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

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27 pages, 1448 KiB  
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
Viewed by 827
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 KiB  
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
Viewed by 331
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 KiB  
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 1 | Viewed by 581
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 KiB  
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
Viewed by 597
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 KiB  
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
Viewed by 1130
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 KiB  
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
Viewed by 1001
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 KiB  
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 1150
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)
27 pages, 3873 KiB  
Review
The Influence of Dietary Supplements on Exercise-Induced Gut Damage and Gastrointestinal Symptoms: A Systematic Review and Meta-Analysis
by Robyn Aitkenhead, Mark Waldron, Gillian E. Conway, Katy Horner and Shane M. Heffernan
Nutrients 2025, 17(3), 443; https://doi.org/10.3390/nu17030443 - 25 Jan 2025
Cited by 1 | Viewed by 4035
Abstract
Endurance exercise, especially under heat stress, temporarily compromises the integrity of the intestinal barrier in healthy individuals. Consequently, there is growing interest in developing effective dietary strategies to alleviate exercise-induced gastrointestinal symptoms and gut damage. This meta-analysis investigated the effects of dietary supplements [...] Read more.
Endurance exercise, especially under heat stress, temporarily compromises the integrity of the intestinal barrier in healthy individuals. Consequently, there is growing interest in developing effective dietary strategies to alleviate exercise-induced gastrointestinal symptoms and gut damage. This meta-analysis investigated the effects of dietary supplements on mitigating these challenges. The search was performed in November 2024 following PRISMA guidelines, and 26 peer-reviewed studies were included across three meta-analyses: (1) gastrointestinal symptoms, (2) circulating intestinal fatty acid-binding protein (i-FABP), and (3) exercise performance. The moderating effect of variables was assessed via sub-group analysis and meta-regression. Overall, there was no pooled effect of supplement interventions on gastrointestinal symptoms (Hedges’ g = 0.42, 95% CI −0.17: 1.02, p = 0.15), and probiotics had a moderate significant effect for gastrointestinal symptoms (Hedges’ g = −0.62, 95% CI −1.01; 1.01, p = 0.05). There was a significant increase in i-FABP concentrations pre- to post exercise ( 106%; Hedges’ g = 1.01, 95% CI 0.63; 1.38, p = 0.01). There were no pooled or sub-group differences for exercise performance for any supplements (p = 0.53). Moderate-to-large heterogeneity was observed across studies (I2 ≥ 58.6%), and candidate moderators (exercise duration, modality, and environmental temperature) had no significant effect on any outcomes (p > 0.05). A significant increase in circulating i-FABP during exercise was observed. However, when examining the effects of different supplement categories, although significance was observed for a select few supplements, the changes in i-FABP, gastrointestinal symptoms, and exercise performance were outside of clinical relevance. Although probiotics showed a moderate significant effect for gastrointestinal symptoms, the conflicting findings across studies may have been due to inadequate control of confounding variables across studies. Further research is required to assess the alternative dietary supplements’ effects on gastrointestinal health and exercise performance, particularly under varied environmental conditions, where more rigorous control for cofounding factors is implemented. Full article
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16 pages, 1586 KiB  
Article
Beyond Nutritional Treatment: Effects of Fitwalking on Physical Capacity and Intestinal Barrier Integrity in BMI-Stratified IBS Patients
by Antonella Bianco, Francesco Russo, Laura Prospero, Giuseppe Riezzo, Isabella Franco, Benedetta D’Attoma, Antonia Ignazzi, Nicola Verrelli, Claudia Beatrice Bagnato, Francesco Goscilo, Domenica Mallardi, Michele Linsalata, Caterina Bonfiglio, Pasqua Letizia Pesole and Annalisa Ferro
Nutrients 2024, 16(23), 4181; https://doi.org/10.3390/nu16234181 - 2 Dec 2024
Cited by 3 | Viewed by 1574
Abstract
Background: Irritable bowel syndrome (IBS) and obesity are associated with intestinal barrier alterations that result in low-grade inflammation. Zonulin and intestinal fatty acid-binding protein (I-FABP) assess gut barrier health, while urinary indican concentrations reflect dysbiosis in the small intestine. Physical activity, such as [...] Read more.
