Search Results (2,071)

The prevalence of diabetes and heart failure rises sharply with age, and their coexistence amplifies cardiovascular and renal risk. Elderly patients display unique clinical and biological profiles characterised by frailty, multimorbidity, and pharmacodynamic variability that challenge conventional treatment strategies. Sodium–glucose co-transporter-2 inhibitors (SGLT2i) have emerged as a cornerstone of cardio–renal–metabolic protection, with the most consistent cardiovascular benefit being the reduction in heart failure hospitalisation, whereas effects on cardiovascular death and major adverse cardiovascular events vary according to baseline cardiovascular risk, heart failure phenotype, diabetic status, and trial design. However, real-world use among the elderly remains limited due to concerns about tolerability, polypharmacy, and cost. This review analyses the pharmacological rationale and evidence base for SGLT2i therapy in older adults, highlighting mechanisms beyond glucose control, quantitative data from pivotal trials, and practical issues for geriatric implementation. Full article

Associated with high morbidity and mortality, cisplatin-induced acute kidney injury (AKI) is a common clinical complication characterized by oxidative stress, inflammation, and mitochondria-associated signaling. Although multiple signaling pathways have been implicated in AKI progression, effective interventions targeting these complex mechanisms are still lacking. As a medicinal fungus with antioxidant and anti-inflammatory properties, Schizophyllum commune (SC) has shown potential biological activities; however, its renoprotective effects in cisplatin-induced AKI remain unclear. Therefore, this study aimed to investigate SC’s protective effects and underlying mechanisms in a cisplatin-induced AKI mouse model. SC treatment improved renal function and attenuated histopathological damage. It reduced oxidative stress and inflammatory responses, as evidenced by the modulation of malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), and pro-inflammatory cytokines. Mechanistically, SC regulated multiple signaling pathways, including mitogen-activated protein kinase (MAPK), toll-like receptor 4/nuclear factor kappa B (TLR4/ NF-κB), PI3K/AKT, nuclear factor erythroid 2–related factor 2/heme oxygenase-1 (Nrf2/HO-1), and the calcium/calmodulin-dependent protein kinase kinase–AMP-activated protein kinase–sirtuin 1 (CaMKK–AMPK–Sirt1) axis. In addition, SC modulated apoptosis, autophagy, and PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy, suggesting improved mitochondrial homeostasis. These findings indicate that SC exerts renoprotective effects and may contribute to cisplatin-induced nephrotoxicity mitigation strategies. Full article

Elabela (ELA/APELA/Toddler) is an endogenous peptide ligand of the apelin receptor APLNR (also known as APJ) and, together with apelin, forms the apelinergic signalling system. Its role in embryonic development, the cardiovascular system, the kidneys and the endothelium is becoming increasingly well characterised, whilst its function in metabolic regulation remains unresolved. Elabela activates pathways essential for metabolic homeostasis—PI3K/Akt, AMPK-related pathways, redox regulation, inflammatory control and pro-survival cascades—but no study has shown that it directly regulates adipocyte lipid metabolism. This narrative review categorises the evidence at the receptor, organ, immunometabolic and intra-adipocyte levels, and also considers the adipose tissue microenvironment as a distinct level of potential relevance. The available data support a role for Elabela as a candidate mediator of lipid-related metabolic dysfunction—via anti-inflammatory, antioxidant and tissue-protective mechanisms—with macrophage lipid metabolism representing the most informative immunometabolic interface. Human studies remain scarce, heterogeneous and limited by a lack of standardisation in assay methods and the unresolved specificity of isoforms. Elabela should therefore be regarded as a candidate indirect modulator of metabolic homeostasis and a candidate biomarker of cardiometabolic stress or adaptation—not as a confirmed direct regulator of adipocyte lipid metabolism. Full article

