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Keywords = I-FABP (intestinal fatty acid-binding protein)

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25 pages, 2021 KB  
Article
Intestinal Microbiome, Fecal Fermentation Profile, and Health Indices in HIV-Positive Men Versus Normal Controls Without HIV
by Mary C. Andreae, William A. Clark, John Sterrett, James Adkins, Jonathan P. Moorman and Brian M. Cartwright
Nutrients 2026, 18(14), 2328; https://doi.org/10.3390/nu18142328 - 16 Jul 2026
Viewed by 568
Abstract
Background/Objectives: Many HIV-positive (HIV+) males receiving highly active antiretroviral therapy (HAART) experience metabolic complications, including non-alcoholic fatty liver disease (NAFLD); lipodystrophy; and intestinal dysbiosis, often characterized by a Prevotella-rich enterotype. Gut microbial fermentation produces short-chain fatty acids (SCFAs), which play important roles [...] Read more.
Background/Objectives: Many HIV-positive (HIV+) males receiving highly active antiretroviral therapy (HAART) experience metabolic complications, including non-alcoholic fatty liver disease (NAFLD); lipodystrophy; and intestinal dysbiosis, often characterized by a Prevotella-rich enterotype. Gut microbial fermentation produces short-chain fatty acids (SCFAs), which play important roles in host metabolism. This study investigated the relationships among HAART, anthropometrics, diet, intestinal permeability, gut microbiota composition, and lipodystrophy in HIV+ males. Methods: Forty males aged 23–60 years were enrolled, including 19 HIV+ participants recruited from the East Tennessee State University (ETSU) Health Infectious Diseases Specialty Clinic and 20 HIV-negative (HIV−) controls recruited through standard methods. Participants provided a stool sample for 16S rRNA gene sequencing, SCFA analysis by gas chromatography, and proximate analysis, and completed a food frequency questionnaire. Lipodystrophy-related measures included body mass index (BMI), hip-to-waist ratio (H:W), and liver health assessment using FibroScan. Blood samples were collected by venipuncture. Serum markers of intestinal permeability, including Claudin-21, flagellin, and intestinal fatty acid-binding protein (IFABP), were quantified by enzyme-linked immunosorbent assay (ELISA). Results: HIV+ males exhibited significantly higher H:W ratios (p = 0.001) and hepatic steatosis (p = 0.0047) than HIV− controls (Welsh’s t-test). Concentrations of isobutyrate (p = 0.0024), isovalerate (p = 0.0008), and valerate (p = 0.0329) were elevated in HIV+ participants, whereas butyrate (p = 0.0014) and total acetate/propionate/butyrate (APB) (p = 0.0046) were higher in HIV− males (Welsh’s t-test). HIV+ participants also showed greater abundances of Prevotella and Lachnospiraceae (Analysis of Compositions of Microbiomes; ANCOM). Retrospective analysis revealed that all HIV+ participants were men who have sex with men (MSM). Conclusions: HIV+ males demonstrated distinct gut microbiome profiles, altered SCFA production, and markers of disrupted lipid metabolism. These findings provide a foundation for future investigations of microbiome-metabolism interactions in HIV+ MSM. Full article
(This article belongs to the Section Nutritional Immunology)
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21 pages, 643 KB  
Review
Biomarkers for Necrotising Enterocolitis—Are We There Yet?
by Anna Jackson, Maria Cifuentes Nino and Janet Berrington
Children 2026, 13(7), 894; https://doi.org/10.3390/children13070894 - 3 Jul 2026
Viewed by 530
Abstract
Necrotising enterocolitis (NEC) remains an important disease for neonatologists, with diagnostic and management challenges and impacts on mortality and neurodisability. NEC can present in a non-specific way, and differentiating from late-onset sepsis (LOS), focal perforation (FIP) and feed intolerance can be difficult. Biomarkers [...] Read more.
Necrotising enterocolitis (NEC) remains an important disease for neonatologists, with diagnostic and management challenges and impacts on mortality and neurodisability. NEC can present in a non-specific way, and differentiating from late-onset sepsis (LOS), focal perforation (FIP) and feed intolerance can be difficult. Biomarkers have been extensively explored as a way to help more definitively identify NEC or rule it out. Many biomarkers that have been studied are blood biomarkers, and several other extensive reviews of biomarkers in NEC exist. In this narrative review, we focus on non-invasive samples, namely stool, urine and saliva, and on tests that are already available as point-of-care tests (POCTs) or are likely to be available as POCTs soon given current technologies. Faecal calprotectin and urinary intestinal fatty acid-binding protein (IFABP) have the most data to currently support their use in larger multi-centre studies and appear most likely to achieve translation into clinical practice. Saliva appears the most under-researched potential source of a non-invasive POCT for a biomarker for NEC. For faecal calprotectin and urinary IFABP, data that are most lacking relate to specificity, particularly the performance of these tests to differentiate NEC from FIP or LOS (occurring in the absence of NEC). We suggest a study design to facilitate moving towards the clinical use of non-invasive biomarkers in NEC. Full article
(This article belongs to the Special Issue Necrotizing Enterocolitis in Newborns)
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11 pages, 1148 KB  
Article
Serum Immunometabolic Biomarkers Reveal Distinct Phenotypes in Chronic Urticaria
by Nilay Duman, Can Muftuoglu, Begüm Tahhan, Tolga Coşkun, Deniz Ece, Ufuk Mert, Sıla Özkal and Ayse Caner
Diagnostics 2026, 16(8), 1148; https://doi.org/10.3390/diagnostics16081148 - 13 Apr 2026
Viewed by 1057
Abstract
Background/Objectives: Chronic urticaria (CU) is a heterogeneous inflammatory disorder generally attributed to mast cell activation. However, emerging evidence suggests that metabolic reprogramming and systemic immune dysregulation also contribute to the disease pathophysiology. This study aimed to investigate the interplay between epithelial barrier [...] Read more.
