Search Results (938)

During pregnancy, the regulation of autophagy and ferroptosis dynamically supports placental development and fetal health. Both processes—autophagy, clearing damaged organelles to maintain placental function, and ferroptosis, driven by iron-dependent lipid peroxidation—are involved in pathological conditions such as preeclampsia. Emerging evidence suggests that gut microbiota-derived metabolites act as key regulators of this balance, yet their specific roles across different trimesters remain unclear. This review compiles evidence on how gut microbiota metabolites, like short-chain fatty acids and trimethylamine N-oxide, serve as trimester-specific modulators of the autophagy–ferroptosis balance during pregnancy. We explain how these metabolites influence pregnancy outcomes by regulating placental autophagy and ferroptosis. Furthermore, we explore potential diagnostic and therapeutic approaches for pregnancy complications, focusing on metabolite-based biomarkers and interventions that target microbial–metabolic interactions. Full article

Schizophrenia (SCZ) is a complex psychiatric disorder with heterogeneous molecular underpinnings that remain poorly resolved by conventional single-omics approaches, limiting biomarker discovery and mechanistic insights. To address this gap, we applied an artificial intelligence (AI)-driven multi-omics framework to an open access dataset comprising plasma proteomics, post-translational modifications (PTMs), and metabolomics to systematically dissect SCZ pathophysiology. In a cohort of 104 individuals, comparative analysis of 17 machine learning models revealed that multi-omics integration significantly enhanced classification performance, reaching a maximum AUC of 0.9727 (95% CI: 0.8889–1.000) using LightGBMXT, compared to 0.9636 (95% CI: 0.8636–1.0000) with CNNBiLSTM for proteomics alone. Interpretable feature prioritization identified carbamylation at immunoglobulin-constant region sites IGKC_K20 and IGHG1_K8, alongside oxidation of coagulation factor F10 at residue M8, as key discriminative molecular events. Functional analyses identified significantly enriched pathways including complement activation, platelet signaling, and gut microbiota-associated metabolism. Protein interaction networks further implicated coagulation factors F2, F10, and PLG, as well as complement regulators CFI and C9, as central molecular hubs. The clustering of these molecules highlights a potential axis linking immune activation, blood coagulation, and tissue homeostasis, biological domains increasingly recognized in psychiatric disorders. These results implicate immune–thrombotic dysregulation as a critical component of SCZ pathology, with PTMs of immune proteins serving as quantifiable disease indicators. Our work delineates a robust computational strategy for multi-omics integration into psychiatric research, offering biomarker candidates that warrant further validation for diagnostic and therapeutic applications. Full article

Background: Exercise-induced fatigue arises primarily from energy substrate depletion and the accumulation of metabolites such as lactate and ammonia, which impair performance and delay recovery. Emerging evidence implicates gut microbiota modulation—particularly via probiotics—as a means to optimize host energy metabolism and accelerate clearance of fatigue-associated by-products. Objective: This study aimed to determine whether live or heat-inactivated Lacticaseibacillus paracasei NB23 can enhance exercise endurance and attenuate fatigue biomarkers in a murine model. Methods: Forty male Institute of Cancer Research (ICR) mice were randomized into four groups (n = 10 each) receiving daily gavage for six weeks with vehicle, heat-killed NB23 (3 × 10¹⁰ cells/mouse/day), low-dose live NB23 (1 × 10¹⁰ CFU/mouse/day), or high-dose live NB23 (3 × 10¹⁰ CFU/mouse/day). Forelimb grip strength and weight-loaded swim-to-exhaustion tests assessed performance. Blood was collected post-exercise to measure serum lactate, ammonia, blood urea nitrogen (BUN), and creatine kinase (CK). Liver and muscle glycogen content was also quantified, and safety was confirmed by clinical-chemistry panels and histological examination. Results: NB23 treatment produced dose-dependent improvements in grip strength (p < 0.01) and swim endurance (p < 0.001). All NB23 groups exhibited significant reductions in post-exercise lactate (p < 0.0001), ammonia (p < 0.001), BUN (p < 0.001), and CK (p < 0.0001). Hepatic and muscle glycogen stores rose by 41–59% and 65–142%, respectively (p < 0.001). No changes in food or water intake, serum clinical-chemistry parameters, or tissue histology were observed. Conclusions: Our findings suggest that both live and heat-treated L. paracasei NB23 may contribute to improved endurance performance, increased energy reserves, and faster clearance of fatigue-related metabolites in our experimental model. However, these results should be interpreted cautiously given the exploratory nature and limitations of our study. Full article