Background: Acute kidney injury (AKI) is one of the more serious complications following cardiac surgery, consistently linked to prolonged mechanical ventilation and higher in-hospital mortality. This study examined whether preoperative anaemia and impaired renal function are associated with AKI and death in a high-risk cardiac-surgery cohort requiring extended postoperative ICU monitoring and how these associations behave after adjustment for procedure type and intraoperative variables. Methods: In this single-centre retrospective cohort study, we screened 950 patients admitted to a cardiothoracic ICU between January 2018 and January 2024. After standard exclusion criteria and an audit of operative records, 553 cardiac-surgery patients formed the principal analysis cohort. AKI was defined by KDIGO criteria using serial postoperative serum-creatinine measurements during the first 7 days. Multivariable logistic regression for AKI and in-hospital mortality was built sequentially: Model A (baseline only); Model B (+procedure type); and Model C (+intraoperative variables: aortic cross-clamp time, intraoperative RBC units, and intraoperative inotrope use). Calibration was assessed by the Hosmer–Lemeshow test. Total cardiopulmonary bypass duration was not separately captured in the institutional database and is disclosed as a limitation. Results: AKI occurred in 174 of 553 patients (31.5%), and in-hospital mortality was 16.6% (92/553). Patients with AKI were older (median 77 vs. 68 years, p < 0.001), with lower preoperative haemoglobin (11.4 vs. 12.3 g/dL, p < 0.001) and lower eGFR (38.1 vs. 63.7 mL/min/1.73 m², p < 0.001). The aortic cross-clamp time was shorter in AKI patients (56 vs. 70 min, p = 0.043), a counterintuitive finding likely reflecting residual confounding by case-mix and procedure selection rather than a protective operative effect. In the fully adjusted multivariable model, the haemoglobin–AKI association attenuated and was no longer independently significant (OR 0.89 per 1 g/dL, 95% CI 0.73–1.08, p = 0.24), while intraoperative RBC transfusion emerged as an independent predictor (OR 1.12 per unit, p = 0.046). For mortality, AKI remained an independent predictor after full adjustment for procedure type and intraoperative variables (OR 7.14, 95% CI 1.45–35.13, p = 0.016), with cross-clamp time (OR 1.30 per 10 min, p = 0.010) and intraoperative RBC units (OR 1.48 per unit, p < 0.001) also independently associated. Both fully adjusted models showed acceptable calibration (Hosmer–Lemeshow p = 0.48 for AKI, p = 0.56 for mortality). Conclusions: In cardiac-surgery patients with a prolonged ICU stay, AKI is independently associated with in-hospital mortality even after adjustment for operative variables. The univariable association between preoperative haemoglobin and AKI is attenuated after adjustment for procedure type and intraoperative transfusion exposure, suggesting confounding or mediation by operative and case-mix factors rather than an independent direct association. The contribution of this analysis is aetiological/analytical rather than predictive (modest discrimination, AUROC 0.67 for AKI), and findings should be interpreted within the selected high-risk ICU ≥ 72 h population. Full article

Acute kidney injury (AKI) caused by ischemia–reperfusion injury (IRI) involves rapid activation of innate immune responses, in which myeloid-derived immune cells critically shape injury severity. Y-box binding protein 1 (YB-1) regulates pro-inflammatory gene expression intracellularly and can be secreted to function extracellularly, yet how these two compartments jointly influence early IRI pathology remains poorly understood. To dissect the roles of intracellular myeloid versus extracellular YB-1, we subjected myeloid-specific Ybx1 knockout, Ybx1^fl/fl × LysM^cre, mice and wild-type (WT) littermates to unilateral renal IRI following administration of either a neutralizing anti-YB-1 antibody or control IgG. Kidney injury, inflammation, immune cell recruitment, neutrophil extracellular trap (NET) formation, antibody localization, and Fcγ receptor expression were assessed by qRT-PCR, histology, immunostaining, Western blotting, and flow cytometry. Myeloid-specific knockout of Ybx1 markedly reduced renal inflammation, neutrophil infiltration, NET formation, and tubular injury. This protective phenotype was lost when extracellular YB-1 was simultaneously reduced: anti-YB-1 treatment in knockout mice restored pro-inflammatory cytokine expression, increased tubular damage markers such as NGAL and KIM-1, exacerbated neutrophil recruitment and NET formation, and led to luminar accumulation of YB-1/anti-YB-1 immune complexes in tubular cells. Mechanistically, Ybx1-deficient myeloid cells exhibited significantly reduced CD16 expression, pointing to impaired Fcγ receptor-mediated phagocytosis as the cause of defective immune complex clearance. In contrast, wild-type mice efficiently cleared extracellular YB-1 complexes and showed no injury aggravation upon antibody treatment. Our findings identify myeloid YB-1 as a central regulator of early inflammatory injury in renal IRI and reveal that its protective depletion becomes pathogenic when extracellular YB-1 is simultaneously neutralized, likely due to unmasked defects in immune complex clearance. Full article

