Search Results (19,420)

Background: Obesity is closely related to dysbiosis. Probiotics may improve metabolism and alleviate inflammation by regulating microbial–host interaction. Methods: Obesity was induced in rats by feeding a high-fat diet, followed by gavage administration of varying doses of BC99 as an intervention. Results: BC99 significantly reduced body weight gain, improved lipid profiles, alleviated systemic inflammation, and enhanced gut barrier integrity. 16S rRNA sequencing revealed that BC99 increased the abundance of beneficial bacteria, including Bacillota, Akkermansia, and Roseburia. Untargeted metabolomics showed that BC99 upregulated anti-inflammatory lysophosphatidylcholines (LysoPCs) and modulated conjugated bile acids (GUDCA, GDCA), which were correlated with enriched bile salt hydrolase (BSH)-active bacteria (e.g., Lachnoclostridium). Conclusions: The results indicate that W. coagulans BC99 effectively reduces weight gain in rats made obese by a high-fat diet and improves metabolic disorders. These effects are associated with remodeling of the gut microbiota and modulation of key metabolites, supporting a potential ‘microbiota–metabolite–host’ axis in rats that warrants further causal validation. Full article

The presence of an unbalanced gut microbiome and the dysregulation of bile acid signalling are considered pivotal causes of various inflammation-based diseases. The Takeda G protein-coupled receptor (TGR5), TGR5 is a bile acid-responsive receptor that modulates inflammatory signalling pathways, making it an enticing molecular target for the discovery of novel anti-inflammatory agents. Herein, a comprehensive in silico approach was employed to identify potential TGR5 agonists from sterol-rich phytocompounds present in Triphala, a traditional polyherbal formulation. Using in silico computational methods, such as molecular docking and molecular dynamics simulations (MDS), we screened the putative agonistic potential of 10 phytocompounds obtained from Terminalia chebula, Terminalia bellirica, and Phyllanthus emblica against the crystal structure of human TGR5 (PDB ID: 7XTQ). Based on binding energy and molecular interactions, ergosterol (−12.34 ± 0.17 kcal/mol) and stigmasterol (−10.35 ± 0.04 kcal/mol) were predicted to be the top and best compounds. Furthermore, the stability of these two compounds in the docked complex was analysed using MDS for 200 ns. The mean Cα RMSD values were 0.22 ± 0.02 nm for both ergosterol- and stigmasterol-bound complexes, compared to 0.21 ± 0.02 nm for the unbound apo protein. Further, the molecular mechanics/Poisson–Boltzmann surface area (MMPBSA) analysis revealed that ergosterol exhibited binding free energy (−139.868 ± 12.318 kJ/mol) comparable to that of the co-crystallised ligand R399 −93.424 ± 8.919 kJ/mol. In silico ADMET predictions indicated acceptable drug-like properties and low toxicity for both compounds. Collectively, these computational findings suggest that ergosterol is a promising putative TGR5 agonist, warranting further experimental validation of its potential role in modulating inflammation-related pathways. Full article

Desulfovibrio spp. are sulfate-reducing bacteria (SRB) associated with conditions such as inflammatory bowel disease (IBD) that are linked to intestinal barrier dysfunction (leaky gut). Previously, we reported that Desulfovibrio vulgaris (DSV) caused increased intestinal permeability by upregulating nuclear transcription factor Snail. However, the signaling mechanisms underlying this effect remain unclear. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that maintains intestinal barrier integrity and negatively regulates Snail and promotes its degradation by proteasomes. Rapamycin has been shown to protect the intestinal barrier and is also known to activate GSK-3. In this study, we investigated whether DSV disrupts intestinal barrier function through modulation of GSK-3 signaling and whether rapamycin could counteract these effects. Using a previously established DSV-induced paracellular permeability model using polarized Caco-2 monolayers, here, we showed that DSV induced inhibitory phosphorylation of GSK-3. Pretreatment of cells with rapamycin prevented DSV- induced phospho- inactivation of GSK-3, suppressed Snail expression and nuclear localization, and significantly reduced DSV-induced barrier permeability. Inhibition of proteasomal degradation with MG132 abolished the protective effects of rapamycin on barrier permeability, supporting a role for GSK-3–mediated proteasomal regulation of Snail. Together, these findings identify GSK-3 signaling as a novel mechanism underlying DSV-induced intestinal barrier dysfunction and highlight rapamycin as a potential therapeutic approach strategy to protect intestinal barrier integrity in response to DSV. Specifically, targeting the GSK-3/Snail pathway may represent a promising strategy to mitigate SRB-associated intestinal barrier disruption. Full article

