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Search Results (963)

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30 pages, 3152 KiB  
Article
Characteristics of Intestinal Barrier State and Immunoglobulin-Bound Fraction of Stool Microbiota in Advanced Melanoma Patients Undergoing Anti-PD-1 Therapy
by Bernadeta Drymel, Katarzyna Tomela, Łukasz Galus, Agnieszka Olejnik-Schmidt, Jacek Mackiewicz, Mariusz Kaczmarek, Andrzej Mackiewicz and Marcin Schmidt
Int. J. Mol. Sci. 2025, 26(16), 8063; https://doi.org/10.3390/ijms26168063 (registering DOI) - 20 Aug 2025
Abstract
The gut microbiota is recognized as one of the extrinsic factors that modulate the clinical outcomes of immune checkpoint inhibitors (ICIs), such as inhibitors targeting programmed cell death protein 1 (PD-1), in cancer patients. However, the link between intestinal barrier, which mutually interacts [...] Read more.
The gut microbiota is recognized as one of the extrinsic factors that modulate the clinical outcomes of immune checkpoint inhibitors (ICIs), such as inhibitors targeting programmed cell death protein 1 (PD-1), in cancer patients. However, the link between intestinal barrier, which mutually interacts with the gut microbiota, and therapeutic effects has not been extensively studied so far. Therefore, the primary goal of this study was to investigate the relationship between intestinal barrier functionality and clinical outcomes of anti-PD-1 therapy in patients with advanced melanoma. Fecal samples were collected from 64 patients before and during anti-PD-1 therapy. The levels of zonulin, calprotectin, and secretory immunoglobulin A (SIgA), which reflect intestinal permeability, inflammation, and immunity, respectively, were measured in fecal samples (n = 115) using an Enzyme-Linked Immunosorbent Assay (ELISA). Moreover, the composition of the immunoglobulin (Ig)-bound (n = 108) and total stool microbiota (n = 117) was determined by the V3–V4 region of 16S rRNA gene sequencing. ELISA indicated a higher baseline concentration of fecal SIgA in patients with favorable clinical outcomes than those with unfavorable ones. Moreover, high baseline concentrations of intestinal barrier state biomarkers correlated with survival outcomes. In the cases of fecal zonulin and fecal SIgA, there was a positive correlation, while in the case of fecal calprotectin, there was a negative correlation. Furthermore, there were differences in the microbial profiles of the Ig-bound stool microbiota between patients with favorable and unfavorable clinical outcomes and their changes during treatment. Collectively, these findings indicate an association between intestinal barrier functionality and clinical outcomes of anti-PD-1 therapy in advanced melanoma patients. Full article
21 pages, 2677 KiB  
Article
A Novel Weizmannia coagulans Strain WC412 with Superior Environmental Resilience Improves Growth Performance of Mice by Regulating the Intestinal Microbiota
by Xue Xiao, Hao Huang, Wendi Yu, Jun Liu, Yuanliang Hu, Xiang Yu and Xicai Zhang
Animals 2025, 15(16), 2446; https://doi.org/10.3390/ani15162446 - 20 Aug 2025
Abstract
The growing demand for sustainable and antibiotic-free animal production has intensified interest in probiotics as functional feed additives. In this study, novel strains of Weizmannia coagulans (WC412 and WC413) were isolated from pickle water—a previously unexplored source for probiotic screening. These isolates, along [...] Read more.
