Intestinal Fatty Acid Binding Protein Concentrations Research Articles

Intestinal fatty acid-binding protein as a potential biomarker for gastrointestinal complications after complex endovascular aortic surgery

ObjectiveThis study aimed to investigate the association between intestinal fatty acid-binding protein, acute gastrointestinal injury grade, and gastrointestinal complications after fenestrated or branched endovascular aortic aneurysm repair. MethodsA total of 17 patients undergoing endovascular aortic repair for thoracoabdominal, juxtarenal, suprarenal or pararenal aneurysm between May 2017 and September 2018 were enrolled. Blood samples were collected preoperatively and during postoperative intensive care. The blood samples were analyzed for intestinal fatty acid-binding protein with enzyme-linked immunosorbent assay. Gastrointestinal function was assessed according to the acute gastrointestinal injury grade every day during postoperative intensive care. ResultsHigher concentrations of intestinal fatty acid-binding protein at 24 h and 48 h correlated to higher acute gastrointestinal injury grade on postoperative days 1, 2 and 3 (p=0.032 and p=0.048, p=0.040 and p=0.018, and p=0.012 and p=0.016, respectively). Patients who developed a gastrointestinal complication within 90 days postoperatively had a higher overall acute gastrointestinal injury grade than those who did not develop a gastrointestinal complication (p<0.001), as well as higher concentrations of intestinal fatty acid-binding protein at 48 h (p=0.019). Patients developing gastrointestinal dysfunction (acute gastrointestinal injury grade ≥2) had a higher frequency of complications (p=0.009) and longer length of stay in the intensive care unit (p=0.008). ConclusionsIn patients undergoing endovascular aortic repair for complex aneurysm increased postoperative plasma intestinal fatty acid-binding protein concentrations and postoperative gastrointestinal dysfunction, evaluated using the acute gastrointestinal injury grade, were associated with gastrointestinal complications, indicating that these measures may be useful in the postoperative management of these patients.

Markers of intestinal barrier damage in patients with chronic insomnia disorder.

Insomnia disorder stands out as one of the prevalent clinical sleep and psychiatric disorders. Prior research has unequivocally demonstrated variations in the diversity and abundance of gut microbiota among individuals with insomnia disorder. These alterations may play a direct or indirect role in the onset and progression of insomnia disorder by compromising the integrity of the intestinal barrier. This study aims to evaluate the impairment of the intestinal barrier in individuals with insomnia disorder by scrutinizing the serum functionality of this barrier. 45 patients with chronic insomnia disorder and 30 matched healthy volunteers were meticulously selected based on inclusion criteria. ELISA technology was employed to measure serum levels of diamine oxidase (DAO), D-lactic acid (D-LA), intestinal fatty acid binding protein (I-FABP), and endothelin (ET). Spearman correlation analysis was used to explore the relationship between intestinal mucosal markers and clinical characteristics. Data were analyzed using SPSS 26.0. Compared to the healthy control group, the insomnia disorder group exhibited significantly elevated scores on subjective mood and sleep scales (GAD-7, PHQ-9, HAMA, HAMD, PSQI, and ISI) (P < 0.05). Overnight PSG indicated a notable increase in bed time, total wake time, sleep onset latency, and wake after sleep onset in individuals with insomnia disorder. Additionally, there was a decrease in sleep efficiency and alterations in sleep structure (increased proportion of N1 and N3 stages, prolonged N1 stage) (P < 0.05). The chronic insomnia disorder group displayed significantly reduced concentrations of serum DAO, D-LA, I-FABP, and ET (P < 0.05). Furthermore, significant positive correlations were identified between intestinal epithelial barrier markers and sleep efficiency, while negative correlations were found with wake after sleep onset, total wake time, PSQI, HAMA, and HAMD. Additionally, D-LA levels were significantly positively correlated with ET concentrations. Individuals with chronic insomnia disorder manifest disruptions in sleep structure, heightened susceptibility to anxiety and depressive moods, and impaired intestinal barrier function. These findings suggest that the occurrence and development of insomnia disorder may be linked to the impairment of the intestinal barrier.