Background/Objectives: Chronic urticaria (CU) is a heterogeneous inflammatory disorder generally attributed to mast cell activation. However, emerging evidence suggests that metabolic reprogramming and systemic immune dysregulation also contribute to the disease pathophysiology. This study aimed to investigate the interplay between epithelial barrier integrity, innate immune regulation, metabolic activity, and mast cell effector mechanisms in CU. Methods: Forty CU patients and 40 healthy controls were evaluated. Clinical parameters included disease severity, disease subtype, antihistamine response, IgE levels, anti-TPO status, gastrointestinal symptoms, and angioedema. Serum levels of histamine, intestinal fatty acid-binding protein (IFABP), soluble CD14 (sCD14), diamine oxidase (DAO), D-lactic acid, endotoxin, zonulin, calprotectin, and related ratios were measured. Disease activity and control were assessed using the UAS7 and UCT scores. Results: CU patients exhibited significantly higher DAO (p = 0.003) and lactic acid (p = 0.004) levels compared to controls, whereas other markers showed no significant differences. In anti-TPO-positive patients, sCD14 levels were reduced (p = 0.024), while histamine/sCD14 (p = 0.005), lactic acid/sCD14 (p = 0.014), IFABP/sCD14 (p = 0.008), and zonulin/sCD14 (p = 0.027) were significantly elevated, suggesting relative amplification of metabolic and barrier-related signals under impaired innate immune regulation. Severe anti-TPO-positive patients exhibited lower sCD14 (p = 0.022) and NLR (p = 0.013) but higher UAS7 (p = 0.032), histamine (p = 0.011), calprotectin (p = 0.041), and CD14-normalized ratios, including histamine (p = 0.003), IFABP (p = 0.028), lactic acid (p = 0.019), zonulin (p = 0.029), and calprotectin (p = 0.011) compared with severe anti-TPO-negative patients, indicating a mast cell-dominant and metabolically active inflammatory phenotype. The lactic acid/DAO ratio was significantly lower in controlled versus uncontrolled CU (p = 0.013) and showed discriminatory potential for disease control. Patients with angioedema had higher CRP (p = 0.038) and UAS7 scores (p < 0.001). Conclusions: CU exhibits marked immunometabolic heterogeneity. Elevated DAO and lactic acid indicate increased histamine turnover and metabolic activation, whereas altered sCD14-normalized biomarker profiles reveal immune dysregulation in anti-TPO-positive patients. Severe CU with features suggestive of thyroid autoimmunity manifests as a mast cell-dominant, metabolically active phenotype with relative suppression of innate immune modulators, contrasting with alternative pathways in other CU phenotypes. The lactic acid/DAO ratio may serve as a candidate biomarker of disease control. These results underscore the importance of phenotype-tailored therapeutic strategies in CU. Full article
(This article belongs to the Special Issue Novel Advances in the Diagnosis of Dermatology)
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17 pages, 4400 KB  
Article
Nanocomposite-Based Dual Electrochemical Immunosensor for Simultaneous Detection of Intestinal Barrier Biomarkers: Intestinal Fatty Acid Binding Protein and Fecal Calprotectin
by Lorena García-Rodrigo, Claudia Ramos-López, Esther Sánchez-Tirado, Lourdes Agüí and Araceli González-Cortés
Biosensors 2026, 16(4), 199; https://doi.org/10.3390/bios16040199 - 1 Apr 2026
Viewed by 1097
Abstract
Disruption of the intestinal barrier is a hallmark of inflammatory bowel disease (IBD) and drives both epithelial injury and neutrophil-mediated inflammation, yet rapid, multiplexed assessment of these processes remains an unmet clinical need. Intestinal fatty acid binding protein (iFABP) and fecal calprotectin (FC) [...] Read more.