The growing demand for sustainable and antibiotic-free animal production has intensified interest in probiotics as functional feed additives. In this study, novel strains of Weizmannia coagulans (WC412 and WC413) were isolated from pickle water—a previously unexplored source for probiotic screening. These isolates, along with three reference strains (W. coagulans S8, S15, and S17), were evaluated for their tolerance to heat, acid, and bile salts. Strain WC412 exhibited superior environmental resilience, as validated by principal component analysis (PCA) for comprehensive stress-tolerance assessment, and was selected for further investigations. A murine model was employed to assess the physiological and microbiological impacts of WC412 supplementation at varying doses. Medium-dose (1 × 107 CFU·mL−1) administration significantly improved body weight gain by 13% (p < 0.05), modulated serum lipid profiles, and increased antioxidant enzyme activity and IgG/IL-2 levels (p < 0.05). Notably, WC412 uniquely enriched beneficial genera (e.g., Fructilactobacillus and Limosilactobacillus) and promoted metabolic pathways linked to short-chain fatty acid production, as revealed by 16S rDNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. These findings highlight WC412 as a robust probiotic candidate for enhancing animal growth performance and gut health through novel microbiota-mediated mechanisms. Full article
(This article belongs to the Section Animal Nutrition)
20 pages, 1430 KiB  
Review
The Importance of an Adequate Diet in the Treatment and Maintenance of Health in Children with Cystic Fibrosis
by Michał Mazur, Agnieszka Malik, Monika Pytka and Joanna Popiołek-Kalisz
Int. J. Transl. Med. 2025, 5(3), 38; https://doi.org/10.3390/ijtm5030038 - 20 Aug 2025
Abstract
This review focuses specifically on pediatric patients with cystic fibrosis. Cystic fibrosis (CF) is a serious inherited disease that affects the respiratory and gastrointestinal systems in children and adolescents, causing chronic inflammation, infections, and impaired nutrient absorption. A key component of patient care [...] Read more.
This review focuses specifically on pediatric patients with cystic fibrosis. Cystic fibrosis (CF) is a serious inherited disease that affects the respiratory and gastrointestinal systems in children and adolescents, causing chronic inflammation, infections, and impaired nutrient absorption. A key component of patient care is monitoring nutritional status, particularly based on BMI, which correlates with lung function and life expectancy. This paper presents the latest guidelines for dietary therapy, including a high-calorie and fat-rich diet supported by pancreatic enzymes, as well as the importance of vitamin and mineral supplementation in the context of CF pathophysiology. The role of modern therapies that modulate CFTR function to improve patients’ quality of life and support antimicrobial therapy is discussed. Particular attention is paid to the role of the gut microbiota and the potential for its modulation by probiotics, highlighting their potential to alleviate inflammation and support the immune system. The conclusions underscore the need for a comprehensive, individualized approach to diagnosis and therapy, which is crucial for improving the quality of life and health prognosis of children with CF. New visual tools and a clinical case study enhance the practical applicability of current recommendations, while emerging areas such as microbiome-targeted interventions and treatment inequalities are also addressed. Full article
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31 pages, 2785 KiB  
Review
Mechanisms and Therapeutic Advances of PXR in Metabolic Diseases and Cancer
by Yuanbo Bi, Sifan Liu, Lei Wang, Daiyin Peng, Weidong Chen, Yue Zhang and Yanyan Wang
Int. J. Mol. Sci. 2025, 26(16), 8029; https://doi.org/10.3390/ijms26168029 (registering DOI) - 20 Aug 2025
Abstract
The pregnane X receptor (PXR), a ligand-activated nuclear receptor, plays a central role in regulating the metabolism of both endogenous substances and xenobiotics. In recent years, increasing evidence has highlighted its involvement in chronic diseases, particularly metabolic disorders and cancer. PXR modulates drug-metabolizing [...] Read more.
The pregnane X receptor (PXR), a ligand-activated nuclear receptor, plays a central role in regulating the metabolism of both endogenous substances and xenobiotics. In recent years, increasing evidence has highlighted its involvement in chronic diseases, particularly metabolic disorders and cancer. PXR modulates drug-metabolizing enzymes, transporters, inflammatory factors, lipid metabolism, and immune-related pathways, contributing to the maintenance of hepatic–intestinal barrier homeostasis, energy metabolism, and inflammatory responses. Specifically, in type 2 diabetes mellitus (T2DM), PXR influences disease progression by regulating glucose metabolism and insulin sensitivity. In obesity, it affects adipogenesis and inflammatory processes. In atherosclerosis (AS), PXR exerts protective effects through cholesterol metabolism and anti-inflammatory actions. In metabolic dysfunction-associated steatotic liver disease (MASLD), it is closely associated with lipid synthesis, oxidative stress, and gut microbiota balance. Moreover, PXR plays dual roles in various cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer. Currently, PXR-targeted strategies, such as small molecule agonists and antagonists, represent promising therapeutic avenues for treating metabolic diseases and cancer. This review comprehensively summarizes the structural features, signaling pathways, and gene regulatory functions of PXR, as well as its role in metabolic diseases and cancer, providing insights into its therapeutic potential and future drug development challenges. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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40 pages, 2700 KiB  
Review
From Microbial Switches to Metabolic Sensors: Rewiring the Gut–Brain Kynurenine Circuit
by Masaru Tanaka and László Vécsei
Biomedicines 2025, 13(8), 2020; https://doi.org/10.3390/biomedicines13082020 - 19 Aug 2025
Abstract
The kynurenine (KYN) metabolic pathway sits at the crossroads of immunity, metabolism, and neurobiology, yet its clinical translation remains fragmented. Emerging spatial omics, wearable chronobiology, and synthetic microbiota studies reveal that tryptophan (Trp) metabolism is regulated by distinct cellular “checkpoints” along the gut–brain [...] Read more.
