Intestinal Fatty Acid-binding Protein Levels Research Articles

Elevated intestinal fatty acid-binding protein levels as a marker of portal hypertension and gastroesophageal varices in cirrhosis

We measured intestinal fatty acid-binding protein (I-FABP) levels, a useful marker of small intestinal mucosal injury, in patients with cirrhosis to determine their relationship with liver function and complications. This cross-sectional study included 71 patients with cirrhosis admitted for treatment of cirrhotic complications or hepatocellular carcinoma (cohort A) and 104 patients with cirrhosis who received direct-acting antiviral therapy for HCV (cohort B). I-FABP levels, measured by ELISA, were evaluated relative to hepatic reserve and compared with non-invasive scoring systems for diagnostic performance in cirrhotic complications. The median I-FABP level in both cohorts were significantly elevated in patients with reduced hepatic reserve (CTP grade A/BC cohort A, 2.33/3.17 ng/mL, p = 0.032; cohort B, 2.46/3.64 ng/mL, p = 0.008) and complications with gastroesophageal varices (GEV; GEV (-)/(+) cohort A, 1.66/3.67 ng/mL, p < 0.001; cohort B, 2.32/3.36 ng/mL; p = 0.003). Further, multiple logistic regression analysis identified I-FABP as the only factor contributing to GEV presence in both cohorts, which outperformed non-invasive scoring systems for GEV diagnosis (sensitivity 84.6%; specificity 84.2%; sensitivity 69.6%; specificity 63.8%, respectively). In conclusion, elevated small-intestinal mucosal injury in patients with cirrhosis was related to reduced hepatic reserve and GEV presence. I-FABP levels reflect portal hypertension and may be useful in cirrhosis management.

Intestinal fatty acid-binding protein (I-FABP) as biomarker of ischemic damage in experimentally induced 12-h small bowel obstruction.

Laboratory tests have low diagnostic specificity for strangulated intestinal obstruction. The diagnostic potential of the intestinal fatty acid-binding protein (I-FABP) expressed in the tips of the intestinal villi continues to be explored. The number of white blood cells, blood plasma levels of L-lactate, C-reactive protein (CRP) and I-FABP were measured in rats with experimentally induced 12-h strangulated and non-strangulated intestinal obstruction. The results of the laboratory tests were compared with the changes in the morphology of the intestinal wall. The studied diagnostic markers, except for CRP, were elevated by 12-h L-lactate and I-FABP concentrations were significantly higher in the strangulated obstruction group than in other groups. L-lactate (cutoff value: 3.01mmol/L) had 86.1% sensitivity and 66.7% specificity for strangulated obstruction (AUC 0.815, p < 0.001). I-FABP levels above 5.432ng/ml indicated strangulated obstruction with 83.33% sensitivity and 88.9% specificity (AUC 0.906, p < 0.001). Villi destruction was observed at 2h in the strangulated obstruction group. I-FABP levels peaked at 4h and plateaued at 12h. Functional changes were observed in the non-strangulated group; they were accompanied by a significant increase in I-FABP concentrations that lasted until 12h. Compared with traditional diagnostic markers of strangulated intestinal obstruction, I-FABP demonstrated higher accuracy in the first 12h, although its concentrations reached the plateau already at 4h and did not increase thereafter. The functional changes in small bowel wall in non-strangulated obstruction were accompanied by continuous increase in I-FABP concentrations up to 12h, which may have influenced the diagnostic accuracy of the marker.

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.

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.

High IL-1β and IL-18 Levels Associate with Gut Barrier Disruption and Monocyte Activation During Chronic SIV Infection with Long-Term Suppressive Antiretroviral Therapy.

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 HIV infection with suppressive antiretroviral therapy (ART), we investigated activation of inflammasome pathways and their association with intestinal epithelial barrier disruption and CVD pathogenesis. Longitudinal blood samples obtained from rhesus macaques with chronic SIV infection and long-term suppressive ART were evaluated for biomarkers of intestinal epithelial barrier disruption (IEBD), 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). Higher plasma levels of 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), during the chronic phase of treated SIV infection. Further, significant correlations of plasma IFABP levels with IL-1β and IL-18 were observed between 10-12 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 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 accelerate CVD pathogenesis. Further research is needed to understand mechanisms by which gut dysfunction and inflammasome activation contribute to HIV-associated CVD and metabolic complications, enabling targeted interventions in people with HIV.

