Plasma Intestinal Fatty Acid-binding Protein Research Articles

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.

Bovine Colostrum in Increased Intestinal Permeability in Healthy Athletes and Patients: A Meta-Analysis of Randomized Clinical Trials.

Increasing intestinal permeability causes chronic inflammation, which is one of the etiological factors of many diseases that presently constitute global challenges. Considering the importance of developing therapies to eliminate the increased intestinal permeability, in this systematic review and meta-analysis, we analyze the impact of bovine colostrum (BC) on the gut barrier and its permeability. Online databases, including PubMed, ISI Web of Science, and Scopus, were searched to find pertinent articles up to March 2022. Weighted mean difference (WMD) and 95% confidence intervals (CI) were considered as effect sizes. The random-effects model was used to pool the study results. A total of ten articles were included in the meta-analysis. The pooled effect revealed a significant reduction in the 5-h urinary lactulose/rhamnose ratio after BC consumption [mean difference (MD): -0.24; 95% CI -0.43 to -0.04; I2 = 99%] and urinary lactulose/mannitol ratio (MD: -0.01; 95% CI -0.02 to -0.001; I2 = 29.8%). No differences were observed in the plasma intestinal fatty acid-binding protein (I-FABP) between BC and control groups (MD: 2.30; 95% CI -293.9 to 298.5; I2 = 92%). BC supplementation significantly reduced intestinal permeability; however, to confirm the results, more randomized clinical trials considering different quality, dose, and duration are needed.

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.

Intestinal injury in paracetamol overdose (ATOM-8).

Paracetamol, a widely used medication, is known for its delayed hepatotoxicity in cases of overdose. However, the potential for intestinal toxicity resulting from very high paracetamol concentrations during absorption is not well explored. This study aims to investigate the presence of intestinal toxicity and its correlation with observations in early and late paracetamol toxicity. Serial samples of 30 patients with acute paracetamol overdose (>10g or 200mg/kg) were prospectively tested. Markers of enterocyte damage, including plasma intestinal fatty acid binding protein (IFABP) and selected gut-related microRNAs (miR-21, miR-122, miR-194, and miR-215), were analyzed. Sub-analysis was performed on patients presenting with hyperlactatemia defined as a lactate greater than 2mmol/L within 12h post ingestion. In paracetamol overdose patients, median plasma IFABP was significantly elevated compared with healthy controls (720μg/L [interquartile range, IQR, 533-1644] vs 270μg/L [IQR 153-558], P<0.001). Four patients had early hyperlactatemia and had significantly higher median plasma IFABP compared with those without early hyperlactatemia (3028μg/L [IQR 1399-3556] vs 574μg/L [IQR 526-943], P=0.007). Furthermore, two microRNAs (miR-122 and miR-215) were downregulated in early hyperlactatemia (P=0.019 and P=0.006, respectively). Plasma IFABP concentrations correlated with paracetamol concentration (Spearman's r=0.55) and lactate (r=0.60). Paracetamol overdose causes concentration-related intestinal toxicity, and this is a possible explanation for the early hyperlactatemia syndrome. Intestinal toxicity has potential impacts on pharmacokinetics of other agents ingested and on the evolution of hepatotoxicity. Further studies are required to explore the mechanisms and prognostic implications of intestinal toxicity.

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.

Associations of HIV and iron status with gut microbiota composition, gut inflammation and gut integrity in South African school-age children: a two-way factorial case-control study.

