Intestinal Fatty Acid Binding Protein Research Articles

Antioxidant supplementation during treatment of outpatient dogs with parvovirus enteritis ameliorates oxidative stress and attenuates intestinal injury: A randomized controlled trial

A prospective randomized controlled clinical study was conducted to determine whether antioxidant supplementation as an adjunct therapy alters hemogram, oxidative stress, serum intestinal fatty acid binding protein-2 (IFABP-2) level, fecal viral load, clinical score (CS) and survivability in outpatient canine parvovirus enteritis (CPVE) dogs. The dogs with CPVE were randomized to one of the five treatment groups: supportive treatment (ST) alone, ST with N-acetylcysteine (ST+NAC), resveratrol (ST+RES), coenzyme Q10 (ST+CoQ10) or ascorbic acid (ST+AA). The primary outcome measures were reduction of CS and fecal HA titre, and enhancement of survivability. Secondary outcome measures were reduction of oxidative stress indices and IFABP-2 level from day 0 to day 7. The mean CS and HA titre were significantly (P < 0.05) decreased from day 0 to 7 in ST and all antioxidant groups. The supplementations of NAC, RES and AA along with ST markedly (P < 0.05) reduced the concentrations of malondialdehyde, nitric oxide and IFABP-2 on day 7 as compared to ST alone. Additionally, NAC and RES supplementations markedly (P < 0.05) improved the total leukocyte count and neutrophil count in CPVE-affected dogs. NAC and RES could serve as better antioxidants for the amelioration of oxidative stress in CPVE but, the antioxidants did not confer any additional benefits in reduction of CS, fecal HA tire, or survivability when compared with ST alone.

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.

IFABP2 as a new prognostic biomarker for secondary non-response in rheumatoid arthritis

Increased intestinal permeability promotes the translocation of bacterial products from the local microbiome to the circulation, inducing inflammation and increasing clinical activity in rheumatoid arthritis (RA). This study evaluates whether intestinal fatty acid binding protein 2 (IFABP2) serum levels are prognostic biomarkers of non-response to conventional synthetic disease-modifying antirheumatic drug therapy (csDMARDs) in RA. The therapeutic schemes administered to 60 women with RA for at least 18months were assessed retrospectively, and the treatment response was classified according to the change in DAS28-ESR over time. Serum levels of IFABP2 and TNF-α were determined by ELISA. Receiver operating characteristics (ROC) curve analysis and logistic regression models were used to assess the predictive value and the association of IFABP2 with the non-responder phenotype in RA patients. Eleven women had a responder phenotype, 23 had a primary non-responder phenotype, and 26 had a secondary non-responder phenotype. Secondary non-responders showed higher DAS28-ESR (P=0.009) and higher IFABP2 serum levels compared to the responder group (P=0.023) and the primary non-responder group (P=0.018). IFABP2 serum levels were positively correlated with chloroquine dose (r=0.581, P=0.007) and negatively correlated with total cholesterol (r=-0.456, P=0.019) in secondary non-responders. The area under the curve (AUC) value of IFABP2 for predicting secondary non-response was 0.736, and IFABP2 serum levels>9.311ng/mL were associated with secondary non-response to csDMARDs (OR=6.00, P=0.003). IFABP2 serum levels are potentially a new biomarker predictive of secondary non-response to csDMARDs in RA, although our findings should be validated externally and in a larger cohort.

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.

Pyroptotic MAITs link microbial translocation with severity of alcohol-associated liver disease.

