Cong Ding’s research while affiliated with Hangzhou First People's Hospital and other places

Acute pancreatitis (AP) is characterized by autodigestion of the pancreas, and some patients may rapidly progress to systemic inflammation, pancreatic necrosis, and multi-organ failure. Numerous studies have detailed the bidirectional communication networks between the pancreas and the intestinal microbiota, as well as its metabolites. Such crosstalk affects the progression of AP and recovery through intestinal barrier disruption. Furthermore, advances in experimental research and clinical studies have indicated that gut microorganisms exhibit distinct alterations in response to different levels of severity and etiologies of AP. This information has greatly expanded our knowledge of the role of the gut microflora and microbial metabolites in the pathology of disease and has reinforced the basis of therapeutic approaches that target candidate intestinal microbiota. In this review, we aim to provide an overview of the composition and diversity of the gut microbial community, to highlight the candidate bacteria and microbiota-derived metabolites responsible for AP, and to elucidate their interactions with and regulation of immune-relevant receptors in intestinal epithelial cells (IECs) in the host. Future research should focus on identifying and characterizing AP-associated bacterial strains, elucidating their distinct pathogenic mechanisms across different etiologies and stages of AP, and leveraging these insights to develop preventive and therapeutic strategies.

Aims: Primary choledocholithiasis is a common digestive disease with high morbidity and relapse. However, the compositions and functions of the bile microbial ecosystem and the pathogenesis of microfloral regulation of host metabolism resulting in stone formation are poorly understood. Main methods: Biliary samples collected from patients with acute cholangitis induced by benign biliary stricture (nonlithiasis group, n = 17) and primary choledocholithiasis (lithiasis group, n = 33) were subjected to multiomics analyses. Furthermore, clinicopathological features collected over a 24-month follow-up period were examined to evaluate the predictive value of candidate microbes. Key findings: Five alpha diversity indices of the bile microbiome were significantly decreased in the lithiasis group. Furthermore, we identified 49 differential bile flora between the two groups, and the relative abundances of 6 bacteria, Actinobacteria, Actinobacteriota, Staphylococcales, Micrococcales, Altererythrobacter and Carnobacteriaceae, were associated with primary choledocholithiasis relapse conditions. Multiomics analyses showed that specific changes in disease-related bacterial taxa were closely related to metabolite variation (low-molecular weight carboxylic acids, sterol liquid and acylcarnitine), which might reflect disease prognosis. According to microbiomic and metabolomic pathway analyses, we revealed that bacterial infections, microbiota-derived amino acid metabolites and secondary bile acid-related pathways were significantly enriched in the stone-formation group, suggesting a novel host-microbial metabolic mechanism of primary choledocholithiasis. Significance: Our study first indicates bile host-microbial dysbiosis modulates the abnormal accumulation of metabolites might further disrupt calcium homeostasis and generate insoluble saponification. Additionally, we determined the predictive value of Actinomycetes phylum reduction for recurrence in primary common bile duct stone patients.

Tumor distant metastasis is the primary cause of death in colorectal cancer (CRC) patients. GL-V9 is a newly synthesized flavonoid derivative with several beneficial biological functions including anti-tumor and anti-inflammation. However, the anti-metastatic effect of GL-V9 and related mechanisms in CRC remains unknown. In this study, the anti-invasive and anti-migratory activities of GL-V9 were investigated in CRC cells. Using MTT assay, cell wound healing assay, and transwell migration assay, we showed that GL-V9 suppressed CRC cell viability, migration, and invasion in a concentration-dependent manner. In addition, the protein expression levels as well as activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were significantly reduced after GL-V9 treatment. Further analysis of the underlying mechanism revealed that GL-V9 inhibited PI3K/Akt signaling pathway upstream of MMP-2 and MMP-9. In conclusion, our study demonstrated that GL-V9 could suppress CRC cell invasion and migration through PI3K/Ak and MMP-2/9 axis. Therefore, GL-V9 might be a potential novel therapeutic agent against CRC metastasis.