Background: Irritable bowel syndrome (IBS) and obesity are associated with intestinal barrier alterations that result in low-grade inflammation. Zonulin and intestinal fatty acid-binding protein (I-FABP) assess gut barrier health, while urinary indican concentrations reflect dysbiosis in the small intestine. Physical activity, such as Fitwalking, aids weight management and improves intestinal permeability. This study assesses the impact of a 12-week Fitwalking program on intestinal barrier health in IBS patients categorized by body mass index (BMI). Methods: Fifty-seven mild IBS patients were categorized as obese (OB = 18), overweight (OW = 24), or normal weight (NW = 15) and assigned to a walking group. Participants walked thrice weekly at moderate intensity for 60 min per session, using the specific Fitwalking technique, supervised by staff. Results: No significant changes in biochemical or anthropometric variables were observed. However, Fitwalking improved the Global Physical Capacity Score (GPCS) by 46%, 48%, and 24% in the NW, OW, and OB groups. Post-intervention, serum zonulin levels notably decreased in OB individuals, suggesting reduced inflammation. OW patients unexpectedly showed increased fecal zonulin levels. OB participants experienced decreased urinary indican levels. Zonulin levels positively correlated with BMI and inversely with GPCS. Conclusions: Regular exercise benefits the intestinal barrier, especially in obese IBS patients. Monitoring zonulin and I-FABP may offer insights into gut barrier integrity and GI injury severity. Future studies should explore longer intervention durations, larger populations, and advanced diagnostic tools to validate findings and investigate the mechanisms behind exercise-induced changes in intestinal permeability and gut health markers. Full article
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28 pages, 2212 KiB  
Review
The Gut Microbiome in Sepsis: From Dysbiosis to Personalized Therapy
by Andrea Piccioni, Fabio Spagnuolo, Marcello Candelli, Antonio Voza, Marcello Covino, Antonio Gasbarrini and Francesco Franceschi
J. Clin. Med. 2024, 13(20), 6082; https://doi.org/10.3390/jcm13206082 - 12 Oct 2024
Cited by 9 | Viewed by 3634
Abstract
Sepsis is a complex clinical syndrome characterized by an uncontrolled inflammatory response to an infection that may result in septic shock and death. Recent research has revealed a crucial link between sepsis and alterations in the gut microbiota, showing that the microbiome could [...] Read more.
Sepsis is a complex clinical syndrome characterized by an uncontrolled inflammatory response to an infection that may result in septic shock and death. Recent research has revealed a crucial link between sepsis and alterations in the gut microbiota, showing that the microbiome could serve an essential function in its pathogenesis and prognosis. In sepsis, the gut microbiota undergoes significant dysbiosis, transitioning from a beneficial commensal flora to a predominance of pathobionts. This transformation can lead to a dysfunction of the intestinal barrier, compromising the host’s immune response, which contributes to the severity of the disease. The gut microbiota is an intricate system of protozoa, fungi, bacteria, and viruses that are essential for maintaining immunity and metabolic balance. In sepsis, there is a reduction in microbial heterogeneity and a predominance of pathogenic bacteria, such as proteobacteria, which can exacerbate inflammation and negatively influence clinical outcomes. Microbial compounds, such as short-chain fatty acids (SCFAs), perform a crucial task in modulating the inflammatory response and maintaining intestinal barrier function. However, the role of other microbiota components, such as viruses and fungi, in sepsis remains unclear. Innovative therapeutic strategies aim to modulate the gut microbiota to improve the management of sepsis. These include selective digestive decontamination (SDD), probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT), all of which have shown potential, although variable, results. The future of sepsis management could benefit greatly from personalized treatment based on the microbiota. Rapid and easy-to-implement tests to assess microbiome profiles and metabolites associated with sepsis could revolutionize the disease’s diagnosis and management. These approaches could not only improve patient prognosis but also reduce dependence on antibiotic therapies and promote more targeted and sustainable treatment strategies. Nevertheless, there is still limited clarity regarding the ideal composition of the microbiota, which should be further characterized in the near future. Similarly, the benefits of therapeutic approaches should be validated through additional studies. Full article
(This article belongs to the Special Issue New Diagnostic and Therapeutic Trends in Sepsis and Septic Shock)
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14 pages, 1897 KiB  
Article
The Association between IL-1β and IL-18 Levels, Gut Barrier Disruption, and Monocyte Activation during Chronic Simian Immunodeficiency Virus Infection and Long-Term Suppressive Antiretroviral Therapy
by Siva Thirugnanam, Chenxiao Wang, Chen Zheng, Brooke F. Grasperge, Prasun K. Datta, Jay Rappaport, Xuebin Qin and Namita Rout
Int. J. Mol. Sci. 2024, 25(16), 8702; https://doi.org/10.3390/ijms25168702 - 9 Aug 2024
Viewed by 1806
Abstract
HIV-induced persistent immune activation is a key mediator of inflammatory comorbidities such as cardiovascular disease (CVD) and neurocognitive disorders. While a preponderance of data indicate that gut barrier disruption and microbial translocation are drivers of chronic immune activation, the molecular mechanisms of this [...] Read more.