Mucosal-associated invariant T cells (MAITs) are markedly reduced in patients with alcohol-associated liver disease (ALD); however, the potential mechanism underlying MAITs' loss remains elusive. Hence, we aimed to explore what induced MAITs' loss and its clinical significance. The characteristics of pyroptotic MAITs were evaluated in a cohort of patients with ALD, including 41 patients with alcohol-associated liver cirrhosis (ALC) and 21 patients with ALC complicated with severe alcoholic hepatitis (ALC + SAH). In patients with ALD, blood MAITs were significantly decreased, hyperactivated, and displayed enhanced cell death through pyroptosis. The frequencies of pyroptotic MAITs increased with disease severity in patients with ALC and patients with ALC + SAH. These frequencies were negatively associated with the frequencies of MAITs and positively correlated with the levels of MAITs' activation, plasma levels of intestinal fatty acid-binding protein (a marker of intestinal enterocyte damage), soluble CD14, lipopolysaccharide-binding protein, and peptidoglycan recognition proteins (surrogate markers of microbial translocation). Pyroptotic MAITs were also found in the liver of patients with ALD. Interestingly, MAITs underwent further activation and pyroptosis in vitro under stimulation by Escherichia coli or direct bilirubin. Notably, blocking IL-18 signaling reduced the activation and frequencies of pyroptotic MAITs. The loss of MAITs in patients with ALD is, at least in part, due to cell death from pyroptosis and is associated with the severity of ALD. Such increased pyroptosis may be affected by dysregulated inflammatory responses to intestinal microbial translocation or direct bilirubin.

Increased Microbial Translocation is a Prognostic Biomarker of Different Immune Responses to ART in People Living with HIV.

Microbial translocation (MT) is a characteristic of human immunodeficiency virus (HIV) infection. Whether MT is also a biomarker of different immune responses to antiretroviral therapy (ART) received by people living with HIV (PLWH) is not known. We examined the presence of MT in a cohort of 33 HIV-infected immunological responders (IRs) and 28 immunological non-responders (INRs) (≥500 and <200 cluster of differentiation (CD)4+ T-cell counts/µL after 2 years of HIV-1 suppression, respectively) with no comorbidities. Plasma samples were used to measure the circulating levels of MT markers. All enrolled study participants had received 2 years of viral-suppression therapy. Levels of lipopolysaccharide (P = 0.0185), LPS-binding protein (P < 0.0001), soluble-CD14 (P < 0.0001), and endogenous endotoxin-core antibody (P < 0.0001) at baseline were significantly higher in INRs than in IRs and were associated with an increased risk of an immunological non-response, whereas the level of intestinal fatty acid-binding protein did not show this association. Analysis of receiver operating characteristic (ROC) curves demonstrated the utility of these individual microbial markers in discriminating INRs after ART in people living with HIV with high sensitivity, specificity, and area under the ROC curve. INRs in HIV infection are characterized by increased MT at baseline. These markers could be used as a rapid prognostic tool for predicting immune responses in people infected with the HIV.

Association of a high-fat diet with I-FABP as a biomarker of intestinal barrier dysfunction driven by metabolic changes in Wistar rats

BackgroundThe epithelial lining of the gut expresses intestinal fatty-acid binding proteins (I-FABPs), which increase in circulation and in plasma concentration during intestinal damage. From the perspective of obesity, the consumption of a diet rich in fat causes a disruption in the integrity of the gut barrier and an increase in its permeability.HypothesisThere is an association between the expression of I-FABP in the gut and various metabolic changes induced by a high-fat (HF) diet.MethodsWistar albino rats (n = 90) were divided into three groups (n = 30 per group), viz. One control and two HF diet groups (15 and 30%, respectively) were maintained for 6 weeks. Blood samples were thus collected to evaluate the lipid profile, blood glucose level and other biochemical tests. Tissue sampling was conducted to perform fat staining and immunohistochemistry.ResultsHF diet-fed rats developed adiposity, insulin resistance, leptin resistance, dyslipidemia, and increased expression of I-FABP in the small intestine compared to the control group. Increased I-FABP expression in the ileal region of the intestine is correlated significantly with higher fat contents in the diet, indicating that higher I-FABP expression occurs due to increased demand of enterocytes to transport lipids, leading to metabolic alterations.ConclusionIn summary, there is an association between the expression of I-FABP and HF diet-induced metabolic alterations, indicating that I-FABP can be used as a biomarker for intestinal barrier dysfunction.

