Search Results (131)

Chronic kidney disease (CKD) is common in older cats, and nutritional management remains the intervention with the strongest clinical evidence. Interest has expanded from conventional control of phosphorus and uremic signs to the gut–kidney axis, in which renal dysfunction may alter the intestinal environment while microbial metabolism generates solutes that accumulate as kidney function declines. This PRISMA-ScR-guided scoping review and critical narrative synthesis evaluates feline evidence on CKD-associated dysbiosis, gut-derived uremic solutes, bile acid metabolism, and microbiome-directed nutrition. The original search covered January 2021 to April 2026, with inclusion of earlier studies and targeted source verification through July 2026. Eligibility was organized into two evidence strata: core feline evidence and contextual evidence. The final revised evidence map comprised 49 unique sources (28 empirical feline sources and 21 contextual sources spanning comparative, methodological, guideline, regulatory, or safety evidence); non-feline evidence was used only for mechanistic, methodological, safety, or translational interpretation and was not pooled with feline clinical outcomes. Cats with CKD have shown lower fecal microbial richness and diversity and higher circulating indoxyl sulfate in small cross-sectional cohorts, but causality remains unproven. Recent work also identified altered secondary bile acids and lower fecal ursodeoxycholic acid; however, Peptacetobacter hiranonis is principally linked to bai-mediated 7α-dehydroxylation, whereas ursodeoxycholic acid formation requires distinct hydroxysteroid dehydrogenase reactions. Complete therapeutic renal diets improve clinical outcomes, but their benefits reflect multiple simultaneous modifications and cannot yet be decomposed into a microbiome-specific effect. Evidence for isolated prebiotics, probiotics, postbiotics, synbiotics, fecal microbiota transplantation, and precision nutrition algorithms is preliminary or absent in feline CKD. The field is constrained by small cohorts, confounding, reliance on 16S rRNA sequencing, compositional data, and limited interlaboratory reproducibility. Current clinical practice should therefore prioritize a palatable complete renal diet, adequate energy and protein intake, muscle condition monitoring, hydration, and constipation management, while microbiome-directed products remain adjunctive or investigational. Full article

Cardiac senescence is not an isolated organ decline but a systemic consequence driven by pathological crosstalk between the heart and its peripheral metabolic organs. In this review, we discard the traditional organ–centric perspective and construct an integrated framework around multi-organ crosstalk axes, including the epicardial adipose tissue–heart axis, the skeletal muscle–heart axis, the gut–heart axis, and the kidney–heart axis. For each axis, we dissect the local molecular mediators—inflammatory cytokines, lipotoxic metabolites, microbiota-derived compounds such as trimethylamine N-oxide (TMAO), renin-angiotensin-aldosterone system (RAAS) effectors, and extracellular vesicle (EV) cargoes—and illustrate how they converge onto common pathways of oxidative stress, impaired autophagy, and cellular senescence. Importantly, we emphasize that these signals do not operate in isolation; they act synergistically through the circulation, converting local organ dysfunction into systemic cardiac aging via convergence onto shared senescence pathways. By redefining aging as a potentially modifiable multi-organ crosstalk, we propose emerging nodal points—senolytics, myokine mimetics, gut microbiota modulation, RAAS/sodium–glucose cotransporter 2 (SGLT2) inhibitors, and integrated lifestyle strategies—to block pathological crosstalk and delay cardiovascular aging. This framework shifts the research focus from isolated organs to systemic multi-organ crosstalk, providing new insights into cardiometabolic aging. Full article