Human immunodeficiency virus (HIV) and iron deficiency (ID) affect many African children. Both HIV and iron status interact with gut microbiota composition and related biomarkers. The study's aim was to determine the associations of HIV and iron status with gut microbiota composition, gut inflammation and gut integrity in South African school-age children. In this two-way factorial case-control study, 8- to 13-year-old children were enrolled into four groups based on their HIV and iron status: (1) With HIV (HIV+) and ID (n = 43), (2) HIV+ and iron-sufficient nonanaemic (n = 41), (3) without HIV (HIV-) and ID (n = 44) and (4) HIV- and iron-sufficient nonanaemic (n = 38). HIV+ children were virally suppressed (<50 HIV RNA copies/ml) on antiretroviral therapy (ART). Microbial composition of faecal samples (16S rRNA sequencing) and markers of gut inflammation (faecal calprotectin) and gut integrity (plasma intestinal fatty acid-binding protein [I-FABP]) were assessed. Faecal calprotectin was higher in ID versus iron-sufficient nonanaemic children (p = 0.007). I-FABP did not significantly differ by HIV or iron status. ART-treated HIV (redundancy analysis [RDA] R2 = 0.009, p = 0.029) and age (RDA R2 = 0.013 p = 0.004) explained the variance in the gut microbiota across the four groups. Probabilistic models showed that the relative abundance of the butyrate-producing genera Anaerostipes and Anaerotruncus was lower in ID versus iron-sufficient children. Fusicatenibacter was lower in HIV+ and in ID children versus their respective counterparts. The prevalence of the inflammation-associated genus Megamonas was 42% higher in children with both HIV and ID versus HIV- and iron-sufficient nonanaemic counterparts. In our sample of 8- to 13-year-old virally suppressed HIV+ and HIV- children with or without ID, ID was associated with increased gut inflammation and changes in the relative abundance of specific microbiota. Moreover, in HIV+ children, ID had a cumulative effect that further shifted the gut microbiota to an unfavourable composition.

Intestinal injury in cardiac arrest is associated with multiple organ dysfunction: A prospective cohort study

BackgroundThe impact of intestinal injury in cardiac arrest is not established. The first aim of this study was to assess associations between clinical characteristics in out-of-hospital cardiac arrest (OHCA) and a biomarker for intestinal injury, Intestinal Fatty Acid Binding Protein (IFABP). The second aim was to assess associations between IFABP and multiple organ dysfunction and 30-day mortality. MethodsWe measured plasma IFABP in 50 patients at admission to intensive care unit (ICU) after OHCA. Demographic and clinical variables were analysed by stratifying patients on median IFABP, and by linear regression. We compared Sequential Organ Failure Assessment (SOFA) score, haemodynamic variables, and clinical-chemistry tests at day two between the “high” and “low” IFABP groups. Logistic regression was applied to assess factors associated with 30-day mortality. ResultsSeveral markers of whole body ischaemia correlated with intestinal injury. Duration of arrest and lactate serum concentrations contributed to elevated IFABP in a multivariable model (p < 0.01 and p = 0.04, respectively). At day two, all seven patients who had died were in the “high” IFABP group, and all six patients who had been transferred to ward were in the “low” group. Of patients still treated in the ICU, the “high” group had higher total, renal and respiratory SOFA score (p < 0.01) and included all patients receiving inotropic drugs. IFABP predicted mortality (OR 16.9 per standard deviation increase, p = 0.04). ConclusionCardiac arrest duration and lactate serum concentrations were risk factors for intestinal injury. High levels of IFABP at admission were associated with multiple organ dysfunction and mortality.Trial registration: ClinicalTrials.gov: NCT02648061.

Reliability of pathophysiological markers reflective of exercise-induced gastrointestinal syndrome (EIGS) in response to 2-h high-intensity interval exercise: A comprehensive methodological efficacy exploration.