The kynurenine (KYN) metabolic pathway sits at the crossroads of immunity, metabolism, and neurobiology, yet its clinical translation remains fragmented. Emerging spatial omics, wearable chronobiology, and synthetic microbiota studies reveal that tryptophan (Trp) metabolism is regulated by distinct cellular “checkpoints” along the gut–brain axis, finely modulated by sex differences, circadian rhythms, and microbiome composition. However, current interventions tackle single levers in isolation, leaving a key gap in the precision control of Trp’s fate. To address this, we drew upon an extensive body of the primary literature and databases, mapping enzyme expression across tissues at single-cell resolution and linking these profiles to clinical trials investigating dual indoleamine 2,3-dioxygenase 1 (IDO1)/tryptophan 2,3-dioxygenase (TDO) inhibitors, engineered probiotics, and chrono-modulated dosing strategies. We then developed decision-tree algorithms that rank therapeutic combinations against biomarker feedback loops derived from real-time saliva, plasma, and stool metabolomics. This synthesis pinpoints microglial and endothelial KYN hotspots, quantifies sex-specific chronotherapeutic windows, and identifies engineered Bifidobacterium consortia and dual inhibitors as synergistic nodes capable of reducing immunosuppressive KYN while preserving neuroprotective kynurenic acid. Here, we highlight a framework that couples lifestyle levers, bio-engineered microbes, and adaptive pharmaco-regimens into closed-loop “smart protocols.” By charting these intersections, this study offers a roadmap for biomarker-guided, multidisciplinary interventions that could recalibrate KYN metabolic activity across cancer, mood, neurodegeneration, and metabolic disorders, appealing to clinicians, bioengineers, and systems biologists alike. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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33 pages, 1617 KiB  
Review
From “Traditional” to “Trained” Immunity: Exploring the Novel Frontiers of Immunopathogenesis in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
by Mario Romeo, Alessia Silvestrin, Giusy Senese, Fiammetta Di Nardo, Carmine Napolitano, Paolo Vaia, Annachiara Coppola, Pierluigi Federico, Marcello Dallio and Alessandro Federico
Biomedicines 2025, 13(8), 2004; https://doi.org/10.3390/biomedicines13082004 - 18 Aug 2025
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic hepatopathy and a leading precursor of hepatocellular carcinoma (HCC) worldwide. Initially attributed to insulin resistance (IR)-driven metabolic imbalance, recent insights highlight a multifactorial pathogenesis involving oxidative stress (OS), chronic inflammation, [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic hepatopathy and a leading precursor of hepatocellular carcinoma (HCC) worldwide. Initially attributed to insulin resistance (IR)-driven metabolic imbalance, recent insights highlight a multifactorial pathogenesis involving oxidative stress (OS), chronic inflammation, and immune dysregulation. The hepatic accumulation of free fatty acids (FFAs) initiates mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, culminating in lipotoxic intermediates and mitochondrial DNA damage. These damage-associated molecular patterns (DAMPs), together with gut-derived pathogen-associated molecular patterns (PAMPs), activate innate immune cells and amplify cytokine-mediated inflammation. Kupffer cell activation further exacerbates OS, while ROS-induced transcriptional pathways perpetuate inflammatory gene expression. Traditional immunity refers to the well-established dichotomy of innate and adaptive immune responses, where innate immunity provides immediate but non-specific defense, and adaptive immunity offers long-lasting, antigen-specific protection. However, a paradigm shift has occurred with the recognition of trained immunity (TI)—an adaptive-like memory response within innate immune cells that enables enhanced responses upon re-exposure to stimuli. Following non-specific antigenic stimulation, TI induces durable epigenetic and metabolic reprogramming, leading to heightened inflammatory responses and altered functional phenotypes. These rewired cells acquire the capacity