Search Results (3,714)

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by Aβ deposition, tau hyperphosphorylation, and neuroinflammation. No effective drugs can slow disease progression. Polysaccharides from traditional Chinese medicine (TCM) exhibit neuroprotective activities (e.g., antioxidant, anti-inflammatory) with good safety. However, their clinical application is limited by low oral bioavailability, poor blood–brain barrier (BBB) permeability, and a pharmacokinetic–pharmacodynamic paradox. The emerging role of the microbiota–gut–brain axis in AD offers a strategy to overcome this paradox. This review summarizes the structural features and classification of TCM polysaccharides (from plants, fungi, and roots/rhizomes) and highlights their anti-AD mechanisms via the gut–brain axis. Acting as prebiotics, these polysaccharides escape upper digestion and are fermented by gut microbiota into short-chain fatty acids (SCFAs) and other metabolites, which enter circulation, cross the BBB, and alleviate AD pathology through metabolic, immune, and neuronal pathways. Outcomes include reduced Aβ deposition and tau phosphorylation, suppressed neuroinflammation, restored synaptic function, and improved cognition. This review provides a theoretical framework for TCM polysaccharide intervention in AD via the gut–brain axis and a pharmacological basis for developing natural product-based AD therapies. Full article

Intestinal health is crucial for the growth and stress resistance of shrimp. Butyrate, a beneficial metabolite of intestinal microbiota and the primary energy substrate for enterocytes, exerts regulatory effects on intestinal health. Butyrates exist in various chemical forms, yet their application in shrimp remains limited. Therefore, in this study, Penaeus monodon were fed diets supplemented with 1% four types of butyrate (monobutyrin, MB; tributyrin, TB; sodium butyrate, SB; poly-β-hydroxybutyrate, PHB) for 56 days, followed by 48 h of acute nitrite stress. A systematic investigation into their influences on the shrimp growth, intestinal health and nitrite stress resistance was conducted. The results showed that the four butyrate types significantly increased the weight gain rate of the shrimp by more than 25% and improved the survival rate under nitrite stress by more than 28% when compared with the control group (p < 0.05). They also improved intestinal mucosal integrity, and enhanced intestinal antioxidant and immune capacities through the activation of the Nrf2 pathway and the upregulation of immune gene expression. Specifically, T-AOC and SOD activities, as well as the expression levels of Nrf2, GPx, Trx, ALF, Pen3, and serP genes, were significantly upregulated in all four butyrate groups, while MDA content was significantly decreased (p < 0.05). In addition, LPO content, CAT and ASC activities, and the expression of HO1, SOD, Crus, and proPO genes exhibited differential changes among the four butyrate groups. Furthermore, the intestinal microflora structure was reshaped by all four butyrate variants, with notable reductions in pathogenic Vibrio alongside elevated abundances of advantageous taxa including Rhodobacteraceae. In conclusion, butyrate can facilitate the growth and anti-stress capacity of P. monodon by improving intestinal health, with the overall efficacy ranked as TB, PHB, MB and SB under the present study conditions. Full article

Epilepsy is increasingly recognized as a systemic disorder involving complex interactions between the brain and peripheral systems. Among these, the gut microbiota has emerged as a key regulator of host metabolism and immune homeostasis through the production of bioactive metabolites that mediate the communication between gut and brain. In recent years, growing evidence has linked gut dysbiosis to epilepsy, particularly in drug-resistant forms, and interventional studies targeting the gut microbiota in animal models suggest that microbiota-driven metabolic alterations may contribute to seizure generation and recurrence, as well as the associated neuropathology and cognitive deficits. In this review, we summarize current knowledge on the role of the gut microbiota–metabolome axis in acquired epilepsy, with a particular focus on short-chain fatty acids (SCFAs) and tryptophan-derived pathways. SCFAs represent major microbial products involved in energy metabolism, inflammation, blood–brain barrier integrity, neurotransmission and epigenetic mechanisms. In parallel, microbiota-dependent tryptophan metabolism represents a central hub linking intestinal microbial activity to brain function through serotonin, kynurenine, and indole pathways. Dysregulation of these pathways may influence neuronal excitability and contribute to seizures. Converging evidence supports the concept that epilepsy is associated with a coordinated alteration of gut microbial composition and host–microbiota metabolic interactions. However, further research is needed to elucidate the mutual communication between the gut and its microbiota and the metabolic flux, and their influence on brain function in neurological conditions. A better understanding of the underlying pathways and mechanisms may highlight novel therapeutic strategies and discover novel biomarkers of disease trajectory. Full article