The study aimed to determine the test-retest reliability of exercise-induced gastrointestinal syndrome (EIGS) biomarkers, and assess the association of pre-exercise short chain fatty acid (SCFA) concentration with these biomarkers in response to prolonged strenuous exercise. Thirty-four participants completed 2h of high-intensity interval training (HIIT) on two separate occasions with at least 5-days washout. Blood samples were collected pre- and post-exercise, and analysed for biomarkers associated with EIGS [i.e., cortisol, intestinal fatty-acid binding protein (I-FABP), sCD14, lipopolysaccharide binding protein (LBP), leukocyte counts, in-vitro neutrophil function, and systemic inflammatory cytokine profile]. Fecal samples were collected pre-exercise on both occasions. In plasma and fecal samples, bacterial DNA concentration was determined by fluorometer quantification, microbial taxonomy by 16S rRNA amplicon sequencing, and SCFA concentration by gas-chromatography. In response to exercise, 2h of HIIT modestly perturbed biomarkers indicative of EIGS, including inducing bacteremia (i.e., quantity and diversity). Reliability analysis using comparative tests, Cohen's d, two-tailed correlation, and intraclass correlation coefficient (ICC) of resting biomarkers presented good-to-excellent for IL-1ra (r = 0.710, ICC = 0.92), IL-10 (r = 0.665, ICC = 0.73), cortisol (r = 0.870, ICC = 0.87), and LBP (r = 0.813, ICC = 0.76); moderate for total (r = 0.839, ICC = 0.44) and per cell (r = 0.749, ICC = 0.54) bacterially-stimulated elastase release, IL-1β (r = 0.625, ICC = 0.64), TNF-α (r = 0.523, ICC = 0.56), I-FABP (r = 0.411, ICC = 0.21), and sCD14 (r = 0.409, ICC = 0.38), plus fecal bacterial α-diversity; and poor for leukocyte (r = 0.327, ICC = 0.33) and neutrophil (r = 0.352, ICC = 0.32) counts. In addition, a medium negative correlation was observed between plasma butyrate and I-FABP (r = -0.390). The current data suggest a suite of biomarkers should be used to determine the incidence and severity of EIGS. Moreover, determination of plasma and/or fecal SCFA may provide some insight into the mechanistic aspects of EIGS instigation and magnitude in response to exercise.

The Impact of Heat Acclimation on Gastrointestinal Function following Endurance Exercise in a Hot Environment

To determine the effects of heat acclimation on gastrointestinal (GI) damage and the gastric emptying (GE) rate following endurance exercise in a hot environment. Fifteen healthy men were divided into two groups: endurance training in hot (HOT, 35 °C, n = 8) or cool (COOL, 18 °C, n = 7) environment. All subjects completed 10 days of endurance training (eight sessions of 60 min continuous exercise at 50% of the maximal oxygen uptake (V·O2max). Subjects completed a heat stress exercise tests (HST, 60 min exercise at 60% V·O2max) to evaluate the plasma intestinal fatty acid-binding protein (I-FABP) level and the GE rate following endurance exercise in a hot environment (35 °C) before (pre-HST) and after (post-HST) the training period. We assessed the GE rate using the 13C-sodium acetate breath test. The core temperature during post-HST exercise decreased significantly in the HOT group compared to the pre-HST (p = 0.004) but not in the COOL group. Both the HOT and COOL groups showed exercise-induced plasma I-FABP elevations in the pre-HST (p = 0.002). Both groups had significantly attenuated exercise-induced I-FABP elevation in the post-HST. However, the reduction of exercise-induced I-FABP elevation was not different significantly between both groups. GE rate following HST did not change between pre- and post-HST in both groups, with no significant difference between two groups in the post-HST. Ten days of endurance training in a hot environment improved thermoregulation, whereas exercise-induced GI damage and delay of GE rate were not further attenuated compared with training in a cool environment.

A multicentric prospective observational study of diagnosis and prognosis features in ICU mesenteric ischemia: the DIAGOMI study