Background: Gut microbiota may influence metabolic and inflammatory responses to exercise through the gut–muscle axis, and probiotic supplementation has been proposed to support adaptation and recovery in endurance athletes. However, evidence in trained populations is inconsistent and is confounded by variability in diet, probiotic strains, dose, and intervention duration. We tested whether a multistrain probiotic, administered against a fully standardized diet, would affect exercise performance and inflammatory, metabolic, and muscle-damage responses. Methods: In this randomized, double-blind, placebo-controlled trial, 30 trained male long-distance runners were randomized and 27 completed the study (probiotic [PRO], n = 13; placebo [PLA], n = 14). All participants followed a standardized, normocaloric meal-box diet for four weeks. Aerobic capacity (peak oxygen uptake, VO₂peak; primary outcome) was assessed by an incremental treadmill test and anaerobic performance by a 30 s Wingate test, before (PRE) and after (POST) supplementation. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), creatine kinase (CK), and lactate (LA) were measured around exercise. Outcomes were analyzed with linear mixed-effects models; the primary estimand was the group × phase interaction. Results: VO₂peak did not differ between groups over time (PLA 55.00 ± 7.60 → 57.33 ± 8.41; PRO 55.40 ± 7.85 → 53.14 ± 5.95 mL·kg⁻¹·min⁻¹; group × phase −3.5 mL·kg⁻¹·min⁻¹, 95% CI −7.0 to −0.1; nominal p = 0.044, not significant after FDR correction, adjusted p = 0.707). No group × phase or group × phase × sampling-time interaction was significant for IL-6, TNF-α, LA, or CK (all interaction p > 0.15), indicating that supplementation did not modify the exercise-induced response of any biomarker; exercise itself robustly increased IL-6, TNF-α, and LA in both groups (p < 0.001). Conclusions: In trained male endurance runners consuming a standardized diet, four weeks of multistrain probiotic supplementation did not significantly affect aerobic or anaerobic performance, LA response, muscle-damage markers, or circulating inflammatory cytokines compared with placebo. Adequately powered trials with prespecified primary endpoints and direct microbiome assessment are needed. Full article

Age-related alterations in the gut microbiota contribute to chronic low-grade inflammation, immune dysregulation, metabolic dysfunction, frailty, sarcopenia, and cognitive decline. Dietary polyphenols and fermentable fiber modulate microbial composition and metabolism, promoting the production of bioactive metabolites, including short-chain fatty acids, secondary bile acids, indole derivatives, and urolithins, which regulate intestinal barrier integrity, immune homeostasis, mitochondrial function, and gut–organ communication. This narrative review critically synthesizes evidence from experimental studies, observational cohorts, randomized controlled trials, systematic reviews, and meta-analyses to examine microbiota-mediated mechanisms linking these dietary components to healthy aging within the geroscience framework. Although mechanistic evidence is compelling, translation into clinically meaningful aging outcomes remains limited because most intervention studies are small and heterogeneous and primarily rely on surrogate biomarkers. Current evidence supports polyphenol- and fiber-rich dietary patterns as biologically plausible strategies for promoting healthy aging through modulation of the gut microbiota; however, establishing causal relationships will require standardized microbiome methodologies, validated microbiome-derived biomarkers, integrated multi-omics approaches, and adequately powered longitudinal studies and randomized controlled trials. Full article

Background: Visceral obesity is increasingly recognised not as a simple excess of adipose tissue, but as a systemic pathological condition characterised by profound metabolic, endocrine, and immune dysregulation. Visceral adipose tissue (VAT) operates as an autonomous neuro-immune-endocrine organ whose dysfunctional expansion drives insulin resistance, atherogenesis, and accelerated cellular ageing through mechanisms converging on chronic low-grade sterile inflammation, referred to as inflammaging. Objectives: This narrative review integrates evidence across four domains: (1) the multi-system clinical complications of visceral obesity and the methodological controversies surrounding its measurement; (2) the cellular heterogeneity, immunometabolic reprogramming, and molecular mechanisms through which excess VAT accelerates biological ageing, with a focus on genomic instability, mitochondrial dysfunction, the NAD⁺/sirtuin regulatory axis, cellular senescence, and inter-organ communication; (3) the role of bioelectrical impedance analysis (BIA)—particularly phase angle—as a non-invasive functional biomarker of biological age and longevity, positioned critically against alternative assessment methods; and (4) current knowledge gaps and priorities for future research. Methods: A narrative review of PubMed/MEDLINE, Google Scholar, and the Cochrane Library was conducted using MeSH terms and free-text keywords including visceral obesity, bioelectrical impedance analysis, phase angle, sarcopenia, inflammaging, mitochondrial dysfunction, cellular senescence, epigenetic clocks, NAD⁺, sirtuin, and longevity, supplemented by citation-tracking of retrieved reviews. English-language articles published up to April 2025 were considered, prioritising systematic reviews, meta-analyses, and prospective cohort studies; formal risk-of-bias tools and quantitative synthesis were not applied, consistent with a narrative review design. Results and Discussion: BIA-derived phase angle constitutes a macroscopic electrobiological correlate of inflammaging: low phase angle values in visceral obese subjects overlap with those of frail elderly individuals, reflecting impaired membrane integrity, loss of active cell mass, and altered ICW/ECW balance. However, this evidence base remains largely cross-sectional and correlative; the directionality and population-specific calibration of BIA-derived indices constitute the principal unresolved methodological questions. Integration with epigenetic clocks, circulating NAD⁺ levels, and gut microbiome indices offers a framework for dynamic biological age assessment, though prospective interventional validation is still lacking. Sarcopenic obesity, evaluated through EWGSOP2 combined with BIA-derived skeletal muscle mass index and handgrip dynamometry, represents a critical comorbidity demanding integrated therapeutic targeting. Conclusions: BIA provides a quantitative, accessible correlate for translating cellular metabolic health into clinically actionable parameters, complementary to rather than a replacement for anthropometric and imaging-based methods. Optimising phase angle and reducing VAT through anti-inflammatory nutrition, exercise, and nutraceutical strategies targeting the NAD⁺/sirtuin and mTOR/AMPK axes constitutes a measurable objective for the promotion of healthy longevity, contingent on the longitudinal, mechanistic studies identified as priorities in this review. Full article