Myocarditis is a clinically challenging form of inflammatory heart disease with heterogeneous etiologies, limited diagnostic tools, no targeted therapies, and a substantial risk of progression to heart failure or sudden cardiac death, particularly in young adults. Emerging evidence has increasingly associated myocarditis with gut microbiota dysbiosis. This review explores the gut–myocarditis axis, highlighting key mechanisms and therapeutic strategies. Significant alterations in gut microbial composition are observed in myocarditis patients and animal models. Gut microbiota influences disease development through multiple pathways: compromised intestinal barrier integrity leading to bacterial translocation and systemic inflammation via MAMP/PRR signaling (e.g., TLRs, NLRs); production of metabolites—including pro-inflammatory trimethylamine N-oxide (TMAO), anti-inflammatory short-chain fatty acids (SCFAs), and immunomodulatory bile acids—that regulate host inflammatory responses, immune cell differentiation, oxidative stress, and fibrotic remodeling; and molecular mimicry, where microbial peptides (e.g., from Bacteroides thetaiotaomicron) trigger cross-reactive autoimmune responses against cardiac proteins. Regarding therapeutic strategies, this review discusses fecal microbiota transplantation (FMT), probiotics, prebiotics, dietary modulation, and emerging approaches including engineered bacteria and oral nanomedicines. Although these strategies hold promise, their efficacy and safety remain to be validated in large-scale clinical trials, and further investigation is warranted. Full article

Gut microbiota dysbiosis is implicated in diverse intestinal and systemic disorders, and prebiotics offer a practical strategy to modify host–microbe interactions. This review evaluates 1-kestose as a candidate precision bioactive component by integrating its chemical structure, enzymatic production, gastrointestinal fate, GH32-dependent microbial utilization, human evidence, and qPCR-based response monitoring. Many commercial fructooligosaccharides contain molecules with different degrees of polymerization, complicating structure–function interpretation. In contrast, 1-kestose is a high-purity trisaccharide fructooligosaccharide and the shortest member of the inulin-type fructans. By comparing 1-kestose with long-chain inulin, we examine how fructan chain length may influence colonic fermentation kinetics, substrate availability, and tolerability. We then discuss the role of GH32 substrate specificity in the selective microbial utilization of 1-kestose and related fructooligosaccharides, particularly by bifidobacteria and representative butyrate producers. Next, we review the mechanistic rationale and preclinical evidence for co-administration of 1-kestose and long-chain inulin. Human intervention studies have evaluated 1-kestose across gastrointestinal, metabolic, immune-related, neonatal, oncological, and bowel-habit contexts, with emerging evidence of potential benefits. One healthy-adult trial has also evaluated co-administration with long-chain inulin, although direct comparative trials remain an important future priority. Finally, we propose a research framework that integrates high-purity 1-kestose, GH32-dependent microbial selectivity, and qPCR-based baseline stratification and response monitoring. Prospective, independently replicated trials are needed to establish clinical effectiveness and determine the value of biomarker-guided intervention and combination strategies. Full article