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.

Intestinal Permeability in Patients Early after Kidney Transplantation Treated with Two Different Formulations of Once-Daily Tacrolimus.

Adequate tacrolimus blood exposure is crucial in the early post-renal transplant period and a gut epithelial barrier integrity may play a role. We prospectively investigated several markers of intestinal permeability in recent kidney transplant recipients (KTRs) treated with different tacrolimus extended-release formulations. Within each of the 49 KTR pairs that received grafts from the same donor, an early randomized conversion was performed from twice-daily (Prograf) to once-daily tacrolimus formulation: Advagraf or Envarsus. Plasma zonulin, calprotectin, circulating lipopolysaccharide (LPS), LPS-binding protein (LBP), intestinal fatty acid binding protein (FABP-2), and CD-14 levels were measured. There was no difference in the recipient age, dialysis vintage, BMI, and residual diuresis between Advagraf and Envarsus groups. FABP-2 and LPS levels were significantly associated with tacrolimus trough level, 3-h level, and area under the curve (AUC) in the Envarsus but not in the Advagraf group. AUC was independently increased by LPS and decreased by age, FABP-2 concentration, and the use of Envarsus formulation as compared with Advagraf. Functional changes of gastrointestinal tract in patients treated with Envarsus may influence intestinal tacrolimus absorption to a greater extent than in Advagraf-treated KTRs and may lead to inadequate variability of tacrolimus exposure early after kidney transplantation.

Efficacy of short-chain polypeptide-based EEN formulas in alleviating intestinal injury in children with Crohn's disease: a single-center study in China.

Short-chain polypeptides are composed of three to nine amino acids, which can be absorbed by the intestinal tract without digestive enzymes and ATP energy. Crohn's disease (CD) is a chronic non-specific disease derived from inflammation and damage of the gastrointestinal tract. In this study, we aim to investigate the effect of short-chain polypeptide-based exclusive enteral nutrition (EEN) formulas on intestinal injury in Chinese children with active CD. From January 2013 to January 2019, a total of 84 consecutive children with a diagnosis of Crohn's disease (CD) in the Department of Pediatric Gastroenterology, Children's Hospital of Nanjing Medical University, were divided into mild and moderate-to-severe active CD groups. Each group was further divided into two subgroups: drug group and short-chain polypeptide plus drug group. Tests were carried out on the levels of intestinal fatty acid binding protein (I-FABP) in the blood, fecal calprotectin (FC), and occludin protein in the intestinal mucosa 1 day before treatment and 8 weeks after treatment. Endoscopic and histopathological observations were detected to compare the changes in intestinal injury in children with active CD. After 8 weeks of treatment, the SES-CD scores and Chiu scores of the ileocecal area and terminal ileum of children with mild active CD and the ileocecal area of children with moderate-to-severe active CD in short-chain polypeptide plus drug group were significantly lower than those in the drug group. The OD value of occludin in the terminal ileum and ileocecal area of children with mild active CD and the ileocecal area of children with moderate-to-severe active CD after short-chain polypeptide-based EEN formulas and drug treatment was significantly higher than those in the drug group (p < 0.05). Meanwhile, the levels of FC and I-FABP were significantly decreased (p < 0.05). The results showed that short-chain polypeptide-based EEN formulas effectively alleviate intestinal injury in children with active CD.

Predictive value of serum markers in the operation evaluation of neonatal necrotizing enterocolitis.

