPDD) is the recommended drug for clinical treatment of patients with COVID-19 in China, but whether it exerts a therapeutic effect by modulating the immune response through gut microbiota remains unclear. In this study, we evaluated the therapeutic effects of QFPDD in pneumonia model mice and performed 16S rRNA sequencing and serum and lung tissue metabolomic analysis to explore the underlying mechanisms during the treatment. Then, Spearman correlation analysis was performed on gut microbiome, serum metabolome, and immune-inflammation-related indicators. Our results suggest that QFPDD can restore the richness and diversity of gut microbiota, and multiple gut microbiota (including Alistipes, Odoribacter, Staphylococcus, Lachnospiraceae_NK4A136_group Enterorhabdus, and unclassified_f_Lachnospiraceae) are significantly associated with immune-inflammation-related indicators. In addition, various types of lipid metabolism changes were observed in serum and lung tissue metabolome, especially glycerophospholipids and fatty acids. A total of 27 differential metabolites (DMs) were significantly correlated with immune-inflammation-related indicators, including 9 glycerophospholipids, 7 fatty acids, 3 linoleic acid, 2 eicosanoids, 2 amino acids, 2 bile acids, and 2 others. Interestingly, these DMs showed a good correlation with the gut microbiota affected by QFPDD. The above results suggest that QFPDD can improve the immune function and reduce inflammation in pneumonia model mice by remodeling gut microbiota and host metabolism.

Qing-Kai-Ling oral liquid alleviated pneumonia via regulation of intestinal flora and metabolites in rats

“…Several metabolomics investigations have elaborated on wide disturbances of metabolites related to intestinal flora dysbiosis in pneumonia (de Vos et al, 2022;Huo et al, 2022). Some studies have reported the protective effect of CMs on pneumonia by regulating intestinal flora disorders and metabolite abnormalities (Lian et al, 2022;Wu et al, 2022). While single omics technologies such as the microbiome, metabolome, and transcriptome have been extensively applied in current studies, it is important to note that each of these technologies reflects only one aspect of the complex interactions between the host, microbiota, and environment (Tian et al, 2022).…”

“…Intestinal flora dysbiosis occurs in pneumonia patients as well as animal models (Feng et al, 2020;Zuo et al, 2020). Furthermore, regulation of intestinal flora and thus therapy in pneumonia can be achieved by the administration of probiotics (e.g., Bacillus subtilis and Enterococcus faecalis) and some Chinese medicines (CMs), such as Qing-Fei-Pai-Du decoction and Xuan-Bai-Cheng-Qi decoction (Manzanares et al, 2016;Zeng et al, 2016;Huo et al, 2022;Wu et al, 2022), which further suggests that regulation of intestinal flora disorders may be a promising approach for the prevention and treatment of pneumonia. Additionally, due to the interaction between intestinal microbiota and lung, intestinal flora dysbiosis can exacerbate lung inflammation (Dang and Marsland, 2019;Zhang D. et al, 2020).…”

“…In addition, metabolic abnormalities have also been implicated in the pathogenesis of pneumonia. There are intestinal flora disturbances and dysregulation of host metabolism in pneumonia animals (Wu et al, 2022), and CMs exert therapeutic effects on pneumonia through potential mechanisms associated with the regulation of 'microbiota-metabolites-host' interaction (Lian et al, 2022). Thus, targeting intestinal flora disorders and metabolic abnormalities could be developed as a novel strategy for preventing and treating pneumonia.…”

Potential herb–drug interactions between anti-COVID-19 drugs and traditional Chinese medicine

“…ACE2, SARS-CoV-2 spike protein, and SARS-CoV-2 3CLpro, which are closely relevant to the infectivity and pathogenicity of COVID-19, are also identified as the potential targets of QFPD 75 . Previous study has shown that several kinds of gut microbiota play an important role in the immune function, and QFPD decoction could restore the diversity of gut microbiota and could be used to treat coronavirus-induced pneumonia, reflected in the up-regulation of the relative abundance of Romboutsia , Turicibacter and Clostridium_sensu_stricto_1 , and the down-regulation of the relative abundance of norank_f_Lachnospiraceae , which is closely related to disease severity and immune dysfunction in COVID-19 patients 76 .…”

“Three medicines and three formulas” in COVID-19: From bench to bedside

“…The comprehensive pharmacokinetic behavior of QFPD in vivo illustrates that QFPD exhibits therapeutic effect via immune regulation, anti-infection, anti-inflammatory activities, thereby ameliorating the symptoms of metabolic disorders [87] . QFPD improved immune function and reduced inflammation in a mouse model of pneumonia by remodeling the gut microbiota and host metabolism [88] . Thus, QFPD and wogonoside may regulate ubiquitin-specific peptidase 14 (USP14) to promote activating transcription factor 2 (ATF2) degradation [89] .…”