Physical performance can be understood as a continuum throughout the life course, ranging from peak athletic ability in early life to the preservation of mobility and functional independence in old age. This narrative review explores whether the biological and genetic pathways involved in athletic performance might also modulate the risk of geriatric motor dysfunctions (GMDs), a conceptual umbrella proposed here for sarcopenia, dynapenia, lower-limb weakness and the motor component of physical frailty. The available evidence suggests a convergence between performance and motor decline in mechanisms such as mitochondrial function and mitophagy, anabolic–catabolic balance, oxidative stress and low-grade chronic inflammation, neuromuscular integrity, satellite cell function, mechanotransduction, myokine-mediated signalling, and the gut–muscle axis. Although classic candidate genes such as ACTN3, ACE and PPARGC1A have been useful for formulating mechanistic hypotheses, genome-wide association studies support a highly polygenic architecture for strength, lean mass, muscle weakness and frailty. These effects are strongly modulated by the exposome, particularly by physical activity, nutrition and comorbidities. Overall, the relationship appears consistent with predominantly beneficial pleiotropy, although context-dependent effects cannot be ruled out. Genetics may influence functional reserve and decline trajectories, but exercise, particularly strength and power training, along with adequate nutrition and the management of comorbidities, remain the primary strategies for preventing or delaying sarcopenia, frailty and lower-limb weakness. Full article

Background and Objectives: The concept of the gut–muscle–brain axis encompasses the intricate, multidirectional interactions between the gut microbiota (GM), physical exercise (PE), and the central nervous system. Within this framework, gut dysbiosis has been implicated in the pathogenesis of Alzheimer’s disease (AD). Given that cognitive functions in AD appear to benefit from PE, it is plausible to hypothesize that these improvements may be partially mediated by PE-induced alterations in GM taxonomy. Therefore, the objective of this study is to evaluate the potential effects of PE in the GM and their implications for AD. Methods: A systematic review was conducted in PubMed, Web of Science and Scopus following the PRISMA guidelines up to July 2025 for preclinical controlled trials that assessed the effects of PE on the GM of AD animal models. A random-effects model meta-analysis was performed to estimate the pooled effect of PE on GM frequency or composition. This study received no external funding. Results: Eight studies were included in the systematic review (sample size, n = 126), of which two could be meta-analyzed. We found that PE significantly reduced Actinobacteria abundance (MD = −0.005%; 95% CI, −0.008 to −0.002; p = 0.001) with no statistically significant evidence of heterogeneity (I² = 89.60%, Q = 0.102, p = 0.950) or publication bias observed (Begg’s test, p = 0.296), but no significant effects were found for other phylums or genera. Conclusions: PE appears capable of modulating the GM of animal models with AD in a selective and heterogeneous manner. Further studies are needed to clarify the mechanisms by which this is possible and to determinate its impact on the pathogenesis of the disease. Full article