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.

253 Understanding the Health Benefits of Feeding Treated Wheat Straw for Weanling Pigs

Abstract Two experiments were conducted to understand the growth and health benefits of including treated wheat straw in weanling pig diets. The first experiment evaluated feeding treated versus untreated wheat straw on young pig growth performance and localized immunological markers. One hundred and ninety-two (PIC 359 x Yorkshire) pigs were weaned at 26.8 ± 1.1 d old (8.3 ± 1.1 kg) and randomly allotted to 24 pens with 8 pigs per pen. Three dietary treatments were fed over a 28-d period, control (CON), control plus 5% untreated wheat straw (UWS), and control plus 5% treated wheat straw (TWS). Diets were formulated to meet or exceed all nutrient requirements of NRC, 2012. Growth performance data was recorded on a weekly basis. One pig per pen (equal number of males and females) was randomly selected for sacrifice and sample collection on d 28. The second experiment evaluated the impact of 5% dietary TWS on the local and systemic health of nursery pigs experiencing a vaccination-induced immune challenge. Twenty barrows (PIC 800 x Yorkshire) were weaned at 27.7 ± 0.75 d (8.6 ± 1.2 kg) and assigned to four pens, with 5 pigs per pen. A heavy and light-weight pen for each treatment (CON and TWS) resulted. All pigs were sacrificed for sample collection on d 42. In both experiments, before euthanasia, blood was collected to assess plasma immunoglobulin A (IgA) and intestinal fatty acid binding protein (iFABP) concentration. Upon sacrifice, segments of the distal ileum and ascending colon were removed to collect mucosal scrapings for the analysis of localized immunological markers interleukin (IL) 6 , IL-10, IL-12, and tumor necrosis factor-alpha (TNF-α). In experiment one, overall ADG and ADFI were similar among treatments. Gain-to-feed ratio of TWS pigs was greater (P &amp;lt; 0.05) than that of UWS pigs and tended to be greater (P = 0.07) than that of CON pigs (0.70, 0.67, and 0.68, respectively; SEM = 0.01). Both straw treatments decreased the expression of ileal and colonic mucosa IL-6, in addition with less expression of ileal IL-12. Plasma IgA concentrations in UWS pigs were greater than those in CON and TWS pigs (P &amp;lt; 0.05). In experiment two, TWS pigs had greater gene expression of colonic TNF-α and IL-6 (P &amp;lt; 0.05). Ileal gene or protein expression of markers did not differ, nor did amounts of plasma IgA or iFABP. Overall, feeding 5% treated wheat straw in the nursery pig diet does not negatively impact growth and results in increased feed efficiency. Nursery diets with 5% treated wheat straw can impact the expression of immune markers in the gut, but the question of how this is related to performance and overall health needs further elucidation.

The Impact of a Short-Term Ketogenic Low-Carbohydrate High-Fat Diet on Biomarkers of Intestinal Epithelial Integrity and Gastrointestinal Symptoms.

Endurance exercise can disturb intestinal epithelial integrity, leading to increased systemic indicators of cell injury, hyperpermeability, and pathogenic translocation. However, the interaction between exercise, diet, and gastrointestinal disturbance still warrants exploration. This study examined whether a 6-day dietary intervention influenced perturbations to intestinal epithelial disruption in response to a 25-km race walk. Twenty-eight male race walkers adhered to a high carbohydrate (CHO)/energy diet (65% CHO, energy availability = 40kcal·kg FFM-1·day-1) for 6 days prior to a Baseline 25-km race walk. Athletes were then split into three subgroups: high CHO/energy diet (n = 10); low-CHO, high-fat diet (LCHF: n = 8; <50g/day CHO, energy availability = 40kcal·kg FFM-1·day-1); and low energy availability (n = 10; 65% CHO, energy availability = 15kcal·kg FFM-1·day-1) for a further 6-day dietary intervention period prior to a second 25-km race walk (Adaptation). During both trials, venous blood was collected pre-, post-, and 1hr postexercise and analyzed for markers of intestinal epithelial disruption. Intestinal fatty acid-binding protein concentration was significantly higher (twofold increase) in response to exercise during Adaptation compared to Baseline in the LCHF group (p = .001). Similar findings were observed for soluble CD14 (p < .001) and lipopolysaccharide-binding protein (p = .003), where postexercise concentrations were higher (53% and 36%, respectively) during Adaptation than Baseline in LCHF. No differences in high CHO/energy diet or low energy availability were apparent for any blood markers assessed (p > .05). A short-term LCHF diet increased intestinal epithelial cell injury in response to a 25-km race walk. No effect of low energy availability on gastrointestinal injury or symptoms was observed.