Indirect Markers of Intestinal Damage in IgA Nephropathy

Introduction: Presence of subclinical intestinal inflammation has repeatedly been shown in IgA nephropathy (IgAN) and the degree of histological inflammation has correlated with abnormal urinary findings. There is lack of noninvasive biomarkers evaluating the presence of subclinical intestinal damage in IgAN. We conducted this study hypothesizing that selected biomarkers regarded as indirect markers of intestinal damage could be elevated in IgAN. Methods: Eighty-five primary IgAN patients (median age 55 years, 54% men) participated in this single-center study in Tampere, Finland. None had end-stage kidney disease or previously diagnosed enteropathies. Celiac disease was excluded with serum transglutaminase 2 antibody (TG2Ab) and endomysial antibody tests and inflammatory bowel disease with fecal calprotectin. Intestinal damage was evaluated from sera with analyses of intestinal fatty-acid binding protein (I-FABP), soluble cluster of differentiation molecule 14 (sCD14), and lipopolysaccharide binding protein. Fourteen people suffering from dyspepsia and 15 healthy people served as controls. Results: I-FABP levels among IgAN patients were higher than in the healthy controls (median 830 pg/mL vs. 289 pg/mL, p < 0.001). Also, sCD14 was increased in IgAN patients compared to dyspepsia controls. Although TG2Ab levels were within the normal range among IgAN patients, they were higher than in the healthy controls (median 1.3 U/mL vs. 0.6 U/mL, p < 0.001). Conclusions: Elevated serum levels of I-FABP were present in primary IgAN patients without known enteropathies. Serum I-FABP may indicate the presence of subclinical intestinal damage. These findings encourage further investigation into the role of the intestine in the pathophysiology of IgAN.

Altered lactate/pyruvate ratio may be responsible for aging-associated intestinal barrier dysfunction in male rats

Some evidence points to a link between aging-related increased intestinal permeability and mitochondrial dysfunction in in-vivo models. Several studies have also demonstrated age-related accumulation of the of specific deletion 4834-bp of “common” mitochondrial DNA (mtDNA) in various rat tissues and suggest that this deletion may disrupt mitochondrial metabolism. The present study aimed to investigate possible associations among the mitochondrial DNA (mtDNA) common deletion, mitochondrial function, intestinal permeability, and aging in rats. The study was performed on the intestinal tissue from (24 months) and young (4 months) rats. mtDNA4834 deletion, mtDNA copy number, mitochondrial membrane potential, and ATP, lactate and pyruvate levels were analyzed in tissue samples. Zonulin and intestinal fatty acid-binding protein (I-FABP) levels were also evaluated in serum. Serum zonulin and I-FABP levels were significantly higher in 24-month-old rats than 4-month-old rats (p = 0.04, p = 0.026, respectively). There is not significant difference in mtDNA4834 copy levels was observed between the old and young intestinal tissues (p > 0.05). The intestinal mitochondrial DNA copy number was similar between the two age groups (p > 0.05). No significant difference was observed in ATP levels in the intestinal tissue lysates between old and young rats (p > 0.05). ATP levels in isolated mitochondria from both groups were also similar. Analysis of MMP using JC-10 in intestinal tissue mitochondria showed that mitochondrial membrane potentials (red/green ratios) were similar between the two age groups (p > 0.05). Pyruvate tended to be higher in the 24-month-old rat group and the L/P ratio was found to be approximately threefold lower in the intestinal tissue of the older rats compared to the younger rats (p < 0.002). The tissue lactate/pyruvate ratio (L/P) was three times lower in old rats than in young rats. Additionally, there were significant negative correlations between intestinal permeability parameters and L/P ratios. The intestinal tissues of aged rats are not prone to accumulate mtDNA common deletion, we suggest that this mutation does not explain the age-related increase in intestinal permeability. It seems to be more likely that altered glycolytic capacity could be a link to increased intestinal permeability with age. This observation strengthens assertions that the balance between glycolysis and mitochondrial metabolism may play a critical role in intestinal barrier functions.