As an eco-friendly strategy for improving intestinal health, production performance, and meat quality in livestock and poultry, live probiotic strains (Lactobacillus, Bifidobacterium, Bacillus), paraprobiotics and postbiotics have exhibited considerable application potential in monogastric livestock in animal husbandry. However, probiotic efficacy is commonly characterized by striking individual heterogeneity, and its intrinsic regulatory basis remains poorly understood. This review systematically summarizes the core mechanisms by which probiotics modulate meat quality, feed efficiency and small intestinal and cecal health in pigs and broilers via the gut–muscle axis, nutrient metabolic axis, and immune regulatory axis. We elucidate the heritable effects of host genetics on shaping the gut microbiome and the fundamental principles underlying genotype–probiotic (G×P) interactions, highlighting that host genetic background represents an important of differential responses to probiotics. Accordingly, we propose integrating microbial genome-wide association studies (mGWAS) and genomic selection to develop novel breeding programs targeting probiotic responsiveness, with the aim of establishing a precision breeding system for probiotic-friendly livestock and poultry. This review may facilitate the paradigm shift of probiotic applications from universal administration to precision intervention, and from single nutritional regulation to host–microbiome synergistic breeding, providing a conceptual framework and innovative strategies for the green, efficient, and sustainable development of animal husbandry. Full article

Pediatric sarcopenic obesity (PSO) is an emerging conceptual framework characterized by the coexistence of excess visceral adiposity and impaired skeletal muscle accretion. Evidence suggests that this pathology is driven by systemic meta-inflammation rooted in the gut microbiota–immunometabolism axis. Dysbiosis, particularly the depletion of infant-type Bifidobacterium, compromises the intestinal barrier, potentially causing metabolic endotoxemia. In preclinical models, this triggers a pro-inflammatory, “Warburg-like” glycolytic shift in innate immune cells, releasing cytokines (IL-6, TNF-$\mathsf{\alpha }$) that heavily upregulate the ubiquitin–proteasome system in developing muscle. To address this cascade, we hypothesize that a targeted synbiotic approach utilizing dietary anthocyanins (e.g., cyanidin-3-O-galactoside) and prebiotic galacto-oligosaccharides (GOS) may offer metabolic benefits. This review clarifies the pharmacokinetic distinction between the systemic toxicity of high-dose injected galactose and the safety of dietary galactosides. Preclinical data suggest that ingested galactosides resist upper gastrointestinal digestion and undergo colonic cleavage by commensal $\mathsf{\beta }$-galactosidase, yielding short-chain fatty acids (SCFAs) that support intestinal permeability while releasing bioactive phenolic aglycones. Systemically, these aglycones may attenuate skeletal muscle catabolism by supporting PI3K/Akt signaling. Synthesizing current preclinical and adult-derived evidence, this review highlights the theoretical therapeutic potential of early-life synbiotic interventions as adjunctive therapies to support healthy muscle developmental trajectories in pediatric populations. Full article

Background and Objectives: Although the association between frailty and constipation in older adults has attracted growing attention, evidence linking the Clinical Frailty Scale (CFS) to colonic transit time (CTT) remains scarce. In this retrospective study, we examined this association using colon capsule endoscopy (CCE). Materials and Methods: We enrolled 124 older adults (64 men, 60 women) aged ≥ 65 years (mean age 74.6 ± 5.6) who underwent CCE for colorectal polyp screening at Aishinkai Nakae Hospital, Japan, between January 2014 and July 2024. CTT was determined at the time of CCE, and frailty was assessed with the Japanese version of the CFS. To avoid the oversimplification inherent in a strict dichotomy, participants were analyzed primarily as three ordered categories—Robust (CFS 1–2; n = 73), Intermediate (CFS 3–4; n = 43), and Frail (CFS 5–7; n = 8)—and, for comparability with previous reports, also as a Robust versus Non-robust (CFS 3–7; n = 51) dichotomy. The independent association between CFS and CTT was examined with three complementary multivariable linear regression models (Model 2: CFS continuous; Model 3: CFS three-category ordinal; Model 3b: CFS three-category dummy with Robust as reference), each adjusted for 10 covariates: age, sex, body mass index, type 2 diabetes mellitus, laxative use, anticholinergic drug use, psychotropic drug use, hypothyroidism, smoking history, and history of abdominal surgery. Results: CTT rose stepwise across the three frailty categories (Robust: 132.0 min [IQR 81.0–229.0], 157.9 ± 99.9; Intermediate: 198.0 min [90.5–267.0], 186.1 ± 99.8; Frail: 241.5 min [199.0–320.5], 295.8 ± 181.3; Kruskal–Wallis p = 0.027; Jonckheere–Terpstra P for trend = 0.017); the dichotomous comparison was concordant (median 214.0 vs. 132.0 min; Mann–Whitney U U = 1441.5; p = 0.033). A graded dose–response-like relationship was further supported by Spearman correlation between the CFS score and CTT (ρ = 0.232; p = 0.009). Women had significantly longer CTT than men (median 189 vs. 121 min; p = 0.013), and the three-group trend was significant within the female subgroup (Kruskal–Wallis p = 0.032) but not within men (p = 0.138). In multivariable analysis, CFS remained independently associated with CTT prolongation both as a continuous score (Model 2: β = 36.6 per 1-point increase; 95% CI 17.3 to 56.0; p < 0.001) and as an ordinal three-category predictor (Model 3: β = 52.7 per one-step advance; 95% CI 19.7 to 85.8; p = 0.002). In the dummy-coded specification (Model 3b), the Frail-versus-Robust contrast was markedly significant (β = 155.4 min; 95% CI 71.5 to 239.3; p < 0.001), whereas the Intermediate-versus-Robust contrast was not (β = 27.0; 95% CI −15.5 to 69.5; p = 0.210). Female sex retained independent significance across models (β ≈ 47–49 min; p = 0.016–0.021). The original dichotomous Non-robust versus Robust specification (Model 1) was no longer significant after full adjustment (p = 0.372). Conclusions: Frailty progression, as assessed by the CFS, is independently and monotonically associated with prolonged CTT in older adults, with the effect becoming statistically manifest predominantly at the more advanced end of the frailty spectrum and particularly in women. Although these findings do not establish causality between frailty and constipation—and frailty itself reflects a multifactorial age-related process that may not be fully reversible—CCE-measured CTT provides an objective, radiation-free physiological biomarker of frailty-related bowel dysfunction that may support risk stratification and inform future interventional trials targeting potentially modifiable components of the gut–muscle axis. Full article