BackgroundNon-occlusive mesenteric ischemia (NOMI) is a challenging diagnosis and is associated with extremely high mortality in critically ill patients, particularly due to delayed diagnosis and when complicated by intestinal necrosis. Plasma citrulline and intestinal-fatty acid binding protein (I-FABP) have been proposed as potential biomarkers, but have never been studied prospectively in this setting. We aimed to investigate diagnostic features, the accuracy of plasma citrulline and I-FABP to diagnose NOMI and intestinal necrosis as well as prognosis.MethodsWe conducted a prospective observational study in 3 tertiary ICU centers in consecutive patients with NOMI suspicion defined by at least two inclusion criteria among: new-onset or worsening circulatory failure, gastrointestinal dysfunction, biological signs and CT-scan signs of mesenteric ischemia. Diagnosis features and outcomes were compared according to NOMI, intestinal necrosis or ruled out diagnosis using stringent classification criteria.ResultsDiagnosis of NOMI was suspected in 61 patients and confirmed for 33 patients, with intestinal necrosis occurring in 27 patients. Clinical digestive signs, routine laboratory results and CT signs of mesenteric ischemia did not discriminate intestinal necrosis from ischemia without necrosis. Plasma I-FABP was significantly increased in presence of intestinal necrosis (AUC 0.83 [0.70–0.96]). A threshold of 3114 pg/mL showed a sensitivity of 70% [50–86], specificity of 85% [55–98], a negative predictive value of 58% [36–93] and a positive predictive value 90% [67–96] for intestinal necrosis diagnosis. When intestinal necrosis was present, surgical resection was significantly associated with ICU survival (38.5%), whereas no patient survived without necrosis resection (HR = 0.31 [0.12–0.75], p = 0.01).ConclusionIn critically ill patients with NOMI, intestinal necrosis was associated with extremely high mortality, and increased survival when necrosis resection was performed. Elevated plasma I-FABP was associated with the diagnosis of intestinal necrosis. Further studies are needed to investigate plasma I-FABP and citrulline performance in less severe forms of NOMI.

Choline, DHA, and Diarrheal Disease Associated with Growth Faltering in a Case-Control Study

ABSTRACTBackgroundChildren with recurrent infectious diarrhea are susceptible to growth faltering. DHA and choline may play a role in this relationship due to their involvement in lipid metabolism, gut immunity, and inflammatory pathways.ObjectivesThis study aimed to characterize the contributions made by DHA and choline status and enteric damage in young children in the association between diarrheal illness and child growth.MethodsA longitudinal case-control study was conducted among children aged 6–36 mo (N = 195) in Cap-Haitien, Haiti. Mother-child dyads were recruited from community health posts and outpatient clinics. Cases were defined as children experiencing acute diarrhea within the last 3 d and matched to healthy controls. Child anthropometry, dietary intake, and blood and stool samples were collected at baseline and follow-up. Plasma DHA, choline, and betaine were determined by LC-MS/MS methods (n = 49) and intestinal fatty acid–binding protein (I-FABP) by ELISA (n = 183). Multivariate regression models were applied with mediation analyses to examine associations and adjust for confounding factors.ResultsAt baseline, mean plasma DHA concentrations (1.03 µg/mL; 95% CI: 0.91, 1.15) were not significantly different between cases and controls, nor was there a difference in mean plasma choline concentrations (4.5 µg/mL; 95% CI: 3.8, 5.1). Mean plasma I-FABP concentrations were significantly higher at follow-up in cases (3.34; 95% CI: 3.28, 3.40) than controls (3.20; 95% CI: 3.13, 3.27; P = 0.002). In adjusted multilinear regression models, higher plasma DHA concentrations at follow-up were associated with a negative change in weight-age z score (P = 0.016), and follow-up I-FABP was inversely associated with height-age z score (P = 0.035). No interaction or mediation effects were found.ConclusionsI-FABP concentrations were significantly higher in cases as compared with controls at follow-up, suggesting ongoing enteric damage and increased risk for malnutrition. Plasma DHA and I-FABP may have a role in childhood growth outcomes.

I-FABP as a Potential Marker for Intestinal Barrier Loss in Porcine Polytrauma.

Polytrauma and concomitant hemorrhagic shock can lead to intestinal damage and subsequent multiple organ dysfunction syndrome. The intestinal fatty acid-binding protein (I-FABP) is expressed in the intestine and appears quickly in the circulation after intestinal epithelial cell damage. This porcine animal study investigates the I-FABP dynamics in plasma and urine after polytrauma. Furthermore, it evaluates to what extent I-FABP can also act as a marker of intestinal damage in a porcine polytrauma model. Eight pigs (Sus scrofa) were subjected to polytrauma which consisted of lung contusion, tibial fracture, liver laceration, and hemorrhagic shock followed by blood and fluid resuscitation and fracture fixation with an external fixator. Eight sham animals were identically instrumented but not injured. Afterwards, intensive care treatment including mechanical ventilation for 72 h followed. I-FABP levels in blood and urine were determined by ELISA. In addition, immunohistological staining for I-FABP, active caspase-3 and myeloperoxidase were performed after 72 h. Plasma and urine I-FABP levels were significantly increased shortly after trauma. I-FABP expression in intestinal tissue showed significantly lower expression in polytraumatized animals vs. sham. Caspase-3 and myeloperoxidase expression in the immunohistological examination were significantly higher in the jejunum and ileum of polytraumatized animals compared to sham animals. This study confirms a loss of intestinal barrier after polytrauma which is indicated by increased I-FABP levels in plasma and urine as well as decreased I-FABP levels in immunohistological staining of the intestine.