The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article

While the gut microbiota of obese children in Mexico has been studied, its relationship with depressive and anxiety symptoms in obese adults remains unexplored. The aim of this study was to describe the gut microbiota profile of Mexican adults with obesity and its association with depression and anxiety. We sequenced the V3-V4 region of the 16S rRNA gene from stool samples of obese adults categorized into four groups: control (OCG), with depressive symptoms (OD), with anxiety symptoms (OAx), or with both (ODAx). Alpha diversity was assessed using t-tests, beta diversity was assessed with PERMANOVA, and taxonomic differences was assessed with LEfSe. Associations between bacterial genera and clinical variables were analyzed using the Maaslin2 library. Bacteroidota was the most prevalent phylum, and Prevotella was the dominant enterotype across all groups. Although overall diversity did not differ significantly, 30 distinct taxonomic biomarkers were identified among groups as follows: 4 in OCG (Firmicutes), 5 in OD (Firmicutes, Bacteroidota), 13 in OAx (Firmicutes, Bacteroidetes, Fusobacteroidota, Proteobacteria), and 8 in ODAx (Firmicutes). This is the first study to identify distinct gut microbiota profiles in obese Mexican adults with depressive and anxiety symptoms. These findings suggest important microbial biomarkers for improving the diagnosis and treatment of mental health conditions in obesity. Full article

Metabolic syndrome is a global health crisis. However, there are no effective therapeutic strategies for metabolic syndrome. Therefore, this study was conducted to find out a novel silkworm-based metabolic syndrome model that bridges microbial ecology and metabolic dysregulation by integrating hemolymph lipids and midgut microbiota. Our results showed that the levels of HDL-C in the hemolymph of the lean silkworm strain were significantly higher than that in the obese silkworm strain. Furthermore, correlation analysis revealed that Lactococcus and Oceanobacillus were positively related to HDL-C levels, while SM1A02 and Pseudonocardia were negatively associated with HDL-C levels. These relationships between the identified bacteria in the midgut and HDL-C, known as the “good” lipid, in the hemolymph could help guide the development of new treatments for obesity and metabolic problems like high cholesterol in humans. Overall, our results not only established a framework for understanding microbiota-driven lipid dysregulation in silkworms but also offered potential probiotic targets and a bacterial biomarker for obesity and metabolic dysfunction intervention in humans. Full article

Faecal microbiota transplantation (FMT) is an emerging therapy for gastrointestinal and neurological disorders, acting via the microbiota–gut–brain axis. Altering gut microbial composition may influence cognitive function, but this has not been tested in cognitively healthy adults. This randomised, double-blinded, placebo-controlled pilot trial investigates whether FMT is feasible and improves cognition in adults with irritable bowel syndrome (IBS). Participants receive a single dose of FMT or placebo via rectal retention enema. Cognitive performance is the primary outcome, assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Secondary outcomes include IBS symptom severity and mood. Tertiary outcomes include microbiome composition and plasma biomarkers related to inflammation, short-chain fatty acids, and tryptophan metabolism. Outcomes are assessed at baseline and at one, three, six, and twelve months following treatment. We hypothesise that FMT will lead to greater improvements in cognitive performance than placebo, with benefits extending beyond practice effects, emerging at one month and persisting in the long term. The findings will contribute to evaluating the safety and efficacy of FMT and enhance our understanding of gut–brain interactions. Full article