Disruption of the intestinal barrier is a hallmark of inflammatory bowel disease (IBD) and drives both epithelial injury and neutrophil-mediated inflammation, yet rapid, multiplexed assessment of these processes remains an unmet clinical need. Intestinal fatty acid binding protein (iFABP) and fecal calprotectin (FC) provide complementary insights into barrier integrity and mucosal inflammation, but conventional ELISA-based assays are time-consuming, low-throughput, and require large sample volumes. Here, we introduce a dual electrochemical sandwich immunosensor enabling simultaneous quantification of iFABP and FC on screen-printed dual carbon electrodes (SPdCEs). Capture antibodies were immobilized via electrografting of p-aminobenzoic acid diazonium salt, while a V2O5/MWCNTs-HRP–streptavidin nanocomposite amplified the electrocatalytic reduction in hydrogen peroxide, enhancing sensitivity. The platform achieved detection limits of 0.01 pg mL−1 (iFABP) and 1 pg mL−1 (FC) with a total assay time of 1 h 20 min and sample volume of just 5 μL, outperforming conventional ELISA in speed and efficiency. High repeatability, reproducibility, and accurate recovery in enriched fecal samples confirmed analytical robustness. By integrating multiplexed detection, nanostructured signal amplification, and robust electrode engineering, this immunosensor provides a rapid, sensitive, and low-volume platform for point-of-care and decentralized monitoring of IBD, enabling timely clinical decision-making and longitudinal patient management. Full article
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13 pages, 254 KB  
Article
Intestinal Permeability Biomarkers for Predicting Cardiometabolic Risk in Type 2 Diabetes Mellitus
by Nursel Dal, Saniye Bilici, Sirin Akin and Perim Fatma Turker
Nutrients 2026, 18(1), 167; https://doi.org/10.3390/nu18010167 - 4 Jan 2026
Cited by 1 | Viewed by 2068
Abstract
Background: Diabetes can increase cardiovascular risk (CVR) through hyperglycemia and intestinal damage. The purpose of this study is to evaluate several intestinal permeability biomarkers in predicting CVR in patients with type 2 diabetes mellitus (T2DM). Methods: This study was conducted in 2024 with [...] Read more.
Background: Diabetes can increase cardiovascular risk (CVR) through hyperglycemia and intestinal damage. The purpose of this study is to evaluate several intestinal permeability biomarkers in predicting CVR in patients with type 2 diabetes mellitus (T2DM). Methods: This study was conducted in 2024 with a total of 70 patients with T2DM, aged 19–64 years (32.9% men, 67.1% women). Socio-demographic data and health status were collected; Framingham Risk Score (FRS), anthropometric measures, and serum parameters (glucose, HbA1c, lipids, CRP, TNF-α, IL-6, trimetilamine-N-oxide (TMAO), zonulin, intestinal fatty acid binding protein (I-FABP)) were evaluated, and visceral adiposity index (VAI) and plasma atherogenic index (PAI) were calculated. Results: The mean age of patients (n = 70) was 55.0 ± 7.55 years. According to FRS, 18.5% of individuals were determined to be at medium–high CVR; a positive correlation was found between BMI, waist–height ratio, body fat ratio, VAI value, and FRS total score (p < 0.05). Serum TMAO, zonulin, and I-FABP levels did not differ between low-risk and medium–high-risk patients (p > 0.05). Serum TMAO, zonulin, and I-FABP levels were positively correlated with TNF-α and IL-6 levels, and serum TMAO and I-FABP levels were positively correlated with triglyceride levels (p < 0.05). Moreover, serum zonulin and I-FABP levels were positively correlated with PAI (p < 0.05). Conclusions: Abdominal obesity and intestinal permeability may affect inflammatory processes and blood lipids in patients with T2DM. Further studies with large samples are needed to examine dietary factors related to the relationship between intestinal permeability and cardiometabolic risk. Full article
(This article belongs to the Special Issue Diet, Gut Health, and Clinical Nutrition)
17 pages, 5942 KB  
Article
cGAS/STING Pathway Mediates Accelerated Intestinal Cell Senescence and SASP After GCR Exposure in Mice
by Santosh Kumar, Kamendra Kumar, Jerry Angdisen, Shubhankar Suman, Bhaskar V. S. Kallakury and Albert J. Fornace
Cells 2025, 14(22), 1767; https://doi.org/10.3390/cells14221767 - 11 Nov 2025
Cited by 4 | Viewed by 2738
Abstract
Long-duration space missions expose astronauts to galactic cosmic radiation (GCR), a complex spectrum of high-charge, high-energy (HZE) ions that pose significant risks of chronic tissue injury. To model these effects, we examined intestinal outcomes in wild-type mice 5 months after low-dose (50 cGy) [...] Read more.