HIV-induced persistent immune activation is a key mediator of inflammatory comorbidities such as cardiovascular disease (CVD) and neurocognitive disorders. While a preponderance of data indicate that gut barrier disruption and microbial translocation are drivers of chronic immune activation, the molecular mechanisms of this persistent inflammatory state remain poorly understood. Here, utilizing the nonhuman primate model of Human Immunodeficiency Virus (HIV) infection with suppressive antiretroviral therapy (ART), we investigated activation of inflammasome pathways and their association with intestinal epithelial barrier disruption (IEBD). Longitudinal blood samples obtained from rhesus macaques with chronic SIV infection and long-term suppressive ART were evaluated for IEBD biomarkers, inflammasome activation (IL-1β and IL-18), inflammatory cytokines, and triglyceride (TG) levels. Activated monocyte subpopulations and glycolytic potential were investigated in peripheral blood mononuclear cells (PBMCs). During the chronic phase of treated SIV infection, elevated levels of plasma IL-1β and IL-18 were observed following the hallmark increase in IEBD biomarkers, intestinal fatty acid-binding protein (IFABP) and LPS-binding protein (LBP). Further, significant correlations of plasma IFABP levels with IL-1β and IL-18 were observed between 10 and 12 months of ART. Higher levels of sCD14, IL-6, and GM-CSF, among other inflammatory mediators, were also observed only during the long-term SIV + ART phase along with a trend of increase in the frequencies of activated CD14+CD16+ intermediate monocyte subpopulations. Lastly, we found elevated levels of blood TG and higher glycolytic capacity in PBMCs of chronic SIV-infected macaques with long-term ART. The increase in circulating IL-18 and IL-1β following IEBD and their significant positive correlation with IFABP suggest a connection between gut barrier disruption and inflammasome activation during chronic SIV infection, despite viral suppression with ART. Additionally, the increase in markers of monocyte activation, along with elevated TG and enhanced glycolytic pathway activity, indicates metabolic remodeling that could fuel metabolic syndrome. Further research is needed to understand the mechanisms by which gut dysfunction and inflammasome activation contribute to HIV-associated metabolic complications, enabling targeted interventions in people with HIV. Full article
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12 pages, 789 KiB  
Article
Markers of Intestinal Permeability and Inflammation in Enterally Fed Children with Cerebral Palsy
by Dorota Mickiewicz-Góra, Katarzyna Sznurkowska, Karolina Skonieczna-Żydecka, Arleta Drozd, Anna Borkowska, Maciej Zagierski, Joanna Troch and Agnieszka Szlagatys-Sidorkiewicz
Nutrients 2024, 16(15), 2447; https://doi.org/10.3390/nu16152447 - 27 Jul 2024
Cited by 1 | Viewed by 1635
Abstract
Cerebral palsy (CP) results in non-progressive damage to the central nervous system, leading to functional disorders of the gastrointestinal tract and requiring enteral nutrition via gastrostomy in some patients. The aim of the study was to assess the impact of enteral nutrition on [...] Read more.