This review introduces a novel integrative framework linking gut dysbiosis, systemic inflammation, and cardiovascular risk in patients with inflammatory bowel disease (IBD). We highlight emerging biomarkers, including short-chain fatty acids (SCFAs), calprotectin, and zonulin, that reflect alterations in the gut microbiome and increased intestinal permeability, which contribute to cardiovascular pathology. Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, and recent evidence identifies IBD, encompassing ulcerative colitis (UC) and Crohn’s disease (CD), as a significant non-traditional risk factor for CVD. This review synthesizes current knowledge on how dysbiosis-driven inflammation in IBD patients exacerbates endothelial dysfunction, hypercoagulability, and atherosclerosis, even in the absence of traditional risk factors. Additionally, we discuss how commonly used IBD therapies may modulate cardiovascular risk. Understanding these multifactorial mechanisms and validating reliable biomarkers are essential for improving cardiovascular risk stratification and guiding targeted prevention strategies in this vulnerable population. Full article

Polyomaviruses are a family of small DNA viruses capable of establishing persistent infections, and they can pose significant pathogenic risks in immunocompromised hosts. While traditionally studied in the context of viral reactivation and immune suppression, recent evidence has highlighted the gut microbiota as a critical regulator of host immunity and viral pathogenesis. This review examines the complex interactions between polyomaviruses, the immune system, and intestinal microbiota, emphasizing the role of short-chain fatty acids (SCFAs) in modulating antiviral responses. We explore how dysbiosis may facilitate viral replication, reactivation, and immune escape and also consider how polyomavirus infection can, in turn, alter microbial composition. Particular attention is given to the Firmicutes/Bacteroidetes ratio as a potential biomarker of infection risk and immune status. Therapeutic strategies targeting the microbiota, including prebiotics, probiotics, and fecal microbiota transplantation (FMT), are discussed as innovative adjuncts to immune-based therapies. Understanding these tri-directional interactions may offer new avenues for mitigating disease severity and improving patient outcomes during viral reactivation. Full article

Recent findings highlight that Reelin, a glycoprotein involved in neural development, synaptic plasticity, and neuroinflammation, plays some specific roles in neurodegenerative disorders associated with aging, such as age-related macular degeneration (AMD) and Alzheimer’s disease (AD). Reelin modulates synaptic function and guarantees homeostasis in neuronal-associated organs/tissues (brain and retina). The expression of Reelin is dysregulated in these neurological disorders, showing common pathways depending on chronic neurogenic inflammation and/or dysregulation of the extracellular matrix in which Reelin plays outstanding roles. Recently, the relationship between AMD and AD has gained increasing attention as they share many common risk factors (aging, genetic/epigenetic background, smoking, and malnutrition) and histopathological lesions, supporting certain pathophysiological crosstalk between these two diseases, especially regarding neuroinflammation, oxidative stress, and vascular complications. Outside the nervous system, Reelin is largely produced at the gastrointestinal epithelial level, in close association with innervated regions. The expression of Reelin receptors inside the gut suggests interesting aspects in the field of the gut–brain–eye axis, as dysregulation of the intestinal microbiota has been frequently described in neurodegenerative and behavioral disorders (AD, autism, and anxiety and/or depression), most probably linked to inflammatory, neurogenic mediators, including Reelin. Herein we examined previous and recent findings on Reelin and neurodegenerative disorders, offering findings on Reelin’s potential relation with the gut–brain and gut–brain–eye axes and providing novel attractive hypotheses on the gut–brain–eye link through neuromodulator and microbiota interplay. Neurodegenerative disorders will represent the ground for a future starting point for linking the common neurodegenerative biomarkers (β-amyloid and tau) and the new proteins probably engaged in counteracting neurodegeneration and synaptic loss. Full article

