Fecal Microbiota Transplantation Alleviates Airway Inflammation in Asthmatic Rats by Increasing the Level of Short-Chain Fatty Acids in the Intestine

Abstract

Asthma is a prevalent chronic inflammatory disorder of the respiratory tract that not only manifests with respiratory symptoms but also often involves intestinal flora disorders and gastrointestinal dysfunction. Recent studies have confirmed the close relationship between the gut and lungs, known as the "gut-lung axis" theory. Fecal microbiota transplantation (FMT), a method for restoring normal intestinal flora, has shown promise in treating common gastrointestinal diseases. The "gut-lung axis" theory suggests that FMT may have significant therapeutic potential for asthma. In this study, we established an Ovalbumin (OVA)-induced rat model of asthma to investigate the protective effect of FMT on airway inflammation and the restoration of intestinal short-chain fatty acids (SCFAs), aiming to explore its underlying mechanism. Rats in the Control group underwent fecal treatment via gavage (Control-FMT, C-FMT group), while rats in the Asthma group underwent fecal treatment via gavage after asthma induction (Asthma-FMT, A-FMT group). Following a two-week period of continuous intragastric administration, various measurements were conducted to assess pulmonary function, peripheral blood neutrophil, lymphocyte, and eosinophil content, lung tissue pathology, and collagen fiber deposition in the lungs. Additionally, neutrophil and eosinophil content in bronchoalveolar lavage fluid (BALF), expression levels of Interleukin-4 (IL-4), IL-5, IL-13, IL-17, IL-33, leukotrienes (LT), thymic stromal lymphopoietin (TSLP), prostaglandin D2 (PGD2) protein and mRNA in lung tissue, and SCFAs content in stool were evaluated. In the C-FMT group, lung function significantly improved, inflammatory cell content in peripheral blood and BALF decreased, lung tissue pathology and collagen fiber deposition significantly improved, the protein and mRNA levels of lung inflammatory factors IL-4, IL-5, IL-13, IL-17, IL-33, LT, TSLP, PGD2 were significantly decreased, and SCFAs such as acetate (C2), propionate (C3), butyrate (C4), isobutyric acid (I-C4), valeric acid (C5), and isovaleric acid (I-C5) content in stool significantly increased. However, the indexes in the A-FMT group did not show significant recovery, and the treatment effect on asthma symptoms in rats was inferior to that in the C-FMT group. Asthma induced intestinal flora disorders in rats, and FMT treatment improved the inflammatory response in asthmatic rat models and corrected their intestinal SCFAs disorders. Encouraging the recovery of intestinal SCFAs may play a significant role, and beneficial bacteria present in feces may improve asthma symptoms by promoting the remodeling of intestinal flora. This experiment provides further scientific evidence supporting the "gut-lung axis" theory.

Keywords: Airway inflammation; Asthma; Fecal bacteria transplantation; Gut-lung axis; Short-chain fatty acid.

Fig. 1

Experimental flow chart

Fig.2

FMT demonstrates an improvement in lung function in the asthmatic rat model (n = 8 per group). The data are presented as mean ± SD. Significance is denoted as ★★ for p < 0.01 and ★ for p < 0.05 compared to the Control group, while ▲▲ indicates p < 0.01 and ▲ denotes p < 0.05 compared to the Asthma group

Fig.3

FMT led to a reduction in the lymphocyte and eosinophil content in the peripheral blood of asthmatic rat models. (n = 8 per group). The data are presented as mean ± SD. Significance is denoted as ★★ for p < 0.01 and ★ for p < 0.05 compared to the Control group, while ▲▲ indicates p < 0.01 and ▲ denotes p < 0.05 compared to the Asthma group. # indicates p < 0.05 compared to the C-FMT group

Fig.4

FMT reduces the levels of neutrophils and eosinophils in the bronchoalveolar lavage fluid of the asthma rat model. (n = 8 per group). The data are presented as mean ± SD. Significance is denoted as ★★ for p < 0.01 and ★ for p < 0.05 compared to the Control group, while ▲▲ indicates p < 0.01 and ▲ denotes p < 0.05 compared to the Asthma group. # indicates p < 0.05 compared to the C-FMT group

Fig. 5

Representative captures in the lung, H&E stain

Fig. 6

Collagen fiber deposition in the lung, Masson stain

Fig. 7

FMT significantly improve the degree of collagen deposition in lung tissue of asthma rats model. n = 8 for each group. Data are presented as mean ± SD.Significance is denoted as ★★ for p < 0.01 and ★ for p < 0.05 compared to the Control group, while ▲▲ indicates p < 0.01 and ▲ denotes p < 0.05 compared to the Asthma group

Fig. 8

FMT significantly reduce the protein content of inflammatory cytokines in lung tissue of asthma rats model. n = 8 for each group. Data are presented as mean ± SD. Significance is denoted as ★★ for p < 0.01 and ★ for p < 0.05 compared to the Control group, while ▲▲ indicates p < 0.01 and ▲ denotes p < 0.05 compared to the Asthma group. # indicates p < 0.05 compared to the C-FMT group

Fig. 9

FMT significantly reduce the mRNA content of inflammatory cytokines in lung tissue of asthma rats model. n = 8 for each group. Data are presented as mean ± SD. Significance is denoted as ★★ for p < 0.01 and ★ for p < 0.05 compared to the Control group, while ▲▲ indicates p < 0.01 and ▲ denotes p < 0.05 compared to the Asthma group. # indicates p < 0.05 compared to the C-FMT group

Fig. 10

FMT resulted in an elevation in the content of Short-Chain Fatty Acids (SCFAs) in the stool of the asthma rat model. The study included a total of 8 rats in each group, and the data are presented as mean ± SD. Significance is denoted as ★★ for p < 0.01 and ★ for p < 0.05 compared to the Control group, while ▲▲ indicates p < 0.01 and ▲ denotes p < 0.05 compared to the Asthma group. # indicates p < 0.05 compared to the C-FMT group