Probiotics may alleviate intestinal damage induced by cardiopulmonary bypass in children.

Intestinal ischaemia-reperfusion injury induced by cardiopulmonary bypass causes intestinal epithelial barrier dysfunction, leading to dysbiosis and bacterial translocation. We conducted a randomized prospective study with 2 objectives: (i) to investigate epithelial barrier dysfunction and bacterial translocation induced by cardiopulmonary bypass and changes in the gut microbiota and (ii) to verify whether probiotics can improve these conditions. Between 2019 and 2020, patients 0-15 years old scheduled to undergo cardiac surgery using cardiopulmonary bypass were enrolled and randomly allocated to 2 groups: the intervention group received probiotics and the control group did not receive probiotics. We analysed the microbiota in faeces and blood, organic acid concentrations in faeces, plasma intestinal fatty acid-binding protein and immunological responses. Eighty-two patients were enrolled in this study. The characteristics of the patients were similar in both groups. The total number of obligate anaerobes was higher in the intervention group than in the control group after postoperative day 7. We identified 4 clusters within the perioperative gut microbiota, and cluster changes showed a corrective effect of probiotics on dysbiosis after postoperative day 7. Organic acid concentrations in faeces, incidence of bacterial translocation, intestinal fatty acid-binding protein levels and immunological responses, except for interleukin -17A, were not markedly different between the 2 groups. Administration of probiotics was able to correct dysbiosis but did not sufficiently alleviate the intestinal damage induced by cardiopulmonary bypass. More effective methods should be examined to prevent disturbances induced by cardiac surgery using cardiopulmonary bypass. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037174 UMIN000035556.

Values of serum intestinal fatty acid-binding protein, fecal calprotectin, and fecal human β-defensin 2 for predicting necrotizing enterocolitis

BackgroundThis study aimed to assess the diagnostic potential of serum intestinal fatty acid-binding protein (I-FABP), fecal calprotectin (FC), and fecal human β-defensin 2 (hBD2) in predicting necrotizing enterocolitis (NEC) in preterm infants.MethodsA prospective cohort of neonates with a gestational age < 32 weeks, suspected of NEC, was enrolled between June 2021 and December 2022. Serum I-FABP, FC, and fecal hBD2 levels were measured upon NEC suspicion, and diagnosis was confirmed through radiological examination or surgical intervention. Diagnostic precision of serum I-FABP, FC, and fecal hBD2 was assessed using a logistic regression model with multiple variables.ResultsThe study included 70 neonates (45 males, 25 females), with 30 developing NEC (40% Stage III, n = 12; 60% Stage II, n = 18) and 40 in the control group. NEC patients exhibited significantly higher serum I-FABP and FC levels (4.76 ng/mL and 521.56 µg/g feces, respectively) than those with other diagnoses (1.38 ng/mL and 213.34 µg/g feces, respectively; p ˂ 0.05 for both biomarkers). Stage II NEC neonates showed elevated fecal hBD2 levels (376.44 ng/g feces) than Stage III NEC neonates and controls (336.87 ng/g and 339.86 ng/g feces, respectively; p ˂ 0.05). No such increase was observed in infants progressing to Stage III NEC. Using a serum I-FABP threshold of > 2.54 ng/mL yielded 76.7% sensitivity, 87.5% specificity, 82.1% positive predictive value (PPV), and 83.3% negative predictive value (NPV). For FC (cutoff > 428.99 µg/g feces), corresponding values were 76.7% sensitivity, 67.5% specificity, 63.9% PPV, and 79.4% NPV.ConclusionSerum I-FABP and FC levels are valuable for early NEC detection and provide insights into disease severity. Low fecal hBD2 levels suggest an inadequate response to luminal bacteria, potentially rendering these infants more susceptible to NEC development or exacerbation.

