Effect of Two Forms of Tenofovir on Duodenal Enterocytes - a Hypothesis for Different Effect of TDF and TAF on Body Weight and Plasma Lipids.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) compared to tenofovir alafenamide (TAF) leads to lower body weight and plasma lipids by an unknown mechanism. We hypothesize that TDF, when absorbed, may damage enterocytes of the proximal duodenum, leading to reduced absorption of nutrients. METHODS: People living with HIV, without significant gastrointestinal symptoms, receiving TDF (n=12) or TAF (n=12) containing regimen underwent esophagogastroduodenoscopies with duodenal biopsies. Plasma/serum concentrations of nutrients absorbed from proximal duodenum and serum intestinal fatty-acid-binding protein (I-FABP), a marker of enterocyte damage, were measured. COX/SDH histochemical staining and electron microscopy (EM) were conducted to evaluate mitochondria. RESULTS: Five patients in TDF (celiac disease (excluded from further analyses), helicobacter gastritis, and three esophagitis) and two in TAF group (two esophagitis) had a pathological finding in esophagogastroduodenoscopy. Villi were flatter (337 (59) vs. 397 (42) µm, p=0.016), crypts non-significantly deeper (200 (46) vs. 176 (27) µm, p=0.2), and villus to crypt ratio lower (1.5 (0.42) vs. 2.5 (0.51), p=0.009) in TDF vs. TAF group. I-FABP concentration was higher in TDF vs. TAF group (3.0 (1.07) vs. 1.8 (0.53) ng/ml, p=0.003). TDF group had numerically but not statistically significantly lower concentrations of folate, vitamins A, B1, D, and E. COX/SDH staining showed signs of mitochondrial damage in 10 participants in TDF and 11 in TAF group. EM studies showed similar mitochondrial damage in both groups. CONCLUSIONS: Duodenal villous alterations may explain TDF-associated decrease in body weight and plasma lipids. Larger studies are needed to evaluate concentrations of nutrients absorbed from duodenum among TDF users.

Monitoring patients with celiac disease on gluten free diet: different outcomes comparing three tissue transglutaminase IgA assays.

OBJECTIVES: Tissue transglutaminase (tTG) IgA antibodies are a hallmark for celiac disease (CD). In CD patients on gluten free diet (GFD) these antibodies are transient. Few studies are available comparing the tTG-IgA assay characteristics for monitoring response to GFD. Since discrepant results were reported in patients on GFD after switching tTG-IgA assays, we conducted a retrospective observational study to monitor GFD response using three different tTG-IgA assays. METHODS: Diagnostic samples from 44 adults and 17 children with CD were included. Of most patients two follow-up samples after introduction of GFD were available. In all samples tTG-IgA were assessed using one fluorochrome-enzyme immuno-assay (FEIA) and two chemiluminescence immuno-assays (CLIA) and intestinal fatty acid binding protein (i-FABP) as surrogate marker for intestinal epithelial damage was measured. RESULTS: Using CLIA assays, normalization of antibody levels was delayed compared to FEIA (p<0.001). Of all samples taken after at least 6 months on GFD with elevated i-FABP indicating intestinal epithelial damage, 40 % had positive tTG-IgA according to the FEIA, 85 and 90 % according to the two CLIA. CONCLUSIONS: Normalization of tTG-IgA in patients on GFD depends on the assay used. Both CLIA appear to be more sensitive in detecting suboptimal treatment response in CD-indicated by elevated i-FABP - when applying the manufacturer's recommended cut-off for the diagnosis of CD.

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

BACKGROUND: The 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. HYPOTHESIS: There is an association between the expression of I-FABP in the gut and various metabolic changes induced by a high-fat (HF) diet. METHODS: Wistar 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. RESULTS: HF 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. CONCLUSION: In 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.

Serum Levels of IFABP2 and Differences in Lactobacillus and Porphyromonas gingivalis Abundance on Gut Microbiota Are Associated with Poor Therapeutic Response in Rheumatoid Arthritis: A Pilot Study.

