PMID- 35673595 OWN - NLM STAT- MEDLINE DCOM- 20220609 LR - 20220724 IS - 1178-2005 (Electronic) IS - 1176-9106 (Print) IS - 1176-9106 (Linking) VI - 17 DP - 2022 TI - The Bufei Jianpi Formula Improves Mucosal Immune Function by Remodeling Gut Microbiota Through the SCFAs/GPR43/NLRP3 Pathway in Chronic Obstructive Pulmonary Disease Rats. PG - 1285-1298 LID - 10.2147/COPD.S359428 [doi] AB - 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-kappaB 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-1beta, 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. CI - (c) 2022 Mao et al. FAU - Mao, Jing AU - Mao J AD - College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. FAU - Li, Ya AU - Li Y AUID- ORCID: 0000-0002-7331-2641 AD - Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. AD - Institute for Respiratory Diseases, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. AD - Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Disease by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. FAU - Bian, Qingqing AU - Bian Q AD - Institute for Respiratory Diseases, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. FAU - Xuan, Yinshuang AU - Xuan Y AD - Institute for Respiratory Diseases, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. FAU - Li, Jingmei AU - Li J AD - Institute for Respiratory Diseases, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. FAU - Wang, Zhikun AU - Wang Z AD - Institute for Respiratory Diseases, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. FAU - Feng, Suxiang AU - Feng S AD - College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. AD - Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. AD - Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Disease by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. FAU - Liu, Xuefang AU - Liu X AD - Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. AD - Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Disease by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. FAU - Tian, Yange AU - Tian Y AD - Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. AD - Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Disease by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. FAU - Li, Suyun AU - Li S AD - Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. AD - Institute for Respiratory Diseases, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. AD - Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Disease by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China. LA - eng PT - Journal Article DEP - 20220601 PL - New Zealand TA - Int J Chron Obstruct Pulmon Dis JT - International journal of chronic obstructive pulmonary disease JID - 101273481 RN - 0 (Drugs, Chinese Herbal) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, rat) RN - 0 (RNA, Ribosomal, 16S) RN - 0 (bufei jianpi) SB - IM MH - Animals MH - Drugs, Chinese Herbal MH - *Gastrointestinal Microbiome MH - Humans MH - Immunity MH - NLR Family, Pyrin Domain-Containing 3 Protein MH - *Pulmonary Disease, Chronic Obstructive MH - RNA, Ribosomal, 16S/genetics MH - Rats MH - Rats, Sprague-Dawley PMC - PMC9167601 OTO - NOTNLM OT - Bufei Jianpi formula OT - chronic obstructive pulmonary disease OT - gut microbiota OT - gut-lung axis OT - mucosal immune function OT - short-chain fatty acids COIS- The authors report no conflicts of interest in relation to this work and declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/06/09 06:00 MHDA- 2022/06/10 06:00 PMCR- 2022/06/01 CRDT- 2022/06/08 01:59 PHST- 2022/01/21 00:00 [received] PHST- 2022/05/22 00:00 [accepted] PHST- 2022/06/08 01:59 [entrez] PHST- 2022/06/09 06:00 [pubmed] PHST- 2022/06/10 06:00 [medline] PHST- 2022/06/01 00:00 [pmc-release] AID - 359428 [pii] AID - 10.2147/COPD.S359428 [doi] PST - epublish SO - Int J Chron Obstruct Pulmon Dis. 2022 Jun 1;17:1285-1298. doi: 10.2147/COPD.S359428. eCollection 2022.