Neonatal necrotizing enterocolitis (NEC) is a common gastrointestinal emergency in newborns. Currently, the pathogenesis of the disease remains unknown. This study aims to determine the application value of serum markers in the selection of operation opportunities for NEC. This study consisted of a retrospective analysis of the clinical data of 150 participants with NEC admitted to Maternal and Child Health Hospital of Hubei Province from March 2017 to March 2022. Participants were assigned to an operation group (n=58) and a nonoperation group (n=92) according to the presence or absence of surgical treatment. Serum sample data for serum C-reactive protein (CRP) and interleukin 6 (IL-6), serum amyloid A (SAA), procalcitonin (PCT), and intestinal fatty acid-binding protein (I-FABP) concentrations were estimated. To compare the differences in overall data and serum markers between the 2 groups, independent factors related to surgical treatment in pediatric patients with NEC were analyzed using logistic regression. The utility of serum markers in selecting surgical options in pediatric patients with NEC was analyzed by constructing a receiver operating characteristic (ROC) curve. CRP, I-FABP, IL-6, PCT, and SAA levels were higher in the operation group than in the nonoperation group (P<0.05). Multivariate logistic regression analysis confirmed that CRP, I-FABP, IL-6, PCT, and SAA were independent related factors of NEC surgical remedy (P<0.05). Meanwhile, ROC curve analysis yielded a serum CRP, PCT, IL-6, I-FABP, and SAA area under curve (AUC) of NEC operation timing of 0.805, 0.844, 0.635, 0.872, and 0.864, respectively; a sensitivity of 75.90%, 86.20%, 60.30%, 82.80%, and 84.50%, respectively; and a specificity of 80.40%, 79.30%, 68.35%, 80.40%, and 80.55%, respectively. The serum markers CRP, PCT, IL-6, I-FABP, and SAA have certain guiding values in the choice of operation opportunity for pediatric patients with NEC.

Lack of IgA and IgA+ switched memory B cells are associated with bacterial translocation in CVID

BackgroundGut bacterial translocation (BT) is linked to immune activation and inflammatory manifestations in CVID, accompanied by evidence of intestinal barrier defect. Here, we investigated the demographic, immunologic and biochemical parameters associated with BT and gut barrier dysfunction in CVID. MethodsWe measured serum biomarkers of BT (bacterial 16S rDNA [bDNA], by qt-PCR) and intestinal barrier defects (intestinal fatty-acid binding protein [I-FABP], by ELISA) in 88 CVID and 17 healthy control (HC) subjects. B cell phenotypes (% class-switched memory B cells [SMB, CD19 +CD27+IgM-IgD-/CD19+] and % IgA+ SMB [CD19+CD27+IgA+/CD19+]) were enumerated by flow cytometry. Results88 CVID subjects aged 21–62 years were recruited (baseline median IgG 202 [IQR 105–357], IgA 7 [< 5–15], IgM 11 [5–28] mg/dL, and SMB 1% [0.15–2.36%]). Serum bDNA and I-FABP were significantly elevated in CVID vs. HC (P < 0.0001, P < 0.001, respectively). Amongst CVID subjects, serum bDNA correlated with I-FABP levels (Spearman r = 0.27, P = 0.029). Serum bDNA and I-FABP levels were not age-dependent in this adult cohort. There were no sex differences in bDNA levels, though higher I-FABP was observed in males (p = 0.02). Serum bDNA and I-FABP were significantly elevated regardless of overt clinical enteropathy, though those with enteropathy had higher median levels vs. those without.Regarding immunologic and biochemical parameters, high serum bDNA was inversely correlated with 1) %IgA+ SMB (Spearman r = –0.52, P = 0.019, n = 23), and 2) serum IgA (Spearman r = –0.34, P = 0.002). Additionally, bDNA was significantly higher in those with elevated LFTs (P = 0.03). A negative trend between bDNA and total SMB was also observed. Gut barrier defect, as probed by I-FABP, was significantly higher in CVID patients with 1) undetectable IgA (p = 0.03), 2) abnormal liver function tests (p = 0.03), and negatively correlated with 3) CD4+ T cell counts (R = –0.34, p = 0.015). Serum bDNA and I-FABP were not associated with baseline IgG, IgM, or other B/T subsets examined. ConclusionLack of IgA and IgA+SMB are main immunologic parameters associated with BT in CVID, while abnormal LFTs may be an indirect indicator for BT and gut barrier defects. Our data suggest a role of IgA+ B cells/IgA as biological determinants of BT, and a link between BT and liver pathologies in CVID.