Intestinal dysbiosis is related to the physiopathology and clinical manifestation of rheumatoid arthritis (RA) and the response to pharmacologic treatment. The objectives of this study were (1) to analyze the effect of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the abundance of gut microbiota's bacteria; (2) to evaluate the relationship between the differences in microbial abundance with the serum levels of intestinal fatty-acid binding protein 2 (IFABP2), cytokines, and the response phenotype to csDMARDs therapy in RA. A cross-sectional study was conducted on 23 women diagnosed with RA. The abundance of bacteria in gut microbiota was determined with qPCR. The ELISA technique determined serum levels of IFABP2, TNF-α, IL-10, and IL-17A. We found that the accumulated dose of methotrexate or prednisone is negatively associated with the abundance of Lactobacillus but positively associated with the abundance of Bacteroides fragilis. The Lactobacillus/Porphyromonas gingivalis ratio was associated with the Disease Activity Score-28 for RA with Erythrocyte Sedimentation Rate (DAS28-ESR) (r = 0.778, p = 0.030) and with the levels of IL-17A (r = 0.785, p = 0.027) in the group treated with csDMARD. Moreover, a relation between the serum levels of IFABP2 and TNF-α (r = 0.593, p = 0.035) was observed in the group treated with csDMARD. The serum levels of IFABP2 were higher in patients with secondary non-response to csDMARDs therapy. In conclusion, our results suggest that the ratios of gut microbiota's bacteria and intestinal permeability seems to establish the preamble for therapeutic secondary non-response in RA.

Effects of oral cystine and glutamine on exercise-induced changes in gastrointestinal permeability and damage markers in young men.

PURPOSE: Although acute prolonged strenuous exercise has been shown to increase markers of gastrointestinal permeability and damage, little is known regarding the efficacy of nutritional supplement interventions on the attenuation of exercise-induced gastrointestinal syndrome. This study addressed the effects of oral amino acid supplementation on markers of gastrointestinal permeability and damage in response to exercise. METHODS: Sixteen active men aged 22.7 ± 2.6 years (mean ± standard deviation) completed placebo or cystine and glutamine supplementation trials in random order. Participants received either a placebo or cystine and glutamine supplements, three times a day for 5 days, separated by a 2-week washout period. On day 6, participants took their designated supplements 30 min before running at a speed corresponding to 75% of maximal oxygen uptake for 1 h, followed by a 4-h rest period. Blood samples were collected pre-exercise, immediately post-exercise, 30 min post-exercise, and 1, 2 and 4 h post-exercise on day 6. The plasma lactulose to mannitol ratio (L:M) and plasma intestinal fatty acid-binding protein (I-FABP) were used as markers of gastrointestinal permeability and damage, respectively. RESULTS: Plasma L:M (linear mixed model, coefficient ± standard error: - 0.011 ± 0.004, P = 0.0090) and changes (i.e., from pre-exercise) in plasma I-FABP (linear mixed model, - 195.3 ± 65.7 coefficient ± standard error (pg/mL), P = 0.0035) were lower in the cystine and glutamine supplementation trial than in the placebo trial. CONCLUSION: Oral cystine and glutamine supplementation attenuated the markers of gastrointestinal permeability and damage after 1 h of strenuous running in young men. TRIAL REGISTRATION NUMBER: UMIN000026008. DATE OF REGISTRATION: 13 December 2018.

Association between enterocyte injury and fluid balance in patients with septic shock: a post hoc exploratory analysis of a prospective observational study.