to produce lipid mediators, cytokines, and matrix-modifying enzymes, reinforcing hepatic inflammation and fibrogenesis. In this context, the concept of immunometabolism has gained prominence, linking metabolic rewiring with immune dysfunction. This literature review provides an up-to-date synthesis of emerging evidence on immunometabolism and trained immunity as pathogenic drivers in MASLD. We discuss their roles in the transition from hepatic steatosis to steatohepatitis, fibrosis, and cirrhosis, and explore their contribution to the initiation and progression of MASLD-related HCC. Understanding these processes may reveal novel immunometabolic targets for therapeutic intervention. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in Non-communicable Diseases)
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27 pages, 2856 KiB  
Article
Harnessing and Degradation Mechanism of Persistent Polyethylene Waste by Newly Isolated Bacteria from Waxworm and Termite Gut Symbionts
by Sameh Samir Ali, Jianzhong Sun, Rania Al-Tohamy, Maha A. Khalil, Tamer Elsamahy, Michael Schagerl, Daochen Zhu and Shimaa El-Sapagh
Microorganisms 2025, 13(8), 1929; https://doi.org/10.3390/microorganisms13081929 - 18 Aug 2025
Abstract
Pollution from synthetic polymers, particularly low-density polyethylene (LDPE), poses a significant environmental challenge due to its chemical stability and resistance to degradation. This study investigates an eco-biotechnological approach involving bacterial strains isolated from insect guts—Bacillus cereus LDPE-DB2 (from Achroia grisella) and [...] Read more.
Pollution from synthetic polymers, particularly low-density polyethylene (LDPE), poses a significant environmental challenge due to its chemical stability and resistance to degradation. This study investigates an eco-biotechnological approach involving bacterial strains isolated from insect guts—Bacillus cereus LDPE-DB2 (from Achroia grisella) and Pseudomonas aeruginosa LDPE-DB26 (from Coptotermes formosanus)—which demonstrate the ability to degrade LDPE, potentially through the action of lignin-modifying enzymes. These strains exhibited notable biofilm formation, enzymatic activity, and mechanical destabilization of LDPE. LDPE-DB2 exhibited higher LDPE degradation efficiency than LDPE-DB26, achieving a greater weight loss of 19.8% compared with 11.6% after 45 days. LDPE-DB2 also formed denser biofilms (maximum protein content: 68.3 ± 2.3 µg/cm2) compared with LDPE-DB26 (55.2 ± 3.1 µg/cm2), indicating stronger surface adhesion. Additionally, LDPE-DB2 reduced LDPE tensile strength (TS) by 58.3% (from 15.3 MPa to 6.4 ± 0.4 MPa), whereas LDPE-DB26 induced a 43.1% reduction (to 8.7 ± 0.23 MPa). Molecular weight analysis revealed that LDPE-DB2 caused a 14.8% decrease in weight-averaged molecular weight (Mw) and a 59.1% reduction in number-averaged molecular weight (Mn), compared with 5.8% and 32.7%, respectively, for LDPE-DB26. Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and gel permeation chromatography (GPC) analyses revealed substantial polymer chain scission and crystallinity disruption. Gas chromatography–mass spectrometry (GC-MS) identified environmentally benign degradation products, including alkanes, alcohols, and carboxylic acids. This study demonstrates a sustainable route to polyethylene biotransformation using insect symbionts and provides insights for scalable, green plastic waste management strategies in line with circular economy goals. Full article
(This article belongs to the Section Environmental Microbiology)
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22 pages, 2821 KiB  
Review
Beyond Green: The Therapeutic Potential of Chlorophyll and Its Derivatives in Diabetes Control
by Giovanni Sartore, Giuseppe Zagotto and Eugenio Ragazzi
Nutrients 2025, 17(16), 2653; https://doi.org/10.3390/nu17162653 - 15 Aug 2025
Viewed by 198
Abstract
Chlorophyll, the green pigment essential for photosynthesis, abundantly found in green vegetables and algae, has attracted growing scientific interest for its potential therapeutic effects, particularly in diabetes management. Recent research highlighted that chlorophyll and its derivatives may beneficially influence glucose metabolism and oxidative [...] Read more.
