Search Results (540)

To investigate whether Echinacea purpurea polysaccharides (EPP) alleviate inflammatory bowel disease (IBD) by modulating gut microbiota, we utilized a mixed antibiotic (ABX)-induced gut dysbiosis model and a co-housing model in rats. ABX treatment severely reduces microbial richness and functional diversity, decreasing SCFA-producing bacteria and impairing the anti-inflammatory effect of SCFA-mediated EPP. Without ABX, EPP significantly ameliorates IBD symptoms and colonic pathology damage in rats, reduces the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) (p < 0.05), inhibits the activation of the TRAF6/NF-κB signaling pathways, and reverses gut microbiota imbalance by partially restoring Bacteroidetes abundance and reducing Firmicutes levels. Among co-housed rats, the EPP-treated group exhibited significantly lower Disease Activity Index (DAI) scores, serum levels of pro-inflammatory factors, and colonic expression of pro-inflammatory pathway-related gene (TRAF6, STAT3) (p < 0.05) without ABX. 16S rRNA gene sequencing revealed a significant reduction in Firmicutes abundance (p < 0.05) alongside significant increases in Bacteroidetes and Actinobacteria abundances, accompanied by elevated levels of acetic acid and propionic acid (p < 0.05). These findings suggest recipient mice restored microbial function and acquired IBD-regulating ability post-microbial exchange. EPP alleviates IBD-related pathological injury by inhibiting the JAK2/STAT3 and TRAF6/NF-κB signaling pathways, with its therapeutic mechanism intricately linked to the microbiota–metabolite–host axis. Full article

Biological aging disrupts liver–gut intercommunication, resulting in the development of insulin resistance and type 2 diabetes, coupled with the imbalance of gut microbiome composition known as gut dysbiosis. Fermented red ginseng (FRG) is a renowned functional food substance showing its notable anti-inflammatory and anti-diabetic effects owing to its unique bioactive compounds known as ginsenosides. However, whether FRG could impact biological aging and age-related metabolic dysfunction is still unclear. The current study aimed to determine the health benefits of FRG in improving age-associated impaired insulin homeostasis and gut dysbiosis in 19-month-old male mice. Mice were fed with a normal chow diet (NCD) or NCD with FRG (300 mg/kg) for 14 weeks. FRG supplementation significantly improved insulin homeostasis by activating the hepatic protein kinase B (AKT) and proline-rich AKT substrate of 40 kDa (PRAS40). We also observed suppressed mRNA expression of proinflammatory cytokines and diminished inflammatory infiltrates in the liver of FRG-fed mice compared with NCD-only controls. Furthermore, alongside a decreased ratio of Firmicutes to Bacteroidetes, FRG administration enriched beneficial genera, including Muribaculaceae, Borkfalkiaceae, Parasutterella, and Clostridia vadin BB60 group, whereas FRG reduced the abundance of Erysipelotrichaceae and Dubosiella at the genus level. In summary, we suggest that FRG can be a potential anti-aging dietary supplement to manage age-driven dysregulation of insulin homeostasis and gut microbiota composition. Full article

Celiac disease (CeD) is a chronic immune-mediated enteropathy triggered by dietary gluten in genetically predisposed individuals which also entails intestinal dysbiosis. This hallmark microbial imbalance provides a rationale for exploring interventions that could modulate the gut ecosystem. Cocoa is a bioactive food rich in polyphenols, theobromine, and fiber, compounds known to have an influence on both immune function and gut microbiota composition. Here, we investigated the effects of cocoa supplementation on the gut microbial profile and predicted functionality in DQ8-D^d-villin-IL-15tg mice, genetically predisposed to CeD. Animals were assigned to a reference group receiving a gluten-free diet (GFD), a gluten-containing diet group (GLI), or the latter supplemented with defatted cocoa (GLI + COCOA) for 25 days. The cecal microbiota was analyzed via 16S rRNA sequencing, and functional pathways were inferred using PICRUSt2. Goblet cell counts and CeD-relevant autoantibodies were measured and correlated with microbial taxa. Cocoa supplementation partially attenuated gluten-induced dysbiosis, preserving beneficial taxa such as Akkermansia muciniphila and Lactobacillus species while reducing opportunistic and pro-inflammatory bacteria. Functional predictions suggested differences in the predicted microbial metabolic potential related to amino acid, vitamin, and phenolic compound metabolism. Cocoa also mitigated goblet cell loss and was inversely associated with anti-gliadin IgA levels. These findings suggest that cocoa, as an adjuvant to a GFD, could be of help in maintaining microbial homeostasis and intestinal health in CeD, supporting further studies to assess its translational potential. Full article

