Qingfeiyin Decoction Inhibits H1N1 Virus Infection via Modulation of Gut Microbiota and Inflammatory Pathways in a Murine Model

Abstract

Influenza virus-caused lung infection and its pandemic outbreaks are a persistent public health challenge. The H1N1 subtype is the most common type of influenza infection observed in humans. Maxingshigantang decoction, a classic formula of Chinese herbal medicine, has been used for the prevention and treatment of respiratory infection for many centuries. Qingfeiyin decoction, based on Maxingshigantang, has been used in the clinic for decades. To explore the underlying mechanisms, according to the traditional Chinese medicine theory “the lung and the large intestine are interior–exterior,” which can be translated to the “gut–lung axis” in a contemporary term, the composition of gut microbiota was determined using 16S rRNA and the transcriptome of the colon was determined by RNA sequencing. The results showed that Qingfeiyin decoction decreased the viral load, alleviated the lung injury, increased the survival rate, partly restored the shortening of the colon caused by the H1N1 virus, and downregulated inflammatory pathways including MAPK, TNFα, and JAK-STAT signaling pathways. Qingfeiyin decoction increased the relative abundance of the genera of Coprococcus, Ruminococcus, Lactobacillus, and Prevotella and prevented the H1N1 virus-induced decrease in the abundance of the genera of Escherichia, Parabacteroides, Butyricimonas, and Anacrotruncus. These results will help better understand the mechanisms for Qingfeiyin decoction’s protective effect against influenza virus infection.

Association of lung-intestinal microecology and lung cancer therapy

“…The theory of “The lung and gastrointestinal tract are external and internal” is an important part of the doctrine of visceral manifestation theory. Qingfeiyin decoction can reduce the viral load, partially recover the colon atrophy caused by H1N1 virus, down-regulate the MAPK, tumor necrosis factor α(TNFα)and other inflammatory pathways, reduce lung injury, and improve the survival rate, which fully reflects the effectiveness of “lung-gut co-treatment”, and this theory has been applied to guide the treatment of refractory lung and intestinal diseases such as COVID-19 and ulcerative colitis, and reliable results have been obtained [ 99 , 100 ].In the treatment of lung cancer, it should not only consider the lung but also the physiological function of the large intestine, and the treatment of intestinal diseases should take into account the physiological function of the lung [ 101 – 104 ], which is called “lung-gut co-treatment”. The physio-pathological relationship between the lung and gastrointestinal tract was shown in the Inner Canon of Yellow Emperor more than 3000 years ago, and modern studies have shown that decoctions named “Xuanbai Chengqi”, “Gegen Qinlian”, and tonic herbs such as ginseng, gardenia, angelica, and astragalus can improve acute lung tissue injury and pathological colon tissue damage caused by lipopolysaccharide (LPS) by regulating lung-intestinal mucosal immune function [ 105 – 107 ].Research on the mechanism of traditional Chinese medicine in the treatment of lung cancer has also made progress.…”

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

“…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). Cangma Huadu granules increased the abundance of Bifidobacterium, Parasutterella, Bacteroides, and Faecalibaculum in the intestine of mice at 7 days of PR8 infection, decreased the viral load and lung damage in the lungs, decreased TNF-a and IL-1b levels, and increased IL-10 levels (89).…”

Exploring the active ingredients and pharmacological mechanisms of the oral intake formula Huoxiang Suling Shuanghua Decoction on influenza virus type A based on network pharmacology and experimental exploration

“…Compared with chemical drugs, traditional Chinese medicine (TCM) with thousands of years of history application in preventing and treating influenza has some advantages in the aspect of few adverse reactions and less drug resistance ( Wei et al, 2019 ). In addition, TCM plays an important role in antiviral by killing the virus directly, inhibiting the replication of the influenza virus, alleviating the inflammatory reaction, and enhancing the body’s immunity ( Li et al, 2022 ).…”