Background/Objectives: Cholesterol homeostasis is often framed as a dietary problem, but circulating low-density lipoprotein (LDL) biology is governed largely by endogenous sterol handling, with the liver acting as the principal integrative organ for cholesterol synthesis, LDL receptor-mediated clearance, very-low-density lipoprotein (VLDL) export, bile acid production, and biliary sterol disposal. This narrative review evaluates the hepatic basis of cholesterol regulation, statin pharmacology, gut microbial sterol metabolism, chronic hepatic inflammation, and a proposed oral–gut–liver–artery axis in atherogenesis. The aim of this narrative review is to clarify which elements of the proposed axis are established, which are supported but incomplete, and which remain hypothesis-generating. Methods: Mechanistic, translational, clinical, and review literature were synthesized to separate established mechanisms from emerging and speculative links. PubMed/MEDLINE, Scopus, and Google Scholar were searched from January 2000 through May 2026. Primary search terms included: cholesterol homeostasis, LDL receptor, SREBP2, statin pleiotropic effects, statin-associated muscle symptoms, gut microbiota cholesterol, bile salt hydrolase, MASLD, Porphyromonas gingivalis liver, phosphorylated dihydroceramides, serine dipeptide lipids Bacteroidetes, ceramide atherosclerosis, and oral–gut–liver–artery axis. Results: LDL/apoB causality and hepatic statin mechanism are well-established. Gut microbiota can alter cholesterol absorption, coprostanol formation, bile acid pools, and portal signaling, but these effects are context-dependent. Hepatic free cholesterol loading and lysosomal sterol stress are strongly implicated in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). Periodontal pathogens, especially Porphyromonas gingivalis, may contribute to liver and vascular inflammation through bacteremia, oral–gut translocation, innate immune activation, and bioactive bacterial sphingolipids. Phosphorylated dihydroceramides (PDHCs) and Bacteroidetes-derived serine dipeptide lipids have been detected in human arterial specimens and shown to enter host ceramide pools, providing a direct lipid metabolic pathway linking microbial community composition to vascular disease. Viridans streptococci and the Streptococcus anginosus group are inflammatory cofactors rather than proven causes of hepatic cholesterol overproduction. Conclusions: The strongest model involves microbial amplification of hepatic cholesterol dysmetabolism, endothelial activation, foam-cell formation, and plaque vulnerability acting on a host-derived LDL/apoB scaffold. This model is testable and should complement guideline-based LDL-lowering therapy. Full article