BACKGROUND: The required fluid volume differs among patients with septic shock. Enterocyte injury caused by shock may increase the need for fluid by triggering a systematic inflammatory response or an ischemia-reperfusion injury in the presence of intestinal ischemia/necrosis. This study aimed to evaluate the association between enterocyte injury and positive fluid balance in patients with septic shock. METHODS: This study was a post hoc exploratory analysis of a prospective observational study that assessed the association between serum intestinal fatty acid-binding protein, a biomarker of enterocyte injury, and mortality in patients with septic shock. Intestinal fatty acid-binding protein levels were recorded on intensive care unit admission, and fluid balance was monitored from intensive care unit admission to Day 7. The association between intestinal fatty acid-binding protein levels at admission and the infusion balance during the early period after intensive care unit admission was evaluated. Multiple linear regression analysis, with adjustments for severity score and renal function, was performed. RESULTS: Overall, data of 57 patients were analyzed. Logarithmically transformed intestinal fatty acid-binding protein levels were significantly associated with cumulative fluid balance per body weight at 24 and 72 h post-intensive care unit admission both before (Pearson's r = 0.490 [95% confidence interval: 0.263-0.666]; P < 0.001 and r = 0.479 [95% confidence interval: 0.240-0.664]; P < 0.001, respectively) and after (estimate, 14.4 [95% confidence interval: 4.1-24.7]; P = 0.007 and estimate, 26.9 [95% confidence interval: 11.0-42.7]; P = 0.001, respectively) adjusting for severity score and renal function. CONCLUSIONS: Enterocyte injury was significantly associated with cumulative fluid balance at 24 and 72 h post-intensive care unit admission. Enterocyte injury in patients with septic shock may be related to excessive fluid accumulation during the early period after intensive care unit admission.

Potential Role of Serum Intestinal Fatty Acid-Binding Protein as a Marker for Early Prediction and Diagnosis of Necrotizing Enterocolitis in Preterm Neonates.

INTRODUCTION: Intestinal fatty acid-binding protein (I-FABP) is located in the apex of mature enterocytes and released into circulation; once the injury of enterocyte happens, its circulating levels are considered an early and sensitive marker of intestinal ischemia as in necrotizing enterocolitis (NEC); because of its small molecular weight, it can be detected in urine. AIMS: The aim was to study the usefulness of both serum and urine I-FABP in early diagnosis of NEC and to correlate the serum and urinary levels. SETTINGS AND DESIGN: This study was case-control design. METHODS: Simultaneous serum and urine samples obtained at the onset of symptoms, in 40 preterms with suspected NEC, with gestational age ± 27.70 weeks and birth weight ± 1.11 kg, i.e., 20 preterms diagnosed at Stage I, 12 preterms at Stage II, and 8 preterms at Stage III, were compared with age- and weight-matched preterms with no NEC. STATISTICAL ANALYSIS: The collected data were tabulated, coded, and then analyzed using the computer program Statistical Package for the Social Science (SPSS version 22). RESULTS: Serum levels of I-FABP in NEC cases were significantly higher than the control group, with a mean of 6005.77 ± 6384.77 and 1480.79 ± 1276.48 pg/ml, respectively (P < 0.001). Urine levels of I-FABP in NEC cases were significantly higher than the control group, with a mean of 5009.22 ± 3941.64 and 2677.62 ± 2257.29 pg/ml, respectively (P = 0.04). Both serum and urine I-FABP levels not only in Stage II are significantly higher than Stage I but also in Stage III are significantly higher than Stage I and II (P < 0.001, P = 0.03, respectively), which showed significant positive correlation with stages of NEC (r = 0.618; P < 0.001; r = 0.306; P = 0.049, respectively). Both serum and urine I-FABP levels had a highly significant positive correlation with each other (r = 0.406 P < 0.0001). Receiving operating characteristic curve showed an area under the curve of 0.92 and 0.81 for serum and urine I-FABP, respectively. CONCLUSIONS: Whether serum or urinary I-FABP is valuable in the diagnosis and prediction of NEC and strongly correlated with the disease severity and with each other.

[Gliadomorphin, casomorphin, and intestinal fatty acid binding protein in children with autism spectrum disorders].