The Association Between Intraoperative Compromised Intestinal Integrity and Postoperative Complications in Cancer Patients

BackgroundBecause of perioperative splanchnic hypoperfusion, the gut wall becomes more permeable for intraluminal microbes to enter the splanchnic circulation, possibly contributing to development of complications. Hypoperfusion-related injured enterocytes release intestinal fatty acid binding protein (I-FABP) into plasma, which is used as proxy of intestinal integrity. This study investigates the occurrence of intestinal integrity loss during oncologic surgery, measured by I-FABP change. Secondary the relationship between compromised intestinal integrity, and related variables and complications were studied.MethodsPatients undergoing oncologic surgery from prospective cohort studies were included. Urine I-FABP samples were collected preoperatively (T0) and at wound closure (T1), and in a subgroup on Day 1 (D1) and Day 2 (D2) postoperatively. I-FABP dynamics were investigated and logistic regression analyses were performed to study the association between I-FABP levels and patient-related, surgical variables and complications.ResultsA total of 297 patients were included with median age of 70 years. Median I-FABP value increased from 80.0 pg/mL at T0 (interquartile range [IQR] 38.0–142.0) to 115 pg/mL at T1 (IQR 48.0–198.0) (p < 0.05). Age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02–1.08) and anesthesia time (OR 1.13, 95% CI 1.02–1.25) were related to stronger I-FABP increase. When comparing I-FABP change in patients experiencing any complications versus no complications, relative I-FABP change at T1 was 145% of T0 (IQR 86–260) versus 113% (IQR 44–184) respectively (p < 0.05).ConclusionsA significant change in I-FABP levels was seen perioperatively indicating compromised intestinal integrity. Age and anesthesia time were related to higher I-FABP increase. In patients experiencing postoperative complications, a higher I-FABP increase was found.

Gastrointestinal function following endurance exercise under different environmental temperatures.

We determined the effects of different environmental temperatures on exercise-induced gastrointestinal (GI) damage and delayed gastric emptying (GE) rate. Eleven trained males completed three trials on different days, consisting of (1) exercise in a thermoneutral environment (CON, 23°C), (2) exercise in a hot environment (HOT, 35°C), and (3) exercise in a cold environment (COLD, 10°C). The subjects performed high-intensity interval-type endurance exercises in all trials. Blood intestinal fatty acid binding protein (I-FABP) levels was determine before and after exercise. We evaluated Tmax (time when the 13C-excretion/h reached a maximum level) as an indication of the GE rate during post-exercise. Rectal temperature during exercise was significantly higher (P < 0.001) in the HOT (38.7 ± 0.3°C) trial compared with the CON (38.2 ± 0.3°C) and COLD (38.2 ± 0.3°C) trials, with no significant difference between the CON and COLD trials. Plasma I-FABP level after exercise (relative to the pre-exercise level) were significantly greater (P = 0.005) in the HOT trial (92.9 ± 69.6%) than in the CON (37.2 ± 31.6%) and COLD (37.6 ± 41.8%) trials. However, there was no significant difference between the CON and COLD trials. Moreover, the Tmax was delayed significantly (P = 0.006) in the HOT trial compared with the CON and COLD trials, with no significant difference between the CON and COLD trials. GI function following endurance exercise was similar between thermoneutral and cold environments, while endurance exercise in a hot environment exacerbated GI function compared with thermoneutral and cold environments.

Influence of the 2000-m ergometer test on indirect markers of intestinal injury in competitive elite rowers in different training phases

BackgroundWe examined the effect of the 2000-m ergometer test on gut injury in competitive elite rowers in two different training phases. Given that inflammatory markers during the competitive phase are higher, we hypothesise that markers of intestinal injury are also more elevated during that phase.MethodsWe performed this study during the preparatory phase (Test I) and competitive phase (Test II) of annual training. We included 10 competitive elite rowers, members of the Polish Rowing Team, in the study after applying the inclusion/exclusion criteria. The participants performed a 2000-m ergometer test during both phases (Tests I and II). We collected blood samples before the test, immediately after the test and after 1 h of recovery. We measured the levels of interleukin 6 (IL-6), intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), lipopolysaccharide-binding protein (LBP), and zonulin.ResultsThere were no significant changes over time in Test I and Test II in the gut integrity markers. There were significantly lower I-FABP and IL-6 levels after the test for Test II compared with Test I. The pre-test LPS level was significantly lower for Test II compared with Test I. The pre-test LBP and zonulin levels were numerically lower in Test II, but the differences were not significant.ConclusionsThe 2000-m ergometer test showed no influence on gut integrity markers. However, there were differences in the response to exercise between Tests I and II. The lower level of gut injury markers after extreme exercise tests carried out during the preparation period may be the result of adaptive mechanisms and could indicate that rationally conducted training significantly decreases intestinal injury.