Microbiome-linked pathologies in humans have significantly increased over recent decades, suggesting that lifestyle changes, particularly those related to diet, have contributed to the disruption of beneficial microbial composition and functions. Specifically, modern processed diets that are low in dietary fiber and high in fat and sugar can lead to the depletion of bacterial taxa over generations and contribute to chronic inflammatory diseases. These pathologies can potentially be prevented by increasing fiber intake, making the promotion of dietary fiber crucial for human health. Despite the recognized importance of fiber integration, there remains a significant gap in the understanding of the use of multiple dietary fibers in food to promote microbiota diversity, as well as which dietary fibers promote specific microbial taxa to restore symbiosis. To address this gap, we conducted an in vitro fermentation study using fecal samples from two individuals. We tested three types of dietary fibers of varying complexity: inulin, pectin, and dextran in a β-glucan–based medium. Samples were collected over a 48 h fermentation period (0–4–8–24–32–48 h) to evaluate temporal shifts in microbial composition and short-chain fatty acid (SCFA) production. Through 16S rRNA gene amplicon sequencing, we found that the introduction of different fibers steered the microbiota of both individuals toward a convergent trajectory by 24–48 h. This result indicated that fiber complexity can reduce inter-individual variation in microbial community structure. Distinct levels of polysaccharide complexity between fiber types modulated specific bacterial taxa, supporting the concept that consuming a diversity of dietary fiber acts on complementary microbial niches. Notably, the observed shifts toward butyrate-associated taxa and reduction of pro-inflammatory lineages with dextran/β-glucan are relevant for pathologies characterized by dysbiosis, such as inflammatory bowel disease (IBD). Together, these results underscore the value of incorporating multiple fibers into food production, including fermented foods, to enhance prebiotic properties, stimulate the growth of fiber-fermenting bacteria, and promote microbial diversity. While these observations derive from a controlled in vitro pilot setting, they support the concept that multi-fiber dietary strategies based on complementary fermentable fibers with prebiotic properties may help shift the microbiome away from a pro-inflammatory state. Accordingly, dietary guidelines and public health approaches aimed at reducing chronic disease risk may benefit from emphasizing the inclusion of composite fiber blends rather than relying solely on single-fiber supplementation. Full article

Microplastics and nanoplastics (MNPs) have been recognized as ubiquitous emerging global pollutants, which are extensively detectable in diverse environmental media and food matrices. Increasing evidence indicates that the intestine is a primary target of orally ingested MNPs and a critical initiating hub for systemic toxicity. Once ingested orally, MNPs can interact with the intestinal mucus layer and epithelial barrier, induce gut microbiota dysbiosis, remodel bile acid and short-chain fatty acid metabolism, and activate oxidative stress, inflammation, apoptosis, and immune imbalance. These gut-derived disturbances may subsequently propagate adverse signals to distal organs through the gut-liver, gut-brain, gut-kidney, gut-lung, gut-reproductive, and gut-mammary axes. Intestinal barrier dysfunction, endotoxin translocation, abnormal microbial metabolites, and microbiota-derived immune signals constitute common mediating pathways linking local intestinal injury to multi-organ toxicity. In addition, smaller particle size, surface oxidation, environmental aging, bio-corona/plastisphere formation, and co-exposure with other contaminants can further modulate the intensity and specificity of gut-organ axis disruption. Prior reviews are limited to separate analyses of single-organ toxicity or isolated gut-organ pathways. To fill this gap, this work synthesizes contemporary mechanistic and experimental evidence to establish a gut-initiated systemic toxicology framework for MNPs. We differentiate direct particle translocation from gut-derived indirect signaling, evaluate the varying robustness of supporting evidence for each gut-organ axis, and underscore nanoscale biointerface properties as key modulators of MNPs systemic toxic potency. Full article

The continuous intensification of modern poultry farming has confronted the industry with a dual crisis involving animal health and food safety. Host defensins, a major class of antimicrobial peptides (AMPs), exhibit broad-spectrum antimicrobial and immunomodulatory activities, demonstrating potential in disease prevention and immune support. By enhancing host innate defense mechanisms, they may complement existing antimicrobial strategies and contribute to reducing antibiotic dependence. Although accumulating evidence highlights the capacity of microbial metabolites to modulate defensin expression, a comprehensive and integrated understanding of the cross-talk between these microbial metabolites and host defensins remains lacking. To bridge this gap, this review summarizes the classification and biological functions of poultry defensins, while synthesizing recent advances in how microbiota-derived metabolites—such as short-chain fatty acids, amino acid derivatives, and secondary bile acids—regulate their expression. By elucidating the underlying receptor-mediated signaling pathways and mechanisms, this review provides strategic insights into leveraging microbial metabolites to stimulate endogenous poultry defensins and offers a reference for the future optimization of immunomodulatory strategies and the improvement of poultry health management. Full article