Background/Objectives: Autism spectrum disorder (ASD) encompasses several neurodevelopmental disorders, whose onset is correlated to genetic and environmental factors. Although the etiopathogenesis is not entirely clear, the involvement of inflammatory processes, the endocannabinoid system, and alterations in the permeability and composition of the intestinal microbiota are known to occur. Methods: This review systematically explores the literature available to date on the most widely used murine models for the study of ASD, the main biomarkers investigated for the diagnosis of ASD, and the therapeutic potential of probiotics, with a particular focus on the use of strains of Lactiplantibacillus (Lpb.) plantarum in in vivo models and clinical trials for ASD. Results: Several studies have demonstrated that targeting multifactorial biomarkers in animal models and patients contributes to a more comprehensive understanding of the complex mechanisms underlying ASD. Moreover, accumulating evidence supports the beneficial effect of probiotics, including Lpb. plantarum, as a promising alternative therapeutic strategy, capable of modulating gut–brain axis communication. Conclusions: Probiotic supplementation, particularly with selected Lpb. plantarum strains, is emerging as a potential complementary approach for ameliorating ASD-related gastrointestinal and behavioral symptoms. However, further large-scale clinical studies are essential to validate their efficacy and determine optimal treatment protocols and dietary strategies. Full article

Background/Objectives: Being overweight and obesity are major public health concerns that demand effective nutritional strategies for weight and body composition management. Beyond excess weight, these conditions are closely linked to chronic inflammation, oxidative stress, and gut dysbiosis, all of which contribute to cardiometabolic risk. Polyphenols—bioactive compounds in plant-based foods—may support improvements in body composition and metabolic health by modulating gut microbiota, reducing oxidative stress, and suppressing inflammation. This systematic review and meta-analysis aimed to evaluate the effects of polyphenol-rich interventions on gut microbiota composition, in combination with either oxidative stress or inflammatory biomarkers, and their potential impact on body composition in overweight or obese adults. Methods: A systematic search of PubMed, Scopus, Cochrane, and Web of Science was conducted through May 2025. Eligible randomized controlled trials included adults (BMI ≥ 25 kg/m²) receiving polyphenol-rich interventions, with reported outcomes on gut microbiota and at least one inflammatory or oxidative stress biomarker. Standardized mean differences (SMDs) were pooled using a random-effects model. Results: Thirteen trials (n = 670) met inclusion criteria. Polyphenol supplementation significantly reduced circulating lipopolysaccharides (LPSs; SMD = −0.56; 95% CI: −1.10 to −0.02; p < 0.04), indicating improved gut barrier function. Effects on cytokines (IL-6, TNF-α) and CRP were inconsistent. Catalase activity improved significantly (SMD = 0.79; 95% CI: 0.30 to 1.28; p < 0.001), indicating enhanced antioxidant defense. Gut microbiota analysis revealed increased butyrate (SMD = 0.57; 95% CI: 0.18 to 0.96; p < 0.001) and acetate (SMD = 0.42; 95% CI: 0.09 to 0.75; p < 0.01), supporting prebiotic effects. However, no significant changes were observed in BMI or body weight. Conclusions: Polyphenol supplementation in overweight or obese adults may reduce metabolic endotoxemia, boost antioxidant activity, and promote SCFAs production. Effects on inflammation and body weight remain unclear. Further long-term trials are needed. Full article

Background: Myeloproliferative neoplasms (MPN), a group of chronic hematologic neoplasms, are driven by inflammatory mechanisms that influence disease initiation and progression. Emerging evidence highlights the gut microbiome and plasma metabolome as pivotal immunomodulators, yet their causal roles in MPN pathogenesis remain uncharacterized. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to systematically evaluate causal relationships between 196 gut microbial taxa, 526 plasma metabolites, and MPN risk. Instrumental variables were derived from genome-wide association studies (GWASs) of microbial/metabolite traits. Validation utilized 16S rRNA sequencing data from NCBI Bioproject PRJNA376506. Mediation and multivariable MR analyses elucidated metabolite-mediated pathways linking microbial taxa to MPN. Results: Our MR analysis revealed that 7 intestinal taxa and 17 plasma metabolites are causally linked to MPN. External validation confirmed the three taxa’s differential abundance in MPN cohorts. Mediation analysis revealed two mediated relationships, of which succinylcarnitine mediated 14.5% of the effect, and lysine 27.9%, linking the Eubacterium xylanophilum group to MPN. Multivariate MR analysis showed that both succinylcarnitine (p = 0.004) and lysine (p = 0.040) had a significant causal effect on MPN. Conclusions: This study identifies novel gut microbiota–metabolite axes driving MPN pathogenesis through immunometabolic mechanisms. The validated biomarkers provide potential therapeutic targets for modulating inflammation in myeloproliferative disorders. Full article

