Chronic kidney disease (CKD) affects approximately 10% of the global population. Muscle atrophy occurs in patients with almost all types of CKD, and the gut microbiome is closely related to protein consumption during chronic renal failure (CRF). This study investigated the effects of Bacteroides plebeius on protein energy consumption in rats with CKD, and our results suggest that Bacteroides plebeius may combat muscle atrophy through the Mystn/ActRIIB/SMAD2 pathway. A total of 5/6 Nx rats were used as a model of muscle wasting in CKD. The rats with muscle wasting were administered Bacteroides plebeius (2 × 10⁸ cfu/0.2 ml) for 8 weeks. The results showed that Bacteroides plebeius administration significantly inhibited muscle wasting in CKD. High‐throughput 16 S rRNA pyrosequencing revealed that supplementation with Bacteroides plebeius rescued disturbances in the gut microbiota. Bacteroides plebeius could also enhance the barrier function of the intestinal mucosa. Bacteroides plebeius may modulate the gut microbiome and reduce protein consumption by increasing the abundance of probiotics and reducing damage to the intestinal mucosal barrier. Our findings suggest that Bacteroides plebeius may combat muscle atrophy through the Mystn/ActRIIB/SMAD2 pathway.

Shenshuai Yingyang Jiaonang (SSYYJN), a traditional Chinese medicine formula, can ameliorate muscle atrophy associated with chronic kidney disease (CKD). However, its mechanisms of action remain unclear. This study is to investigate the molecular mechanisms involved in the effects of SSYYJN in ameliorating muscle atrophy associated with CKD in rats. Methods: The chemical compounds of SSYYJN were identified by UPLC-Q-Orbitrap HRMS. Considering the dose-response relationship of the identified compounds, male SD rats were randomly divided into Sham, Model, SSYYJN, and α-Keto Acid (KA) groups. Subsequently, we assessed the therapeutic and anti-ferroptotic effects of SSYYJN. Network pharmacology studies were used to predict the molecular mechanism of SSYYJN on ferroptosis and were further verified for accuracy. A total of 42 active compounds were identified from SSYYJN. SSYYJN alleviated muscle atrophy caused by CKD, as evidenced by changes in body weight, serum biochemical indices, mass and histopathology of the skeletal muscle, and the levels of MuRF1. SSYYJN reduced the levels of iron, MDA, and ROS, increased the levels of GSH, NAPDH, and Gpx4. Network pharmacology analysis indicated that SSYYJN exerted anti-ferroptotic effects that were closely related to the HIF-1α signaling pathway. Molecular protein and genetic test results showed that SSYYJN increased HIF-1α protein and increased SLC7A11. SSYYJN attenuates muscle atrophy in CKD by inhibiting ferroptosis through the activation of the HIF-1α/SLC7A11 pathway and might be a promising traditional Chinese medicine for muscle atrophy in CKD.

The alteration of gut microbiota during critical illness is associated with adverse clinical outcomes. This connection between intestinal dysbiosis and poor outcomes has prompted the idea that restoring healthy microbial communities could offer a novel approach to life-support treatment for patients with severe pneumonia. In this study, using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we demonstrated that alterations in intestinal microbiota structure during pneumonia exacerbate disease outcomes. A notable feature of these alterations is the reduction in the relative levels of Streptococcus salivarius ( S. salivarius ). In combination with metabolomics analysis, we found that the administration of S. salivarius increased the level of ilexgenin A (IA) in mice, which enhances the resistance of mice to Pseudomonas aeruginosa ( P. aeruginosa )-induced pneumonia. Mechanistically, IA regulates lipopolysaccharide-induced overexpression of macrophage inflammation through Toll-like receptor 4 (TLR4)-mediated NF-κB and MAPK signaling pathways. Our findings reveal the role of the microbial–immune axis in pneumonia, highlighting the potential of S. salivarius and IA in providing promising treatment strategies for pneumonia. IMPORTANCE: One of the major challenges faced by the clinical microbiome research community is to convert the connections between dysbiosis and negative clinical outcomes into rationalized and targeted therapeutic interventions. In the present work, 30 fecal samples from pneumonia and non-pneumonia patients were subjected to FMT and 16S rRNA analysis. The results revealed that a characteristic feature of gut microbiota dysbiosis in pneumonia hosts is the reduction of S. salivarius . Supplementation with S. salivarius can effectively enhance the resistance of mice to P. aeruginosa pneumonia. Moreover, we confirmed the anti-inflammatory effects of IA derived from S. salivarius both in vivo and in vitro . Thus, these findings enhance our understanding of how gut microbiota influences the outcomes of pneumonia and underscore the potential of S. salivarius as a precision microbial therapeutic for combating pneumonia.

Lung squamous cell carcinoma (LUSC) is highly metastatic and has a poor prognosis. Traditional Chinese medicine plays an important role in comprehensive LUSC treatment. Particularly, Smilax china L. (S. china) possesses anti-tumour activity, and gypsum has antipyretic properties; when combined, they can exert a synergistic anti-tumour effect by entering the lung meridian. Although prescriptions containing S. china are clinically used in traditional Chinese medicine to treat various tumours, the efficacy and mechanism of S. china–gypsum plaster in LUSC remain unclear. Here, we aimed to screen and verify the potential target genes of S. china–gypsum in LUSC treatment. The target genes of S. china and gypsum S. china were predicted using database analysis. cell viability, crystal violet staining, cell wound healing, immunofluorescence, flow cytometry, and reverse transcription polymerase chain reaction assays were conducted to assess the inhibitory effect and mechanism of S. china–gypsum on SK-MES-1 cells. We identified 57 intersection genes of the S. china–gypsum drug pair and LUSC. Among them, four genes (APOBEC3A, CHRM1, S1PR2, and TOP2A) affecting LUSC prognosis were differentially expressed. Correlation analysis showed that APOBEC3A, S1PR2, and TOP2A were associated with LUSC. S. china (25–200 µg/ml) and gypsum (5–200 ng/ml), alone or combined, significantly inhibited SK-MES-1 cell proliferation. S. china–gypsum (50 µg/ml + 25 ng/ml) inhibited SK-MES-1 cell wound healing, colony formation and proliferation; down-regulated TOP2 expression and increased apoptosis and APOBEC3A and S1PR2 expression. Our findings highlight the in vitro inhibitory effects of S. china–gypsum on LUSC and suggest APOBEC3A, S1PR2, and TOP2A as potential targets of the S. china drug pair in LUSC treatment.