Background/Objectives: Postbiotics are increasingly recognized as biologically active products of microorganisms with emerging potential as microbiome-inspired therapeutic interventions. While most microbiome-based strategies focus on modifying microbial composition, restoration of microbial signaling has received comparatively less attention. This review examines postbiotics through the lens of microbial signaling restoration and proposes a unified Metabolite–Immune–Redox (MIR) axis linking microbial-derived signals with immune regulation, redox homeostasis, endothelial integrity, and host resilience. Methods: This narrative review synthesizes current evidence on postbiotics, microbial metabolites, structural microbial components, and extracellular vesicles, with emphasis on their roles in immunometabolic regulation, redox biology, endothelial function, and host-directed interventions. Results: Current evidence suggests that short-chain fatty acids, indole derivatives, bile acid metabolites, and microbial extracellular vesicles are important mediators of host–microbe communication. These signals influence interconnected pathways involving mitochondrial function, inflammasome activity, immune calibration, endothelial and glycocalyx homeostasis, and disease tolerance. The review highlights the endothelium as an underrecognized therapeutic target and discusses biomarkers, including soluble thrombomodulin, von Willebrand factor, and D-dimer, as potential tools for identifying patients most likely to benefit from host-directed interventions. Major translational challenges include product heterogeneity, incomplete mechanistic characterization, uncertain exposure–response relationships, and unresolved regulatory considerations. Conclusions: The proposed MIR axis provides a hypothesis-generating framework for understanding how restoration of microbial signaling may contribute to precision host-directed therapeutic strategies. Further mechanistic and clinical studies are needed to validate this concept and define its translational potential in inflammatory, infectious, and critical illness settings. Full article

Camel milk (CM), which is produced by both Camelus dromedarius and Camelus bactrianus, is gaining increasing popularity as a value-added functional dairy product, but the science of managing its shelf life has progressed more slowly than its commercial expansion. Unlike bovine milk, CM lacks β-lactoglobulin (β-LG), has a unique casein (CN) micelle structure with a high β-CN-to-αs1-CN ratio, and low κ-CN protein content, and contains an unusually rich bioactive protein fraction including lactoferrin (LF), immunoglobulin G (IgG), lysozyme (LZ), and peptidoglycan recognition protein (PGRP). These compositional characteristics imbue CM with both significant inherent antimicrobial benefits and place it at risk of processing weaknesses that do not have direct analogs in bovine dairy science. The review discusses three key areas of CM shelf life science that have not been sufficiently addressed in the published literature. The first relates to physicochemical mechanisms of deterioration, including lipid oxidation of polyunsaturated fatty acids (PUFA), destabilization of CN micelles in the structural absence of β-LG, and Maillard browning during thermal treatment and storage of powder. The second addresses the fate of bioactive proteins, with the majority being lactoferrin (LF), immunoglobulin G (Igs), and heavy chain-only antibodies (HCAbs), under both thermal and non-thermal processing conditions. The third looks at new non-thermal preservation methods, such as high-pressure processing (HPP), pulsed electric field (PEF), ultrasonication, ultraviolet irradiation, cold plasma, and electromagnetic (EM) field treatment, and functional packaging innovations, which contribute to longer shelf life. Of the non-thermal options examined, HPP at 200–400 MPa today provides the most mechanistically proven evidence for camel-specific microbial deactivation with satisfactory quality preservation. The latest primary CM research also indicates that processing with EMs in the 850 mT range can potentially be as effective as conventional pasteurization in microbial control and may be more effective than pasteurization in retaining desirable bioactive markers, although this result needs to be independently replicated before more responsible conclusions can be drawn. The review ends with four priority research gaps: standardized kinetic shelf life modeling frameworks, systematic characterization of bioactive protein stability under commercial processing conditions, life cycle assessment of preservation chains across the camel dairy supply continuum, and the urgent validation of camel-specific pasteurization adequacy indicators to replace bovine alkaline phosphatase, which remains active in CM after conventional high-temperature short-time (HTST) pasteurization. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by progressive insulin resistance, impaired glucose regulation, and elevated cardiometabolic risk. Despite the availability of pharmacological therapies, long-term glycemic control remains suboptimal in many patients, highlighting the need for effective adjunctive nutritional strategies. Probiotic yogurt containing well-characterized bacterial consortia has been proposed as one such approach, given its potential to modulate gut microbiota composition, increase short-chain fatty acid (SCFA) production, improve intestinal barrier integrity, and attenuate low-grade systemic inflammation. A narrative review was conducted by searching PubMed, Scopus, and Google Scholar databases using terms related to probiotic yogurt, synbiotic yogurt, insulin sensitivity, T2DM, gut microbiota, Lactobacillus, and Bifidobacterium. Priority was given to randomized controlled trials (RCTs), meta-analyses, and systematic reviews, supplemented by mechanistically relevant preclinical studies. The reviewed evidence indicates that probiotic yogurt generally produces more consistent improvements in long-term metabolic markers, particularly glycated hemoglobin (HbA1c) and lipid profile, than in acute fasting glucose responses. Several trials also report reductions in fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR), combined with improvement in the quantitative insulin sensitivity check index (QUICKI), particularly when yogurt is enriched with prebiotic substrates such as inulin and konjac glucomannan. Probiotic yogurt formulated with well-selected microbial consortia may serve as a safe complementary intervention for improving insulin sensitivity and overall metabolic control in T2DM patients. Full article