The association between gastrointestinal injury, complaints, and food intake in 60-km ultramarathon runners.

We aimed to assess the association between gastrointestinal (GI) injury, complaints, and food intake in 60-km ultramarathon runners. Thirty-three ultramarathon runners provided pre- and post-race blood samples for assessment of GI injury by intestinal fatty-acid binding protein (I-FABP), and inflammatory response by interleukin (IL)-6, IL-8, tumour necrosis factor alpha (TNF-α), and C-reactive protein (CRP). GI complaints and nutritional intake were reported by a post-race questionnaire. GI complaints were reported by 73% of the runners, of which 20% reported 1 or 2 severe complaints. IL-6, IL8, TNF-α, and CRP increased significantly from pre- to post-race (P < 0.001 for all biomarkers), while I-FABP did not (1375 [IQR: 1264-2073] to 1726 [IQR: 985-3287] pg/mL; P = 0.330). The 'GI complaints score', as the integral of the number and severity of GI complaints, did not correlate with ΔI-FABP (rs: -0.050, P = 0.790) or energy intake (rs: 0.211, P = 0.260). However, there was a significant negative correlation between energy intake and ΔI-FABP (rs: -0.388, P = 0.031). In conclusion, GI complaints were neither associated with food intake nor GI injury as assessed by plasma I-FABP response. Energy intake, however, was inversely related to the I-FABP response to exercise. This finding suggests that substantial energy intakes during exercise may prevent exercise-induced GI injury as assessed by the I-FABP response. Novelty: No association between gastrointestinal complaints and gastrointestinal injury (I-FABP response) or food intake was present. There was an inverse correlation between energy intake and plasma I-FABP response, suggesting that higher energy intakes may prevent gastrointestinal injury as assessed by the I-FABP response.

Acute L-glutamine supplementation does not improve gastrointestinal permeability, injury or microbial translocation in response to exhaustive high intensity exertional-heat stress