Chlorophyll, the green pigment essential for photosynthesis, abundantly found in green vegetables and algae, has attracted growing scientific interest for its potential therapeutic effects, particularly in diabetes management. Recent research highlighted that chlorophyll and its derivatives may beneficially influence glucose metabolism and oxidative stress, key factors in diabetes. This review examines current knowledge on how chlorophyll compounds could aid diabetes control. Chlorophyll and its derivatives appear to support glucose regulation primarily through actions in the gastrointestinal tract. They modulate gut microbiota, improve glucose tolerance, reduce inflammation, and alleviate obesity-related markers. While chlorophyll itself does not directly inhibit digestive enzymes like α-glucosidase, its derivatives such as pheophorbide a, pheophytin a, and pyropheophytin a may slow carbohydrate digestion, acting as α-amylase and α-glucosidase inhibitors, reducing postprandial glucose spikes. Additionally, chlorophyll enhances resistant starch content, further controlling glucose absorption. Beyond digestion, chlorophyll derivatives show promise in inhibiting glycation processes, improving insulin sensitivity through nuclear receptor modulation, and lowering oxidative stress. However, some compounds pose risks due to photosensitizing effects and toxicity, warranting careful consideration. Chlorophyllin, a stable semi-synthetic derivative, also shows potential in improving glucose and lipid metabolism. Notably, pheophorbide a demonstrates insulin-mimetic activity by stimulating glucose uptake via glucose transporters, offering a novel therapeutic avenue. Overall, the antioxidant, anti-inflammatory, and insulin-mimicking properties of chlorophyll derivatives suggest a multifaceted approach to diabetes management. While promising, these findings require further clinical validation to establish effective therapeutic applications. Full article
(This article belongs to the Special Issue Diet and Nutrition: Metabolic Diseases---2nd Edition)
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15 pages, 1378 KiB  
Article
Grape Pomace and Ferulic Acid Improve Antioxidant Enzyme Activity and Gut Histomorphometry in Heat-Stressed Finishing Pigs
by María A. Ospina-Romero, Leslie S. Medrano-Vázquez, Araceli Pinelli-Saavedra, Miguel Ángel Barrera-Silva, Martín Valenzuela-Melendres, Miguel Ángel Martínez-Téllez, Reyna Fabiola Osuna-Chávez, María del Refugio Robles-Burgueño and Humberto González-Rios
Animals 2025, 15(16), 2382; https://doi.org/10.3390/ani15162382 - 13 Aug 2025
Viewed by 190
Abstract
Given the restrictions on animal growth promoters, alternative plant-based additives—particularly those rich in phenolic compounds, such as agro-industrial by-products—have been explored. These additives help to mitigate heat stress, which negatively affects productivity by impacting intestinal health and antioxidant status. This study evaluated the [...] Read more.
Given the restrictions on animal growth promoters, alternative plant-based additives—particularly those rich in phenolic compounds, such as agro-industrial by-products—have been explored. These additives help to mitigate heat stress, which negatively affects productivity by impacting intestinal health and antioxidant status. This study evaluated the effects of individual and combined supplementation of ferulic acid (FA) and grape pomace (GP) on antioxidant enzyme activity, as well as intestinal histomorphometry, in finishing pigs under heat stress. Forty Yorkshire × Duroc pigs were randomly assigned to four treatments: control, 25 mg/kg FA, 2.5% GP, and MIX (FA + GP). FA supplementation increased intestinal villus height, while GP increased villus width in the duodenum and jejunum (p < 0.05). Antioxidant enzyme activity (SOD, CAT, and GPx) increased in pigs supplemented with GP (p < 0.05). These results suggest that GP and FA have potential as functional additives in monogastric diets, improving intestinal health and muscle antioxidant status and contributing to growth modulation. Full article
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24 pages, 1647 KiB  
Review
Exploring Exopolysaccharides Produced in Indigenous Mexican Fermented Beverages and Their Biotechnological Applications
by Julián Fernando Oviedo-León, Abril Ramírez Higuera, Jorge Yáñez-Fernández, Humberto Hernández-Sánchez and Diana C. Castro-Rodríguez
Fermentation 2025, 11(8), 463; https://doi.org/10.3390/fermentation11080463 - 12 Aug 2025
Viewed by 470
Abstract
Indigenous Mexican fermented beverages, such as pulque, colonche, tepache, and water kefir, are pillars of the country’s cultural and gastronomic heritage. Their sensory attributes and health-promoting properties arise from complex microbial consortia, in which lactic acid bacteria (LAB), mainly Lactobacillus and Leuconostoc, [...] Read more.