Cerebral palsy (CP) results in non-progressive damage to the central nervous system, leading to functional disorders of the gastrointestinal tract and requiring enteral nutrition via gastrostomy in some patients. The aim of the study was to assess the impact of enteral nutrition on intestinal inflammation expressed by stool calprotectin and intestinal permeability determined by fecal zonulin and IFABP, and to determine whether CP affects these parameters. The study group consisted of 30 children with CP, fed enterally (Cerebral Palsy Enteral Nutrition—CPEN), and two reference groups: 24 children with CP, fed orally with a standard diet (CPC—Cerebral Palsy Controls) and 24 healthy children (HC—healthy controls). The differences between these groups and between the combined CP groups (CPG and CPEN + CPC) and HC were analyzed. Fecal zonulin, calprotectin, and intestinal fatty acid-binding protein 2 (IFABP2) levels were determined by ELISA. The concentrations of fecal calprotectin and zonulin were significantly higher in the CPEN group than in the CPC group (p = 0.012, p = 0.025). When comparing the CPG (n = 53) with the HC group (n = 24), statistically significant differences were observed for calprotectin (p = 0.000018, higher in the CPG) and IFABP (p = 0.021, higher in HC). Enteral nutrition was associated in our cohort with increased fecal calprotectin and zonulin. Children with cerebral palsy presented with increased fecal calprotectin but not increased intestinal permeability expressed by stool zonulin. Full article
(This article belongs to the Special Issue Nutrition, Gut Permeability, and Inflammation)
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20 pages, 2481 KiB  
Article
Gut Microbiota and Biomarkers of Intestinal Barrier Damage in Cirrhosis
by Irina Efremova, Roman Maslennikov, Oleg Medvedev, Anna Kudryavtseva, Anastasia Avdeeva, George Krasnov, Filipp Romanikhin, Mikhail Diatroptov, Maria Fedorova, Elena Poluektova, Anna Levshina and Vladimir Ivashkin
Microorganisms 2024, 12(3), 463; https://doi.org/10.3390/microorganisms12030463 - 25 Feb 2024
Cited by 26 | Viewed by 2932
Abstract
Gut dysbiosis and subclinical intestinal damage are common in cirrhosis. The aim of this study was to examine the association of intestinal damage biomarkers (diamine oxidase [DAO], claudin 3, and intestinal fatty acid binding protein [I-FABP; FABP2]) with the state of the gut [...] Read more.
Gut dysbiosis and subclinical intestinal damage are common in cirrhosis. The aim of this study was to examine the association of intestinal damage biomarkers (diamine oxidase [DAO], claudin 3, and intestinal fatty acid binding protein [I-FABP; FABP2]) with the state of the gut microbiota in cirrhosis. The blood levels of DAO were inversely correlated with blood levels of claudin 3, lipopolysaccharide (LPS), presepsin, TNF-α, and the severity of cirrhosis according to Child–Pugh scores. The blood level of I-FABP was directly correlated with the blood level of claudin 3 but not with that of DAO. Patients with small intestinal bacterial overgrowth (SIBO) had lower DAO levels than patients without SIBO. There was no significant difference in claudin 3 levels and I-FABP detection rates between patients with and without SIBO. The DAO level was directly correlated with the abundance of Akkermansiaceae, Akkermansia, Allisonella, Clostridiaceae, Dialister, Lactobacillus, Muribaculaceae, Negativibacillus, Ruminococcus, Thiomicrospiraceae, Verrucomicrobiae, and Verrucomicrobiota; and it was inversely correlated with the abundance of Anaerostipes, Erysipelatoclostridium, and Vibrio. The I-FABP level was directly correlated with Anaerostipes, Bacteroidia, Bacteroidota, Bilophila, Megamonas, and Selenomonadaceae; and it was inversely correlated with the abundance of Brucella, Pseudomonadaceae, Pseudomonas, and Vibrionaceae. The claudin 3 level was directly correlated with Anaerostipes abundance and was inversely correlated with the abundance of Brucella, Coriobacteriia, Eggerthellaceae, and Lactobacillus. Full article
(This article belongs to the Special Issue The Interplay between Microbiota and Human Complex Traits)
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13 pages, 1877 KiB  
Article
Combined Turmeric, Vitamin C, and Vitamin D Ready-to-Drink Supplements Reduce Upper Respiratory Illness Symptoms and Gastrointestinal Discomfort in Elite Male Football Players
by David J. Clayton, Ross Burbeary, Connor Parker, Ruth M. James, Chris Saward, Eleanor L. Procter, William J. A. Mode, Carla Baker, John Hough, Neil C. Williams, Harry Rossington and Ian Varley
Nutrients 2024, 16(2), 243; https://doi.org/10.3390/nu16020243 - 12 Jan 2024
Cited by 3 | Viewed by 6152
Abstract
Elite football is associated with the increased risk of illness, although targeted supplementation can reduce illness risk. This study assessed the effects of a supplement containing turmeric root within a black pepper and fat-soluble blend, vitamin C and vitamin D, on upper respiratory [...] Read more.