Type 1 Diabetes (T1D) is thought to result from the interaction of genetic and environmental factors, with different studies highlighting a potential role for the gut microbiota and its metabolites in modulating immune responses and disease development. We hypothesized that patients with T1D exhibited altered levels of circulating bacterial metabolites compared with healthy controls (HC), and that these metabolite profiles were associated with key demographic, clinical, and analytical features of the disease. A total of 91 T1D patients and 58 HC were recruited. Plasma samples were collected and analyzed with gas chromatography coupled to mass spectrometry for the detection of the metabolites: short-chain fatty acids (SCFAs: acetate [AA], propionate [PA], isobutyrate [IBA], butyrate [BA], isovalerate [IVA], valerate [VA], and methyl valerate [MVA]), medium-chain fatty acids (MCFAs: hexanoate [HxA] and heptanoate [HpA]) and para-cresol (p-cresol). We also calculated the ratios between the different SCFAs with AA. T1D patients showed significantly higher circulating AA levels than HC, along with reduced PA/AA and IBA/AA ratios, indicating an altered SCFA profile. SCFA diversity was lower in T1D patients, with reduced detection of BA, and total SCFA levels were increased mainly due to elevated AA. AA levels were higher and SCFA ratios lower in women with T1D compared with healthy women, while p-cresol levels were higher in men with T1D than in healthy men. In T1D patients, AA levels positively correlated with HbA1c, whereas PA/AA, IBA/AA, and BA/AA ratios showed negative correlations, particularly in women. MV/AA and non-AA/AA ratios were inversely associated with glucose levels, again, mainly in women. p-cresol levels correlated positively with age and ferritin and were higher in T1D patients with liver dysfunction or hypertension. Therefore, we can conclude that T1D is associated with a marked alteration in circulating gut-derived metabolites, characterized by increased AA levels, particularly in women, and an imbalance in SCFA ratios that correlates with glycemic control. These findings, together with the associations observed for p-cresol and metabolic comorbidities, support a role for the gut microbiota–host metabolic axis in T1D. Full article

Obesity is closely linked to dyslipidemia, hepatic injury, and chronic inflammation through disturbances in the gut–liver axis. Here, we evaluated the anti-obesity effects of L. rhamnosus (Lacticaseibacillus rhamnosus) CU262 in a high-fat diet (HFD) mouse model and elucidated mechanisms using an integrated multi-omics strategy. Male C57BL/6 mice received CU262 during 12 weeks of HFD feeding. Phenotypes, serum/liver biochemistry, gut microbiota (16S rRNA sequencing), fecal short-chain fatty acids (SCFAs), and hepatic transcriptomes (RNA-seq) were assessed. CU262 significantly attenuated weight gain and adiposity; improved serum TC, TG, LDL-C and HDL-C; lowered ALT/AST and FFA; and mitigated oxidative stress and inflammatory imbalance (↓ IL-6/TNF-α, ↑ IL-10). CU262 restored alpha diversity, reduced the Firmicutes/Bacteroidetes ratio, enriched beneficial taxa (e.g., Akkermansia), and increased acetate and butyrate. Liver transcriptomics showed CU262 reversed HFD-induced activation of cholesterol/steroid biosynthesis and endoplasmic reticulum stress, with downregulation of key genes (Mvk, Mvd, Fdps, Nsdhl, and Dhcr7) and Pcsk9, yielding negative enrichment of steroid and terpenoid backbone pathways and enhancement of oxidative phosphorylation and glutathione metabolism. Correlation analyses linked Akkermansia and SCFAs with improved lipid/inflammatory indices and repression of cholesterol-synthetic and stress-response genes. These findings demonstrate that CU262 alleviates HFD-induced metabolic derangements via microbiota-SCFA-hepatic gene network reprogramming along the gut–liver axis, supporting its potential as a functional probiotic for obesity management. Full article