Long-duration space missions expose astronauts to galactic cosmic radiation (GCR), a complex spectrum of high-charge, high-energy (HZE) ions that pose significant risks of chronic tissue injury. To model these effects, we examined intestinal outcomes in wild-type mice 5 months after low-dose (50 cGy) 33-ion mixed-field GCR simulation (GCRsim). GCRsim induced sustained DNA double-strand breaks (DSBs) and oxidative stress, as shown by elevated γH2AX foci and 4-HNE staining. Intestinal epithelial cells (IECs) exhibited pronounced senescence, marked by increased SA-β-gal activity, p16 upregulation, LaminB1 loss, and induction of senescence-associated secretory phenotype (SASP) cytokines (Cxcl10, IL-6, IL-1β, Icam1). GCRsim also elevated circulating LINE-1 DNA and reduced expression of DNA-degrading nucleases (DNase2, TREX1), indicating impaired extracellular DNA clearance. Targeted molecular study revealed persistent activation of the cGAS–STING pathway, with elevated cGAS, STING, pTBK1, pIKKα/β, and nuclear pIRF3, pIRF7, and p65, consistent with chronic innate immune signaling. Functionally, GCRsim altered nutrient absorption gene expression—upregulating glucose transporters (Slc2a2, Slc2a5, Slc5a1) and gut hormones (Cck, Gip), while downregulating cholesterol/fat transporters (Npc1, Npc1l1). Biochemical markers supported intestinal injury, with decreased serum citrulline and increased intestinal fatty acid-binding protein (I-FABP), indicating barrier compromise. Collectively, these findings demonstrate that GCRsim drives sustained intestinal dysfunction, highlighting the need for countermeasures to protect GI health during deep-space missions. Full article
(This article belongs to the Section Cellular Aging)
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17 pages, 566 KB  
Review
Intestinal Permeability and Depression—A Narrative Review of Selected Blood-Based Biomarkers
by Anca C. Bibolar, Bianca D. Crecan-Suciu, Ramona L. Păunescu, Vlad-I. Nechita, Olivia Verisezan-Roșu and Ioana V. Micluția
Int. J. Mol. Sci. 2025, 26(20), 10076; https://doi.org/10.3390/ijms262010076 - 16 Oct 2025
Cited by 3 | Viewed by 5051
Abstract
The intestinal barrier has recently gained attention as a contributor to the pathophysiology of depression. This narrative review examines the current literature on blood-based markers of intestinal permeability in patients with depression. A structured search of PubMed and EMBASE was performed. Both recent [...] Read more.
The intestinal barrier has recently gained attention as a contributor to the pathophysiology of depression. This narrative review examines the current literature on blood-based markers of intestinal permeability in patients with depression. A structured search of PubMed and EMBASE was performed. Both recent and older studies were included to capture key mechanisms and theoretical foundations. We focused on zonulin, intestinal fatty acid-binding protein (I-FABP), lipopolysaccharides (LPS), LPS-binding protein (LBP), and soluble CD14 (sCD14). While several studies report altered intestinal permeability markers in individuals with depression, results remain inconsistent. Factors such as small sample sizes and variability in measurement procedures complicate interpretation. In some cases, altered biomarker levels were associated with disease severity or response to antidepressant treatment, suggesting a potential role in patient stratification. However, current evidence does not support their routine use in clinical settings. Further research is needed to clarify their value in psychiatric populations. If validated, these markers may help identify inflammation-related depression subtypes and guide more precise treatment strategies. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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20 pages, 2357 KB  
Article
Betaine Supplementation Improves 60 km Cycling Time Trial Performance and One-Carbon Metabolism in Cyclists During Recovery
by David C. Nieman, Camila A. Sakaguchi, James C. Williams, Jackie Lawson and Kevin C. Lambirth
Nutrients 2025, 17(17), 2765; https://doi.org/10.3390/nu17172765 - 26 Aug 2025
Cited by 1 | Viewed by 5800
Abstract
Background/Objectives: This study examined the effects of 2 weeks of betaine versus placebo supplementation (3 g/d) on 60 km cycling performance, gut permeability, and shifts in plasma metabolites. Methods: Participants included 21 male and female non-elite cyclists. A randomized, placebo-controlled, double-blind, crossover design [...] Read more.
Background/Objectives: This study examined the effects of 2 weeks of betaine versus placebo supplementation (3 g/d) on 60 km cycling performance, gut permeability, and shifts in plasma metabolites. Methods: Participants included 21 male and female non-elite cyclists. A randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and a 2-week washout period. Supplementation periods were followed by a 60 km cycling time trial. Six blood samples were collected before and after supplementation (overnight fasted state), and at 0 h, 1.5 h, 3 h, and 24 h post-exercise. Five-hour urine samples were collected pre-supplementation and post-60 km cycling after ingesting a sugar solution containing lactulose 5 g, 13C mannitol 100 mg, and 12C mannitol 1.9 g in 450 mL water. Other outcome measures included plasma intestinal fatty acid binding protein-1 (I-FABP), muscle damage biomarkers (serum creatine kinase, myoglobin), serum cortisol, complete blood cell counts, and shifts in plasma metabolites using untargeted metabolomics. Results: The time to complete the 60 km cycling bout differed significantly between the betaine and placebo trials (mean ± SE, 112.8 ± 2.3, 114.2 ± 2.6 min, respectively, (−1.41 ± 0.7 min) (effect size = 0.475, p = 0.042). No trial differences were found for I-FABP (interaction effect, p = 0.076), L:13CM (p = 0.559), the neutrophil/lymphocyte ratio (p = 0.171), serum cortisol (p = 0.982), serum myoglobin (p = 0.942), or serum creatine kinase (p = 0.694). Untargeted metabolomics showed that 214 metabolites exhibited significant trial treatment effects and 130 significant trial x time interaction effects. Betaine versus placebo supplementation was linked to significant increases in plasma betaine, dimethylglycine (DMG), sarcosine, methionine, S-adenosylhomocysteine (SAH), alpha-ketoglutaramate, and 5′methylthioadensone (MTA), and decreases in plasma carnitine and numerous acylcarnitines. Conclusions: Betaine supplementation modestly improved 60 km cycling performance but had no effect on gut permeability. The metabolomics data supported a strong influence of 2-week intake of betaine on the one-carbon metabolism pathway during the 24 h recovery period. Full article
(This article belongs to the Section Sports Nutrition)
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27 pages, 1448 KB  
Systematic Review
Leaky Gut Biomarkers as Predictors of Depression and Suicidal Risk: A Systematic Review and Meta-Analysis
by Donato Morena, Matteo Lippi, Matteo Scopetti, Emanuela Turillazzi and Vittorio Fineschi
Diagnostics 2025, 15(13), 1683; https://doi.org/10.3390/diagnostics15131683 - 1 Jul 2025
Cited by 19 | Viewed by 6774
Abstract
Background: The gut–brain axis (GBA) has been demonstrated to be involved in normal neurodevelopment, with its dysfunction potentially contributing to the onset of mental disorders. In this systematic review and meta-analysis, we aimed to examine the relationship between levels of specific biomarkers [...] Read more.