ABSTRACT Purpose: Exertional-heat stress adversely distrupts (GI) barrier integrity and, through subsequent microbial translocation (MT), can result in potentially fatal exertional-heat stroke. Acute glutamine (GLN) supplementation is a potential nutritional countermeasure, although the practical value of current supplementation regimens is questionable. Method: Ten males completed two high-intensity exertional-heat stress tests (EHST) involving running in the heat (40°C and 40% relative humidity) at lactate threshold to volitional exhaustion. Participants ingested GLN (0.3 g kg FFM−1) or a non-calorific placebo (PLA) one hour prior to the EHST. Venous blood was drawn pre-, post- and one-hour post-EHST. GI permeability was assessed using a serum dual-sugar absorption test (DSAT) and small intestinal epithelial injury using plasma Intestinal Fatty-Acid Binding Protein (I-FABP). MT was assessed using the Bacteroides/total 16S DNA ratio. Results: Volitional exhaustion occurred after 22:19 ± 2:22 (minutes: seconds) in both conditions, during which whole-body physiological responses and GI symptoms were not different (p > 0.05). GI permeability (serum DSAT) was greater following GLN (0.043 ± 0.020) than PLA (0.034 ± 0.019) (p = 0.02; d = 0.47), but small intestine epithelial injury (I-FABP) increased comparably (p = 0.22; = 0.16) following the EHST in both trials (GLN Δ = 1.25 ± 0.63 ng ml−1; PLA Δ = 0.92 ± 0.44 ng ml−1). GI MT (Bacteroides/total 16S DNA ratio) was unchanged in either condition following the EHST (p = 0.43). Conclusion: Acute low-dose (0.3 g kg−1 fat free mass) GLN supplementation ingested one hour before high-intesity exertional-heat stress worsened GI permeability, but did not influence either small intestinal epithilial injury or microbial translocation. Abbreviations: ANOVA: Analysis of variance; CV: Coefficient of Variation; DSAT: Dual Sugar Absorption Test; EDTA: Ethylenediaminetetraacetic acid; EHST: Exertional Heat Stress Test; ELISA: Enzyme Linked Immunosorbent Assay; FFM: Fat Free Mass; GI: Gastrointestinal; GFR: Glomerular Filtration Rate; GLN: Glutamine; HPLC: High Performance Liquid Chromatography; HR: Heart Rate; I-FABP: Intestinal Fatty-Acid Binding Protein; ISAK: International Society for the Advancement of Anthropometric Kinanthropometry; L/R: Lactulose-to-Rhamnose; LT: Lactate Threshold; MT: Microbial Translocation; mVAS: Modified Visual Analogue Scale; PBS: Phosphate-Buffered Saline; PLA: Placebo; qPCR: Quantitative Polymerase Chain Reaction; RH: Relative Humidity; RPE: Rate of Perceived Exertion; SD: Standard Deviation; SEM: Sensor Electronics Module; Tcore: Core Body Temperature; Tbody: Mean Body Temperature; Tskin: Mean Skin Temperature; TS: Thermal Sensation; V̇O2max: Maximal Oxygen Uptake. Highlights The pathophysiology of exertional-heat stroke is widely hypothesised to be at least in part attributable to a systemic inflammatory response caused by the leak of gastrointestinal microbes into the circulating blood. Acute high-dose (0.9 g kg FFM−1) L-glutamine supplementation is widely promoted as a practical strategy to protect gastrointestinal barrier integrity during exertional-heat stress. However, previously validated doses are often poorly tolerated and cannot be recommended for widespread implementation. This study examined the efficacy of low-dose (0.30 g kg FFM−1; ∼20 grams) acute L-glutamine supplementation on small intestinal injury, permeability, and microbial translocation in response a high-intensity exertional-heat stress test to exhaustion (20–30 min). This type of exercise accounts for the majority of exertional-heat stroke cases in the military. Despite being universally well-tolerated across all participants, acute low-dose L-glutamine supplementation worsened gastrointestinal permeability, without influencing either small intestinal injury or microbial translocation. These findings do not support the application of low-dose L-glutamine supplementation to help prevent exertional-heat stroke.

Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants.

BackgroundOral rotavirus vaccines (RVV) are poorly immunogenic in low-income countries. Environmental enteric dysfunction (EED) resulting from poor water, sanitation and hygiene (WASH) may contribute. We therefore tested associations between EED and RVV immunogenicity, and evaluated the effect of improved WASH on EED.MethodsWe measured nine biomarkers of EED among Zimbabwean infants born to mothers enrolled in a cluster-randomised 2 × 2 factorial trial of improved WASH and improved feeding between November 2012 and March 2015 (NCT01824940). We used multivariable regression to determine associations between EED biomarkers and RVV seroconversion, seropositivity and geometric mean titer. Log-binomial regression was used to evaluate the effect of improved WASH on EED.FindingsAmong 303 infants with EED biomarkers and immunogenicity data, plasma intestinal fatty-acid binding protein and stool myeloperoxidase were positively associated with RVV seroconversion; adjusted RR 1.63 (95%CI 1.04, 2.57) and 1.29 (95%CI 1.01, 1.65), respectively. There were no other associations between RVV immunogenicity and either individual biomarkers or EED domains (intestinal permeability, intestinal damage, intestinal inflammation and microbial translocation). EED biomarkers did not differ between randomised WASH and non-WASH groups.InterpretationWe found no evidence that EED was associated with poor RVV immunogenicity. Contrary to our hypothesis, there was weak evidence that EED was associated with increased seroconversion. EED biomarkers were not affected by a package of household-level WASH interventions.