Effect of HCV treatment with DAAs on serum intestinal fatty acid binding protein (I-FABP) as a marker of intestinal permeability in HCV/HIV co-infected patients

BackgroundHCV and HIV co-infected patients develop cirrhosis more rapidly than HCV mono-infection. Intestinal injury and microbial translocation are postulated mechanisms for the rapid progression of cirrhosis.AimStudy the effect of HCV treatment with DAAs on serum intestinal fatty acid binding protein (I-FABP) as a marker of intestinal injury in HCV/HIV co-infected patients and its relation to hepatic fibrosis. Comparing the level of I-FABP in HCV mono-infection and HCV/HIV co-infection was a secondary aim.MethodsI-FABP levels were measured in 50 non-cirrhotic HCV/HIV co-infected patients pre- and post-HCV treatment (SVR 12) (25 patients were HIV treatment naive, and 25 patients were on HAART) and in 25 chronic HCV patients as a control group. Hepatic fibrosis was assessed by FIB4 score, APRI score, and transient elastography.ResultsHCV/HIV co-infected patients had significantly higher levels of I-FABP compared to the HCV-mono-infected patients (P = 0.001). After HCV treatment in HCV/HIV co-infected patients, I-FABP level was significantly elevated (P < 0.001) and was positively correlated with baseline FIB4 values and serum ALT levels (r = 0.283, P-value = 0.047) and (r = 0.340, P-value = 0.016), respectively.ConclusionHCV/HIV co-infection is associated with significantly higher intestinal injury and subsequent hepatic fibrosis than HCV mono-infection. HIV infection is associated with intestinal epithelial injury and microbial translocation and may play a role in the persistence of systemic inflammation after HCV eradication.

Circulating markers of intestinal barrier injury and inflammation following exertion in hypobaric hypoxia

ABSTRACT Hypoxia induced intestinal barrier injury, microbial translocation, and local/systemic inflammation may contribute to high-altitude associated gastrointestinal complications or symptoms of acute mountain sickness (AMS). Therefore, we tested the hypothesis that six-hours of hypobaric hypoxia increases circulating markers of intestinal barrier injury and inflammation. A secondary aim was to determine if the changes in these markers were different between those with and without AMS. Thirteen participants were exposed to six hours of hypobaric hypoxia, simulating an altitude of 4572 m. Participants completed two 30-minute bouts of exercise during the early hours of hypoxic exposure to mimic typical activity required by those at high altitude. Pre- and post-exposure blood samples were assessed for circulating markers of intestinal barrier injury and inflammation. Data below are presented as mean ± standard deviation or median [interquartile range]. Intestinal fatty acid binding protein (Δ251 [103-410] pg•mL−1; p = 0.002, d = 0.32), lipopolysaccharide binding protein (Δ2 ± 2.4 μg•mL−1; p = 0.011; d = 0.48), tumor necrosis factor-α (Δ10.2 [3-42.2] pg•mL−1; p = 0.005; d = 0.25), interleukin-1β (Δ1.5 [0-6.7] pg•mL−1 p = 0.042; d = 0.18), and interleukin-1 receptor agonist (Δ3.4 [0.4-5.2] pg•mL−1 p = 0.002; d = 0.23) increased from pre- to post-hypoxia. Six of the 13 participants developed AMS; however, the pre- to post-hypoxia changes for each marker were not different between those with and without AMS (p > 0.05 for all indices). These data provide evidence that high altitude exposures can lead to intestinal barrier injury, which may be an important consideration for mountaineers, military personnel, wildland firefighters, and athletes who travel to high altitudes to perform physical work or exercise.