Diet therapy for autism spectrum disorders (ASD) remains one of the most popular alternative therapies. despite conflicting opinions regarding the effectiveness of the dietary approach. According to the theory of exorphin intoxication, gluten and casein peptides enter the bloodstream through the mucous membrane of the small intestine, penetrate the blood-brain barrier and affect the neurons of the cerebral cortex. The wellknown hypothesis of the relationship between autism and gluten intolerance is based on this theory. The aim of this work was to study the correlation between the blood concentration of intestinal fatty acid - binding protein (I-FABP) and gliadomorphin and casomorphin as markers of opioid intoxication, depending on the use of diet therapy in children with ASD. Material and methods. The study included 85 patients aged 3 to 15 years with an established diagnosis of ASD. The first group consisted of 36 children who followed a gluten-free diet (GFD) for at least 6 months, 3 of them also followed a casein-free diet (CFD), the second group included 49 patients with ASD who had no dietary restrictions. The concentration of I-FABP, gliadomorphin, and casomorphin in the blood serum was determined by enzyme immunoassay in all patients. Results. In children with ASD who followed GDD, the average values of the studied parameters were significantly lower than in patients with ASD who have no dietary restrictions: gliadomorphine - 0.98±1.27 vs 1.68±0.97 ng/ml, casomorphine - 1.62± 0.76 vs 2.37±0.53 pg/ml, I-FABP - 156.2±102.16 vs 528.26±255.95 pg/ml (p0.01). In patients with ASD using diet therapy, there was a significant increase in gliadomorifin (r=0.64, p=0.0001) and casomorphin (r=0.53, p=0.001) with an increase in I-FABP. In children with ASD, not adhering GFD, there was also an increase in blood gliadomorphin (r=0.30, p=0.036) with an increase in I-FABP level; this trend was not observed relative to casomorphin (r=-0.0050, p=0.973). Perhaps, with the expansion of the sample, this pattern will also be observed in children who are on a regular diet. Conclusion. When including diet therapy in the therapeutic treatment of autism, it is necessary to take into account the individual intolerance to gluten and casein, conduct additional examinations in order to specify the nature of the intolerance and the need to prescribe a diet.

Intestinal fatty acid-binding protein mediates atherosclerotic progress through increasing intestinal inflammation and permeability.

Atherosclerosis is one of leading phenotypes of cardiovascular diseases, featured with increased vascular intima-media thickness (IMT) and unstable plaques. The interaction between gastrointestinal system and cardiovascular homeostasis is emerging as a hot topic. Therefore, the present study aimed to explore the role of an intestinal protein, intestinal fatty acid-binding protein (I-FABP/FABP2) in the atherosclerotic progress. In western diet-fed ApoE-/- mice, FABP2 was highly expressed in intestine. Silence of intestinal Fabp2 attenuated western diet-induced atherosclerotic phenotypes, including decreasing toxic lipid accumulation, vascular fibrosis and inflammatory response. Mechanistically, intestinal Fabp2 knockdown improved intestinal permeability through increasing the expression of tight junction proteins. Meanwhile, intestinal Fabp2 knockdown mice exhibited down-regulation of intestinal inflammation in western diet-fed ApoE-/- mice. In clinical patients, the circulating level of FABP2 was obviously increased in patients with cardiovascular disease and positively correlated with the value of carotid intima-media thickness, total cholesterol and triglyceride. In conclusion, FABP2-induced intestinal permeability could address a potential role of gastrointestinal system in the development of atherosclerosis, and targeting on intestinal FABP2 might provide a therapeutic approach to protect against atherosclerosis.

Strongyloides stercoralis Infection in Solid Organ Transplant Patients Is Associated With Eosinophil Activation and Intestinal Inflammation: A Cross-sectional Study.

BACKGROUND: Strongyloidiasis can cause devastating morbidity and death in immunosuppressed patients. Identification of reliable biomarkers for strongyloidiasis in immunosuppressed patients is critical for the prevention of severe disease. METHODS: In this cross-sectional study of solid organ transplant (SOT) candidates and recipients, we quantified Strongyloides-specific IgG to the recombinant NIE-Strongyloides antigen and/or to a soluble extract of S. stercoralis somatic antigens ("crude antigen") using enzyme-linked immunosorbent assays (ELISAs). We also measured peripheral eosinophilia, 4 different eosinophil granule proteins, and intestinal fatty acid-binding protein (IFABP). RESULTS: We evaluated serum biomarkers in 149 individuals; 77 (52%) pre-SOT and 72 (48%) post-SOT. Four percent (6/149) tested positive by NIE ELISA and 9.6% (11/114) by crude antigen ELISA (overall seropositivity of 9.4% [14/149]). Seropositive patients had higher absolute eosinophil counts (AECs) than seronegative patients (P = .004). AEC was positively correlated to the levels of eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) (P < .05), while IFABP was positively related to the 2 other eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]; Spearman's r = 0.3090 and 0.3778, respectively; P < .05; multivariate analyses slopes = 0.70 and 2.83, respectively). CONCLUSIONS: This study suggests that, in SOT patients, strongyloidiasis triggers both eosinophilia and eosinophil activation, the latter being associated with intestinal inflammation. These data provide insight into the pathogenesis of S. stercoralis infection in the immunocompromised population at high risk of severe strongyloidiasis syndromes.