Impaired intestinal permeability in patients with multiple sclerosis.

A number of recent studies have shown that the intestinal microbiome, part of the brain-gut axis, is implicated in the pathophysiology of multiple sclerosis. An essential part of this axis, is the intestinal barrier and gastrointestinal disorders with intestinal barrier dysregulation appear to be linked to CNS demyelination, and hence involved in the etiopathogenesis of multiple sclerosis (MS). The aim of this study was to evaluate the integrity of the intestinal barrier in patients with clinically definite multiple sclerosis (CDMS) and clinically isolated syndrome (CIS) using two serum biomarkers, claudin-3 (CLDN3), a component of tight epithelial junctions, and intestinal fatty acid binding protein (I-FABP), a cytosolic protein in enterocytes. Serum levels of CLDN3 in 37 MS patients and 22 controls, and serum levels of I-FABP in 46 MS patients and 51 controls were measured using commercial ELISA kits. Complete laboratory tests excluded the presence of gluten-related disorders in all subjects. Thirty MS patients received either disease-modifying drugs (DMD), immunosuppression (IS) or corticosteroid treatment. CLDN3 levels were only significantly higher in the MS patients treated with DMD or IS compared to the control group (P=0.006). There were no differences in I-FABP serum levels between the groups. Serum CLDN3 levels did not correlate with serum I-FABP levels in CDMS, in CIS patients or controls. In multiple sclerosis patients, the intestinal epithelium may be impaired with increased permeability, but without significant enterocyte damage characterized by intracellular protein leakage. Based on our data, CLDN3 serum levels appear to assess intestinal dysfunction in MS patients but mainly in treated ones.

Association of markers of inflammation and intestinal permeability in suicidal patients with major mood disorders

BackgroundPatients with major mood disorders are at high risk of suicidal behavior compared to the general population. Suicide is a public health concern, accounting for around 1.2% of deaths worldwide. Understanding its underlying mechanisms may help identify predictive biomarkers and design novel targeted treatments. Immune dysfunctions, in particular affecting the gut-brain axis, are of interest given their dual involvement in mood disorders and suicidal behavior. We thus explored the possible relationships between suicide attempt (SA) and circulating biomarkers of intestinal permeability and systemic inflammation in patients with major depressive disorder (MDD) or bipolar disorder (BD) with and without a history of SA. Method137 patients with BD and 168 with MDD were included, and among them, 133 had a history of SA and 172 did not. Among them, 104 were males (34%) and 201 females (66%). Depressive symptoms were evaluated using the Inventory of Depressive Symptomatology clinical scale (IDS-C30). Circulating levels of intestinal fatty acid binding protein (IFABP), calprotectin, apolipoprotein E (ApoE), lipopolysaccharides binding protein (LBP), lipopolysaccharides (LPS), soluble beta-2-microglobulin (B2m), and C-reactive protein (CRP), were determined. Multivariate linear regressions were performed according to the gender status given the proportion of the herein studied male and female individuals and the higher propensity of females to experience SA as compared to males. ResultsAfter adjusting for confounding variables, patients in the SA group had significantly higher CRP, and lower IFABP levels in comparison to the NSA group. LimitationsThe unavailability of confounding variables such as dietary habits, should be noted. In addition, the cross-sectional nature of the study hampers the identification of causative effects. ConclusionAlthough preliminary, our observations revealed associations between markers of inflammation and intestinal permeability in patients with suicidal behavior warranting further confirmation in larger cohorts.