Investigating the Association Between Diet-Induced "Leaky Gut" and the Development of Prediabetes.

Chronic consumption of a high-calorie diet compromises the gut microbiota and the integrity of the intestinal wall, which causes translocation of bacterial lipopolysaccharides (LPS) into the blood. This elicits the secretion of pro-inflammatory cytokines, resulting in inflammation. However, how a high-fat high carbohydrate diet affects intestinal permeability and its possible role in the development of prediabetes have not been investigated. This study investigated the effects of HFHC diet-induced prediabetes on gut microbiota and intestinal permeability in male Sprague Dawley rats. The animals were randomly assigned into the non-prediabetic (NPD) and diet-induced prediabetic (PD) groups (n=6) for 20 weeks. Then, the fecal samples were analyzed to measure the gut microbiota level of Firmicutes, Bacteroidetes, and Proteobacteria in both animal groups. Blood glucose, plasma insulin, serum zonulin, plasma LPS, soluble CD14, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and intestinal fatty-acid binding protein (IFABP) concentrations were measured. The PD group had a reduction in the Firmicutes and an increase in Bacteroidetes and Proteobacteria levels compared to those in the NPD group. Blood glucose, insulin concentration, serum zonulin, and plasma sCD14 concentrations in the PD group increased significantly, while plasma LPS concentrations were similar to the NPD group. Concentrations of plasma TNF-α, IL-6, CRP, and IFABP, an intracellular protein expressed in the intestine, increased in PD compared to the NPD group. the study results cumulatively suggest that chronic consumption of the HFHC diet may be associated with the dysregulation of gut microbiota, leading to increased intestinal permeability.

Intestinal injury and vasculitis biomarkers in cats with feline enteric coronavirus and effusive feline infectious peritonitis.

To investigate intestinal injury, repair and vasculitis biomarkers that may illuminate the progression and/or pathogenesis of feline infectious peritonitis (FIP) or feline enteric coronavirus (FECV) infection. A total of 40 cats with effusive FIP (30 with abdominal effusion, AE group; 10 with thoracic effusion, TE group) and 10 asymptomatic but FECV positive cats (FECV group), all were confirmed by reverse transcription polymerase chain reaction either in faeces or effusion samples. Physical examinations and effusion tests were performed. Trefoil factor-3 (TFF-3), intestinal alkaline phosphatase (IAP), intestinal fatty acid binding protein (I-FABP), myeloperoxidase-anti-neutrophilic cytoplasmic antibody (MPO-ANCA) and proteinase 3-ANCA (PR3-ANCA) concentrations were measured both in serum and effusion samples. Rectal temperature and respiratory rate were highest in the TE group (p<0.000). Effusion white blood cell count was higher in the AE group than TE group (p<0.042). Serum TFF-3, IAP and I-FABP concentrations were higher in cats with effusive FIP than the cats with FECV (p<0.05). Compared with the AE group, TE group had lower effusion MPO-ANCA (p<0.036), higher IAP (p<0.050) and higher TFF-3 (p<0.016) concentrations. Markers of intestinal and epithelial surface injury were higher in cats with effusive FIP than those with FECV. Compared to cats with abdominal effusions, markers of apoptosis inhibition and immunostimulation to the injured epithelium were more potent in cats with thoracic effusion, suggesting the possibility of a poorer prognosis or more advanced disease in these patients.