Background: The gut–brain axis (GBA) has been demonstrated to be involved in normal neurodevelopment, with its dysfunction potentially contributing to the onset of mental disorders. In this systematic review and meta-analysis, we aimed to examine the relationship between levels of specific biomarkers of intestinal permeability or inflammation and scores of depressive symptoms or suicidality. Methods: All studies investigating the link between depressive symptoms and/or suicidality and biomarkers associated with intestinal permeability or inflammation were included. Studies providing data for comparisons between two groups—depressive or suicidal patients vs. healthy controls, or suicidal vs. non-suicidal patients—were included in the meta-analysis. Studies examining the correlation between depressive symptoms and biomarker levels were also included into the review. Data were independently extracted and reviewed by multiple observers. A random-effects model was employed for the analysis, and Hedge’s g was pooled for the effect size. Heterogeneity was assessed using the I2 index. Results: Twenty-two studies provided data for inclusion in the meta-analysis, while nineteen studies investigated the correlation between depressive symptoms and biomarker levels. For depressive symptoms, when compared to the controls, patients showed significantly increased levels of intestinal fatty acid-binding protein (I-FABP) (ES = 0.36; 95% CI = 0.11 to 0.61; p = 0.004; I2 = 71.61%), zonulin (ES = 0.69; 95% CI = 0.02 to 1.36; p = 0.044; I2 = 92.12%), antibodies against bacterial endotoxins (ES = 0.75; 95% CI = 0.54 to 0.98; p < 0.001; I2 = 0.00%), and sCD14 (ES = 0.11; 95% CI = 0.01 to 0.21; p = 0.038; I2 = 10.28%). No significant differences were found between the patients and controls in levels of LPS-binding protein (LBP) and alpha-1 antitrypsin (A-1-AT). For suicidality, four studies were identified for quantitative analysis, three of which focused on I-FABP. No significant differences in I-FABP levels were observed between suicidal patients and the controls (ES = 0.24; 95% CI = −0.30 to 0.79; p = 0.378; I2 = 86.44%). Studies investigating the correlation between depressive symptoms and levels of intestinal permeability and inflammation biomarkers did not provide conclusive results. Conclusions: A significant difference was observed between patients with depressive symptoms and controls for biomarkers of intestinal permeability (zonulin, which regulates tight junctions), inflammatory response to bacterial endotoxins (antibodies to endotoxins and sCD14—a soluble form of the CD14 protein that modulates inflammation triggered by lipopolysaccharides), and acute intestinal epithelial damage (I-FABP, released upon enterocyte injury). Studies investigating suicidality and related biomarkers were limited in number and scope, preventing definitive conclusions. Overall, these findings suggest that biomarkers of gut permeability represent a promising area for further investigation in both psychiatric and forensic pathology. They may have practical applications, such as supporting diagnostic and therapeutic decision-making in clinical settings and providing pathologists with additional information to help determine the manner of death in forensic investigations. Full article
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14 pages, 850 KB  
Article
Intestinal Biomarkers in Preterm Infants: Influence of Mother’s Own Milk on Fecal Calprotectin and of Gestational Age on IFABP Concentrations
by Carla Balcells-Esponera, Victoria Aldecoa-Bilbao, Cristina Borràs-Novell, Miriam López-Abad, Anna Valls Lafón, Marta Batllori Tragant, Montserrat Izquierdo Renau, Beatriz del Rey Hurtado de Mendoza, Ana Herranz-Barbero and Isabel Iglesias-Platas
Nutrients 2025, 17(13), 2177; https://doi.org/10.3390/nu17132177 - 30 Jun 2025
Cited by 1 | Viewed by 1803
Abstract
Background/Objectives: Calprotectin and intestinal fatty acid-binding protein (IFABP) may reflect the intestinal maturation process of very preterm infants (VPI) but have also been associated with gut inflammation. To establish normative values for fecal calprotectin (FC) and urinary intestinal fatty acid-binding protein (uIFABP) in [...] Read more.