Monocyte activation, HIV, and cognitive performance in East Africa.

Chronic inflammation associated with monocyte activation has been linked to HIV-related cognitive outcomes in resource-rich settings. Few studies have investigated this relationship in the African context where endemic non-HIV infections may modulate effects. We characterized immune activation biomarkers in Kenyan and Ugandan participants in relation to neuropsychological testing performance (NTP) from the African Cohort Study (AFRICOS). We focused on activation markers associated with monocytes (sCD14, sCD163, neopterin), T cells (HLA-DR+CD38+ on CD4+ and CD8+ T lymphocytes), and microbial translocation (intestinal fatty acid-binding protein, I-FABP). The HIV-infected (n = 290) vs. HIV-uninfected (n = 104) groups were similar in age with mean (SD) of 41 (9.5) vs. 39 (9.9) years, respectively (p = 0.072). Among HIV-infected participants, the mean (SD) current CD4+ count was 402 (232); 217 (75%) were on combination antiretroviral therapy (cART) and 199 (69%) had suppressed plasma HIV RNA. sCD14 was inversely correlated to NTP (r = - 0.14, p = 0.037) in models that included both HIV-infected and uninfected individuals, adjusted for HIV status and research site, whereas sCD163 was not (r = 0.041, p = 0.938). Neither of the T cell activation markers correlated with NTP. In the HIV-infected group, I-FABP was inversely associated with NTP (r = - 0.147, p = 0.049), even among those with suppressed plasma virus (r = - 0.0004, p = 0.025). Among the full group, HIV status did not appear to modulate the effects observed. In this cohort from East Africa, sCD14, but not sCD163, is associated with cognitive performance regardless of HIV status. Findings among both HIV-infected and HIV-uninfected groups is supportive that HIV and non-HIV-related inflammatory sources contribute to cognitive performance in this setting.

Association between Enterocyte Injury and Mortality in Patients on Hemodialysis Who Underwent Cardiac Surgery: An Exploratory Study.

BACKGROUND: Intestinal ischemia and enterocyte injury are significant causes of death after cardiac surgery. Hemodialysis is a well-known risk factor for intestinal ischemia. However, the relationship between enterocyte injury and mortality is unclear. This exploratory study assessed the association between intestinal fatty acid-binding protein (I-FABP), a specific marker of enterocyte injury, at intensive care unit (ICU) admission and in-hospital mortality in patients on hemodialysis who underwent cardiac surgery with cardiopulmonary bypass. MATERIALS AND METHODS: Forty-seven consecutive patients on long-term hemodialysis who underwent elective cardiac surgery (median age, 70 y; men, 27 [57%]) were prospectively enrolled. The association between serum I-FABP levels at ICU admission and in-hospital mortality was compared with the associations between serum I-FABP levels and prognostic severity scores, vasoactive-inotropic scores, and lactate levels. RESULTS: Only I-FABP levels at ICU admission were significantly related to in-hospital mortality (odds ratio, 5.54; 95% confidence interval [CI], 1.08-28.43) in the simple logistic regression analysis. Univariate and multiple linear regression analyses indicated prolonged cardiopulmonary bypass (ρ, 0.49; 95% CI, 0.15-0.83), higher mean norepinephrine dose (ρ, 0.07; 95% CI, 0.02-0.12), lower mean dopamine dose (ρ, -0.51; 95% CI, -0.94 to -0.08), and intra-aortic balloon pump use (ρ, 3.63; 95% CI, 1.68-5.59) were significant risk factors for high I-FABP levels. CONCLUSIONS: Enterocyte injury at ICU admission was associated with in-hospital mortality after cardiac surgery for patients on hemodialysis. Intraoperative hidden hypoperfusion of the intestine may impact prognoses. Enterocyte injury prevention, early diagnosis, and intervention for intestinal ischemia might be required to improve outcomes.