Indigenous Mexican fermented beverages, such as pulque, colonche, tepache, and water kefir, are pillars of the country’s cultural and gastronomic heritage. Their sensory attributes and health-promoting properties arise from complex microbial consortia, in which lactic acid bacteria (LAB), mainly Lactobacillus and Leuconostoc, acetic acid bacteria (AAB), primarily Acetobacter, and yeasts such as Saccharomyces and Candida interact and secrete exopolysaccharides (EPSs). Dextran, levan, and heteropolysaccharides rich in glucose, galactose, and rhamnose have been consistently isolated from these beverages. EPSs produced by LAB enhance the viscosity and mouthfeel, extend the shelf life, and exhibit prebiotic, antioxidant, and immunomodulatory activities that support gut and immune health. Beyond food, certain EPSs promote plant growth, function as biocontrol agents against phytopathogens, and facilitate biofilm-based bioremediation, underscoring their biotechnological potential. This review integrates recent advances in the composition, biosynthetic pathways, and functional properties of microbial EPSs from Mexican fermented beverages. We compare reported titers, outline key enzymes, including dextransucrase, levansucrase, and glycosyltransferases, and examine how fermentation variables (the substrate, pH, and temperature) influence the polymer yield and structure. Finally, we highlight emerging applications that position these naturally occurring biopolymers as sustainable ingredients for food and agricultural innovation. Full article
(This article belongs to the Special Issue The Health-Boosting Power of Fermented Foods and Their By-Products)
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13 pages, 726 KiB  
Review
Symphony of Digestion: Coordinated Host–Microbiome Enzymatic Interplay in Gut Ecosystem
by Volodymyr I. Lushchak
Biomolecules 2025, 15(8), 1151; https://doi.org/10.3390/biom15081151 - 11 Aug 2025
Viewed by 531
Abstract
Digestion was once viewed as a host-driven process, dependent on salivary, gastric, pancreatic, and intestinal enzymes to break down macronutrients. However, new insights into the gut microbiota have redefined this view, highlighting digestion as a cooperative effort between host and microbial enzymes. Host [...] Read more.
Digestion was once viewed as a host-driven process, dependent on salivary, gastric, pancreatic, and intestinal enzymes to break down macronutrients. However, new insights into the gut microbiota have redefined this view, highlighting digestion as a cooperative effort between host and microbial enzymes. Host enzymes initiate nutrient breakdown, while microbial enzymes, especially in the colon, extend this process by fermenting resistant polysaccharides, modifying bile acids, and transforming phytochemicals and xenobiotics into bioactive compounds. These microbial actions produce metabolites like short-chain fatty acids, which influence gut barrier function, immune regulation, and metabolism. I propose two frameworks to describe this interaction: the “duet,” emphasizing sequential enzymatic cooperation, and the “orchestra,” reflecting a spatially and temporally coordinated system with host–microbiota feedback. Disruption of this symbiosis, through antibiotics, inflammation, diet, or aging, leads to dysbiosis, impaired digestion, and contributes to metabolic, neurologic, cardiovascular, and inflammatory diseases. Recognizing digestion as a dynamic, integrated system opens new paths for therapies and nutrition. These include enzyme-targeted prebiotics, probiotics, postbiotics, and personalized diets. Embracing this systems-level perspective enables innovative diagnostics and treatments, aiming to restore enzymatic balance and improve digestive and systemic health. Full article
(This article belongs to the Special Issue Digestive Enzymes in Health and Disease)
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28 pages, 4141 KiB  
Review
Advances in Intestinal-Targeted Release of Phenolic Compounds
by Yunxuan Tang, Wenjing Liu, Jiayan Zhang, Bai Juan, Ying Zhu, Lin Zhu, Yansheng Zhao, Maria Daglia, Xiang Xiao and Yufeng He
Nutrients 2025, 17(16), 2598; https://doi.org/10.3390/nu17162598 - 9 Aug 2025
Viewed by 439
Abstract
Phenols are natural compounds with considerable bioactivities. However, the low bioavailability and chemical instability of phenols limit their biological functions. This review summarizes recent progress in phenol delivery systems that account for the specific physiological conditions of the gastrointestinal tract. It focuses on [...] Read more.