Background: Esophageal achalasia is a rare motility disorder characterized by impaired lower esophageal sphincter (LES) relaxation and food stasis. Surgical interventions, including Heller myotomy with fundoplication or peroral endoscopic myotomy (POEM), effectively alleviate symptoms but induce significant anatomical and functional alterations. In various gastrointestinal surgeries, microbiota have been implicated in modulating clinical outcomes; however, their role in achalasia surgery remains unexplored. Methods: We performed a narrative literature search of various databases to identify studies exploring potential interactions between the gastroesophageal microbiota, achalasia pathophysiology, and surgical treatment, proposing clinical implications and future research avenues. Results: Chronic esophageal stasis in achalasia promotes local dysbiosis by facilitating aberrant bacterial colonization. Surgical restoration of esophageal motility and gastroesophageal transit induces substantial shifts in the microbial ecosystem. Analogous microbiota alterations following procedures such as fundoplication, gastrectomy, and bariatric surgery underscore the significant impact of mechanical modifications on microbial composition. Comprehensive microbiota profiling in patients with achalasia may enable the identification of dysbiotic phenotypes predisposed to complications, thereby providing personalized therapeutic interventions including probiotics, prebiotics, dietary modulation, or targeted antibiotic therapy. These insights hold promise for clinical benefits, including the mitigation of inflammation and infection, monitoring of surgical efficacy through microbial biomarkers, and optimization of postoperative nutritional strategies to reestablish microbial homeostasis, ultimately enhancing patient outcomes beyond conventional treatment paradigms. Conclusions: The gastroesophageal microbiota is a compelling mediator of surgical outcomes in achalasia. Future investigations integrating microbiological and inflammatory profiling are warranted to elucidate the functional role of the gastroesophageal microbiota and assess its potential as a biomarker and therapeutic target. Full article

Cardiac surgery, particularly procedures involving cardiopulmonary bypass (CPB), is associated with a high risk of postoperative complications, including systemic inflammatory response syndrome (SIRS), postoperative atrial fibrillation (POAF), and infection. Growing evidence suggests that the gut–heart axis, through mechanisms involving intestinal barrier integrity and gut microbiota homeostasis, may influence these outcomes. This review summarizes the relationship between gut microbiota composition and the inflammatory response in patients undergoing cardiac surgery and the extent to which these alterations impact clinical outcomes. The reviewed studies consistently show that cardiac surgery induces notable alterations in microbial diversity and composition during the perioperative period. These changes, indicative of dysbiosis, are characterized by a reduction in health-associated bacteria such as Blautia, Faecalibacterium, and Bifidobacterium and an increase in opportunistic pathogens. Inflammatory biomarkers were frequently elevated postoperatively, even in patients without evident complications. Key microbial metabolites and biomarkers, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and bile acids (BAs), were implicated in modulating inflammation and clinical outcomes. Additionally, vitamin D deficiency emerged as a contributing factor, correlating with increased systemic inflammation and a higher incidence of POAF. The findings suggest that gut microbiota composition prior to surgery may influence the severity of the postoperative inflammatory response and that perioperative modulation of the gut microbiota could represent a novel approach to improving surgical outcomes. However, the relationship between dysbiosis and acute illness in surgical patients is confounded by factors such as antibiotic use and other perioperative interventions. Large-scale, standardized clinical studies are needed to better define these interactions and guide future therapeutic strategies in cardiac surgery. Full article