The gut microbiota has emerged as a central regulator of the gut–brain axis, profoundly influencing neural, immune, and metabolic homeostasis. Increasing evidence indicates that disturbances in microbial composition and function contribute to the onset and progression of neurodegenerative diseases (NDs) through mechanisms involving neuroinflammation, oxidative stress, and impaired neurotransmission. Gut dysbiosis is characterized by a loss of microbial diversity, a reduction in beneficial commensals, and an enrichment of pro-inflammatory taxa. These shifts alter intestinal permeability and systemic immune tone, allowing microbial metabolites and immune mediators to affect central nervous system (CNS) integrity. Metabolites such as short-chain fatty acids (SCFAs), tryptophan derivatives, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO) modulate blood–brain barrier (BBB) function, microglial activation, and neurotransmitter synthesis, linking intestinal imbalance to neuronal dysfunction and cognitive decline. Disruption of this gut–brain communication network promotes chronic inflammation and metabolic dysregulation, key features of neurodegenerative pathology. SCFA-producing and tryptophan-metabolizing bacteria appear to exert neuroprotective effects by modulating immune responses, epigenetic regulation, and neuronal resilience. The aim of this work was to comprehensively explore the current evidence on the bidirectional communication between the gut microbiota and the CNS, with a focus on identifying the principal molecular, immune, and metabolic mechanisms supported by the strongest and most consistent data. By integrating findings from recent human studies, this review sought to clarify how microbial composition and function influence neurochemical balance, immune activation, and BBB integrity, ultimately contributing to the onset and progression of neurodegenerative processes. Collectively, these findings position the gut microbiota as a dynamic interface between the enteric and CNS, capable of influencing neurodegenerative processes through immune and metabolic signaling. Full article

Down Syndrome Regression Disorder (DSRD) is a rare but severe neuropsychiatric condition characterized by abrupt loss of speech, autonomy, and cognitive abilities in individuals with Down syndrome, often associated with immune dysregulation and gut–brain axis dysfunction. We report the case of an 11-year-old girl with Down syndrome who developed developmental regression at age five, in temporal proximity to a family transition (the birth of a younger sibling), with loss of continence, language, and comprehension, alongside persistent behavioral agitation and gastrointestinal symptoms. Laboratory assessment revealed Giardia duodenalis infection, elevated fecal calprotectin and secretory IgA, and microbial imbalance with overgrowth of Streptococcus anginosus and S. sobrinus. The patient received a single oral dose of tinidazole (2 g), daily folinic acid (1 mg/kg), and a 90-day course of transcranial and abdominal photobiomodulation (PBM) (1064 nm, 10 min per site). Post-treatment, stool analysis showed normalized inflammation markers and restoration of beneficial bacterial genera (Bacteroides, Bifidobacterium, Lactobacillus) with absence of Enterococcus growth. Behaviorally, she exhibited marked recovery: CARS-2-QPC decreased from 106 to 91, ABC from 63 to 31, and ATEC from 62 to 57, alongside regained continence, speech, and fine-motor coordination. These outcomes suggest that abdominal and transcranial PBM, by modulating mitochondrial metabolism, mucosal immunity, and microbiota composition, may facilitate systemic and neurobehavioral recovery in DSRD. This translational case supports further investigation of PBM as a non-invasive, multimodal therapy for neuroimmune regression in genetic and developmental disorders including validation through future randomized controlled clinical trials. Full article

