Approximately, 33.6% of nondiabetic solid organ transplantation recipients who received tacrolimus developed hyperglycemia. Whether the tacrolimus‐induced gut microbiota is involved in the regulation of hyperglycemia has not been reported. Hyperglycemia was observed in a tacrolimus‐treated mouse model, with reduction in taxonomic abundance of butyrate‐producing bacteria and decreased butyric acid concentration in the cecum. This tacrolimus‐induced glucose metabolic disorder was caused by the gut microbiota, as confirmed by a broad‐spectrum antibiotic model. Furthermore, oral supplementation with butyrate, whether for remedy or prevention, significantly increased the butyric acid content in the cecum and arrested hyperglycemia through regulation of glucose‐regulating hormones, including GLP‐1, PYY and insulin, in serum. The butyrate‐GRP43‐GLP‐1 pathway in the intestine crypts may involve in the pathogenesis of normalization of hyperglycemia caused by the tacrolimus. Therefore, tacrolimus affects glucose metabolism through the butyrate‐associated GLP‐1 pathway in the gut, and oral supplementation with butyrate provides new insights for the prevention and treatment of tacrolimus‐induced hyperglycemia in transplant recipients.

Chronic renal failure, progressing to the irreversible condition of ESKD, requires efficient RRT, typically dialysis or kidney transplantation (1). Compared with dialysis, kidney transplantation significantly benefits the survival and quality of life of ESKD patients and carries less of a burden. This minireview summarizes the development of kidney transplantation in China in recent years. In addition, we briefly introduce the human organ sharing system in China, which helps achieve justifiable, fair, and transparent organ allocation.

Mycophenolate mofetil (MMF) is one of the most used immunosuppressive drugs in organ transplantation, but frequent gastrointestinal (GI) side effects through unknown mechanisms limit its clinical use. Gut microbiota and its metabolites were recently reported to play a vital role in MMF-induced GI toxicity, but the specific mechanism of how they interact with the human body is still unclear. Here, we found that secondary bile acids (BAs), as bacterial metabolites, were significantly reduced by MMF administration in the gut of mice. Microbiome data and fecal microbiota transfer model supported a microbiota-dependent effect on the reduction of secondary BAs. Supplementation of the secondary BA lithocholic acid (LCA) alleviated MMF-induced weight loss, colonic inflammation, and oxidative phosphorylation damage. Genetic deletion of the vitamin D3 receptor (VDR), which serves as a primary colonic BA receptor, in colonic epithelial cells (VDR^ΔIEC) abolished the therapeutic effect of LCA on MMF-induced GI toxicity. Impressively, we discovered that paricalcitol, an FDA-approved VDR agonist that has been used in clinics for years, could effectively alleviate MMF-induced GI toxicity. Our study reveals a previously unrecognized mechanism of gut microbiota, BAs, and VDR signaling in MMF-induced GI side effects, offering potential therapeutic strategies for clinics.

Acute kidney injury (AKI) severely impairs renal function. In early AKI, tubular cells release damage-associated molecular patterns (DAMPs) that induce neutrophil recruitment. Infiltrating neutrophils can exacerbate kidney injury through degranulation or formation of neutrophil extracellular traps (NETs), but the specific DAMPs mediating early neutrophil chemotaxis remain unclear. We integrated single-cell and spatial transcriptomic data from early AKI kidneys to identify signaling pathways underlying crosstalk between injured tubular cells and neutrophils. A murine unilateral ischemia–reperfusion injury (uIRI) model was then established, with intraperitoneal administration of the anti-inflammatory drug mesalazine (5-aminosalicylic acid, 5-ASA) during the perioperative period, followed by assessment of renal histopathology and function. In vitro, polymorphonuclear neutrophils (PMNs) were isolated from mouse peripheral blood and co-cultured with renal tubular cells in a Transwell migration system under hypoxia/reoxygenation (H/R), with 5-ASA treatment or Spp1 knockdown to evaluate effects on PMN migration. Integrated single-cell and spatial transcriptomic analyses revealed that injured tubular cells upregulate Spp1, which interacts with Cd44 on neutrophils. In vivo and in vitro, injured tubular cells released Spp1 in a paracrine manner, enhancing Cd44⁺ neutrophil migration, impairing tubular regeneration, and aggravating AKI progression. 5-ASA attenuated this process by suppressing Spp1 expression and paracrine signaling, thereby reducing early Cd44⁺ neutrophil infiltration, promoting tubular cell proliferation, and improving renal function. This study provides the first evidence that tubular cell-derived Spp1 functions as a key DAMP mediating the early recruitment of Cd44⁺ neutrophils in AKI. By inhibiting paracrine Spp1, 5-ASA limits neutrophil migration and ameliorates renal injury, supporting its therapeutic potential in AKI. Targeting Spp1 may represent a promising new strategy for AKI treatment.

Introduction: Emerging research emphasizes the critical role of local microbiota in shaping the tumor microenvironment (TME) and influencing cancer progression. Lung adenocarcinoma (LUAD) is distinguished by unique bacterial communities that appear to regulate immune responses, gene expression, and patient outcomes. Methods: We compiled microbiome profiles from several cancer types—including LUAD, lung squamous cell carcinoma (LUSC), breast carcinoma (BRCA), and thyroid carcinoma (THCA)—using public databases. Non-negative matrix factorization (NMF) was employed to categorize LUAD cases based on TME features, while DESeq2 was used to pinpoint bacterial taxa with differing abundance. Multi-omics networks were developed to integrate microbial, transcriptomic, and clinical data. For in vitro verification, we conducted siRNA-mediated knockdown of the long non-coding RNA LCIIAR and ISG15 in Lewis lung carcinoma cells, followed by proliferation assays. Results: In contrast to LUSC, BRCA, and THCA, LUAD exhibited distinct microbial populations, with notable enrichment of Cylindrospermopsis, Cyanothece, and Sulfolobus. NMF clustering identified two LUAD subtypes with differing prognoses. One longer survival cluster, marked by reduced bacterial presence and stronger antitumor immunity—reflected in stronger immune response, increased effector T cells activity, and greater immune cell infiltration. A competing endogenous RNA (ceRNA) network analysis established a link between LCIIAR and ISG15, both overexpressed in LUAD and associated with worse survival outcomes. Knockdown LCIIAR or ISG15 through siRNA significantly inhibited lung cancer cell proliferation, pointing to their roles in tumor growth and ceRNA-mediated regulation. Conclusion: LUAD features a distinctive microbiota that engages with inflammatory and ceRNA regulatory pathways. These observations underscore the value of targeting microbiome-influenced mechanisms, such as the LCIIAR–ISG15 axis, as a promising approach to enhance treatment outcomes in lung adenocarcinoma.