Clear cell renal cell carcinoma (ccRCC) is notorious for its clinical unpredictability. While Aquaporin-1 (AQP1) is a major water channel in healthy kidneys, its specific role and regulatory mechanisms in ccRCC remain unclear. Using bioinformatics analysis of 610 TCGA-KIRC patients (RNA sequencing and DNA methylation), single-cell transcriptomics of 27,402 cells, and experimental validation (CCK-8, scratch, Transwell, and xenograft assays, with Western blotting, HE staining, and immunohistochemistry), we systematically characterized AQP1 expression, regulation, and function. AQP1 was significantly downregulated in ccRCC via promoter hypermethylation, with single-cell analysis confirming tumor cell-specific loss. Low AQP1 correlated with worse prognosis; multivariate Cox regression identified AQP1 as an independent protective factor (HR = 0.510, p < 0.001), and a prognostic nomogram showed good predictive accuracy for 1-, 3-, and 5-year survival. AQP1 overexpression suppressed proliferation, migration, invasion, and xenograft growth, accompanied by upregulation of TNF-α, TNFRSF1A, Bax, and Cleaved Caspase-3 and reduced Vimentin, suggesting activation of TNF-related pro-apoptotic signaling. AQP1 is epigenetically silenced in ccRCC and suppresses tumor growth via TNF-mediated apoptosis, establishing it as an independent prognostic biomarker and candidate therapeutic target. Full article

Background: Hungry bone syndrome (HBS) is a frequent and potentially severe complication following parathyroidectomy in patients with chronic kidney disease (CKD) and secondary (SHPT) or tertiary hyperparathyroidism (THPT). We aimed to identify preoperative risk factors associated with the development of HBS in this population. Methods: We conducted a retrospective cohort study including 99 adult patients with CKD-associated SHPT or THPT who underwent parathyroidectomy at Hospital San Vicente Fundación between 2018 and 2024. HBS was defined as corrected serum calcium <8.5 mg/dL requiring intravenous calcium supplementation for at least 72 h postoperatively. Clinical, biochemical, and histopathological variables were evaluated. Multivariable logistic regression analysis was performed to identify independent predictors of HBS, and model discrimination was assessed using the area under the receiver operating characteristic curve (AUC). Results: Overall, 40.4% of patients developed HBS after parathyroidectomy. Compared with patients without HBS, those with HBS more frequently had preoperative musculoskeletal symptoms (82.5% vs. 32.2%), higher preoperative intact parathyroid hormone levels (2135 vs. 1561 pg/mL), and parathyroid adenoma on histology (57.5% vs. 25.4%). In multivariable analysis, preoperative musculoskeletal symptoms (OR 10.92; 95% CI 2.32–51.43) and parathyroid adenoma (OR 6.16; 95% CI 1.38–27.54) were independently associated with increased risk of HBS. Conversely, higher preoperative calcium levels (OR 0.36; 95% CI 0.16–0.85) and the use of calcitriol or vitamin D receptor activators (OR 0.24; 95% CI 0.07–0.81) were protective factors. The final model demonstrated good discrimination (AUC = 0.86; 95% CI 0.77–0.93). Conclusions: HBS is a common complication after parathyroidectomy in patients with CKD-associated SHPT or THPT. Preoperative musculoskeletal symptoms and parathyroid adenoma were associated with increased risk, whereas higher calcium levels and calcitriol/vitamin D receptor activator use appeared protective. Early identification of high-risk patients may facilitate perioperative risk stratification and targeted management strategies. Full article

Selenium (Se) is an essential trace element that exerts pleiotropic effects on host physiology, yet the mechanisms by which it coordinates systemic health remain incompletely understood. Emerging evidence regards the gut microbiota as a key mediator of Se biological functions, giving rise to the Se–gut–tissue axis. This review synthesizes the current research progresses on how dietary Se may shape gut microbial composition and metabolism, and how these microbial shifts are associated with protective effects in both intestinal and extra-intestinal tissues. Se sources (particularly organic or new synthetic form) may bidirectionally interact with gut bacteria by enriching beneficial genera such as Akkermansia, Lactobacillus, and butyrate-producing Clostridia, while suppressing opportunistic pathogens. This microbial remodeling strengthens intestinal barrier integrity, enhances antioxidant and anti-inflammatory responses (e.g., via GPX, TrxR, and NF-κB suppression), and generates bioactive metabolites, notably short-chain fatty acids and secondary bile acids. Through these mechanisms, the Se–gut–microbiota axis may regulate distal organ homeostasis, including the liver (ameliorating NAFLD and acute injury), brain (counteracting neurodegeneration and modulating serotonin/GABA), muscle (improving mass and Se deposition), kidney (attenuating uremic toxin-induced ferroptosis), and reproductive organs. Despite encouraging progress, challenges remain in establishing causality, optimizing dose–response relationships, and translating findings into precision interventions. Full article