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

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

Assessing environmental enteric dysfunction via multiplex assay and its relation to growth and development among HIV-exposed uninfected Tanzanian infants.

Environmental enteric dysfunction (EED) may contribute to poor growth and development in young children. While validated EED biomarkers are currently lacking, multiplex assays are able to capture multiple domains of the condition. The purpose of this exploratory study was to examine the relationship between biomarkers of EED and subsequent growth and development among Tanzanian HIV-exposed uninfected (HEU) infants. We enrolled 467 infants of mothers living with HIV who had participated in a trial of vitamin D3 supplementation during pregnancy. Infant serum samples collected at 6 weeks (n = 365) and 6 months (n = 266) were analyzed for anti-flagellin and anti-lipopolysaccharide (LPS) IgA and IgG via ELISA as well as the 11-plex Micronutrient and EED Assessment Tool (MEEDAT), which incorporates two biomarkers of EED [intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14)]. Outcomes were 12-month growth [length-for-age z-score (LAZ), weight-for-length z-score (WLZ), and weight-for-age z-score (WAZ)] and development [Caregiver Reported Early Development Instruments (CREDI) z-scores] and were assessed using linear regression. In primary analyses, higher quartiles of 6-month anti-LPS IgG concentrations were significantly associated with lower LAZ at 12 months (ptrend = 0.040). In secondary analyses, higher log2-transformed 6-week anti-flagellin IgA and 6-month anti-LPS IgA concentrations were significantly associated with lower LAZ at 12 months. No associations were observed between I-FABP or sCD14 and infant growth. However, higher log2-transformed 6-week sCD14 concentrations were significantly associated with lower overall CREDI z-scores, while higher log2-transformed 6-month I-FABP concentrations were significantly associated with higher overall CREDI z-scores. Unlike anti-flagellin and anti-LPS Igs, MEEDAT's biomarkers of EED (I-FABP and sCD14) were not associated with subsequent linear growth among HEU infants in Tanzania. The relationship between EED and infant development warrants further study.

Protective effects of α-terpineol and Bacillus coagulans on intestinal function in weaned piglets infected with a recombinant Escherichia coli expressing heat-stable enterotoxin STa.

This study was to investigate the impact of α-terpineol (α-TPN) and Bacillus coagulans (B. coagulans) on weaned piglets infected with Enterotoxigenic Escherichia coli (ETEC). Thirty-two weaned piglets were assigned into four treatments: Control group (basal diet), STa group (basal diet + 1 × 1010 CFU ETEC), TPN+STa group (basal diet + 0.01% α-TPN + ETEC) and BC+STa group (basal diet + 2 × 106 CFU B. coagulans + ETEC). Result showed that both α-TPN and B. coagulans could alleviate diarrhea (decreased diarrhea rate), intestinal injury (improved intestinal morphology, decreased blood I-FABP concentration, increased protein expression level of Occludin), oxidative stress (increased GSH-Px activity and decreased MDA content) and inflammation (altered concentration of TNF-α, IL-1β in blood) induced by ETEC infection. Mechanism investigation further demonstrated that the beneficial effects of α-TPN and B. coagulans supplementation upon ETEC infection may be achieved by decreasing the protein expression levels of caspase-3, AQP4 and p-NF-κB and decreasing the gene expression levels of INSR and PCK1. Besides, α-TPN supplementation could specifically decreased expression level of gene b 0,+ AT, and B. coagulans supplementation could specifically decreased expression level of gene AQP10 and protein HSP70 in ETEC-infected weaned piglets. These results suggested that α-TPN and B. coagulans can be used as antibiotic alternatives against ETEC infection in weaned piglets.

Gastric ultrasound, citrulline, and intestinal fatty acid-binding protein as markers of gastrointestinal dysfunction in critically ill patients: A pilot prospective cohort study.