The global push to eliminate antibiotic growth promoters in poultry has accelerated the demand for effective natural alternatives. β-Glucans—branched polysaccharides derived from Saccharomyces cerevisiae cell walls—enhance immunity and gut health; however, their mechanistic effect on the somatotropic axis and meat quality in broilers remains unresolved. Herein, the hypothesis that dietary β-glucan modulates somatotropic signaling to improve growth performance and breast muscle quality was tested with 240 one-day-old Ross 308 chicks allocated to three groups—untreated control, 250 mg β-glucan/kg feed, and 1 g β-glucan/kg feed—and reared for 35 d. Growth performance, plasma growth hormone (GH) and prolactin (PRL), somatotropic axis gene expression in liver and breast muscle, and postmortem meat quality were assessed. β-Glucan supplementation significantly elevated final body weight, breast muscle weight, and plasma GH and PRL, and upregulated hepatic IGF-1 and muscle GH receptor mRNA at 35 d, and hepatic GH receptor mRNA at 17 d. Muscle pH was higher and relative drip loss lower in supplemented birds 72 h postmortem. These results support the hypothesis and identify 1 g β-glucan/kg feed as an effective dose for improving growth and meat quality through somatotropic axis modulation—a novel mechanistic demonstration in broiler chickens. Full article

Cognitive frailty, characterized by the coexistence of physical frailty and cognitive impairment, has emerged as a major challenge in aging populations and is closely linked to sarcopenia, neurodegeneration, and chronic inflammation. Increasing evidence suggests that the gut microbiota acts as a central regulator of neuromuscular and neurocognitive aging through the integrated gut–brain–muscle axis. This review highlights how microbial dysbiosis, reduced short-chain fatty acid (SCFA) production, systemic endotoxemia, and altered microbial metabolites contribute to mitochondrial dysfunction, neuroinflammation, anabolic resistance, and impaired neuroplasticity. Key signaling mediators, including SCFAs, bile acids, tryptophan-derived metabolites, cytokines, and myokines such as irisin, brain-derived neurotrophic factor (BDNF), and cathepsin B, orchestrate bidirectional communication among the gut, skeletal muscle, and brain. We further discuss the role of exercise-induced microbiota remodeling and muscle endocrine signaling in promoting mitochondrial biogenesis and cognitive resilience. In addition, emerging translational strategies including probiotics, prebiotics, postbiotics, polyphenol-rich functional foods, marine bioactives, and precision nutrition are explored as potential interventions targeting this axis. Collectively, the gut–brain–muscle axis provides a novel systems biology framework for understanding cognitive frailty and developing integrated therapeutic strategies for healthy longevity. Full article

Mitochondrial dysfunction in colonic smooth muscle cells (SMCs) is closely associated with impaired gut motility in functional constipation (FC), but the underlying molecular mechanisms remain incompletely understood. The mitochondrial unfolded protein response (UPR^mt) is a critical pathway for maintaining mitochondrial proteostasis, and heat shock factor 1 (HSF1) acts as an important upstream regulator of this response. In the present study, we employed a loperamide-induced FC mouse model, combined with single-cell transcriptomic, molecular, and functional analyses to characterize the HSF1-UPR^mt pathway in colonic SMCs and to investigate its role in FC. Single-cell transcriptomic analysis of colon tissue from FC mice revealed marked downregulation of UPR^mt-associated genes in colonic SMCs. Immunofluorescence, Western blotting, and RT-qPCR analyses of colonic tissue confirmed that HSF1 expression was reduced in colonic SMCs, along with the downregulation of the UPR^mt components, including HSP60, mtHSP70, and LONP1. These molecular changes were accompanied by mitochondrial structural damage, seen by transmission electron microscopy, and by functional impairments, including reduced mitochondrial membrane potential, elevated mtROS production, decreased ATP levels, and diminished activities of respiratory chain complexes I–V. AAV9-mediated overexpression of HSF1 reactivated the UPR^mt pathway, improved mitochondrial function, and ameliorated constipation, whereas shRNA-mediated knockdown of HSF1 further suppressed UPR^mt activity and aggravated mitochondrial damage, indicating that HSF1 bidirectionally regulates this pathway. Complementary experiments in primary colonic SMCs confirmed that this regulatory mechanism operates in a cell-autonomous manner, as modulation of HSF1 expression produced corresponding changes in the UPR^mt pathway, in the expression of mitochondrial respiratory chain complex subunits (ATP5A, NDUFA9, COX1, SDHA, UQCRC1), and in ATP production, mirroring the in vivo findings. Collectively, these results demonstrate that HSF1 plays a pivotal role in maintaining mitochondrial homeostasis in colonic SMCs through regulation of the UPR^mt pathway and that HSF1 dysfunction is closely associated with slowed gut motility in FC. These findings offer a new mechanistic perspective on FC and point to the HSF1–UPR^mt axis as a potential therapeutic target. 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