The Bufei Jianpi Formula Improves Mucosal Immune Function by Remodeling Gut Microbiota Through the SCFAs/GPR43/NLRP3 Pathway in Chronic Obstructive Pulmonary Disease Rats

Abstract

Purpose Bufei Jianpi formula (BJF), a traditional Chinese medicine, is an effective and safe therapeutic formula for chronic obstructive pulmonary disease (COPD). BJF treatment is known to reduce the incidence of loose stools in rats with COPD. It is unclear whether BJF regulates gut microbiota. This study examined whether BJF improved mucosal immune function by remodeling the gut microbiota and modulating metabolites in COPD rats. Methods Sixty Sprague Dawley (SD) rats were randomized into control, model, BJF, aminophylline (APL), and probiotics (PBT) groups. The stable COPD rat model was duplicated using repeated cigarette smoke inhalation and lipopolysaccharide (LPS) injection. Normal saline, BJF, APL, or PBT were intragastrically administered from weeks eight to twelve, and then the rats were sacrificed at week thirteen. Lung and colon tissues were removed; feces were collected. Pulmonary function, histopathology, levels of inflammatory factors, and activation of NF-κB in the lung tissues were evaluated. Gut microbiota were analyzed using 16S rRNA gene sequencing; fecal short-chain fatty acid (SCFA) concentrations were determined using gas chromatography/mass spectrometry. Mucosal immune response-related genes and proteins were determined using quantitative polymerase chain reaction and Western blotting. Results BJF improved pulmonary function and reduced lung inflammation. Further, BJF treatment altered the gut microbiota composition and significantly increased the abundance of Firmicutes and the ratio of Firmicutes to Bacteroides, raising SCFA levels, including acetate, butyrate, and propionate levels. However, the abundance of Bacteroidetes, Proteobacteria, Spirochaetes, Clostridiaceae, and Treponema decreased after BJF administration. BJF decreased the gene and protein expression of NLRP3, Caspase-1, IL-8, and IL-1β, and increased GPR43 expression. Conclusion Overall, BJF administration improved mucosal immune function by remodeling the gut microbiota and suppressing the SCFAs/GPR43/NLRP3 pathway in COPD rats. This study provides evidence for the mechanisms underlying BJF-induced improvements in COPD and supports clinical application of BJF.

Pharmacological effects of Bufei Jianpi granule on chronic obstructive pulmonary disease and its metabolism in rats

“…For the high dose, we used two times the medium dose, and for low dose, we used two times below the medium dose, to investigate the dose–effect relationship. Except for the blank group, for rats in the other groups, the COPD model was established by administering LPS combined with smoking according to the method with minor modification ( Shin et al, 2017 ; Mao et al, 2022 ; Pelgrim et al, 2022 ). The administration intervention was started in the 6th week, twice a day.…”

“…A total of 24 SD rats were randomly classified into the blank group, blank administration group, model group, and model administration group. In the model groups, the rat model of COPD was established by administering LPS combined with the smoking method ( Shin et al, 2017 ; Mao et al, 2022 ; Pelgrim et al, 2022 ), while in the administration groups, rats were gavaged with 2.36 g/kg solution of BJG, twice a day for 7 consecutive days. The blank group and the model group were given the same amount of normal saline.…”

Inflammatory Response: A Crucial Way for Gut Microbes to Regulate Cardiovascular Diseases

“…One is being recognized by the immune cells directly and induced innate or adaptive immune responses [ 26 , 27 ], which is confirmed in inflammatory bowel disease [ 28 ]. The other is to modify the function of immune cells by producing active substances, such as short-chain fatty acids (SCFAs), indoleacetic acid (IAA), trimethylamine N -oxide (TMA-O) [ 29 , 30 , 31 , 32 ].…”

Targeting Lung–Gut Axis for Regulating Pollution Particle–Mediated Inflammation and Metabolic Disorders

“…Nevertheless, treatment with SCFAs may stimulate the GPR41/43 axis and reduce HDAC levels, thus inhibiting inflammation [ 110 ]. Bufei Jianpi formula (BJF), a type of traditional Chinese medicine, alleviates lung inflammation and improves lung function, significantly increasing the Firmicutes population, the Firmicutes -to- Bacteroidetes ratio, and SCFA levels [ 111 ]. BJF also downregulates the expression of the NLRP3/Caspase-1/IL-8/IL-1β axis by upregulating SCFA/GPR43 signaling [ 111 ].…”

“…Bufei Jianpi formula (BJF), a type of traditional Chinese medicine, alleviates lung inflammation and improves lung function, significantly increasing the Firmicutes population, the Firmicutes -to- Bacteroidetes ratio, and SCFA levels [ 111 ]. BJF also downregulates the expression of the NLRP3/Caspase-1/IL-8/IL-1β axis by upregulating SCFA/GPR43 signaling [ 111 ]. In ovalbumin (OVA)-challenged mice, butyrate administration could alleviate lung inflammation and mucus generation, with reduced numbers of lung-infiltrated eosinophils and Th9 cells [ 112 ].…”