Background/Objectives: Calprotectin and intestinal fatty acid-binding protein (IFABP) may reflect the intestinal maturation process of very preterm infants (VPI) but have also been associated with gut inflammation. To establish normative values for fecal calprotectin (FC) and urinary intestinal fatty acid-binding protein (uIFABP) in VPI and to study their correlations with demographic and clinical factors. Methods: A cohort of VPI (born before or at 32.0 weeks of gestation) was recruited in two neonatal intensive care units. Urine and fecal samples were collected at 1, 4 and 8 weeks of life to measure urinary IFABP (normalized to creatinine as uIFABP/Cr) and FC, respectively. UIFABP was determined by ELISA and FC by fluoroenzyme immunoassay. Results: 194 newborns had at least one valid biomarker measurement. The study cohort mean gestational age was 28.9 ± 2.3 weeks and mean birth weight 1178 ± 365 g. Although uIFABP/Cr concentrations differed between the two centres, they were negatively correlated with gestational age, with a statistically significant correlation observed in both centres at week 4 (Hospital Clínic: Spearman’s rho −0.500; p = 0.000 and Hospital Sant Joan de Déu: Spearman’s rho −0.474; p = 0.000). Conversely, FC showed a positive significant correlation at the same time point (Spearman’s rho 0.302; p = 0.006). At week one, FC increased with antibiotic exposure (28 mcg/g of stool per antibiotic day, 95%CI 3–57; p = 0.028). FC at week 4 was inversely correlated with mother’s own milk (MOM) exposure during the first month (Spearman’s rho −0.253; p = 0.023). Conclusions: uIFABP/Cr and FC are associated with gestational age at 4 weeks and FC is also influenced by antibiotic treatment and MOM exposure. Full article
(This article belongs to the Special Issue What’s New in Breastfeeding?)
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14 pages, 1678 KB  
Article
Evaluation of Defensins as Markers of Gut Microbiota Disturbances in Children with Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
by Aldona Wierzbicka-Rucińska, Ewa Konopka, Sebastian Więckowski, Wojciech Jańczyk, Anna Świąder-Leśniak, Jolanta Świderska, Joanna Trojanek, Zbigniew Kułaga, Piotr Socha and Joanna Bierła
J. Clin. Med. 2025, 14(10), 3505; https://doi.org/10.3390/jcm14103505 - 16 May 2025
Cited by 5 | Viewed by 2020
Abstract
Until recently, it was believed that bacterial translocation occurs as a result of leaky gut syndrome or sepsis. To confirm or exclude the process of bacterial translocation, biomarkers can be used. One such biomarker is defensins, which indicate immune activity, as defensins are [...] Read more.
Until recently, it was believed that bacterial translocation occurs as a result of leaky gut syndrome or sepsis. To confirm or exclude the process of bacterial translocation, biomarkers can be used. One such biomarker is defensins, which indicate immune activity, as defensins are cationic peptides with antibacterial properties produced by intestinal epithelial cells. Also, fatty acid-binding proteins (I-FABP and L-FABP) can serve as useful serological markers for intestinal epithelial damage, indicating impaired intestinal permeability or organ damage, as high concentrations of them are found in tissues and low concentrations in blood serum. In the context of obesity, the integrity of the intestinal barrier, which can be disrupted by dietary fat, leads to increased intestinal permeability. Since bacterial translocation and microbiota contribute to obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) associated with metabolic dysfunction, intestinal barrier markers can be used to study the role of the gut–liver axis. The aim of this study was to gain insight into the pathogenesis of MASLD and examine the impact of bacterial translocation markers and intestinal and hepatic fatty acid-binding proteins (I-FABP and L-FABP) in children with MASLD. Method: We examined 60 children with MASLD and overweight/obesity (MASLD was diagnosed based on increased liver echogenicity in ultrasound and elevated ALT activity), aged 14.5 years (range 8.5 to 15.8); 33 children with overweight/obesity without MASLD, aged 13.0 years (range 11.4 to 15.8); and 16 healthy controls aged 11.0 years (range 7.0 to 16.2). Defensin, I-FABP, and L-FABP levels were measured using commercial kits: ELISA kits (Drg Medtek) were used to assess α-5 and α-6 defensin concentrations (HBD5, HBD6). I-FABP and L-FABP concentrations were measured using commercial ELISA kits (Hycult Biotech Inc., Wayne, PA, USA). ANOVA analysis was used to compare results across the three study groups. Results: A significant difference was found for the following tests among children with MASLD, obesity, and healthy controls: defensin 6 (14.4 ng/mL vs. 6.13 ng/mL vs. 17.2 ng/mL, respectively), L-FABP (9168 pg/mL vs. 7954 pg/mL vs. 7620 pg/mL, respectively), and I-FABP (272 pg/mL vs. 321 pg/mL vs. 330 pg/mL, respectively). No differences were found in defensin 5 levels (median 567.2 pg/mL vs. 485.7 pg/mL vs. 601.8 pg/mL). No differences were observed in cholesterol levels (HDL, LDL) or triglyceride concentrations, as well as apolipoprotein levels. Conclusions: Based on our study, it was concluded that inflammation and intestinal barrier damage lead to increased L-FABP levels, as it is released from enterocytes in response to oxidative stress or tissue damage. Defensin 6 may indirectly affect L-FABP through microbiota regulation and protection of the intestinal barrier. Defensin 6 also exerts antimicrobial activity and may accompany liver inflammation, with its increased concentration in comparison to obesity explained by the activation of defense mechanisms. Full article
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17 pages, 2609 KB  
Article
Tranilast Reduces Intestinal Ischemia Reperfusion Injury in Rats Through the Upregulation of Heme-Oxygenase (HO)-1
by Emilio Canovai, Ricard Farré, Gert De Hertogh, Antoine Dubois, Tim Vanuytsel, Jacques Pirenne and Laurens J. Ceulemans
J. Clin. Med. 2025, 14(9), 3254; https://doi.org/10.3390/jcm14093254 - 7 May 2025
Cited by 5 | Viewed by 2128
Abstract
Background: Intestinal ischemia reperfusion injury (IRI) is a harmful process that occurs during intestinal infarction and intestinal transplantation (ITx). It is characterized by severe inflammation which disrupts the mucosal barrier, causing bacterial translocation and sepsis. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) (TL) is a synthetic compound [...] Read more.