The Role of Gastrointestinal-Related Fatty Acid-Binding Proteins as Biomarkers in Gastrointestinal Diseases.

The fatty acid-binding proteins play a major role in intracellular transportation of long-chain fatty acids. Nine fatty acid-binding proteins have been identified, with each having individual tissue-specific functions in addition to regulation of fatty acids. This review focuses on the three fatty acid-binding proteins found in the gastrointestinal tract and discusses their role as diagnostic or disease monitoring markers in neonatal necrotizing enterocolitis, acute mesenteric ischemia, celiac disease, and inflammatory bowel disease. Of these three fatty acid-binding proteins, intestinal fatty acid-binding protein is of the most interest due to its exclusive expression in the gastrointestinal tract. The elevation of intestinal fatty acid-binding protein in blood and urine reflects enterocyte damage, regardless of the underlying cause. The short half-life of intestinal fatty acid-binding protein also means it is a relatively sensitive marker. In contrast, there is currently less evidence to support liver fatty acid-binding protein and ileal bile acid-binding protein as sensitive biomarkers in these conditions. More extensive studies with specific endpoints are required to validate the roles of these fatty acid-binding proteins in gastrointestinal diseases.

Effects of Escherichia coli strain Nissle 1917 on exercise-induced disruption of gastrointestinal integrity.

PURPOSE: The aim of the current study was to investigate the effects of the probiotic Escherichia coli strain Nissle 1917 (EcN) on the exercise-induced disruption of gastrointestinal (GI) integrity and the associated release of damage and inflammatory markers. METHODS: After a pre-performance test, 19 untrained subjects (aged 18-35 years) passed two identical exhaustive treadmill exercise tests in an intensity corresponding to 60-80% VO2max in a test-retest design. The exercise tests were separated by a time period of 4 weeks. During this period, all subjects ingested 5 ml of an EcN suspension daily. Serum samples were taken before, immediately following and 3 h after both exercise tests. They were analyzed for indicators of GI integrity (zonulin; claudin-3; LPS), various damage and redox markers (I-FABP, GOT; GPT; TBARS) and inflammatory parameters (hsCRP; leucocytes). GI complaints were evaluated by a questionnaire. RESULTS: The intake of EcN resulted in a significantly lower increase in I-FABP and TBARS after exercise (p < 0.05). In contrast, no effect of EcN supplementation was found for hsCRP and leucocyte numbers. Similarly, no differences were found for levels of zonulin and claudin-3. Exercise-associated GI complaints were not affected by the probiotic supplement. CONCLUSION: The probiotic EcN reduced the exercise-associated increase in oxidative stress. This antioxidative mechanism probably leads to a reduction of GI epithelial damage after exhaustive exercise. The lack of EcN effects on other markers of GI permeability and systemic inflammation is most likely due to an inadequate exercise load, with rather small and insignificant exercise effects on these parameters.

Normative values for circulating intestinal fatty acid binding protein and calprotectin across gestational ages.

BACKGROUND: Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality. Serum biomarkers to aid diagnosis, such as intestinal fatty acid binding protein (IFABP) and calprotectin, are actively being investigated; however, the normative values of these markers among healthy premature and term infants remains unknown. We sought to identify normative values for the serum concentrations of IFABP and calprotectin across gestational (GA) and post-menstrual age. METHODS: We collected serum from infants (24-40 weeks GA) in the first week of life and at multiple time points in a sub-cohort of premature infants (24-29 weeks GA), excluding sepsis or known intestinal disease. IFABP and calprotectin were measured using ELISA. Groups were compared with descriptive statistics and mixed effects linear regression. RESULTS: One hundred twelve infants had specimens in the first week of life, and 19 premature infants had longitudinal specimens. IFABP concentration in the first week of life was low and did not differ across gestational ages. Longitudinally, IFABP increased 4% per day (P < 0.001). Calprotectin concentration in the first week of life was more variable. An inverse relationship between day of life and calprotectin level was found in the longitudinal cohort (P < 0.001). CONCLUSIONS: Serum IFABP and calprotectin fluctuate over time. Infants had low levels of IFABP during the first week of life, independent of gestational age, and levels increased longitudinally in premature infants. Calprotectin levels generally declined over time. Normative data for infants is necessary to establish meaningful cut-off levels for clinical use.