Phenols are natural compounds with considerable bioactivities. However, the low bioavailability and chemical instability of phenols limit their biological functions. This review summarizes recent progress in phenol delivery systems that account for the specific physiological conditions of the gastrointestinal tract. It focuses on the delivery materials for intestinal targeting and the synergistic benefits of co-encapsulating phenols with other functional ingredients. To achieve targeted release of phenols in the digestive tract, factors such as pH, digestive enzymes, and gut microbiota should be fully considered in delivery system designing. Materials like chitosan, sodium alginate, pectin, and guar gum offer effective protection and targeted delivery of phenols due to their pH sensitivity and enzyme-degradable properties. Co-delivery systems that combine phenols with carotenoids or probiotics improve the functional properties of phenols, such as antioxidant activity, anti-inflammatory effect, and regulation of gut microbiota. Probiotics can enhance phenolic compound absorption and probiotic survival in a phenolic–probiotic co-encapsulation system through debonding, bioconversion, and synergistic effects. Full article
(This article belongs to the Special Issue Food Functional Factors and Nutritional Health)
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26 pages, 13273 KiB  
Article
EGCG and Taurine Synergistically Ameliorate Lipid Metabolism Disorder by Modulating Gut Microbiota and PPARα/FAS Signaling Pathway
by Yang Xiao, Mingyue Yang, Meihong Cai, Haihui Zhang, Kai Hu and Yuqing Duan
Nutrients 2025, 17(16), 2595; https://doi.org/10.3390/nu17162595 - 9 Aug 2025
Viewed by 584
Abstract
Background/Objectives: The synergistic effects of epigallocatechin gallate (EGCG) and taurine in modulating lipid metabolism abnormalities in rats were investigated, and along with their potential mechanisms. Methods/Result: Compared to intervention with EGCG/taurine alone, EGCG combined with taurine (1:3) not only reduced triglyceride (TG) generation [...] Read more.
Background/Objectives: The synergistic effects of epigallocatechin gallate (EGCG) and taurine in modulating lipid metabolism abnormalities in rats were investigated, and along with their potential mechanisms. Methods/Result: Compared to intervention with EGCG/taurine alone, EGCG combined with taurine (1:3) not only reduced triglyceride (TG) generation in HepG2 cells (46.2%, 75.2%, respectively), but also significantly decreased the total cholesterol (TC) (33.3%, 41.8%), low-density lipoprotein cholesterol (LDL-C) (32.3%, 29.2%) in rats, while the high-density lipoprotein cholesterol (HDL-C) increased by 12.7% and 33.5%. In addition, the combination of EGCG and taurine not only inhibited lipogenic enzyme activity, but also enhanced the levels of lipid catabolic enzymes and antioxidant enzymes, and alleviated hepatic injury. Furthermore, it significantly modulated gut microbiota composition by altering the abundances of Bacteroidetes, Firmicutes, and Proteobacteria, improving intestinal flora balance. Metabolomic profiling showed that reducing N-linoleoyl proline, cortisol, and 3-isocholanolic acid, and increasing phospholipid metabolites are the main ways methods for normalizing lipid metabolism in rats. The combination also elevated short-chain fatty acid (SCFA) synthesis, preserving intestinal barrier integrity; it also promoted lipid catabolism and energy expenditure via activating Peroxisome proliferator- activated receptor alpha (PPARα) and suppressing hepatic fatty acid synthase (FAS)- mediated lipogenesis. Conclusion: These findings indicated that EGCG and taurine can synergistically regulate lipid metabolism abnormalities, which may offer a strategy for regulating lipid metabolism anomalies. Full article
(This article belongs to the Special Issue Dietary Patterns and Gut Microbiota)
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23 pages, 8415 KiB  
Article
Zeta CrAss-like Phages, a Separate Phage Family Using a Variety of Adaptive Mechanisms to Persist in Their Hosts
by Igor V. Babkin, Valeria A. Fedorets, Artem Y. Tikunov, Ivan K. Baykov, Elizaveta A. Panina and Nina V. Tikunova
Int. J. Mol. Sci. 2025, 26(16), 7694; https://doi.org/10.3390/ijms26167694 - 8 Aug 2025
Viewed by 185
Abstract
Bacteriophages of the order Crassvirales are highly abundant and near-universal members of the human gut microbiome worldwide. Zeta crAss-like phages comprise a separate group in the order Crassvirales, and their genomes exhibit greater variability than genomes of crAss-like phages from other families within [...] Read more.
