The gut microbiota plays a critical role in regulating the severity of IAV infection by modulating host immunity [
59]. Studies have shown that manipulating the gut microbiota to influence both innate and adaptive immunity is an effective approach to combating viral infections [
60]. Following influenza virus infection, CCR9
+ CD4
+ T cells, which are effector cells derived from the lung, are recruited to the small intestine where they secrete Interferon-γ(Interferon-γ, IFN-γ). This leads to an imbalance in the gut microbiota that promotes Th17 cell polarization in the small intestine. Ultimately, this results in IL-17 A secretion, which mediates immune damage [
61]. Numerous studies have demonstrated that traditional Chinese medicine can have antiviral effects by regulating the gut microbiota and modulating host immunity. For example, GeGen QinLian decoction (GeGen QinLian decoction, GQD) composed of
Scutellariae Radix, Coptidis Rhizoma, Puerariae Lobatae Radix, and
Glycyrrhizae Radix et Rhizoma, exhibits the effects of relieving muscle tension, clearing heat, and stopping diarrhea. Studies have shown that the treatment with GQD can increase
Akkermansia_muciniphila, Desulfovibrio_C21_c20, and
Lactobacillus_salivarius in the intestines of mice infected with influenza A virus, while reducing
Escherichia coli. This leads to a decrease in the mortality rate and improved lung inflammation in influenza-infected mice. Furthermore, the combination of GQD with fecal microbiota transplantation can suppress the inflammatory differentiation of CD4 + T cells and exhibit systemic protection. These findings suggest that GQD can influence systemic immunity by modulating the gut microbiota [
62]. The Feixi Tiaozhi Fang (FTF) is composed of
Astragalus membranaceus, Saposhnikovia divaricata, Angelica dahurica, Ardisia crenata, Magnolia biondii, Prunus armeniaca, Lepidium apetalum and
Glycyrrhiza uralensis. Liu et al. [
63] have shown that FTF can increase Desulfovibrio in the gut microbiota of rats, while decreasing
Ralstonia and Blautia in the lung microbiota. FTF has been found to significantly elevate the levels of sIgA and SCFAs in lung and intestinal tissues, indicating its ability to regulate the composition and structure of the lung and gut microbiota, as well as the levels of sIgA in the lung and gut. Moreover, a correlation analysis between the gut microbiota and sIgA in rats revealed a negative correlation between
g__Lactobacillus and gut mucosal sIgA, suggesting that
g__Lactobacillus may inhibit intestinal mucosal immunity. Xuanfei Baidu decoction(The composition consists of
Ephedrae Herba, Polygoni Cuspidati Rhizoma et Radix, Glycyrrhizae Radix et Rhizoma, Coicis Semen, Gypsum Fibrosum, Atractylodis Rhizoma, Artemisia Annua Herba, Pogostemonis Herba, Descurainiae Semen Lepidii Semen, Verbenae Herba, Phragmitis Rhizoma, Exocarpium, and
Armeniacae Semen Amarum) has been found to regulate gut microbiota diversity and positively correlate with the changes in
Bacteroides, Escherichia-Shigella, Eubacterium nodatum, Turicibacter, and
Clostridium sensu stricto 1, which are associated with TNF-a levels. Additionally, Xuanlung Baidu decoction can reconstruct gut immunity by down-regulating the Th1/Th2 ratio [
64]. Rosin acid has been shown to regulate the relative abundance of inflammatory bacteria in the gut microbiota of mice by reducing the levels of Anaerotruncus and
Christensenella, and increasing the levels of
Kurthia, Citrobacter, and
Klebsiella. Moreover, it can modulate the Th17/Treg balance in the spleen of mice and down-regulate serum TNF-α and IL-17 A levels [
65]. Finally, the inflammation-nourishing syrup, a traditional Chinese medicine formulation, has been demonstrated to improve the inflammatory response by modulating gut microbiota, increasing the production of microbial-derived short-chain fatty acids, and regulating the Th1/Th2 and Treg/Th17 cell balance [
66]. These findings highlight the important role of traditional Chinese medicine in regulating gut microbiota to impact immune function and alleviate inflammation in the context of influenza infection (as shown in Fig.
1).