Accuracy of citrulline, I-FABP and d-lactate in the diagnosis of acute mesenteric ischemia

Early diagnosis of acute mesenteric ischemia (AMI) remains a clinical challenge, and no biomarker has been consistently validated. We aimed to assess the accuracy of three promising circulating biomarkers for diagnosing AMI—citrulline, intestinal fatty acid-binding protein (I-FABP), and d-lactate. A cross-sectional diagnostic study enrolled AMI patients admitted to the intestinal stroke center and controls with acute abdominal pain of another origin. We included 129 patients—50 AMI and 79 controls. Plasma citrulline concentrations were significantly lower in AMI patients compared to the controls [15.3 μmol/L (12.0–26.0) vs. 23.3 μmol/L (18.3–29.8), p = 0.001]. However, the area under the receiver operating curves (AUROC) for the diagnosis of AMI by Citrulline was low: 0.68 (95% confidence interval = 0.58–0.78). No statistical difference was found in plasma I-FABP and plasma d-lactate concentrations between the AMI and control groups, with an AUROC of 0.44, and 0.40, respectively. In this large cross-sectional study, citrulline, I-FABP, and d-lactate failed to differentiate patients with AMI from patients with acute abdominal pain of another origin. Further research should focus on the discovery of new biomarkers.

The Intestinal Barrier Function and Intra-Abdominal Pressure Depend on Postoperative Analgesia Technique in Children with Appendicular Peritonitis.

Introduction Peritonitis is one of the risk factors for the development of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). The plasma citrulline and intestinal fatty acid-binding protein (I-FABP) are informative markers of intestinal barrier function. The aim of this study was to determine the correlation of the plasma citrulline and I-FABP with intra-abdominal pressure (IAP) and their relation to analgesia techniques in children suffering from appendicular peritonitis. Materials and Methods 74 children operated for appendicular peritonitis were randomized into three groups of postoperative analgesia: “Opioids” (n = 25), intravenous morphine of 10 mcg/kg/h; “Lidocaine” (n = 23), intravenous lidocaine with initial bolus of 1.5 mg/kg and then infusion of 1.5 mg/kg/h; and “EA” (n = 26), epidurally 0.25% bupivacaine with initial bolus of 1 mg/kg and then infusion of 0.4 mg/kg/year. Retrospectively patients in each group were divided into the following subgroups: “without IAH” (n = 33), “IAH” (n = 27), and “ACS” (n = 14). We detected citrulline and I-FABP in plasma on day 1 (D1) and day 3 (D3) of hospital stay. Results The patients without IAH on D1 presented significantly higher plasma citrulline (23.7 (16.0–31.3) nmol/ml) and lower I-FABP (76.9 (32.6–121.1) pg/ml) levels compared with patients in subgroup “IAH” (9.3 (7.3–11.3) nmol/ml and 226.0 (161.8–290.3) pg/ml, respectively) and subgroup “ACS” (6.9 (5.3–8.6) nmol/ml and 1011.7 (731.9–1291.5) pg/ml, respectively). The IAP had strong inverse correlation (rs = −0.74; p < 0.00001) with citrulline and positive strong correlation (rs = 0.73; p < 0.00001) with I-FABP. The citrulline in patients with IAH during three days postoperatively increased significantly in “Lidocaine” to 72% (p=0.01) and in “EA” to 138% (p=0.02), but it decreased to 13% (p=0.37) in “Opioids” group. In children with ACS, citrulline on D3 was significantly higher than that on D1 and increased in “Lidocaine” to 59% (p=0.05) and in “EA” to 134% (p=0.001), but in “Opioids” it decreased to 30% (p=0.48). The I-FABP in patients with IAH decreased to 12% in “Lidocaine” group (p=0.86) and to 75% in “EA” group (p=0.01), but it increased to 37% (p=0.57) in “Opioids” group. During observation period, I-FABP in patients with ACS decreased significantly in “Lidocaine” to 42% (p=0.05) and in “EA” to 96% (p=0.003), but it increased in “Opioids” to 63% (p=0.22). Conclusions The IAP was inversely correlated with plasma citrulline and positively correlated with I-FABP in children with appendicular peritonitis. Epidural analgesia is the most protective for intestinal wall barrier function in patients at risk of IAH and ACS.