Gastrointestinal (GI) dysfunction is common in the intensive care unit (ICU), although there is no consensus on biomarkers of GI dysfunction. We aimed to evaluate ultrasound-based gastric antrum measurements and serum intestinal fatty acid-binding protein (IFABP) and citrulline levels in relation to GI dysfunction in critically ill patients. Adult critically ill patients receiving enteral nutrition and stayed for in the ICU for ≥48 h was included. GI dysfunction was described using Gastrointestinal Dysfunction Score (GIDS). Gastric antrum measurements, including craniocaudal (CC) diameter, anteroposterior diameter, and antral-cross sectional area (CSA), as well as serum levels for IFABP and citrulline, were prospectively recorded at baseline and on day 3 and day 5 of enteral nutrition. The receiver operating characteristic (ROC) analysis was performed to evaluate gastric ultrasound parameters, serum IFABP, and citrulline concentrations in predicting GI dysfunction. Thirty-nine participants with a median age of 60 years were recruited and 46.2% of participants had GI dysfunction. ROC analysis revealed that the cutoff value of CSA score to predict GI dysfunction was 4.48 cm2 , which provided 72.7% sensitivity and 77.2% specificity (area under the curve = 0.768, 95% CI: 0.555-0.980). At baseline, gastric residual volume was highly correlated with CC diameter and CSA (r = 0.764, P < 0.001 and r = 0.675, P < 0.001, respectively). Serum IFABP and citrulline levels had no correlation with GI dysfunction or gastric ultrasound parameters (P > 0.05). CSA was associated with GI dysfunction in critically ill patients. Serum IFABP and citrulline concentrations were poor in predicting GI dysfunction.

Resveratrol attenuated high intensity exercise training-induced inflammation and ferroptosis via Nrf2/FTH1/GPX4 pathway in intestine of mice.

Moderate exercise has beneficial effects for human health and is helpful for the protection against several diseases. However, high intensity exercise training caused gastrointestinal syndrome. Resveratrol, a plant extract, plays a vital role in protecting various organs. However, whether resveratrol protected mice against high intensity exercise training-induced intestinal damage remains unclear. In this study, our objective was to investigate the protective effects and mechanism of resveratrol in high intensity exercise training-treated mice. Mice were treated with swimming exercise protocol and/or resveratrol (15 mg/kg/day) for 28 consecutive days. Then, the mice were sacrificed, and a series of evaluation indicators, including inflammatory factors and intestinal permeability of the gut, were measured based on this model. The expressions of inflammatory factors (tumor necrosis factor (TNF)-α; interferon (IFN)-γ, interleukin (IL)-6 and IL-10), oxidative stress (Nrf2, glutathione (GSH), hydrogen peroxide (H2 O2), catalase (CAT) and malondialdehyde(MDA)), intestinal barrier (gut permeability, ZO-1, Occludin and Claudin-1 as well as ferroptosis (Fe2+, Fe3+, SLC7A11, glutathioneperoxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1)) were measured, respectively. High intensity exercise training induced colon damage, manifested as inflammation (increased TNF-α, IFN-γ and IL-6 concentrations, and decreased IL-10 concentration), oxidative stress (the increase of H2O2 and MDA concentration, and the reduced CAT and GSH activities), intestinal barrier injury (increased gut permeability and intestinal fatty-acid binding protein concentration,and inhibited ZO-1, Occludin and Claudin-1 expressions) and ferroptosis (the increased of Fe2+ and Fe3+ concentrations, and suppressed phosphorylated Nrf2, SLC7A11, GPX4 and FTH1), which was relieved by resveratrol treatment in mice. Resveratrol attenuated high intensity exercise training-induced inflammation and ferroptosis through activating Nrf2/ FTH1/GPX4 pathway in mouse colon, which providing new ideas for the prevention and treatment of occupational disease in athlete.