Bacteriophages of the order Crassvirales are highly abundant and near-universal members of the human gut microbiome worldwide. Zeta crAss-like phages comprise a separate group in the order Crassvirales, and their genomes exhibit greater variability than genomes of crAss-like phages from other families within the order. Zeta crAss-like phages employ multiple adaptation mechanisms, ensuring their survival despite host defenses and environmental pressure. Some Zeta crAss-like phages use alternative genetic coding and exploit diversity-generating retroelements (DGRs). These features suggest complex evolutionary relationships with their bacterial hosts, sustaining parasitic coexistence. Mutations in tail fiber proteins introduced by DGR can contribute to their adaptation to changes in the host cell surface and even expand the range of their hosts. In addition, the exchange of DNA polymerases via recombination makes it possible to overcome the bacterial anti-phage protection directed at these enzymes. Zeta crAss-like phages continuously adapt due to genetic diversification, host interaction tweaks, and counter-defense innovations, driving an evolutionary arms race with hosts. Based on the genome characteristics of the Zeta crAss-like phages, we propose to separate them into the Echekviridae family (“эчәк”—“intestines” in Tatar) following the tradition of using the word “intestines” in different languages, suggested previously. Full article
(This article belongs to the Special Issue Bacteriophage—Molecular Studies (6th Edition))
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19 pages, 300 KiB  
Review
Sprouted Grains as a Source of Bioactive Compounds for Modulating Insulin Resistance
by Yan Sun, Caiyun Li and Aejin Lee
Appl. Sci. 2025, 15(15), 8574; https://doi.org/10.3390/app15158574 - 1 Aug 2025
Viewed by 465
Abstract
Sprouted grains are gaining attention as a natural and sustainable source of bioactive compounds with potential benefits in managing insulin resistance (IR), a hallmark of obesity-related metabolic disorders. This review aims to synthesize current findings on the biochemical changes induced during grain germination [...] Read more.
Sprouted grains are gaining attention as a natural and sustainable source of bioactive compounds with potential benefits in managing insulin resistance (IR), a hallmark of obesity-related metabolic disorders. This review aims to synthesize current findings on the biochemical changes induced during grain germination and their relevance to metabolic health. We examined recent in vitro, animal, and human studies focusing on how germination enhances the nutritional and functional properties of grains, particularly through the synthesis of compounds such as γ-aminobutyric acid, polyphenols, flavonoids, and antioxidants, while reducing anti-nutritional factors. These bioactive compounds have been shown to modulate metabolic and inflammatory pathways by inhibiting carbohydrate-digesting enzymes, suppressing pro-inflammatory cytokines, improving redox balance, and influencing gut microbiota composition. Collectively, these effects contribute to improved insulin sensitivity and glycemic control. The findings suggest that sprouted grains serve not only as functional food ingredients but also as accessible dietary tools for preventing or alleviating IR. Their role in delivering multiple bioactive molecules through a simple, environmentally friendly process highlights their promise in developing future nutrition-based strategies for metabolic disease prevention. Full article
(This article belongs to the Special Issue New Insights into Bioactive Compounds)
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