Sauna dehydration as a new physiological challenge model for intestinal barrier function

The intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-ɣ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.

Intestinal fatty acid‐binding protein and acute gastrointestinal injury grade in postoperative cardiac surgery patients

Gastrointestinal complications post cardiac surgery are infrequent but difficult to diagnose and carry a high mortality. Plasma intestinal fatty acid-binding protein (I-FABP) concentrations and the relationship between I-FABP, gastrointestinal dysfunction, and postoperative outcomes were investigated in patients who developed gastrointestinal dysfunction (acute gastrointestinal injury [AGI] grade ≥2) and those with normal gastrointestinal function. Patients with (AGI 2 group, n = 11) and without (matched controls, AGI 0 group, n = 22) early postoperative gastrointestinal dysfunction were extracted from a larger single-center prospective observational study, including adults undergoing elective cardiac surgery with extracorporeal circulation, and investigated in this nested case-control analysis. Both groups displayed variations in I-FABP concentrations with higher I-FABP on postoperative Day 1 compared to baseline and postoperative Days 2 and 3 (p < .001 and p = .005, respectively). The AGI 2 group had higher I-FABP concentrations on Day 2 compared to the AGI 0 group (p = .024). I-FABP on Day 2 correlated positively with AGI grade over the first 3 days (p = .036, p = .021 and p = .018, respectively). High I-FABP (defined as fourth quartile concentrations) on Day 1 was associated with more prolonged surgical procedures (p < .05). Furthermore, fourth quartile I-FABP on Day 1 and early gastrointestinal dysfunction were associated with higher frequencies of postoperative organ dysfunction (p < .05) and gastrointestinal complications (p < .05), and higher 365-day mortality. The present study indicates an association between intraoperative gastrointestinal injury, postoperative gastrointestinal dysfunction and gastrointestinal complications. A high-powered study is needed to further explore this relationship and the interpretation of I-FABP concentrations in individual cardiac surgery patients.

Associations Between Biomarkers of Environmental Enteric Dysfunction and Oral Rotavirus Vaccine Immunogenicity in Rural Zimbabwean Infants

Abstract Background Oral rotavirus vaccines (RVV) are poorly immunogenic in low-income countries. Environmental enteric dysfunction (EED) resulting from poor water, sanitation and hygiene (WASH) may contribute. We therefore tested associations between EED and RVV immunogenicity, and evaluated the effect of improved WASH on EED. Methods We measured nine biomarkers of EED among Zimbabwean infants born to mothers enrolled in a cluster-randomised 2 × 2 factorial trial of improved WASH and improved feeding between November 2012 and March 2015 (NCT01824940). We used multivariable regression to determine associations between EED biomarkers and RVV seroconversion, seropositivity and geometric mean titer. Log-binomial regression was used to evaluate the effect of improved WASH on EED. Findings Among 303 infants with EED biomarkers and immunogenicity data, plasma intestinal fatty-acid binding protein and stool myeloperoxidase were positively associated with RVV seroconversion; adjusted RR 1.63 (95%CI 1.04, 2.57) and 1.29 (95%CI 1.01, 1.65), respectively. There were no other associations between RVV immunogenicity and either individual biomarkers or EED domains (intestinal permeability, intestinal damage, intestinal inflammation and microbial translocation). EED biomarkers did not differ between randomised WASH and non-WASH groups. Interpretation We found no evidence that EED was associated with poor RVV immunogenicity. Contrary to our hypothesis, there was weak evidence that EED was associated with increased seroconversion. EED biomarkers were not affected by a package of household-level WASH interventions. Funding This work was supported by the Wellcome Trust. The SHINE trial was funded by the Bill & Melinda Gates Foundation; UK Department for International Development (UK Aid); Swiss Agency for Developmentand Cooperation and US National Institutes of Health.