Background: Intestinal ischemia reperfusion injury (IRI) is a harmful process that occurs during intestinal infarction and intestinal transplantation (ITx). It is characterized by severe inflammation which disrupts the mucosal barrier, causing bacterial translocation and sepsis. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) (TL) is a synthetic compound with powerful anti-inflammatory properties. Objective: To investigate the effect of pretreatment with TL in a validated rat model of intestinal IRI (60 min of ischemia). Methods: TL (650 mg/kg) was administered by oral gavage 24 and 2 h before the onset of ischemia. Experiment 1 examined 7-day survival in 3 study groups (sham, vehicle+IRI and TL+IRI, n = 10/group). In Experiment 2, the effects on the intestinal wall integrity and inflammation were studied after 60 min of reperfusion using 3 groups (sham, IRI and TL+IRI, n = 6/group). The following end-points were studied: L-lactate, intestinal fatty acid-binding protein (I-FABP), histology, intestinal permeability, endotoxin translocation, pro- and anti-inflammatory cytokines and heme oxygenase-1 (HO-1) levels. Experiment 3 examined the role of HO-1 upregulation in TL pretreatment, by blocking its expression using Zinc protoporphyrin (ZnPP) at 20 mg/kg vs. placebo (n = 6/group). Results: Intestinal IRI resulted in severe damage of the intestinal wall and a 10% 7-day survival. These alterations led to endotoxin translocation and upregulation of pro-inflammatory cytokines. TL pretreatment improved survival up to 50%, significantly reduced inflammation and protected the intestinal barrier. The HO-1 inhibitor ZnPP, abolished the protective effect of TL. Conclusions: TL pretreatment improves survival by protecting the intestinal barrier function, decreasing inflammation and endotoxin translocation, through upregulation of HO-1.This rat study of severe intestinal ischemia reperfusion injury demonstrates a novel role for Tranilast as a potential therapy. Administration of Tranilast led to a marked reduction in mortality, inflammation and intestinal permeability and damage. The study proved that Tranilast functions through upregulation of heme oxygenase-1. Full article
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12 pages, 766 KB  
Article
Lactobacillus plantarum Supplementation on Sport Performance, Biomarkers of Intestinal Damage, and Oxidative Stress in Recreational Athletes
by Asier Santibañez-Gutierrez, Julen Fernández-Landa, Natalia Busto, Nikola Todorovic, Julio Calleja-González and Juan Mielgo-Ayuso
J. Funct. Morphol. Kinesiol. 2025, 10(2), 131; https://doi.org/10.3390/jfmk10020131 - 15 Apr 2025
Cited by 7 | Viewed by 3799
Abstract
Background: In recent years, interest in probiotic supplementation has increased among athletes due to its potential benefits on sports performance. Thus, the aim of this trial was to investigate Lactobacillus plantarum’s effects on sports performance, intestinal damage, and oxidative stress biomarkers. Methods [...] Read more.
Background: In recent years, interest in probiotic supplementation has increased among athletes due to its potential benefits on sports performance. Thus, the aim of this trial was to investigate Lactobacillus plantarum’s effects on sports performance, intestinal damage, and oxidative stress biomarkers. Methods: Twenty-two physically active participants, nine females and thirteen males (age: 32.8 ± 5.2 years; height: 1.73 ± 0.1 m (meters); body mass: 72.2 ± 10.3 kg (kilograms) volunteered in this randomized, double-blind, placebo-controlled, parallel study. The participants performed a strenuous exercise session, and immediately after, their perceived exertion was assessed and blood samples were drawn to assess intestinal damage (IFABP: intestinal fatty acid binding protein) and oxidative stress (PC: protein carbonyls; TAC: total antioxidant capacity; total proteins; GSSG: glutathione disulfide; GSH: reduced glutathione and catalase). Twenty-four hours later, the participants ranked their recovery status and completed various sports performance tests: CMJ (countermovement jump), RAST (running-based anaerobic sprint), and YOYO IR1 (YOYO intermittent recovery test level 1). This was followed by a four-week supplementation period, in which the participants ingested one probiotic capsule per day containing 10 billion CFU (colony forming units) of Lactobacillus plantarum or a placebo capsule (dextrose). Results: The paired samples t-test revealed a significantly better result in the YOYO IR1 test in the probiotic group, while a significant reduction was observed in the TAC levels in the placebo group. Conclusions: The results suggest that Lactobacillus plantarum supplementation could increase YOYO IR1 sports performance test scores and may mitigate TAC value reduction. Full article
(This article belongs to the Special Issue Sports Nutrition and Body Composition)
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15 pages, 2181 KB  
Article
The Role of I-FABP, REG3α, sCD14-ST, and LBP as Indicators of GI Tract Injury in MODS Patients
by Yermek Turgunov, Alina Ogizbayeva, Sofiko Assamidanova, Dmitriy Matyushko, Miras Mugazov, Dana Amanova, Shynggys Nuraly and Yerzhan Sharapatov
Diagnostics 2025, 15(5), 515; https://doi.org/10.3390/diagnostics15050515 - 20 Feb 2025
Cited by 8 | Viewed by 3037
Abstract
Background/Objectives: The aim of this study was to evaluate potential biomarkers of bacterial translocation (lipopolysaccharide-binding protein (LBP) and soluble CD14 subtype (sCD14-ST)) and intestinal wall damage (intestinal fatty acid binding protein (I-FABP), Zonulin, and regenerating islet-derived protein-3α (REG3α)) in patients with multiple [...] Read more.