Background: Growing evidence indicates that oral microbiome dysbiosis contributes to systemic inflammation, immune activation, and neural dysfunction. These processes may influence the onset and progression of major neuropsychiatric and neurodegenerative disorders. This review integrates clinical, epidemiological, and mechanistic findings linking periodontal pathogens and oral microbial imbalance to Alzheimer’s disease (AD), Parkinson’s disease (PD), depression, and anxiety. Methods: A narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar to identify recent studies examining alterations in the oral microbiota, microbial translocation, systemic inflammatory responses, blood–brain barrier disruption, cytokine signaling, and neural pathways implicated in brain disorders. Results: Evidence from human and experimental models demonstrates that oral pathogens, particularly Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, can disseminate systemically, alter immune tone, and affect neural tissues. Their virulence factors promote microglial activation, cytokine release (IL-1β, IL-6, TNF-α), amyloid-β aggregation, and α-synuclein misfolding. Epidemiological studies show associations between oral dysbiosis and cognitive impairment, motor symptoms in PD, and alterations in mood-related taxa linked to stress hormone profiles. Immunometabolic pathways, HPA-axis activation, and the oral–gut–brain axis further integrate these findings into a shared neuroinflammatory framework. Conclusions: Oral dysbiosis emerges as a modifiable contributor to neuroinflammation and brain health. Periodontal therapy, probiotics, prebiotics, synbiotics, and targeted inhibitors of bacterial virulence factors represent promising strategies to reduce systemic and neural inflammation. Longitudinal human studies and standardized microbiome methodologies are still needed to clarify causality and evaluate whether restoring oral microbial balance can modify the course of neuropsychiatric and neurodegenerative disorders. Full article

Osteoarthritis (OA) is one of the most common and burdensome musculoskeletal disorders and a major cause of pain, disability, and reduced quality of life worldwide. In recent years, increasing attention has been paid to extra-articular factors influencing its development and progression, opening new avenues of research into pathophysiological mechanisms and potential therapies. One of the most promising areas concerns the role of the gut–joint axis and related alterations in the gut microbiome. Numerous studies indicate that an imbalance of gut bacteria, increased intestinal permeability, and low-grade inflammation may contribute to the progression of degenerative joint processes. The mechanisms through which the microbiota influences the immune system and host metabolism are becoming increasingly well understood, including pathways involving short-chain fatty acids, tryptophan metabolites, and bile acids. Despite growing evidence linking dysbiosis to the pathogenesis of OA, effective therapeutic strategies based on microbiome modulation remain under active investigation. Among the most frequently studied approaches are probiotics, dietary interventions, and more advanced strategies such as gut microbiota transplantation and targeted modulation of microbial metabolites. However, before these methods can become part of routine treatment, extensive clinical trials and a clearer understanding of causal relationships between the microbiome and joint degeneration are required. This article summarises the current state of knowledge regarding the role of the gut microbiome in osteoarthritis, outlines key research findings, and highlights current and potential therapeutic directions. Full article

The aim of this pilot study was to comprehensively evaluate the gut microbiota, mycobiome, and metabolomic profile of six 4-month-old crossbred pigs (A–F) originating from the same litter and from a specific breeding facility intended for preclinical transplantation experiments, in order to assess their physiological uniformity and identify potential health-related risks prior to inclusion in a kidney transplantation study. The results demonstrated an overall high degree of microbial and metabolic uniformity among the animals, confirming the stability and suitability of the selected breeding source for experimental purposes. At the same time, several individual differences of potential clinical relevance were observed. Animals A, E, and F exhibited signs of microbial and metabolic imbalance, including reduced diversity, increased oxidative activity, and the presence of potentially pathogenic taxa (Porphyromonadaceae bacterium DJF B175, Aspergillus). In contrast, animals B, C, and D showed a balanced metabolic and microbial profile without pathological deviations. The obtained results highlight the importance of preoperative assessment of the gut bacteriome, mycobiome, and metabolome when selecting animals for transplantation experiments. Such a selective screening approach may contribute to the early identification of physiological deviations, reduction of interindividual variability, and increased reliability and translational potential of preclinical studies. Full article

