Gut-Lung Microbiota in Chronic Pulmonary Diseases: Evolution, Pathogenesis, and Therapeutics.

The microbiota colonized in the human body has a symbiotic relationship with human body and forms a different microecosystem, which affects human immunity, metabolism, endocrine, and other physiological processes. The imbalance of microbiota is usually linked to the aberrant immune responses and inflammation, which eventually promotes the occurrence and development of respiratory diseases. Patients with chronic respiratory diseases, including asthma, COPD, bronchiectasis, and idiopathic pulmonary fibrosis, often have alteration of the composition and function of intestinal and lung microbiota. Gut microbiota affects respiratory immunity and barrier function through the lung-gut microbiota, resulting in altered prognosis of chronic respiratory diseases. In turn, lung dysbiosis promotes aggravation of lung diseases and causes intestinal dysfunction through persistent activation of lymphoid cells in the body. Recent advances in next-generation sequencing technology have disclosed the pivotal roles of lung-gut microbiota in the pathogenesis of chronic respiratory diseases. This review focuses on the association between the gut-lung dysbiosis and respiratory diseases pathogenesis. In addition, potential therapeutic modalities, such as probiotics and fecal microbiota transplantation, are also evaluated for the prevention of chronic respiratory diseases.

Rgl-exomiR-7972, a novel plant exosomal microRNA derived from fresh Rehmanniae Radix, ameliorated lipopolysaccharide-induced acute lung injury and gut dysbiosis.

Plant-derived exosome-like nanoparticles (ELNs) have been proposed as a novel therapeutic tool for preventing human diseases. However, the number of well-verified plant ELNs remains limited. In this study, the microRNAs in ELNs derived from fresh Rehmanniae Radix, a well-known traditional Chinese herb for treating inflammatory and metabolic diseases, were determined by using microRNA sequencing to investigate the active components in the ELNs and the protection against lipopolysaccharide (LPS)-induced acute lung inflammation in vivo and in vitro. The results showed that rgl-miR-7972 (miR-7972) was the main ingredient in ELNs. It exerted stronger protective activities against LPS-induced acute lung inflammation than catalpol and acteoside, which are two well-known chemical markers in this herb. Moreover, miR-7972 decreased the production of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), reactive oxygen species (ROS) and nitric oxide (NO) in LPS-exposed RAW264.7 cells, thereby facilitating M2 macrophage polarization. Mechanically, miR-7972 downregulated the expression of G protein-coupled receptor 161 (GPR161), activating the Hedgehog pathway, and inhibited the biofilm form of Escherichia coli via targeting virulence gene sxt2. Therefore, miR-7972 derived from fresh R. Radix alleviated LPS-induced lung inflammation by targeting the GPR161-mediated Hedgehog pathway, recovering gut microbiota dysbiosis. It also provided a new direction for gaining novel bioactivity nucleic acid drugs and broadening the knowledge on cross-kingdom physiological regulation through miRNAs.

Cephalosporins-induced intestinal dysbiosis exacerbated pulmonary endothelial barrier disruption in streptococcus pneumoniae-infected mice.

Antibiotic abuse is growing more severe in clinic, and even short-term antibiotic treatment can cause long-term gut dysbiosis, which may promote the development and aggravation of diseases. Cephalosporins as the broad-spectrum antibiotics are widely used for prevention and treatment of community-acquired respiratory tract infection in children. However, their potential consequences in health and disease have not been fully elaborated. In this study, the effects of cefaclor, cefdinir and cefixime on intestinal microbiota and lung injury were investigated in Streptococcus pneumoniae (Spn)-infected mice. The results showed that the proportion of coccus and bacillus in intestinal microbiota were changed after oral administration with cefaclor, cefdinir and cefixime twice for 10 days, respectively. Compared with the Spn-infected group, the proportion of Bifidobacterium and Lactobacillus in intestine were significantly reduced, while Enterococcus and Candida was increased after cephalosporin treatment. Furthermore, 3 cephalosporins could obviously increase the number of total cells, neutrophils and lymphocytes in BALF as well as the serum levels of endotoxin, IL-2, IL-1ß, IL-6 and TNF-α. Mechanically, cephalosporins accelerated Spn-induced pulmonary barrier dysfunction via mediating the mRNA expressions of endothelial barrier-related proteins (Claudin 5, Occludin, and ZO-1) and inflammation-related proteins (TLR4, p38 and NF-κB). However, all of those consequences could be partly reversed by Bifidobacterium bifidum treatment, which was closely related to the elevated acetate production, indicating the protective effects of probiotic against antibiotic-induced intestinal dysbiosis. Therefore, the present study demonstrated that oral administration with cephalosporins not only disrupted intestinal microecological homeostasis, but also increased the risk of Spn infection, resulting in severer respiratory inflammation and higher bacterial loads in mice.