FAM3A, FAM3B, FAM3C and FAM3D are members of the “family with sequence similarity 3” (FAM3) gene family, an emerging class of cytokine-like proteins with a unique structural globular β-β-α fold and distinct biological functions. With widespread expression in tissue, organs and in many cell types, their specific roles in human diseases have been the focus of much research. FAM3A acts as a positive regulator of metabolic health, typically activating canonical pro-survival and metabolic pathways. FAM3B, also called PANDER (PANcreatic DERived Factor), exerts critical physiological functions in the regulation of glycemic levels via promotion of hepatic glucose production and pancreatic β-cell insulin secretion. FAM3C, also named ILEI (Interleukin-like EMT inducer), is involved as an inducer of epithelial–mesenchymal transition (EMT) and cancer metastasis, as well as osteoblast differentiation and bone mineralization. FAM3D is a gut-secreted protein and potential regulator of gastrointestinal homeostasis and microbiota-induced inflammation. Here we provide an overview of previous studies supporting that FAM3 proteins act through putative membrane receptors and co-partners, including fibroblast growth factor receptor (FGFR), leukemia inhibitory factor receptor (LIFR), formyl peptide receptor (FPR1/2), to activate diverse downstream signaling pathways on different cellular contexts. Basic and clinical studies suggest that the FAM3 family influences both obesity, diabetes, and other metabolic disorders; thus, its expression may have diagnostic potential. The differential and often cancer-specific expression patterns make members of the FAM3 family promising candidates for biomarkers and therapeutic targets of some types of neoplasia. Full article

Necrotizing enterocolitis (NEC) is a major cause of illness and death in preterm infants and is increasingly linked to long-term neurodevelopmental issues among survivors. Usually seen as a gastrointestinal disease, NEC is rarely viewed from a brain-centered perspective. In this Perspective, we suggest that NEC should be understood as a disorder of the gut–brain axis affecting neurodevelopment. We combine clinical and experimental evidence showing that intestinal inflammation, microbial imbalance, epithelial barrier failure, and systemic immune activation during NEC all contribute to the disruption of early brain development. We contend that neurodevelopmental damage is a key feature of NEC rather than just a secondary effect of prematurity. Recognizing NEC as a gut–brain axis disorder is crucial for research models, treatment approaches, and assessing long-term outcomes in affected infants. Full article

The use of agro-industrial waste to obtain biochar has emerged as an environmentally friendly, low-cost, effective, profitable, and sustainable strategy for the removal of aflatoxin B1 (AFB1), a highly toxic and carcinogenic mycotoxin of importance in poultry production systems because it can cause serious economic losses, affect hatchability, egg production, and the growth of birds, and can cause their death. In this sense, the objective of the present study was to obtain a sustainable and low-cost biochar derived from agro-industrial coconut shell waste (BCS) and evaluate its AFB1 adsorption capacity using a conventional method based on buffer solutions and an in vitro avian digestion model that simulates the conditions of the gastrointestinal tract of the broiler chicken. The results showed that the adsorption capacity of BCS on AFB1 (250 ng/mL) at both pH 5.0 and 1.2 was close to 100%, while at pH 6.8, the adsorption of AFB1 was 86.24%. However, in the in vitro avian digestibility model, the adsorption capacity of BSC on AFB1 was 32.96%, thus highlighting the importance of considering factors that can affect the adsorption capacity of materials before in vivo studies, as this can lead to overestimations of results and, therefore, ineffective treatments or unexpected results in animals. Full article

Background: Obesity and its related metabolic complications, including non-alcoholic fatty liver disease (NAFLD) and insulin resistance, constitute an escalating global public health challenge, with high-fat diet (HFD) exposure recognized as a primary etiological driver. This study aimed to systematically evaluate the therapeutic effects of pepper leaf extracts (PLE), spinach extracts (SE), and obeticholic acid (OCA) on HFD-induced metabolic dysfunction in mice. Methods: Integrated phenotypic, histopathological, gut microbial, bile acid, and metabolomic analyses were applied to evaluate the intervention effects. Results: Our results demonstrated that 16-week dietary intervention with PLE, SE, or OCA all effectively mitigated HFD-induced obesity, pathological adipose remodeling, hepatic steatosis, systemic insulin resistance, and intestinal barrier dysfunction. Mechanistically, PLE effectively restored intestinal barrier integrity and reshaped the dysbiotic gut microbiota, with a marked enrichment of beneficial bacterial taxa closely linked to intestinal barrier maintenance, and normalized the disrupted cecal bile acid profile in HFD-fed mice. Furthermore, untargeted metabolomic analysis revealed that PLE reprogrammed disordered systemic metabolism, with significant modulation of key pathways involved in bile acid homeostasis, amino acid metabolism, and energy metabolism. Conclusions: In summary, this study provides evidence that PLE effectively attenuates HFD-induced metabolic disorders through modulation of the gut microbiota–bile acid–metabolome axis and restoration of intestinal barrier integrity. The superior therapeutic efficacy of PLE compared with SE and OCA, coupled with its favorable safety profile, positions PLE as a promising novel natural candidate for the prevention and treatment of obesity and its associated metabolic complications. Full article