Cadmium is a widespread environmental xenobiotic that poses serious risks to hepatic, renal, and male reproductive functions. Natural compounds such as silymarin, a bioactive extract from Silybum marianum, have gained attention for their protective potential against xenobiotic-induced toxicity. This study investigated whether subchronic oral administration of silymarin (30 mg/kg) mitigates cadmium-induced toxicity (5 mg/kg) in adult rats over six weeks. Twenty-four rats were assigned to four groups: control, cadmium-exposed, silymarin-treated, and co-treated. Biochemical, hematological, oxidative stress, and reproductive parameters were assessed. Sperm quality was evaluated using CASA, and testicular tissues were examined histologically. Cadmium exposure significantly reduced body weight (−30.8%), elevated transaminases (AST, ALT; p < 0.01), increased serum creatinine and total cholesterol, and induced multi-organ oxidative stress, as reflected by elevated malondialdehyde and markedly reduced SOD, CAT, and thiol group levels in testicular, hepatic, and renal tissues (p < 0.01). Sperm concentration dropped from 75.2 to 21.8 × 10⁶/mL, with total motility falling to 35% and progressive motility to 18%, accompanied by severe seminiferous tubule degeneration (Score III in 5 rats). Co-administration of silymarin partially restored these parameters, sperm concentration recovered to 38.5 × 10⁶/mL, total motility improved to 50.2%, and antioxidant enzyme activities and liver/kidney biomarkers showed significant but incomplete recovery (p < 0.05). Molecular docking revealed favorable binding affinities of silybin toward GPx (−8.4 kcal/mol), CAT (−8.3 kcal/mol), and SOD (−6.4 kcal/mol), offering a preliminary computational hypothesis suggesting possible interactions between silybin and antioxidant enzymes, pending experimental validation. Silymarin alone exerted no adverse effects. These findings establish silymarin as a partial but promising multi-organ cytoprotectant against cadmium toxicity, and highlight the need for future studies optimizing dosing strategies, exploring longer treatment durations, and investigating combination approaches with metal chelators or Nrf2-activating agents to achieve complete tissue recovery. Full article

Background/Objectives: Arsenic (ARS) exposure is a major cause of kidney injury, driven by oxidative stress, inflammation, fibrosis, and apoptosis. This study evaluated the renoprotective effects of morin (MOR) and morin-loaded PLGA nanoparticles (MOR–PGNPs) against ARS-induced nephrotoxicity in rats. Methods: Sixty male Sprague Dawley rats were randomly allocated into six groups (n = 10 per group). The control group received corn oil. The MOR group received MOR (100 mg/kg), and the MOR–PGNPs group received the same dose of MOR encapsulated in PLGA nanoparticles. ARS was administered at 10 mg/kg for 14 days. Co-treated groups received ARS together with either MOR or MOR–PGNPs, with a 28 min interval between administrations. Renal function markers (serum urea, creatinine, uric acid, renal KIM-1), oxidative stress and antioxidant parameters (Nrf2/HO-1, CAT, SOD, GPx, ROS, MDA), inflammatory mediators (TLR4/NF-κB, TNF-α, IL-6, IL-1β), fibrotic markers (TGF-β1, fibronectin), and apoptotic proteins (caspase-3, caspase-8, Bax, Bcl-2) were assessed, alongside histopathological and ultrastructural evaluations. Results: ARS exposure significantly impaired renal function, increased KIM-1, suppressed Nrf2/HO-1 signaling, reduced antioxidant enzyme activities, and elevated ROS and MDA levels. It also activated TLR4/NF-κB signaling, upregulated pro-inflammatory cytokines and fibrotic markers, and increased pro-apoptotic proteins while downregulating Bcl-2. MOR co-treatment partially ameliorated these alterations. MOR–PGNPs produced potentially enhanced protection, restoring kidney function markers, enhancing antioxidant defenses, and markedly attenuating inflammation, fibrosis, and apoptosis. Histopathological and ultrastructural analyses confirmed preservation of glomerular and tubular architecture, mitochondrial integrity, and minimal cytoplasmic vacuolization in the MOR–PGNPs group. Conclusions: MOR–PGNPs at 100 mg/kg effectively mitigated ARS-induced renal damage through antioxidant, anti-inflammatory, antifibrotic, and anti-apoptotic mechanisms, supporting PLGA-based morin nanoparticles as a promising and safe renoprotective strategy. Full article