Effects of prebiotic consumption on serum intestinal fatty acid-binding protein levels in patients with diabetes: A case-control study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a condition involving several molecular mechanisms related to the intestinal microbiota for its development. Intestinal fatty acid-binding protein (I-FABP) is a sensitive marker to study enterocyte damage. A prebiotic is a non-digestible food ingredient that improves host health by selectively stimulating the growth and/or activities of bacteria in the colon. We aimed to clarify the currently described effects of prebiotics in the prevention and management of T2DM. METHODS: In this case-control study, we chose 68 participants with T2DM and 52 healthy participants. Both groups were further divided based on consumption of prebiotics. Forty participants with T2DM consumed prebiotics, and 28 did not; 30 healthy volunteers consumed prebiotics, and 22 did not. We used the analysis of variance to compare the inflammation levels between the case and control groups. Multiple linear regression was performed for the significantly correlated groups to estimate the influence of prebiotics on inflammation level. RESULTS: Age was a significant factor for difference in I-FABP levels (standardized coefficient: 0.06; P = .047). The analysis of eating habits showed that vegetarian diets produced lower I-FABP levels than non-vegetarian diets (standardized coefficient: -2.55; P = .022). Results showed that patients with T2DM who consumed prebiotics expressed lower I-FABP levels, reflecting an improvement in inflammation level, than the healthy volunteers who did not consume prebiotics (standardized coefficient: -3.20; P = .019). CONCLUSIONS: For patients with T2DM, prebiotics supplemented produced no significant impact on serum I-FABP levels.

Diagnostic accuracy of urinary intestinal fatty acid binding protein in detecting colorectal anastomotic leakage.

BACKGROUND: Anastomotic leakage (AL) remains a severe complication following colorectal surgery, having a negative impact on both short- and long-term outcomes. Since timely detection could enable early intervention, there is a need for the development of novel and accurate, preferably, non-invasive markers. The aim of this study was to investigate whether urinary intestinal fatty acid binding protein (I-FABP) could serve as such a marker. METHODS: This prospective multicenter cross-sectional phase two diagnostic study was conducted at four centers in the Netherlands between March 2015 and November 2016. Urine samples of 15 patients with confirmed colorectal AL and 19 patients without colorectal AL on postoperative day 3 were included. Urinary I-FABP levels were determined using enzyme-linked immunosorbent assays and adjusted for urinary creatinine to compensate for renal dysfunction. RESULTS: Urinary I-FABP levels were significantly elevated in patients with confirmed AL compared to patients without AL on postoperative day 3 (median: 2.570 ng/ml vs 0.809 ng/ml, p = 0.006). The area under the receiver operating characteristics curve (AUROC) was 0.775, yielding a sensitivity of 80% and specificity of 74% at the optimal cutoff point (> 1.589 ng/ml). This difference remained significant after calculation of I-FABP/creatinine ratios (median: 0.564 ng/µmol vs. 0.158 ng/µmol, p = 0.040), with an AUROC of 0.709, sensitivity of 60% and specificity of 90% at the optimal cutoff point (> 0.469 ng/µmol). CONCLUSIONS: Levels of urinary I-FABP and urinary I-FABP/creatinine were significantly elevated in patients with confirmed AL following colorectal surgery, suggesting their potential as a non-invasive biomarker for colorectal anastomotic leakage.

Serum Markers Associated with Severity and Outcome of Hantavirus Pulmonary Syndrome.