Elite football is associated with the increased risk of illness, although targeted supplementation can reduce illness risk. This study assessed the effects of a supplement containing turmeric root within a black pepper and fat-soluble blend, vitamin C and vitamin D, on upper respiratory symptoms (URS), gastrointestinal symptoms (GIS), muscle soreness, and markers of inflammation and gut permeability in elite male footballers. Twenty-three footballers completed 3 weeks of no intervention (CON), followed by 16 weeks of daily consuming 60 mL of a commercially available supplement containing raw turmeric root (17.5 g, estimated to contain 700 mg of curcumin), vitamin C (1000 mg), and vitamin D3 (3000 IU/75 mcg) (SUP). URS and GIS were measured daily. Immediately (0 h), 40, and 64 h after six competitive matches (two in CON, four in SUP), the subjective soreness and plasma concentrations of creatine kinase [CK], c-reactive protein [CRP], and intestinal fatty-acid binding protein [I-FABP] were assessed. URS incidence (p < 0.001), GIS (p < 0.05), and plasma [I-FABP] at 0 h (p < 0.05) were greater during CON versus SUP. At 40 h, [CRP] was greater than 0 h during CON (p < 0.01) but not SUP (p = 0.204). There were no differences in soreness or [CK]. This study indicates that turmeric root, vitamin C, and vitamin D supplementation over 16 weeks can reduce URS, GIS, and post-match [I-FABP] in elite footballers. Full article
(This article belongs to the Section Sports Nutrition)
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21 pages, 872 KiB  
Systematic Review
The Impact of Biomarkers on the Early Detection of Acute Mesenteric Ischemia
by Aleksandar Zafirovski, Marija Zafirovska, Dimitrij Kuhelj and Tadeja Pintar
Biomedicines 2024, 12(1), 85; https://doi.org/10.3390/biomedicines12010085 - 29 Dec 2023
Cited by 8 | Viewed by 3344
Abstract
Background: acute mesenteric ischemia (AMI) is a life-threatening condition that is caused by inadequate blood flow through the mesenteric vessel and is related to high mortality rates due to systemic complications. This study aims to systematically review the available literature concerning the major [...] Read more.
Background: acute mesenteric ischemia (AMI) is a life-threatening condition that is caused by inadequate blood flow through the mesenteric vessel and is related to high mortality rates due to systemic complications. This study aims to systematically review the available literature concerning the major findings of possible biomarkers for early detection of acute mesenteric ischemia in the human population. Methods: studies that measured the performance of biomarkers during acute mesenteric ischemia were identified with the search of PubMed, Embase, Medline, and Cochrane library. Results: from a total of 654 articles, 46 articles examining 14 different biomarkers were filtered, falling within our inclusion criteria. Intestinal fatty acid-binding protein (I-FABP) was the most commonly researched biomarker regarding AMI, with sensitivity ranging from 61.5% to 100% and specificity ranging from 40% to 100%. The second most commonly researched biomarker was D-dimer, with a sensitivity of 60–100% and a specificity of 18–85.71%. L-lactate had a sensitivity of 36.6–90.91% and a specificity of 64.29–96%. Several parameters within the blood count were examined as potential markers for AMI, including NLR, PLR, MPV, RDW, DNI, and IG. Citrulline, interleukin 6 (IL-6), and procalcitonin (PCT) were the least-researched biomarkers. Conclusion: different biomarkers showed different accuracies in detecting AMI. I-FABP and D-dimer have been the most researched and shown to be valuable in the diagnosis of AMI, whereas L-lactate could be used as an additional tool. Ischemia-modified albumin (IMA), alpha glutathione S-transferase (αGST), interleukin 6 (IL-6), and citrulline showed potential use in their respective studies. However, further research needs to be done on larger sample sizes and with controls to reduce bias. Several studies showed that neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), mean platelet volume (MPV), red-cell distribution width (RDW), delta neutrophil index (DNI), and immature granulocytes (IGs) might be useful, as well at the same time be widely distributed and affordable in combination with other markers presenting higher specificity and sensitivity. Full article
(This article belongs to the Topic Biomarker Development and Application)
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