The neonatal development period from the time of birth can be considered the period of greatest physiological changes throughout the human lifespan. These changes are partly due to dietary or environmental factors and are also modulated by genetic, neuronal, and humoral influences. The focus of research is increasingly on the microbial colonization of the neonatal intestine, since the establishment of a healthy, symbiotic newborn microbiota not only corresponds closely with nutrient metabolism, immune functions, and growth, but also with the brain as part of the so-called “gut–brain axis”. At the same time, a critical time window of opportunity opens up for the early infant microbiota, which is accessible to modulating approaches in favor of normal infant development. Although the definition of “normal” microbiota in infants still remains challenging, the microbiota of infants delivered at term can be discussed as the gold standard—provided they were exclusively breastfed and have not been exposed to antibiotics. Advances in sequencing technologies now also allow us to identify and characterize the microbiota at the strain level and to provide the scientific rationale for new approaches to modulate the early-life microbiome in a more targeted and personalized way—applicable also for formula-fed children who cannot be supplied with human milk. This review addresses the challenges associated with the “healthy” development of a newborn during the first weeks and months of life and discusses potentially modifiable external factors in light of the requirements for the establishment of a functional gut microbiota, gastrointestinal system, and gut–brain axis. Full article

Background: Metabolic syndrome (MetS) and alcohol-related liver disease (ALD) are increasingly recognized as interconnected disorders linked by shared mechanisms of lifestyle-driven metabolic reprogramming. Alterations in systemic and hepatic metabolic pathways—including insulin signaling, lipid metabolism, mitochondrial bioenergetics, and redox homeostasis—reduce hepatic resilience to alcohol exposure and accelerate liver disease progression. Objective: This narrative review aims to integrate clinical, epidemiological, and mechanistic evidence published over the past two decades to examine how modifiable lifestyle factors contribute to metabolic reprogramming linking metabolic syndrome and alcohol-related liver disease with prioritization of high-level clinical evidence (cohort studies, meta-analyses, and guidelines). Key Findings: Modifiable lifestyle exposures such as alcohol consumption, cigarette smoking, unhealthy dietary patterns, and physical inactivity converge on common metabolically mediated pathways, including insulin resistance, dysregulated lipid metabolism and lipotoxicity, mitochondrial dysfunction, oxidative stress, chronic low-grade inflammation, and gut–liver axis perturbations. These processes are reflected in altered metabolite profiles involving lipid species, bile acids, tricarboxylic acid cycle intermediates, and microbiota-derived metabolites, shaping a metabolic–hepatic continuum. Among these, alcohol consumption and metabolic dysfunction show the strongest and most consistent associations with liver disease progression, with evidence supporting synergistic rather than additive effects. Conclusions: The coexistence of metabolic dysfunction and alcohol exposure is consistently associated with synergistic worsening of liver-related outcomes, including fibrosis progression, cirrhosis, and hepatocellular carcinoma. Recognition of metabolic alcohol-related liver disease (MetALD) underscores the need for integrated lifestyle-based strategies targeting alcohol consumption, smoking cessation, dietary quality, and physical activity to modulate shared metabolic and inflammatory pathways. A metabolically informed, systems-level approach may improve risk stratification, prevention, and management across the metabolic–hepatic continuum. Full article