Citrulline, Intestinal Fatty Acid-Binding Protein and the Acute Gastrointestinal Injury Score as Predictors of Gastrointestinal Failure in Patients with Sepsis and Septic Shock.

Gastrointestinal (GI) failure can be both a cause of sepsis and a consequence of the systemic pro-inflammatory response in sepsis. Changes in biomarkers of enterocyte damage, citrulline and I-FABP (intestinal fatty acid binding protein), may indicate altered intestinal permeability and damage. The study group consisted of patients with sepsis (N = 28) and septic shock (N = 30); the control group included patients without infection (N = 10). Blood samples were collected for citrulline and I-FABP and a 4-point AGI score (acute GI injury score) was calculated to monitor GI function on days 1, 3, 5, 7, and 10. Citrulline concentrations in the study group were lower than in the control. Lower values were also noted in septic patients with shock when compared to the non-shock group throughout the study period. I-FABP was higher in the septic shock group than in the sepsis group only on days 1 and 3. Citrulline was lower in patients with GI failure (AGI III) when compared to AGI I/II, reaching significance on days 7 (p = 0.034) and 10 (p = 0.015); moreover, a higher AGI score was associated with an increased 28 day mortality (p = 0.038). The results indicate that citrulline measurements, along with the AGI assessment, have clinical potential in monitoring GI function and integrity in sepsis.

Effect of dietary bile acids supplementation on growth performance, feed utilization, intestinal digestive enzyme activity and fatty acid transporters gene expression in juvenile leopard coral grouper (Plectropomus leopardus)

This study aimed to evaluate the effects of dietary bile acids on growth performance, feed utilization, body composition, digestive enzyme activity, and related gene expression in juvenile leopard coral grouper (Plectropomus leopardus). Five diets with varying levels of dietary bile acids (0, 0.15, 0.3, 0.45 and 0.6%) were formulated and each diet was fed to triplicate groups of 15 fish (13.14 ± 0.14 g) for ten weeks. Results showed that the significant enhancement in weight gain (WG) and specific growth rate (SGR) was observed in fish fed 0.3% bile acids (P &amp;lt; 0.05). Additionally, feed conversion ratio (FCR) was significantly improved with bile acids inclusion (P &amp;lt; 0.05). Higher feed intake was also recorded in bile acids inclusion groups, and significantly up-regulated gene expression of hypothalamus neuropeptide Y (NPY) was found in 0.3% group compared with the control group (P &amp;lt; 0.05). Dietary bile acids (0.3%) significantly decreased lipid deposition in the whole-body (P &amp;lt; 0.05), and lower hepatosomatic index (HSI) and viscerosomatic index (VSI) were also found in this group. Moreover, intestinal trypsin and lipase activities were significantly increased in 0.3% group (P &amp;lt; 0.05) to promote feed digestion. In addition, the relative expression levels of intestinal fatty acid binding protein 2 (FABP2) significantly up-regulated with inclusion of dietary bile acids, suggesting an enhancement of fatty acid transport (P &amp;lt; 0.05). In contrast, cholesterol transport related genes NPC1 like intracellular cholesterol transporter 1 (NPC1L1) and CD36 were notably down-regulated as bile acids inclusion (P &amp;lt; 0.05). This study provides valuable information for the formulation of diets for juvenile coral trout and indicates that dietary bile acids could potentially be used to improve growth performance and feed utilization.

Relevance of biomarkers indicating gut damage and microbial translocation in people living with HIV.