BACKGROUND: Hantavirus pulmonary syndrome (HPS) is caused by Andes virus (ANDV) and related hantaviruses in the Americas. Despite a fatality rate of 40%, the pathogenesis of HPS is poorly understood and factors associated with severity, fatality, and survival remain elusive. METHODS: Ninety-three ANDV-infected HPS patients, of whom 34 had a fatal outcome, were retrospectively studied. Serum levels of cytokines and other inflammation-associated markers were analyzed using multiplex immunoassay and enzyme-linked immunosorbent assay. Associations with disease severity, fatal outcome, and survival were identified using logistic regression. RESULTS: HPS patients exhibited increased serum levels of markers associated with inflammation, intestinal damage, and microbial translocation compared to controls. Patients with fatal outcome displayed higher levels of interleukin (IL) 6, IL-10, interferon-γ, soluble tumor necrosis factor-related apoptosis-inducing ligand, and intestinal fatty acid-binding protein (I-FABP) than survivors. Levels of complement factor 5/5a were higher in survivors compared with fatal cases. IL-6 and I-FABP, the latter a marker for intestinal damage, were by multivariate analyses identified as independent markers associated with disease severity (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.01-5.01) and fatal outcome (OR, 1.64; 95% CI, 1.01-2.64), respectively. CONCLUSIONS: HPS patients displayed a multifaceted, systemic inflammatory response, with IL-6 and I-FABP as independent markers of disease severity and fatality, respectively.

Leaky gut biomarkers in depression and suicidal behavior.

OBJECTIVE: Inflammation is associated with major depressive disorder (MDD) and suicidal behavior. According to the 'leaky gut hypothesis', increased intestinal permeability may contribute to this relationship via bacterial translocation across enterocytes. We measured plasma levels of gut permeability markers, in patients with a recent suicide attempt (rSA), MDD subjects with no history of a suicide attempt (nsMDD), and healthy controls (HC), and related these markers to symptom severity and inflammation. METHOD: We enrolled rSA (n = 54), nsMDD (n = 13), and HC (n = 17). Zonulin, intestinal fatty acid binding protein (I-FABP), soluble CD14, and interleukin-6 (IL-6) were quantified in plasma. Montgomery-Åsberg Depression Rating Scale (MADRS) and Suicide Assessment Scale (SUAS) were used for symptom assessments. RESULTS: The rSA group displayed higher I-FABP and lower zonulin levels compared with both the nsMDD and the HC groups (all P < 0.001). IL-6 correlated positively with I-FABP (r = 0.24, P < 0.05) and negatively with zonulin (r = -0.25, P < 0.05). In all subjects, I-FABP levels correlated positively with MADRS (r = 0.25, P < 0.05) and SUAS scores (r = 0.38, P < 0.001), and the latter correlation was significant also in the nsMDD group (r = 0.60, P < 0.05). CONCLUSION: The 'leaky gut hypothesis' may improve our understanding of the link between inflammation and suicidal behavior. These findings should be considered preliminary until replicated in larger cohorts.

The effect of bovine colostrum supplementation on intestinal injury and circulating intestinal bacterial DNA following exercise in the heat.

PURPOSE: Exercise-induced changes in intestinal permeability are exacerbated in the heat. The aim of this study was to determine the effect of 14 days of bovine colostrum (Col) supplementation on intestinal cell damage (plasma intestinal fatty acid-binding protein, I-FABP) and bacterial translocation (plasma bacterial DNA) following exercise in the heat. METHODS: In a double-blind, placebo-controlled, crossover design, 12 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac) consisting of 60 min treadmill running at 70% maximal aerobic capacity (30 °C, 60% relative humidity). Blood samples were collected pre-exercise (Pre-Ex), post-exercise (Post-Ex) and 1 h post-exercise (1 h Post-Ex) to determine plasma I-FABP concentration, and bacterial DNA (for an abundant gut species, Bacteroides). RESULTS: Two-way repeated measures ANOVA revealed an arm × time interaction for I-FABP (P = 0.005, with greater Post-Ex increase in Plac than Col, P = 0.01: Plac 407 ± 194% of Pre-Ex vs Col, 311 ± 134%) and 1 h Post-Ex (P = 0.036: Plac 265 ± 80% of Pre-Ex vs Col, 229 ± 56%). There was no interaction (P = 0.904) but there was a main effect of arm (P = 0.046) for plasma Bacteroides/total bacterial DNA, with lower overall levels evident in Col. CONCLUSION: This is the first investigation to demonstrate that Col can be effective at reducing intestinal injury following exercise in the heat, but exercise responses (temporal pattern) of bacterial DNA were not influenced by Col (although overall levels may be lower).