Exploring I-FABP, endothelin-1 and L-lactate as biomarkers of acute intestinal necrosis: a case-control study

Objective Acute intestinal necrosis (AIN) is a disease with devastating high mortality. AIN due to obstructed arterial blood flow has a blurred clinical presentation. Timely diagnosis is paramount, and a blood-based biomarker is warranted to increase patient survival. We aimed to assess intestinal fatty acid binding protein (I-FABP) and endothelin-1 as diagnostic biomarkers for AIN. To our knowledge, this is the first study exploring endothelin-1 in AIN patients from a general surgical population. Design We conducted a single-centre nested case–control study comparing acutely admitted AIN patients to age- and sex-matched non-AIN patients during 2015–2016. I-FABP and endothelin-1 were analysed using an enzyme-linked immunosorbent assay. L-lactate levels were also measured in all patients. Cut-offs were estimated using receiver operator characteristic curves, and the diagnostic performance was estimated using the area under the receiver operator characteristic curve (AUC). Results We identified 43 AIN patients and included 225 matched control patients. Median levels of I-FABP, endothelin-1 and L-lactate were 3550 (IQR: 1746–9235) pg/ml, 3.91 (IQR: 3.33–5.19) pg/ml and 0.92 (IQR: 0.74–1.45) mM in AIN patients and 1731 (IQR: 1124–2848) pg/ml, 2.94 (IQR: 2.32–3.82) pg/ml and 0.85 (IQR: 0.64-1.21) mM in control patients, respectively. The diagnostic performances of endothelin-1 and of I-FABP + endothelin-1 combined were moderate. Endothelin-1 alone revealed an AUC of 0.74 (0.67; 0.82). The sensitivity and specificity of endothelin-1 were 0.81 and 0.64, respectively. Conclusion I-FABP and endothelin-1 are promising biomarkers for AIN, with moderate diagnostic performance compared with the commonly used biomarker L-lactate. Preregistration ClinicalTrials.gov: NCT05665946.

IFABP levels predict visceral malperfusion in the first hours after open thoracoabdominal aortic repair.

Intestinal ischemia after open thoracoabdominal aortic repairs, is a rare but devastating complication, associated with high mortality. Notoriously challenging to diagnose, visceral malperfusion necessitates immediate surgical attention. Intestinal fatty acid-binding protein (IFABP) has been proposed as a biomarker for the diagnosis of intestinal wall damage. In this prospectively conducted, observational study we evaluated the diagnostic capacity of IFABP levels in patients' serum and their correlation with visceral malperfusion. 23 patients undergoing open thoracoabdominal aortic repairs were included in this study and 8 of them were diagnosed postoperatively with visceral malperfusion-defined as a partial or complete thrombotic occlusion of the superior mesenteric artery and/or the coeliac trunk. IFABP levels and laboratory parameters often associated with intestinal ischemia (leucocytes, CRP, PCT and lactate) were measured at baseline, directly postoperatively, and at 12, 24 and 48 h after surgery. Postoperative visceral malperfusion-as revealed in CT angiography-was assessed and the predictive ability of IFABP levels to detect visceral malperfusion was evaluated with receiver-operator curve analysis. Patients with visceral malperfusion had a relevant risk for a fatal outcome (p = .001). IFABP levels were significantly elevated directly postoperatively and at 12 h after surgery in cases of visceral malperfusion. High IFABP concentrations in serum detected visceral malperfusion accurately during the first 12 h after surgery, with the maximum diagnostic ability achieved immediately after surgery (AUC 1, Sensitivity 100%, Specificity 100%, p < .001). We conclude, that IFABP measurements during the first postoperative hours after open thoracoabdominal aortic surgery can be a valuable tool for reliable and timely detection of visceral malperfusion.

Gut barrier protein levels in serial blood samples from critically ill trauma patients during and after intensive care unit stay.