Intestinal Fatty Acid-binding Protein in Patients with Psoriasis: A Marker of Impaired Intestinal Permeability Barrier and its Relation to Demographic Data and Clinical Characteristics

Abstract Background: Alterations of intestinal microbiota may play a role in the pathogenesis of psoriasis. Dysbiosis may cause disruption of the intestinal barrier, which contributes to immune activation by translocation of microbial antigens and metabolites. Intestinal fatty acid-binding protein (I-FABP) serves as a biomarker of enterocyte damage. Purpose: The aim of this study was to investigate serum concentration of I-FABP in patients with psoriasis. Methods: A cross-sectional hospital-based study on fifty psoriatic patients and thirty-five age and sex-matched healthy volunteers as a control group were enrolled in the study, serum I-FABP concentration was measured using an enzyme-linked immunosorbent assay. Results: Concentration of serum I-FABP was higher in patients compared to controls (P = 0.04). The serum level of I-FABP was higher in patients with skin phototype IV than in those with skin phototype III (P = 0.040). There were significant positive statistical correlations between I-FABP with age and disease duration. Conclusion: I-FABP, a biomarker for gut permeability, is increased in psoriasis and correlates with disease duration and age. Further investigations are needed to determine whether reinforcing intestinal barrier may be a new therapeutic target in psoriasis.

HIV-Associated Microbial Translocation May Affect Cytokine Production of CD56bright NK Cells via Stimulation of Monocytes.

The mechanisms involved in HIV-associated natural killer (NK) cell impairment are still incompletely understood. We observed HIV infection to be associated with increased plasma levels of IFABP, a marker for gut epithelial barrier dysfunction, and LBP, a marker for microbial translocation. Both IFABP and LBP plasma concentrations were inversely correlated with NK cell interferon-γ production, suggesting microbial translocation to modulate NK cell functions. Accordingly, we found lipopolysaccharide to have an indirect inhibitory effect on NK cells via triggering monocytes' transforming growth factor-β production. Taken together, our data suggest increased microbial translocation to be involved in HIV-associated NK cell dysfunction.

The role of environmental enteric dysfunction in the pathogenesis of Schistosoma mansoni-associated morbidity in school-aged children.

BackgroundStudies have implicated schistosomiasis as a cause of intestinal barrier disruption, a salient feature of environmental enteric dysfunction (EED), as eggs translocate from the sterile bloodstream through the gut wall. We examined the longitudinal impact of praziquantel (PZQ) treatment on a) EED biomarkers and b) Insulin growth factor I (IGF-1), a key driver of childhood linear growth, since EED has been implicated in linear growth stunting.Methodology290 children infected with S. mansoni in Brazil were treated with PZQ at baseline. EED biomarkers lipopolysaccharide (LPS) and intestinal fatty acid binding-protein (I-FABP) were measured, as well as IGF-1 at baseline, 6 and 12-months. Multivariate regression analysis was applied to assess associations between S. mansoni intensity and plasma biomarkers (LPS, I-FABP, and IGF-1), controlling for potential confounding variables.Principal findingsAt baseline, S. mansoni infection intensities were 27.2% light, 46.9% moderate, and 25.9% heavy. LPS concentrations were significantly reduced at the 12-month visit compared to baseline (p = 0.0002). No longitudinal changes were observed for I-FABP or IGF-1 in the 6- or 12-month periods following baseline treatment. After 6-months, I-FABP concentration was significantly higher in high vs low intensity (p = 0.0017). IGF-1 concentrations were significantly lower among children with high and moderate vs low intensity infections at each study visit.Conclusions/significanceWe report that S. mansoni infection impacts LPS, I-FABP and IGF-1. These findings suggest a mechanistic role for EED in schistosomiasis-related morbidities, particularly linear growth.

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.

Biomarkers of environmental enteric dysfunction and adverse birth outcomes: An observational study among pregnant women living with HIV in Tanzania.

