Alleviation of allergic asthma by rosmarinic acid via gut-lung axis.

BACKGROUND: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. PURPOSE: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. METHODS: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. RESULTS: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. CONCLUSIONS: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.

Bacterial butyrate mediates the anti-atherosclerotic effect of silybin.

Silybin (SIL) is a versatile bioactive compound used for improving liver damage and lipid disorders and is also thought to be beneficial for atherosclerosis (AS). The goal of this study was to investigate the efficacy of SIL in the treatment of AS in ApoE-/-mice fed a high-fat diet and explore the mechanism underlying treatment outcomes. We found that SIL significantly alleviated AS-related parameters, including the extent of aortic plaque formation, hyperlipidemia, and adhesion molecule secretion in the vascular endothelium. 16 S rRNA gene sequencing analysis, together with the application of antibiotics, showed that intestinal butyrate-producing bacteria mediated the ameliorative effect of SIL on AS. Further analysis revealed that SIL facilitated butyrate production by increasing the level of butyryl-CoA: acetate CoA-transferase (BUT). The increased expression of monocarboxylic acid transporter-1 (MCT1) induced by butyrate and MCT4 induced by SIL in the apical and basolateral membranes of colonocytes, respectively, resulted in enhanced absorption of intestinal butyrate into the circulation, leading to the alleviation of arterial endothelium dysfunction. Moreover, the SIL-mediated increase in intestinal butyrate levels restored gut integrity by upregulating the expression of tight junction proteins and promoting gut immunity, thus inhibiting the AS-induced inflammatory response. This is the first study to show that SIL can alleviate AS by modulating the production of bacterial butyrate and its subsequent absorption.

Soil microbial communities response to different fertilization regimes in young Catalpa bungei plantation.

Fertilization is a fundamental aspect of global forest management that enhances forest productivity and drastically affects soil microbial communities. However, few studies have investigated the differences and similarities in the responses of below-ground microbial communities to different fertilization schemes. The effects of fertilization regimes on the composition and diversity of soil fungal and bacterial communities were investigated in a young Catalpa bungei plantation in Shandong Province, Eastern China. Soil microbial communities were assessed undergoing three types of fertilization: (i) no fertilization (CK), (ii) hole fertilization (HF), and (iii) the integration of water and fertilizer (WF). We further analyzed the effects of soil depth (i.e., 0-20 and 20-40 cm) on the structure of soil microbial communities. Our results indicated that the diversity of bacteria (e.g., Chao1 and Shannon indices) reduced undergoing fertilization, and WF had a higher negative impact on bacterial diversity than HF. A lower bacterial diversity was observed in the subsoil compared to the topsoil. In contrast to bacterial diversity, fungal diversity had a slightly increasing trend in the fertilized environments. The primary bacterial function was metabolism, which was independent of fertilization or soil depth. Among fungal functional guilds, symbiotic soil fungi decreased obviously in the fertilized stand, whereas saprotrophic fungi increased slowly. According to the structural equation models (SEM), the diversity and composition of bacterial and fungal communities were jointly regulated by soil nutrients (including N and P contents) directly affected by fertilization and soil layer. These findings could be used to develop management practices in temperate forests and help sustain soil microbial diversity to maintain long-term ecosystem function and services.