Background: Patients with chronic kidney disease (CKD) exhibit reduced serum levels of n-3 polyunsaturated fatty acids (PUFA). Alterations in fatty acid profiles may contribute to increased cardiovascular risk and potentially accelerate CKD progression. Aim: The aim of the study was to assess whether fatty acid profiles measured a decade earlier predicted CKD progression and cardiovascular events. Additionally, the impact of dietary patterns at baseline was evaluated. Methods: The study comprised 77 patients with CKD whose serum fatty acid profiles had been assessed approximately a decade earlier. Follow-up data on CKD progression, cardiovascular events, and all-cause mortality were collected. Dietary habits were assessed using a food frequency questionnaire. The composite endpoint was defined as renal replacement therapy initiation or occurrence of stroke, myocardial infarction, or death. Results: Higher n-3 PUFA content was significantly associated with a lower risk of the composite endpoint in Cox regression analysis (HR = 0.63; 95% CI: 0.40–0.99; p = 0.044). Significant differences in event-free survival were observed in patients with higher n-3/n-6 PUFA ratios (log-rank test, χ² = 4.58, p = 0.032). Patients who experienced stroke or myocardial infarction had significantly higher levels of n-6 PUFA (32.85% vs. 29.94% Mann–Whitney U test, p = 0.037) and lower n-3/n-6 PUFA ratios (0.07 vs. 0.08, Mann–Whitney U test, p = 0.045). Eicosapentaenoic acid (EPA) content was significantly lower at baseline in patients who required renal replacement therapy during follow-up compared with those who did not experience this outcome (0.66% [0.48–0.82] vs. 0.88% [0.64–1.13], Mann–Whitney U test, p = 0.02). Conclusions: Lower serum n-3 PUFA levels were observed in patients who reached the composite endpoint during follow-up. A higher n-3/n-6 PUFA ratio showed a protective effect in survival analysis, and higher EPA content was associated with a lower risk of renal replacement therapy initiation. A more favorable fatty acid profile may be linked to improved cardiovascular and renal outcomes. Further studies are needed to clarify the role of fatty acid profiles in long-term outcomes among patients with CKD, in whom cardiovascular disease remains the leading cause of death. Full article

Preeclampsia (PE) is a severe pregnancy-specific hypertensive disorder characterized by immune microenvironment dysregulation at the maternal–fetal interface, with decidual macrophage phenotypic imbalance being a key pathological feature. The Ghrelin/growth hormone secretagogue receptor-1a (GHSR-1a) axis exerts immunomodulatory and anti-inflammatory effects, but its role in regulating decidual macrophage infiltration and phenotypic marker expression in PE remains unclear. In this study, we first detected the expression of the Ghrelin/GHSR-1a axis in decidual tissues from 10 healthy pregnant women and 12 PE patients via immunohistochemistry (IHC). We then established a lipopolysaccharide (LPS)-induced PE-like rat model to investigate the axis’s functional role and underlying mechanisms. Intriguingly, clinical analysis revealed a severity-dependent compensatory escalation of the Ghrelin/GHSR-1a axis in PE decidual tissues, potentially representing an endogenous antagonistic response to pregnancy-associated pathological stress. In the animal model, exogenous Ghrelin supplementation reversed LPS-induced PE-like phenotypes, including hypertension, proteinuria, fetal growth restriction (FGR), and placental dysfunction, and alleviated pathological damage to the maternal liver, kidney, and placenta. Mechanistically, Ghrelin modulated decidual macrophage phenotypic marker expression by downregulating the M1 marker CD86 and upregulating the M2 marker CD163 and promoted trophoblast invasion and spiral artery remodeling by restoring laminin, α-cytokeratin 7 (α-CK7), and α-smooth muscle actin (α-SMA) expression in placental tissue. All protective effects of Ghrelin were abrogated by co-administration of D-lys-3-GHRP-6, a specific GHSR-1a antagonist, confirming the dependence on the Ghrelin/GHSR-1a axis. Collectively, our findings suggest that the Ghrelin/GHSR-1a axis is compensatorily upregulated in PE and may exert a protective role by regulating decidual macrophage phenotypic marker expression and improving placental function, providing preliminary evidence that this axis merits further investigation as a potential research target for PE. Full article

