Qin-Qiao-Xiao-Du formula alleviate influenza virus infectious pneumonia through regulation gut microbiota and metabolomics

Abstract

Qin-Qiao-Xiao-Du (QQXD), a traditional Chinese medicine (TCM) formula, has been used in the clinical treatment of influenza virus pneumonia. However, the effects and mechanisms of QQXD on influenza virus pneumonia remain unknown. Therefore, this study explores the mechanisms of QQXD in the treatment of influenza virus pneumonia from the point of view of intestinal flora and metabolism. The results showed that QQXD was able to reduce mortality, weight loss, lung viral load, lung index, and lung injury in influenza virus mice. A cytokine array found that the QQXD attenuated the expression of serum IL-1α, IL-4, IL-12(P70), and TNF-α. Subsequently, 16s rRNA gene sequencing showed that QQXD could increase the relative abundances of Gemmiger, Anaerofustis, Adlercreutzia, and Streptococcus and decrease those of Dehalobacteriu, Burkholderia, Prevotella, Butyrimimonas, Delftia, and others. Meanwhile, targeted metabolic profiling analysis showed that QQXD could regulate nitrogen metabolism, phenylalanine metabolism, valine, leucine, and isoleucine biosynthesis. Correlation analysis demonstrated that the regulatory effect of QQXD on the cyanoamino acid metabolism pathway was associated with changes in the abundance of Parabacteroides, Pediococcus, and Clostridium in influenza mice. In conclusion, our study revealed that QQXD can inhibit influenza virus replication, suppress cytokine storms, and protect mice from influenza virus infection pneumonia. The mechanisms are likely to be related to improved gut microbiota dysbiosis, increased intestinal carbohydrate metabolism, and up-regulated cyanoamino acid metabolism pathways.

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).…”

“…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.…”

The gut-lung axis in influenza A: the role of gut microbiota in immune balance

“…Transplantation of fecal microbiota isolated from mice orally administered GeGen QinLian Decoction to IAVinfected mice decreased the splenic Th17/Treg ratio and reduced the inflammatory damage effect in lung tissue, while an increase in Akkermansia_muciniphila, Desulfovibrio_C21_c20, and Lactobacillus_salivarius and a decrease in Escherichia_coli was observed in the intestine of the transplanted mice (14). Qin-Qiao-Xiao-Du decoction modulates the composition of the GM of IAVinfected mice and also inhibits virus proliferation in the lung and reduces plasma expression of IL-1a, IL-4, IL-12, and TNF-a (88). These effects may be related to the fact that it modulates the abundance of cyanoamino acid metabolism pathway-associated bacteria in the intestine, Parabacteroides, Pediococcus, and Clostridium (88).…”

“…Qin-Qiao-Xiao-Du decoction modulates the composition of the GM of IAVinfected mice and also inhibits virus proliferation in the lung and reduces plasma expression of IL-1a, IL-4, IL-12, and TNF-a (88). These effects may be related to the fact that it modulates the abundance of cyanoamino acid metabolism pathway-associated bacteria in the intestine, Parabacteroides, Pediococcus, and Clostridium (88). Qingfeiyin decoction increased the abundance of Coprococcus, Ruminococcus, Lactobacillus, and Prevotella in the gut, reduced the abundance of Escherichia, Parabacteroides, Butyricimonas, and Anacrotruncus after H1N1 virus infection, down-regulated JAK-STAT, MAPK signaling pathway, reduced lung damage, reduced lung viral load, and improved survival rate (90).…”

Liquid chromatography‐mass spectrometry‐based metabolomics reveals the comprehensive metabolites in Dioscorea opposita Thunb. peel

“…Metabolomics is a powerful tool for obtaining comprehensive information regarding the biochemical constituents of a biological system [9,10], and has shown unique advantages in the study of pharmaceuticals [11][12][13] and food science [14,15] field. UHPLC-quadrupole/orbitrap HRMS (UHPLC-Q-Orbitrap HRMS) is one of the most widely employed analytical tools in metabolomics studies [16], because of the efficient separation capabilities of UHPLC and excellent structural elucidation by HRMS [17].…”