In an effort to better manage critically ill patients hospitalised in the intensive care unit (ICU) after experiencing multiple traumas, the present study aimed to assess whether plasma levels of intestinal epithelial cell barrier proteins, including occludin, claudin-1, junctional adhesion molecule (JAM-1), tricellulin and zonulin, could be used as novel biomarkers. Additional potential markers such as intestinal fatty acid-binding protein (I-FABP), D-lactate, lipopolysaccharide (LPS) and citrulline were also evaluated. We also aimed to determine the possible relationships between the clinical, laboratory, and nutritional status of patients and the measured marker levels. Plasma samples from 29 patients (first, second, fifth and tenth days in the ICU and on days 7, 30 and 60 after hospital discharge) and 23 controls were subjected to commercial enzyme-linked immunosorbent assay (ELISA) testing. On first day (admission) and on the second day, plasma I-FABP, D-lactate, citrulline, occludin, claudin-1, tricellulin and zonulin levels were high in trauma patients and positively correlated with lactate, C-reactive protein (CRP), number of days of ICU hospitalisation, Acute Physiology and Chronic Health Evaluation II (APACHE II) score and daily Sequential Organ Failure Assessment (SOFA) scores (P < 0.05-P < 0.01). The results of the present study showed that occludin, claudin-1, tricellulin and zonulin proteins, as well as I-FABP, D-lactate and citrulline, may be used as promising biomarkers for the evaluation of disease severity in critically ill trauma patients, despite the complexity of the analysis of various barrier markers. However, our results should be supported by future studies.

Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure.

The gut microbiota in patients with chronic heart failure (HF) is characterized by low bacterial diversity and reduced ability to synthesize beneficial metabolites. These changes may facilitate leakage of whole bacteria or bacterial products from the gut into the bloodstream, which may activate the innate immune system and contribute to the low-grade inflammation seen in HF. In this exploratory cross-sectional study, we aimed to investigate relationships between gut microbiota diversity, markers of gut barrier dysfunction, inflammatory markers, and cardiac function in chronic HF patients. In total, 151 adult patients with stable HF and left ventricular ejection fraction (LVEF) < 40% were enrolled. We measured lipopolysaccharide (LPS), LPS-binding protein (LBP), intestinal fatty acid binding protein (I-FABP), and soluble cluster of differentiation 14 (sCD14) as markers of gut barrier dysfunction. N-terminal pro-B-type natriuretic peptide (NT-proBNP) level above median was used as a marker of severe HF. LVEF was measured by 2D-echocardiography. Stool samples were sequenced using 16S ribosomal RNA gene amplification. Shannon diversity index was used as a measure of microbiota diversity. Patients with severe HF (NT-proBNP > 895 pg/ml) had increased I-FABP (p < 0.001) and LBP (p = 0.03) levels. ROC analysis for I-FABP yielded an AUC of 0.70 (95% CI 0.61-0.79, p < 0.001) for predicting severe HF. A multivariate logistic regression model showed increasing I-FABP levels across quartiles of NT-proBNP (OR 2.09, 95% CI 1.28-3.41, p = 0.003). I-FABP was negatively correlated with Shannon diversity index (rho = -0.30, p = <0.001), and the bacterial genera Ruminococcus gauvreauii group, Bifidobacterium, Clostridium sensu stricto, and Parasutterella, which were depleted in patients with severe HF. In patients with HF, I-FABP, a marker of enterocyte damage, is associated with HF severity and low microbial diversity as part of an altered gut microbiota composition. I-FABP may reflect dysbiosis and may be a marker of gut involvement in patients with HF.

Evaluation of Some Intestinal Biomarkers in the Determination of Intestinal Damage in Calves with Coccidiosis

