Abstract
Emerging evidence has revealed the presence in animals of a bidirectional regulatory “lung-gut axis” that provides resistance to respiratory infections. Clues to the existence of this system stem from observations that respiratory infections are often accompanied by gastrointestinal symptoms, whereby intestinal microbiota appear to play pivotal roles in combating pathogenic infections. Importantly, short-chain fatty acids (SCFAs) produced by the gut microbiota appear to serve as the biological link between host immune defenses and gut flora. Streptococcus pneumoniae (S.pn), the main cause of lower respiratory tract infections, is involved in more than 1.189 million deaths per year. QingFei Yin (QFY) is known for its excellent therapeutic efficacy in combating bacterial lung infections. In this study, effects of S.pn infection on gut homeostasis were assessed using 16S RNA-based microbiota community profiling analysis. In addition, potential mechanisms underlying QFY recipe beneficial therapeutic effects against bacterial pneumonia were explored using S.pn-infected gut microbiota-depleted mice. Results of data analysis indicated that QFY treatment alleviated lung infection-associated pathogenic processes, while also promoting repair of disordered gut flora and counteracting S.pn infection-associated decreases in levels of SCFAs, particularly of acetate and butyrate. Mechanistically, QFY treatment suppressed inflammatory lung injury through inhibition of the host NF-κB-NLRP3 pathway. These results inspired us to identify precise QFY targets and mechanisms underlying QFY anti-inflammatory effects. In addition, we conducted an in-depth evaluation of QFY as a potential treatment for bacterial pneumonia.
Highlights
As the largest and most complex micro-ecosystem of the human body, the intestinal microbiota has emerged as a positive player in host defenses against pathogens, especially those involved in respiratory infections (McAleer and Kolls, 2018)
The lung W/D ratio was reduced after Qingfei Yin (QFY) treatment (P < 0.05), suggesting that QFY treatment of infected mice significantly reduced pulmonary edema and preserved host immune system balance during S.pn infection
Micro-CT scans and hematoxylin and eosin (H&E) staining were used to investigate lung inflammation induced by S.pn infection, as well as protective effects of QFY against lung tissue injury
Summary
As the largest and most complex micro-ecosystem of the human body, the intestinal microbiota has emerged as a positive player in host defenses against pathogens, especially those involved in respiratory infections (McAleer and Kolls, 2018). The concept of crosstalk occurring between intestinal microbiota and the pulmonary immune system is currently widely accepted and is supported by recent observations. This concept is not new, but was documented 2000 years ago in the medical books of the Yellow Emperor’s Classic of Internal Medicine, where it was described as “The exterior-interior relationship between the lung and the large intestine.”. Pulmonary infection has been shown to trigger disorder of gut bacteria that induce intestinal injury (Perrone et al, 2012). Respiratory symptoms can occur after intestinal injury, further supporting the claim that such symptoms may be a consequence of intestinal floral disruption
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