SummaryBackgroundEnvironmental enteric dysfunction (EED) may contribute to adverse birth outcomes in low-resource settings. We examined the associations of EED biomarkers with birth outcomes in pregnant women living with human immunodeficiency virus in Dar es Salaam, Tanzania.MethodsWe performed a cohort study of 706 HIV-infected pregnant women. Maternal serum samples collected at 32 weeks gestation were analyzed for markers of EED (anti-flagellin and anti-LPS immunoglobulins, intestinal fatty acid-binding protein [I-FABP] and soluble CD14), systemic inflammation (C-reactive protein and α1-acid glycoprotein [AGP]), and growth hormone resistance (insulin-like growth factor 1 [IGF-1] and fibroblast growth factor 21 [FGF21]. Associations of biomarkers categorized into quartiles with birth outcomes (birthweight, gestational duration, birthweight-for-gestational age, and stillbirth) were assessed using linear and log-binomial regression models adjusted for multiple sociodemographic and clinical variables.FindingsMaternal EED biomarkers were not significantly associated with birthweight, gestation duration, or birthweight-for-gestational age. However, higher quintiles of I-FABP concentrations were associated with greater risk of stillbirth (ptrend=0·02). Higher AGP was associated with lower birthweight and was associated with increased risk of small-for-gestational age births. Higher IGF-1 was associated with higher birthweight and birthweight-for-gestational age while higher FGF21 was associated with shorter gestation and higher risk of preterm birth.InterpretationMaternal biomarkers of EED, systemic inflammation, and growth hormones were differentially associated with birth outcomes. Biomarkers of EED may be useful to identify pregnant women at risk of adverse birth outcomes, but further research is needed to confirm these findings and elucidate biological mechanisms.Funding10.13039/100000002National Institutes of Health.

Diabetes exacerbated sepsis-induced intestinal injury by promoting M1 macrophage polarization via miR-3061/Snail1 signaling

BackgroundMacrophages play important roles in diabetes and sepsis-related intestinal injury. Accumulating evidence suggests that microRNAs (miRNAs) act as the fundamental link between macrophage polarization and tissue injury. However, the underlying mechanisms of miRNAs in regulating macrophage polarization–related intestinal injury under diabetes and sepsis conditions remain unclear.MethodsThe cecal ligation and puncture (CLP)–induced sepsis models were established in male wild-type (WT) and diabetic mice. Clodronate liposome was used to deplete macrophage. H&E staining, inflammatory cytokines [tumor necrosis factor–α (TNF-α), interleukin-1β (IL-1β), and IL-6], and intestinal mucosal barrier function markers [occludin, ZO-1, lipopolysaccharide (LPS), and intestinal fatty acid binding protein (iFABP)] were used to assess elevated intestinal damage. miRNA array, RNA-seq, and bioinformatic analysis were performed to detect the miRNA and messenger RNA (mRNA) expression and the potential regulation mechanism. In vitro, RAW264.7 cells were cultured in the absence or presence of high glucose and LPS, miR-3061 mimics, and Snail small interfering RNA stimulation, respectively, for further mechanism studies. Luciferase reporter assay was used to confirm the interplay between miRNA and its target genes.ResultsCompared with WT CLP mice, the diabetic CLP mice showed severe intestinal damage characterized by significant increases in Chui’s scores, expression of inflammatory cytokines (TNF-α, IL-1β, and IL-6), serum LPS and iFABP concentration, and significant reductions in tight junction protein occludin and ZO-1 levels. Macrophage depletion reversed the intestinal damage caused by CLP. The bioinformatic analysis revealed that miR-3061/Snail1 might be a potential regulation axis of macrophage polarization. Furthermore, high glucose and LPS stimulation increased M1 macrophage and reduced the levels of miR-3061, which was negatively associated with Snail1 in RAW264.7 cells. Mechanistic studies demonstrated that miR-3061 regulated macrophage polarization by targeting the Snail1 mRNA 3′‐untranslated region. Moreover, miR-3061 overexpression suppressed Snail1 expression and inhibited M1 macrophage and inflammatory cytokines.ConclusionThis study elucidated that diabetes exacerbated sepsis-induced intestinal injury by promoting M1 macrophage polarization and further demonstrated that the miR-3061/Sani1 axis may be the potential target of macrophage polarization.