Metabolic syndrome (MetS) is a multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, hypertension, and impaired glucose metabolism, significantly increasing the risk of type 2 diabetes and cardiovascular disease. Recent evidence highlights the important role of the gut–brain axis in the pathogenesis of MetS through complex interactions between the gut microbiota, immune system, endocrine signaling, and host genetics. This narrative review provides an integrative overview of the mechanisms linking dysbiosis to metabolic dysfunction, with particular emphasis on gut microbiota alterations, intestinal permeability, chronic low-grade inflammation, and microbial metabolites such as short-chain fatty acids and lipopolysaccharides. The review also discusses the neural, endocrine, and immune pathways involved in gut–brain communication, including the role of gut-derived neurotransmitters in metabolic regulation. In addition, the contribution of host genetic susceptibility and epigenetic regulation is explored, highlighting how gene–microbiome interactions influence individual metabolic responses and disease risk. Recent advances in multi-omics technologies and precision medicine suggest that personalized approaches targeting both microbial and genetic factors may improve prevention and treatment strategies for MetS. Furthermore, microbiota-targeted interventions, including dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation, are discussed as emerging therapeutic perspectives. Overall, this review emphasizes the importance of considering MetS as a systemic disorder driven by interconnected biological networks involving microbiota, metabolism, immunity, and genetics. Full article