Insects are widely distributed across the globe and exhibit strong adaptability in diverse living environments, a capability closely linked to the diversity of their gut microbiota. The composition of insect gut bacteria varies with species, living environment, diet, and development stage. In recent years, the widespread application of culture-independent strategies based on molecular biology techniques has provided substantial information for studies on the interaction mechanisms between insects and their gut microbiota. However, culture-dependent strategies aimed at isolating pure cultures remain indispensable. Only by integrating multi-techniques such as bacterial isolation and pure culture, axenic insect technology, and molecular biology can in-depth research be conducted on key gut bacteria of insects. This review summarizes culture-dependent and -independent strategies used for the analysis of the diversity and functions of insect gut microbiota, focusing on the traditional methods and new strategies for microbial cultivation, multi-omics techniques, and axenic insect technology. Recent studies showed that the application of integrated techniques is powerful for illustrating the microbial function and evolution of gut microbiota, and the interactions between intestinal bacteria and their hosts. Studies have shown that the insect gut microbiota plays important roles in the promotion of host growth and development by regulating host metabolic pathways, contributing to host nutrition, and supporting the host in defending against pathogens or degrading toxic compounds. Future research directions and strategies are also proposed, providing insights into further exploration of the interaction mechanisms between symbiotic insect gut bacteria and their hosts, as well as future applications in various fields. Full article

This study aimed to investigate the changes in the meat quality characteristics of Duolang sheep using rumen metagenomic and muscle metabolomic analyses across different age groups. A total of 24 three-month-old male Duolang sheep were selected and reared, and samples of longissimus thoracis muscle and rumen contents were collected at 4, 6, and 8 months of age to evaluate meat quality, metabolites, rumen metagenome, and volatile fatty acids (VFAs). The results indicated that the lightness (L*_45min) and yellowness (b*_45min) of the longissimus thoracis muscle at 45 min post-slaughter were significantly higher at 4 and 6 months than at 8 months of age (p < 0.05). In terms of ruminal VFAs, butyrate concentration was significantly higher at 6 months than at 4 months (p < 0.05), and valerate concentration exhibited a quadratic relationship with age (p = 0.02). With increasing age, the relative abundances of Prevotella and Fibrobacter increased, whereas those of Methanobrevibacter and Bacteroides decreased (p < 0.05), leading to shifts in functional pathways related to amino acid, lipid, and carbohydrate and energy metabolism. Untargeted metabolomics revealed that muscle betaine and inosine peaked at 4 months of age, whereas L-arginine, L-proline, and inosinic acid were most abundant at 6 months of age (p < 0.05). Correlation analysis revealed that the b*_45min was positively associated with ruminal concentrations of propionate, butyrate, and valerate, as well as with the relative abundances of key Selenomonadales taxa (p < 0.05). Inosinic acid exhibited a positive correlation with the abundance of the genus Sodaliphilus and ruminal butyrate concentration (p < 0.05), while Sodaliphilus abundance was negatively correlated with inosine (p < 0.05). In summary, this study demonstrates that age-related variations in the meat quality of Duolang sheep are closely associated with rumen microbial ecology and muscle metabolites, offering novel insights into the molecular mechanisms underlying meat quality formation and identifying potential biomarkers. Full article

Background: Lung cancer is the most common malignancy worldwide and has the highest mortality rate. Although therapeutic approaches have improved over recent years, the clinical efficacy of lung cancer treatment remains limited. Therefore, there is an urgent need to develop novel and effective immunotherapeutic strategies for lung cancer. Methods: In this study, we constructed a novel bacterial complex vaccine (Neo-BCV, hereafter referred to as BCV) and investigated its anti-tumor effects and underlying mechanisms in a murine lung cancer model. We further explored the role of the gut microbiota, bile acid metabolism, and T-cell function in BCV-mediated anti-tumor immunity. In addition, we performed a preliminary evaluation of the clinical safety of BCV in human subjects. Results: BCV treatment significantly enhanced the infiltration of CD4⁺ and CD8⁺ T cells into the tumor immune microenvironment and promoted the secretion of anti-tumor effector molecules. Mechanistically, BCV markedly increased the abundance of Lactobacillus reuteri (L. reuteri) in the gut microbiota and reduced serum levels of taurocholic acid (TCA). Further experiments confirmed that L. reuteri directly degrades TCA, and decreased TCA levels restored the effector functions of CD4⁺ and CD8⁺ T cells. Conclusions: This study demonstrates that BCV remodels the gut microbiota and enhances anti-tumor immunity by regulating the L. reuteri–TCA axis to restore T-cell function. This mechanism provides a new strategy for improving the tumor immune microenvironment and supports further investigation and development of BCV as a therapeutic candidate for lung cancer. Full article