Background/Objectives: The aim of this study was to evaluate potential biomarkers of bacterial translocation (lipopolysaccharide-binding protein (LBP) and soluble CD14 subtype (sCD14-ST)) and intestinal wall damage (intestinal fatty acid binding protein (I-FABP), Zonulin, and regenerating islet-derived protein-3α (REG3α)) in patients with multiple organ dysfunction syndrome (MODS). Methods: The study involved 327 patients divided into two groups: Group 1 comprised 227 patients with MODS (main group), while Group 2 comprised 100 patients with identical pathologies but without MODS (control group). To examine these biomarkers in the blood, venous blood was taken in the control group on the day of admission to the hospital, in patients with MODS on the first day of MODS staging, and later on Days 3 and 7 of its development. Levels of these markers in blood serum were determined by enzyme-linked immunosorbent assays according to the manufacturers’ instructions. Results: In the control group, values of all the investigated markers were lower than in the group of MODS patients (p < 0.0001). In the main group, the mortality rate was 44.9% (n = 102). The values of sCD14-ST on Day 1 and of I-FABP and REG3α on Days 1 and 3 were higher in deceased MODS patients (p < 0.05), while LBP levels on Day 7 were conversely lower in the deceased patients (p = 0.006). SOFA and APACHE II scores were higher in the deceased patients (p < 0.0001). Conclusions: In MODS patients, the increased I-FABP, REG3α, and sCD14-ST but decreased LBP levels may indicate increased intestinal wall permeability and bacterial translocation, which may exacerbate the course of multiple organ dysfunction and increase the risk of mortality. Despite the limitations of this study, the studied potential biomarkers can be considered noteworthy candidates for identifying MODS patients at high risk of mortality. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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14 pages, 228 KB  
Article
Study of Blood Biomarkers in Athletes with Lower Gastrointestinal Symptoms After an Ultra-Trail Race
by Joshua Teyssier, Sébastien Perbet, Bruno Pereira, Stéphane Bergzoll, Mathieu Kuentz, Julie Durif, Vincent Sapin, Matthieu Jabaudon and Damien Bouvier
J. Clin. Med. 2025, 14(3), 1024; https://doi.org/10.3390/jcm14031024 - 6 Feb 2025
Viewed by 2412
Abstract
Background/Objectives: To investigate the value of intestinal fatty acid-binding protein (I-FABP), D-Lactate, interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1Ra), tumor necrosis factor-alpha (TNF-alpha), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), electrolytes and creatinine in athletes with [...] Read more.
Background/Objectives: To investigate the value of intestinal fatty acid-binding protein (I-FABP), D-Lactate, interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1Ra), tumor necrosis factor-alpha (TNF-alpha), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), electrolytes and creatinine in athletes with lower gastrointestinal symptoms in a cohort of ultra-trailers. Methods: This is a prospective study set in the ultra-trail of Puy Mary Aurillac, a 105 km race. Athletes included were given two questionnaires to collect demographic data and clinical signs related to the race. Blood samples were also collected before and 1 h after the race. Biomarker results were interpreted according to the occurrence of exercise-induced lower gastrointestinal symptoms, and whether the race was completed or forfeited. Results: Of the 76 runners included, 35 (45.5%) presented lower gastrointestinal symptoms. Runners that presented these symptoms had significantly higher IL-10 concentrations (8.7 pg/mL (interquartile range (IQR): 4.2–1.6)) when compared to runners without symptoms (4.8 pg/mL (IQR: 2.4–9)) (p = 0.01). The pre/post-race amplitude of IL-1Ra variation was greater in the group of runners with lower gastrointestinal symptoms (median: +231% (IQR: 169–551)) compared to runners without symptoms (median: +172% (IQR: 91–393)) (p = 0.04). Finally, the 13 (16.9%) runners who forfeited the race displayed lower AST (p < 0.001), LDH (p = 0.002) and IL-6 (p = 0.002) concentrations, compared to runners who finished the race. These lower concentrations were independent from running time. Conclusions: IL-10 and IL-1Ra could be associated with the occurrence of lower gastrointestinal symptoms. Full article
(This article belongs to the Section Sports Medicine)
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