Short-chain fatty acids (SCFAs), acetate, propionate, and butyrate, are typically produced in a 3:1:1 ratio, respectively, via microbial fermentation of non-digestible carbohydrates, and to a lesser degree, from undigested protein. The effects of individual SCFAs on adipocyte function have been described; however, the effects of SCFAs in combination on adipocyte function remain unknown. Mature 3T3-L1 adipocytes were treated with a 1 mM total dose of acetate, propionate, and butyrate combined in a 3:1:1 ratio, respectively, for 24 h ± lipopolysaccharide (LPS, 10 ng/mL) under both normoxic and hypoxic (via the addition of 100 µM cobalt chloride) environmental conditions. In both normoxic and hypoxic LPS-stimulated conditions, SCFAs increased the secretion of adiponectin and reduced the secretion of resistin, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1/C-C motif chemokine ligand (CCL)2, and RANTES/CCL5, in addition to reducing intracellular protein levels of activated (i.e., the ratio of phosphorylated-to-total) nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) p65 and signal transducer and activator of transcription 3 (STAT3) (p < 0.05). Additionally, SCFA treatment reduced leptin secretion only in LPS-stimulated normoxic environmental conditions compared to control (p < 0.05). In normoxic conditions, SCFA + LPS increased mRNA expression of genes involved in fat storage), fatty acid recycling, and lipolysis, whereas in hypoxic conditions, SCFA + LPS decreased mRNA expression of genes involved in fat storage and triglyceride synthesis (p < 0.05), indicating different effects of SCFAs on adipocyte metabolic function depending on hypoxia status. Collectively, combined SCFAs in a 3:1:1 ratio beneficially modify the adipocyte adipokine secretory profile under both normoxic and hypoxic environmental conditions. Full article

Background: Type 2 diabetes mellitus (T2DM) is associated with altered gut microbiota and reduced short-chain fatty acid production, which may contribute to insulin resistance. However, evidence on fecal Short Chain Fatty Acid (SCFA) profiles in African populations remains limited. This study quantified fecal SCFAs in individuals with and without T2DM using Gas Chromatography–Mass Spectrophotometry (GC-MS) with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) derivatization. Methods: A cross-sectional study included 140 adults (92 non-diabetic and 48 T2DM). Fecal SCFAs were extracted, derivatized using BSTFA, and analysed by GC–MS. Associations between SCFAs, diabetes status, and HbA1c were evaluated using non-parametric statistics. Results: The GC–MS method demonstrated strong linearity (R² = 0.9917–0.9978), acceptable recovery, and reproducibility. Acetic, propionic, butyric, pentanoic, hexanoic, and heptanoic acids were detected, with acetic acid being most abundant in both groups. T2DM participants had higher median SCFA levels, although only butyric acid differed significantly (p = 0.027). HbA1c was significantly higher in the T2DM group (p < 0.001). No significant associations were observed between SCFAs and HbA1c in either group. Age differed significantly between groups, with T2DM participants older than non-diabetic controls. Conclusions: Most fecal SCFA profiles were comparable between individuals with T2DM and healthy controls. However, butyric acid was significantly elevated in the T2DM group, indicating that not all SCFAs exhibited similar patterns between the study groups. These findings suggest that fecal SCFAs alone may not serve as reliable biomarkers of T2DM in this population and highlight the influence of complex host–microbiome–environment interactions suggesting that dietary and microbial factors may outweigh disease status in determining SCFA variability in this cohort setting. Full article

Parkinson’s disease (PD), a debilitating neurodegenerative disorder, is primarily characterized by motor impairments and concurrent gastrointestinal disturbances. Increasing evidence has highlighted the critical role of the microbiota–gut–brain axis (MGBA) in the pathogenesis of PD. This study investigated the neuroprotective potential of sodium hyaluronate (SH) in a mouse model of PD and its underlying mechanisms via the MGBA. In the oral pre-treatment study, three doses (7.5, 15, and 30 mg/kg/day) were evaluated. The results showed that the high dose (SH-H, 30 mg/kg/day) significantly ameliorated motor disorders and gastrointestinal functional disorders. Therefore, SH-H was selected for subsequent mechanistic investigations. Mechanistically, SH-H restored gut microbiota homeostasis, increased fecal short-chain fatty acid (SCFA) levels, and improved the integrity of the intestinal and blood–brain barrier (BBB). Thus, SH reduced the transfer of lipopolysaccharide (LPS) from the intestine to serum and the substantia nigra (SN), suppressing activation of the LPS-TLR4/MyD88/NF-κB signaling pathway. These effects alleviated neuroinflammation, protected dopaminergic neurons, and reduced the aggregation of α-synuclein (α-syn). In summary, SH attenuated PD-related pathological changes by restoring gut microbiota homeostasis and modulating the MGBA, suggesting that SH may represent a potential therapeutic strategy for PD. Full article