Rheumatoid arthritis (RA) is frequently accompanied by depression, a comorbidity arising from the interplay of chronic systemic inflammation, neuroimmune activation, oxidative stress, and dysregulation of the gut–brain axis. Increasing evidence suggests that nanomedicine offers unique opportunities for the integrated management of RA-associated depression by enabling precise modulation of both peripheral inflammation and central nervous system (CNS) pathology. This review outlines the biological mechanisms linking RA and depression—including cytokine cascades, mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, and microbial metabolite imbalance—and highlights recent progress in nanocarrier platforms capable of dual-site intervention. Liposomes, polymeric nanoparticles (NPs), exosomes, inorganic nanozymes, and emerging carbon-based nanomaterials have demonstrated the ability to target inflamed synovium, reprogram macrophage phenotypes, traverse the blood–brain barrier (BBB), suppress microglial overactivation, enhance neuroplasticity, and restore gut microbial homeostasis. Furthermore, stimulus-responsive nanoplatforms activated by ROS, pH, enzymes, or hypoxia provide spatiotemporally controlled drug release, thereby improving therapeutic precision. Finally, we discuss integrative designs such as dual-targeting nanomedicines, co-delivery systems, and microbiota-modulating nano-interventions, which offer promising strategies for the comprehensive treatment of RA-associated depression. This review aims to provide mechanistic insights and design principles to guide the development of next-generation nanomedicine for coordinated systemic-central modulation in RA comorbidity. Full article

Oxidative stress arises from an imbalance between reactive oxygen species (ROS) and antioxidant defense mechanisms and disrupts the structural integrity of macromolecules such as lipids, proteins, and DNA. This biochemical imbalance triggers the pathogenesis of cardiovascular and neurodegenerative diseases and leads to lipid oxidation and quality degradation in food systems. Plant-derived bioactive compounds (BACs) such as polyphenols and terpenes develop versatile molecular strategies to mitigate this oxidative damage. In addition to their direct radical scavenging effects, polyphenols stimulate the synthesis of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) by activating the Nrf2–Keap1 signaling pathway. Terpenes, on the other hand, create a specialized protective shield in lipid-based matrices through “chain-breaking” reactions and a “slingshot” mechanism that externally halts the oxidation of γ-terpinene. In food engineering applications, these compounds meet the demand for “clean-label” products by providing alternatives to synthetic antioxidants such as BHA and BHT. Specific terpenes, such as carnosic acid, demonstrate higher performance in inhibiting lipid oxidation compared to their synthetic counterparts. Although BAC use extends the shelf life of products while maintaining color and flavor stability, potential interactions with protein digestibility necessitate dosage management. From a clinical perspective, these compounds suppress inflammatory responses by inhibiting the NF-κB pathway and contribute to the prevention of chronic diseases by modulating the gut microbiota. This review evaluates the capacity of BACs to manage oxidative stress in food preservation technologies and human health through a mechanistic and application-based approach. Full article