Exertional, But Not Passive, Hyperthermia Increases Gastrointestinal Permeability

Exertional hyperthermia reduces splanchnic blood flow which leads to gastrointestinal ischemia. This is associated with increased gastrointestinal perturbations and endotoxemia which are potential precursors of exertional heat stroke. However, whether hyperthermia alone can result in significant disruption to gastrointestinal integrity remains unclear. PURPOSE: To determine whether exertional or passive hyperthermia contributes to greater changes in gastrointestinal permeability METHODS: 16 physically active males (mean ± SD; age: 26 ± 3, VO2max: 65 ± 6 ml/kg/min) completed three randomised trials. Blood samples were obtained at baseline and after (a) 70% VO2max run (RUN; Tdb: 30.0 ± 0.1 °C, RH: 71 ± 1%), (b) 50% VO2max walk (WALK; Tdb: 30.0 ± 0.0 °C, RH: 71 ± 0%) and (c) passive heating via warm water immersion at 42 °C (PaH). Serum concentrations of I-FABP, LPS and IL-6 were determined using ELISA. Gastrointestinal temperature (Tgi), heart rate (HR), physiological strain index (PSI) and changes in blood biomarkers were assessed using 1-way ANOVA or paired t-test with p < 0.05 as statistically significant. RESULTS: Participants observed similar baseline Tgi (37.0 ± 0.2 °C, p = 0.204) and HR (63 ± 7 bpm; p = 0.118). End Tgi was similar for RUN (39.4 ± 0.2 °C) and PaH (39.3 ± 0.3 °C, p = 0.289), but lower in WALK (37.9 ± 0.3 °C, p < 0.001). Mean PSI was greatest in RUN (7.4 ± 0.5), followed by PaH (5.2 ± 0.6) and WALK (3.1 ± 0.7, p < 0.001). Serum concentrations of I-FABP, LPS and IL-6 were similar at baseline (p > 0.05). Serum I-FABP and IL-6 concentrations increased from baseline to post-trial in RUN (I-FABP: 797 ± 467 pg/ml vs 1801 ± 1432 pg/ml, p = 0.007; IL-6: 4.3 ± 3.4 pg/ml vs 9.3 ± 5.4 pg/ml, p < 0.001) and WALK (I-FABP: 772 ± 460 pg/ml vs 1121 ± 966 pg/ml, p = 0.044; IL-6: 4.5 ± 4.1 pg/ml vs 9.1 ± 8.5 pg/ml, p = 0.004) but not in PaH (I-FABP: 888 ± 572 pg/ml vs 893 ± 550 pg/ml, p = 0.935; IL-6: 5.3 ± 5.4 pg/ml vs 5.5 ± 5.2 pg/ml, p = 0.285). No differences in post-trial serum LPS concentrations were observed (p = 0.337). CONCLUSION: Hyperthermia alone may be insufficient to trigger changes in gastrointestinal permeability. Disruptions to gastrointestinal integrity during exertional hyperthermia may instead be exercise-induced, stemming from mechanical and metabolic stress arising from physical exertion. Supported by NUS Internal Research Funding

Detection of Bacterial DNA in the Plasma of Psoriasis Patients and its Association with Serum Intestinal Fatty Acid Binding Protein Concentration

Background: There is evidence of the role of microorganisms, in particular in the throat and skin in psoriasis pathogenesis. This study aimed to investigate the presence of bacterial DNA (bacDNA) in patients' plasma and its association with gut barrier integrity . Methodology: Plasma was collected from 60 psoriasis patients in the flare up stage and 40 healthy controls. BacDNA was detected by PCR amplification using a 16S ribosomal DNA primer. The amplified DNA fragments were then sequenced to determine their bacterial origin. Results: Bacterial DNA was detected in 51 of 60 patients and only in 4 of 40 healthy controls. BacDNA sequencing results revealed that these bacterial species originated from the gut and skin. On the other hand, intestinal fatty acid binding protein (I-FABP) was measured by ELISA technique to investigate the integrity of the intestinal barrier. Serum concentrations of I-FABP were significantly higher in psoriasis patients compared with the healthy group and were positively correlated with the presence of bacDNA in patients' plasma. Conclusion: These findings suggest that psoriasis flare up is associated with translocation of bacteria and its metabolites into the blood stream, causing an immune system response. The specific mechanism of bacDNA in the pathogenesis of psoriasis needs to be comprehensively studied. Keywords: psoriasis, gut barrier, I-FABP, skin-gut axes