The intestinal barrier has the daunting task of allowing nutrient absorption while limiting the entry of microbial products into the systemic circulation. HIV infection disrupts the intestinal barrier and increases intestinal permeability, leading to microbial product translocation. Convergent evidence has shown that gut damage and an enhanced level of microbial translocation contribute to the enhanced immune activation, the risk of non-AIDS comorbidity, and mortality in people living with HIV (PLWH). Gut biopsy procedures are invasive, and are not appropriate or feasible in large populations, even though they are the gold standard for intestinal barrier investigation. Thus, validated biomarkers that measure the degree of intestinal barrier damage and microbial translocation are needed in PLWH. Hematological biomarkers represent an objective indication of specific medical conditions and/or their severity, and should be able to be measured accurately and reproducibly via easily available and standardized blood tests. Several plasma biomarkers of intestinal damage, i.e., intestinal fatty acid-binding protein (I-FABP), zonulin, and regenerating islet-derived protein-3α (REG3α), and biomarkers of microbial translocation, such as lipopolysaccharide (LPS) and (1,3)-β-D-Glucan (BDG) have been used as markers of risk for developing non-AIDS comorbidities in cross sectional analyses and clinical trials, including those aiming at repair of gut damage. In this review, we critically discuss the value of different biomarkers for the estimation of gut permeability levels, paving the way towards developing validated diagnostic and therapeutic strategies to repair gut epithelial damage and to improve overall disease outcomes in PLWH.

Discovery of the First-in-Class Intestinal Restricted FXR and FABP1 Dual Modulator ZLY28 for the Treatment of Nonalcoholic Fatty Liver Disease.

The prevalence of nonalcoholic steatohepatitis (NASH) is increasing rapidly worldwide, and NASH has become a serious problem for human health. Recently, the selective activation of the intestinal farnesoid X receptor (FXR) was considered as a more promising strategy for the treatment of NASH with lesser side effects due to reduced systemic exposure. Moreover, the inhibition of intestinal fatty acid binding protein 1 (FABP1) alleviated obesity and NASH by reducing dietary fatty acid uptake. In this study, the first-in-class intestinal restricted FXR and FABP1 dual-target modulator ZLY28 was discovered by comprehensive multiparameter optimization studies. The reduced systemic exposure of ZLY28 might provide better safety by decreasing the on- and off-target side effects in vivo. In NASH mice, ZLY28 exerted robust anti-NASH effects by inhibiting FABP1 and activating the FXR-FGF15 signaling pathway in the ileum. With the above attractive efficacy and preliminary safety profiles, ZLY28 is worthy of further evaluation as a novel anti-NASH agent.

Obesity Exacerbates Acute Gastrointestinal Injury and Intestinal Barrier Dysfunction in Early-Stage Acute Pancreatitis.

The impact of obesity on the severity of acute pancreatitis and subsequent acute gastrointestinal injury remains an important consideration. This study aimed to determine the clinical relationship between obesity and acute gastrointestinal injury in earlystage acute pancreatitis. This was a prospective study that enrolled 194 acute pancreatitis patients. The median body mass index was 26.5 (7.0) kg/m2. Considering etiology of acute pancreatitis, 90 patients had gallstones, 48 had hypertriglyceridemia, 36 were alcohol users, and 20 were others. A total of 116 patients had mild acute pancreatitis and the rest had severe acute pancreatitis. The median of bedside index of severity in acute pancreatitis score was 1 (2) and the serum concentration of C-reactive protein was 80.5 (60.0) mg/L. Acute pancreatitis was accompanied by multiple organ dysfunction in 60 cases and by pancreatic necrosis in 34. A total of 52 patients were admitted to intensive care unit. The values of body mass index were higher in patients with severe acute pancreatitis than those with mild acute pancreatitis. A similar trend emerged in patients with hyperlipidemic acute pancreatitis compared to other causes. Body mass index had a positive relationship with bedside index of severity in acute pancreatitis scores. Noticeably, body mass index was statistically raised from gastrointestinal injury grade 1 to grade 4. The values of body mass index also showed relevance with intestinal barrier function evaluated by d-lactate, diamine oxidase, and intestinal fatty acid binding proteins. Furthermore, body mass indexes were statistically higher in patients having adverse outcomes of acute pancreatitis. This prospective study showed that obesity might contribute to increasing the severity of acute pancreatitis and aggravate subsequent intestinal injury in early-stage acute pancreatitis.