This study aimed to assess the usefulness of injury biomarkers specific to the intestines in identifying the presence and degree of intestinal epithelial damage in coccidiosis-infected calves. Forty calves of various breeds and sexes, aged 21 days to 60 days, were used in the study. Of these, 30 were in the experimental group, and 10 were healthy control. The McMaster Oocyte counting technique was used to diagnose Eimeria and confirm clinical coccidiosis. Cases with clinical signs and more than 5,000 oocysts in gram feces were included in the study. All calves had blood samples drawn at the 0 th hours and 72 nd hours. Blood gas measurements were performed with a blood gas analyzer. Hemogram was performed with an automated hematologic analyzer. Bovine-specific enzyme-linked immunosorbent analysis (ELISA) test kits were used to measure the intestinal fatty acid binding protein (I-FABP), trefoil factor-3 (TFF-3), intestinal alkaline phosphatase (IAP), claudin-3 (CLD-3), intestinal smooth muscle actin (ACTG2), and interleukin-8 (IL-8) biomarkers from serum samples. Calves with coccidiosis received a single dose of toltrazuril (15 mg/kg) and supportive care. Before treatment (0 th hours) in coccidiosis-infected calves, serum I-FABP and CLD-3 levels were greater than in healthy calves (p<0.05), and after treatment (72 nd hours), serum TFF-3 and ACTG2 levels were higher than in healthy calves. There was a significant decrease in serum IL-8 levels in coccidiosis-infected calves after treatment (72 nd hours) compared to pre-treatment (0 th hours) (p<0.05). I-FABP, TFF-3, CLD-3, ACTG2, and IL-8 are helpful and reliable biomarkers that can be utilized to assess the presence of intestinal epithelium injury in coccidiosis-infected calves.

Translocation of bacterial LPS is associated with self-reported cognitive abilities in men living with HIV receiving antiretroviral therapy

BackgroundGut damage allows translocation of bacterial lipopolysaccharide (LPS) and fungal β-D-glucan (BDG) into the blood. This microbial translocation contributes to systemic inflammation and risk of non-AIDS comorbidities in people living with HIV, including those receiving antiretroviral therapy (ART). We assessed whether markers of gut damage and microbial translocation were associated with cognition in ART-treated PLWH.MethodsEighty ART-treated men living with HIV from the Positive Brain Health Now Canadian cohort were included. Brief cognitive ability measure (B-CAM) and 20-item patient deficit questionnaire (PDQ) were administered to all participants. Three groups were selected based on their B-CAM levels. We excluded participants who received proton pump inhibitors or antiacids in the past 3 months. Cannabis users were also excluded. Plasma levels of intestinal fatty acid binding protein (I-FABP), regenerating islet-derived protein 3 α (REG3α), and lipopolysaccharides (LPS = were quantified by ELISA, while 1–3-β-D-glucan BDG) levels were assessed using the Fungitell assay. Univariable, multivariable, and splines analyses were performed.ResultsPlasma levels of I-FABP, REG3α, LPS and BDG were not different between groups of low, intermediate and high B-CAM levels. However, LPS and REG3α levels were higher in participants with PDQ higher than the median.Multivariable analyses showed that LPS association with PDQ, but not B-CAM, was independent of age and level of education. I-FABP, REG3α, and BDG levels were not associated with B-CAM nor PDQ levels in multivariable analyses.ConclusionIn this well characterized cohort of ART-treated men living with HIV, bacterial but not fungal translocation was associated with presence of cognitive difficulties. These results need replication in larger samples.

The Imbalance Between Intestinal Th17 and Treg Cells Is Associated with an Incomplete Immune Reconstitution During Long-Term Antiretroviral Therapy in Patients with HIV.

Studies assessing the gut mucosal immune balance in HIV-infected patients using intestinal samples are scarce. In this study, we used intestinal mucosal specimens from the ileocecal region of seven immunological nonresponders (INRs), nine immunological responders (IRs), and six HIV-negative controls. We investigated T helper 17 (Th17) and T regulatory (Treg) cell counts and their ratio, zonula occludens-1 (ZO-1), intestinal fatty acid-binding protein (I-FABP), tumor necrosis factor-α, CD4+ T cell counts, HIV DNA, and cell-associated HIV RNA. The results showed that INRs had lower Th17 and higher Treg cell counts than IR, resulting in a significant difference in the Th17/Treg ratio between IRs and INRs. In addition, INRs had lower ZO-1 and higher I-FABP levels than IRs. The Th17/Treg ratio was positively associated with ZO-1 and negatively associated with I-FABP levels. There was a positive correlation between Th17/Treg ratio and CD4+ T cell counts and a negative correlation between the Th17/Treg ratio and HIV DNA in the intestine. Our study suggests that the imbalance of Th17/Treg in the intestine is a characteristic of incomplete immune reconstitution to antiretroviral therapy and is associated with intestinal damage.