Background/Objectives: Immunoglobulin A nephropathy (IgAN) is a type of chronic kidney disease (CKD) and the most common cause of kidney failure in patients <40 years of age. Previous economic models in CKD have generally defined health states solely by the progression of CKD. This manuscript presents an alternative method which also considers the level of proteinuria in a CKD patient. Methods: A cohort-level state transition model was developed, comparing the health benefits of sparsentan, a dual endothelin angiotensin receptor antagonist, to irbesartan, an angiotensin receptor blocker, in IgAN. Within four UP/C (proteinuria) states, patients are assigned to three sub-health states according to CKD stage. Patients with end-stage renal disease are grouped together, irrespective of UP/C, and are stratified instead by renal replacement therapy modality. Transition matrices are derived from a combination of data from PROTECT, a clinical trial comparing sparsentan to irbesartan, and the UK RaDaR registry. Health-related quality of life data from a general CKD population is used as a proxy. Results: Patients with IgAN who were modelled to receive treatment with sparsentan had an estimated total undiscounted life years of 25.5 years, a gain of 0.9 years in comparison with irbesartan. Patients were also more likely to spend more time in earlier CKD stages while in pre-ESRD. This translated to significant quality-adjusted life year gains for patients treated with sparsentan in comparison with irbesartan. Conclusions: This study presents a new structure for health economic models in IgAN that more comprehensively captures the effect of proteinuria in combination with CKD progression. This new approach ultimately allows for the more robust implementation of clinical trial data in IgAN and estimates of the cost-effectiveness of new treatments. Full article

Chronic kidney disease (CKD) represents a considerable health burden for both humans and veterinary patients globally. Renal fibrosis is the final common pathway for the progression of CKD to end-stage renal disease, which can eventually lead to renal failure. Thymoquinone (TQ), the primary bioactive constituent of Nigella sativa, has demonstrated significant antifibrotic potential; however, the specific molecular mechanisms underlying its renoprotective effects remain incompletely elucidated. This study aimed to investigate how TQ alleviates renal fibrosis to support its potential as a therapeutic agent. TQ’s renoprotective effects were evaluated in a murine unilateral ureteral obstruction (UUO) model using histopathology, Western blotting, immunofluorescence, and RT-qPCR. Network pharmacology and untargeted metabolomics were integrated to identify key pathways, which were further assessed through in vivo and in vitro experiments. TQ treatment attenuated UUO-induced renal interstitial injury. TQ treatment downregulated α-smooth muscle actin (α-SMA) and fibronectin, thereby suppressing myofibroblast activation and extracellular matrix (ECM) accumulation. Integrated multi-omics analyses indicated that the antifibrotic activity of TQ is associated with modulation of the PI3K/AKT signaling axis. Subsequent in vivo and in vitro studies suggested that TQ protects against renal injury by inhibiting aberrant PI3K/AKT signaling. This study found that TQ ameliorates renal interstitial fibrosis in UUO mice. The underlying mechanism appears to involve suppression of myofibroblast activation and ECM accumulation via inhibition of PI3K/AKT signaling. These findings highlight the therapeutic potential of TQ for renal fibrosis. Full article

The gut microbiota regulates host physiology and drives extraintestinal diseases through the gut–X axis. Bile acids (BAs) function as key mediators of this interorgan crosstalk by activating nuclear and membrane receptors (FXR, TGR5, PXR, VDR). Traditional Chinese Medicine (TCM) demonstrates efficacy across multiple organ systems through multi-component formulations. This narrative review synthesizes evidence from preclinical and clinical studies supporting that TCM exerts systemic protection via strategic modulation of the microbiota–BA–host receptor axis, which functions as a core regulatory circuit within a larger network of microbial metabolites. Mechanistically, representative TCM formulas remodel gut microbial ecology and reinforce intestinal barrier integrity, leading to optimized BA profiles. These favorable BA signatures engage tissue-specific receptor signaling to resolve inflammation, mitigate fibrosis, and restore metabolic homeostasis across the gut–heart, gut–kidney, gut–liver, gut–bone, and gut–endocrine axes. Support for this causal relationship is provided by microbiota depletion, fecal transplantation, and multi-omics studies, collectively suggesting that TCM’s benefits are microbiota-dependent and at least partially BA-mediated. Moreover, context-dependent modulation of BA receptors, such as differential regulation of FXR, enables TCM to achieve pathology-specific outcomes. Current evidence is derived predominantly from preclinical models, and clinical data remain lacking. Nonetheless, the microbiota–BA–organ axis thus provides a potential framework for understanding TCM’s systemic actions and establishes a molecular basis for developing microbiome-informed precision therapeutics. Future directions include patient stratification and precision intervention design inspired by TCM’s ecological modulation strategies. Full article