Mycobacterium vaccae alleviates allergic airway inflammation and airway hyper‐responsiveness in asthmatic mice by altering intestinal microbiota

Host immunity can influence the composition of the gut microbiota and consequently affect disease progression. Previously, we reported that a Mycobacterium vaccae vaccine could ameliorate allergic inflammation in asthmatic mice by regulating inflammatory immune processes. Here, we investigated the anti‐inflammatory effects of M. vaccae on allergic asthma via gut microbiota modulation. An ovalbumin (OVA)‐induced asthmatic murine model was established and treated with M. vaccae. Gut microbiota profiles were determined in 18 BALB/c mice using 16S rDNA gene sequencing and metabolomic profiling was performed using liquid chromatography quadrupole time‐of‐flight mass spectrometry. Mycobacterium vaccae alleviated airway hyper‐reactivity and inflammatory infiltration in mice with OVA‐induced allergic asthma. The microbiota of asthmatic mice is disrupted and that this can be reversed with M. vaccae. Additionally, a total of 24 differential metabolites were screened, and the abundance of PI(14:1(9Z)/18:0), a glycerophospholipid, was found to be correlated with macrophage numbers (r = 0.52, p = 0.039). These metabolites may affect chemokine (such as macrophage chemoattractant protein‐1) concentrations in the serum, and ultimately affect pulmonary macrophage recruitment. Our data demonstrated that M. vaccae might alleviate airway inflammation and hyper‐responsiveness in asthmatic mice by reversing imbalances in gut microbiota. These novel mechanistic insights are expected to pave the way for novel asthma therapeutic strategies. Diagram of the possible mechanisms. Dysbiosis of gut microbiota changed the microbial metabolism (such as PI(14:1(9Z)/18:0)) in asthmatic mice, which might lead to an increase in chemokines (such as macrophage chemoattractant protein‐1 [MCP‐1]) in the serum, eventually leading to the recruitment of lung macrophages. Mycobacterium vaccae may reverse this process via the gut–lung axis, thereby improving airway hyper‐responsiveness and airway inflammation in asthma. This figure was drawn using the Figdraw software.