Solid-state fermentation (SSF) is a long-established biotechnological approach gaining renewed interest for its ability to enhance nutrient availability and improve the functional properties of agro-industrial by-products. This strategy is particularly relevant for early post-weaning piglets, which are highly susceptible to weaning stress due to an immature digestive system and a gut microbiota not yet adapted to solid feed. In this study, the fermentation parameters of flaxseed cake were optimized using a Plackett–Burman experimental design. Protease activity was selected as the response variable due to its relevance for improving protein degradation and potential digestibility in fermented feed ingredients. Accordingly, based on the statistical analysis, the conditions selected for the in vivo trial were 1% molasses, 0.5% yeast extract, 0.05% CaCl₂, 0.5% NaCl, 7.5% inoculum (4.12 × 10⁹ CFU/mL), 60% moisture, and 72 h fermentation. Fermentation time was identified as the main factor positively influencing protease production, while higher CaCl₂ concentrations and inoculum levels negatively affected enzyme activity. Optimization increased protease activity, microbial viability and free amino acid content. In addition, SSF reorganizes the carbohydrate profile by reducing structural fiber fractions, with neutral detergent fiber and acid detergent fiber decreasing by 27% and 29%, respectively, while simultaneously increasing soluble carbohydrates by 14.67%. Phytic acid content being also reduced by 23.81%. A pilot nutritional trial on post-weaned piglets (35 days old) showed that including 8% fermented flaxseed cakes (FFSC group) improved body weight, average daily gain, feed conversion ratio, and diarrhea score, without affecting average daily feed intake, compared with 8% unfermented flaxseed cakes (FSC group). These performance improvements were accompanied by changes in fermentation metabolites and gut microbial composition. Lower isovalerate concentrations suggested reduced proteolysis, while higher propionate levels may contribute to increased blood glucose availability in the FFSC group. These changes coincided with a shift in microbial composition, characterized by a reduced abundance of methanogenic archaea and increased abundances of taxa such as Lactobacillus, Enterococcus, and members of the Lachnospiraceae and Eubacteriaceae families. Full article

Gut ischemia/reperfusion (I/R) injury releases damage-associated molecular patterns (DAMPs), such as extracellular cold-inducible RNA-binding protein (eCIRP). Milk fat globule–epidermal growth factor VIII-derived oligopeptide 3 (MOP3) is a novel peptide enabling macrophage uptake of eCIRP via αvβ3-integrin. MOP3 reduces inflammation in gut I/R, but its mechanisms are not completely understood. We hypothesized MOP3 promotes macrophage polarization toward an anti-inflammatory, M2-like phenotype in gut I/R. We induced gut I/R in mice through 60 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Intestines were evaluated for macrophage polarization by flow cytometry and immunofluorescence histology. Peritoneal cavity macrophages were isolated from mice and treated with eCIRP, MOP3, α_vβ₃-antibody, and/or naïve IgG for 4 or 24 h. Polarity was assessed by flow cytometry, qPCR, and ELISA. Compared to the sham, the M2 proportion after gut I/R decreased by 22.7%, and the M1 proportion increased by 241%. MOP3 treatment increased the M2 proportion by 64.3%, and the M1 proportion decreased by 22.7%. In eCIRP-stimulated macrophages, MOP3 treatment increased M2-like and reduced M1-like cell-surface markers, gene expression, and cytokine levels. α_vβ₃ antibody dramatically reduced MOP3′s effects. MOP3 promotes M2 polarization through α_vβ₃ integrin-mediated clearance of eCIRP, a novel mechanism whereby MOP3 reduces gut I/R injury. Full article

Emerging evidence strongly suggests that gut microbiota dysbiosis plays a significant role in the development and progression of both type 1 and type 2 diabetes mellitus. Quantitative and qualitative changes in the intestinal microbiota’s composition are linked to these distinct pathomechanisms. In type 1 diabetes mellitus, dysbiosis is thought to initiate or accelerate the autoimmune destruction of pancreatic beta cells. This may occur through increased intestinal permeability, which allows microbial components and endotoxins to enter the systemic circulation. This exposure triggers inflammatory and autoimmune responses in individuals who are genetically predisposed. Conversely, in type 2 diabetes mellitus, gut dysbiosis contributes significantly to the characteristic metabolic derangements. Specific microbial shifts can lead to impaired energy metabolism, contributing to insulin resistance in peripheral tissues. Furthermore, dysbiosis is associated with the altered production of microbial metabolites, such as short-chain fatty acids, and the induction of low-grade chronic inflammation, which contribute to the pathogenesis of type 2 diabetes mellitus. Hyperglycemia, dyslipidemia and other metabolic changes also influence the gut microbiota. Understanding these type-specific microbial roles offers potential for novel diagnostic and therapeutic strategies. Full article