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder influenced not only by genetics, diet, and lifestyle but also by the gut microbiota. Dysbiosis (imbalances in microbial composition) can disrupt gut barrier integrity, alter microbial metabolites, and trigger low-grade inflammation, contributing to insulin resistance and β-cell dysfunction. Nutritional interventions, such as probiotics, prebiotics, synbiotics, postbiotics, and bioactive food components, represent potential therapeutic approaches for ameliorating gut eubiosis and advancing glycemic regulation. This narrative review incorporates evidence from selected studies identified by searches in PubMed, Scopus, and Google Scholar for studies published up to November 2025. The methodology included a structured literature search of in vitro, animal, and human studies, with a focus on intervention trials and mechanistic research. There are many positive signals from randomized controlled trials (RCTs), but heterogeneity and short follow-up limit definitive recommendations. Evidence from clinical and experimental studies indicates a beneficial effect on fasting glucose, hemoglobin A1c, and inflammatory markers, though heterogeneity of the individual and the variability in study designs limit generalization. There is insufficient evidence to recommend microbiota modulation as standard therapy in any disease. Key knowledge gaps include standardized interventions, stratified analyses by medication use (e.g., metformin), clinically meaningful endpoints, and long-term safety data. This review summarizes current knowledge on gut microbiota-driven mechanisms in T2DM and evaluates emerging microbiota-targeted therapies as adjunctive strategies for metabolic improvement. Full article

Chronic diseases, characterized by their high prevalence and protracted course, represent a paramount challenge to global public health, necessitating effective, evidence-based preventive strategies. While functional foods are widely recognized for their potential, a comprehensive synthesis elucidating their multitargeted mechanisms within a “food-medicine homology” framework and a clear trajectory from broad-spectrum health promotion to targeted intervention remains lacking. This review bridges this critical gap by systematically evaluating the scientific evidence and application potential of functional foods, with a specific focus on key bioactive compounds—β-glucan, omega-3 polyunsaturated fatty acids (PUFAs), dietary fiber, and catechins. We provide a critical analysis of how these components orchestrate synergistic effects at molecular, cellular, and systemic levels to counteract core pathological processes, including oxidative stress, chronic inflammation, metabolic dysregulation, and gut microbiota imbalance. Our unique contribution lies in integrating the ancient wisdom of food-medicine homology with modern multi-omics and evidence-based research, thereby proposing a refined nutritional intervention paradigm. The review offers critical insights into the convergent actions of these bioactives, their dose-response relationships substantiated by clinical meta-analyses, and the emerging role of gut microbiota-derived metabolites. Furthermore, this review also explores the emerging evidence for synergistic interactions among these key bioactives, proposing that their combined use may yield amplified and more network-based protective effects against chronic diseases through complementary mechanisms, aims to develop integrated prevention strategies targeting both cardiometabolic and neurodegenerative diseases. The integrated prevention strategies systematically connect mechanistic insights into bioactive compounds, evaluates the strength of clinical evidence, and examines the implications for regulatory standards and societal acceptance, thereby bridging the gap between basic science, clinical application, and public health policy. The “mechanism-to-evidence-to-regulation” framework in this review links molecular insights with clinical validation and regulatory implications, offering a holistic perspective rarely addressed in existing literature. Full article

Microinflammation serves as a central mechanism linking metabolic diseases and cancer. This study integrates gene expression profiles from irritable bowel syndrome (IBS), obesity, type 2 diabetes (T2D), colorectal cancer (CRC), renal cell carcinoma (RCC), and pancreatic cancer (PC) to identify shared molecular drivers of inflammation-mediated pathology. Weighted gene co-expression network analysis (WGCNA) revealed three highly preserved modules (blue, brown, turquoise) enriched in RNA processing, spliceosome assembly, ribosome biogenesis, and proteostasis regulation. Key hub genes, along with regulatory miRNAs have interconnected networks that modulate transcription, mRNA maturation, protein synthesis, and inflammatory signaling. Although classical inflammatory pathways were not directly enriched, their activity appears to be indirectly shaped by disruptions in RNA-processing and proteostasis machinery. Additionally, gut microbiota-derived products and altered metabolic states may further reinforce these transcriptional and post-transcriptional imbalances. Collectively, these findings reveal conserved molecular signatures that bridge microinflammation, metabolic disease, and oncogenesis, and highlight potential diagnostic and therapeutic targets centered on RNA regulation, proteostasis, and miRNA-mediated control Full article