Markers Of Gut Integrity Research Articles

Wheat germ supplementation has modest effects on gut health markers but improves glucose homeostasis markers in adults classified as overweight: A randomized controlled pilot study

Wheat germ (WG), a by-product of flour milling, is rich in bioactive substances that may help improve health complications associated with increased adiposity. This study investigated the effects of WG on gut health, metabolic, and inflammatory markers in adults classified as overweight. We hypothesized that WG, because of its many bioactive components, would improve gut health and metabolic, and inflammatory markers in overweight adults. Forty adults (18-45 years old) and with a body mass index between 25 and 30 kg/m2 participated in this single-blinded randomized controlled pilot study. Participants consumed the study supplements containing 30 g of either cornmeal (control, CL) or WG daily for 4 weeks. Primary outcome variables were gut health markers including gut microbiota, gut integrity markers, and fecal short-chain fatty acids, whereas secondary outcome variables included metabolic and inflammatory parameters assessed at baseline and at the end of supplementation. Thirty-nine participants (n = 19 and 20 for CL and WG group, respectively) completed the study. The genus Faecalibacterium was significantly higher in the WG group compared to CL post-supplementation but no significant changes in other gut health markers, short-chain fatty acids, inflammatory markers, and lipid profiles were observed. Compared with baseline, WG improved markers of glucose homeostasis including insulin (P = .02), homeostatic model assessment of insulin resistance (P = .03), glycated hemoglobin (P = .07), and the pro-inflammatory adipokine, resistin (P = .04). However, these parameters after intervention were not different with control. Our findings suggest that WG supplementation have modest effects on gut health but may provide an economical option for individuals to improve glycemic control.

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

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

Association between Fecal Microbiota, SCFA, Gut Integrity Markers and Depressive Symptoms in Patients Treated in the Past with Bariatric Surgery-The Cross-Sectional Study.

(1) Background: Depressive symptoms often appear after surgical treatment. (2) Methods: We involved 41 adults who underwent bariatric surgery a minimum of 6 months before the study and had the Beck scale ≥12. We analysed patients' mental state, gut barrier markers, faecal short chain fatty acids, and microbiota. (3) Results: Gut microbiota composition differed significantly among patients undergoing two different types of surgery (F = 1.64, p = 0.00002). Additionally, we discovered an association between short chain fatty acids and the Beck scale (F = 1.22, p = 0.058). The rearrangement of bacterial metabolites may be due to the patients' use of increased dietary protein, with insufficient intake of products containing vegetable fiber (Diet Quality Index (DQI-I )adequacy 22.55 (±3.46) points). (4) Conclusions: Bariatric surgery affects the gut microbiota, which may play an important role in the development of depressive and gastrointestinal symptoms in patients after bariatric surgery. Low fiber consumption and increased levels of faecal isobutyric acid may lead to intestinal inflammation. There is a need for further research on this topic including a larger sample size.

Abstract 13277: Hiv and Race Are Independently Associated With Endothelial Dysfunction

Objective: Assessing the vascular function in HIV + compared to HIV - with assessment of body composition, inflammation, and gut integrity markers. Introduction: HIV and ART are associated with an increased risk of CVD. Thus, the need for a non-invasive test to detect increased risk or early signs of CVD. Hypothesis: HIV and non-white race are independently associated with vascular dysfunction. High viral load, BMI, and inflammation damage endothelial function. Methods: We included participants ≥18 years, with peripheral arterial tonometry testing (EndoPAT2000) between 2014-2022. HIV + had a stable ART regimen, and a VL ≤400 c/mL. We measured the vessel’s adaptability with Reactive Hyperemia Index (RHI) (normal>1.67) and elasticity with Augmentation Index (AI) (normal<-10). We assessed markers of systemic inflammation, immune activation, and gut integrity. We used linear mixed models to estimate endothelial dysfunction with a significant p-value<0.05. Results: Overall, 511 participants (296 HIV+ and 215 HIV-) were included. The estimated RHI among HIV+ was 13% lower (p=0.01) compared to HIV-. In Non-White, the estimated RHI was 9% lower (p=0.001) than in White. Every 1% increase in BMI we would expect RHI to increase 0.17% (p=0.01). At the time of EndoPAT, the estimated RHI was 8% lower (p=0.04) among PI antiretroviral therapy use compared to HIV+ who were taking NRTI or NNRTIs. The estimated odds of having endothelial dysfunction (RHI ≤ 1.67) is 1.56 times greater (95% CI: 1.05, 2.31) in Non-White compared to White, independent of HIV status [OR=1.4 (95% CI: 0.94, 2.13)]. There was not enough evidence to suggest that inflammation, gut, or monocyte markers, current or nadir CD4, duration of HIV, or current treatment with NRTI or NNRTIs at the time of EndoPat was associated with endothelial dysfunction. Conclusions: HIV and non-white race are independently associated with endothelial dysfunction. PI use was associated with vascular dysfunction in all racial groups.

Dietary intervention of prebiotics and vitamins on gut health of children

PurposeGut health has multidimensional impact on childhood growth and development. Diet being the major modulator of gut health, this study aims to hypothesize if supplementation of dietary prebiotics and vitamins can impact gut environment of healthy children.Design/methodology/approachA double-blind placebo-controlled trial was conducted with parallel allocation of children 8–13 years of age to placebo or test group. Test group was supplemented with 1.5 g of formulation comprising prebiotics and vitamins, and to placebo, maltodextrin (1.5 g) was supplemented. After four weeks, the effect on markers of gut health (i.e. beneficial microbes, and gut integrity markers such as secretory Immunoglobulin A [sIgA] and calprotectin concentration) was evaluated in feces of children.FindingsSignificant increase of 17.1% in fecal bifidobacteria counts (p = 0.04) was observed in the test group compared to placebo after four weeks. Also, fecal calprotectin concentration decreased (20%) significantly (p = 0.01) in test group compared to placebo. In addition, the test group showed significant improvement in fecal sIgA and lactobacilli compared to baseline concentration (p = 0.01 and 0.001, respectively).Research limitations/implicationsThis study demonstrates that prebiotic (and vitamin) intervention may influence health outcomes in children by positively modulating markers of gut health.Originality/valueThere are limited studies demonstrating the efficacy of prebiotic and vitamins on gut health of school age children.

Impact of Heroin and HIV on Gut Integrity and Immune Activation.

Background:Altered gut integrity is central to HIV-related immune activation. Opioids may promote similar changes in gut permeability and/or increase systemic inflammation, potentially augmenting processes already occurring in people with HIV (PWH).Setting:Urban hospital systems in Cleveland, Ohio, and surrounding communities.Methods:This is a prospectively enrolled, cross-sectional study including people with and without HIV using heroin and people with and without HIV who have never used heroin, matched by age, sex, and CD4+ T-cell count (PWH only) to compare markers of gut integrity, microbial translocation, systemic inflammation, and immune activation.Results:A total of 100 participants were enrolled. Active heroin use was associated with higher concentrations of lipopolysaccharide-binding protein (LBP), beta-D-glucan (BDG), high-sensitivity C-reactive protein (hsCRP), soluble tumor necrosis factor-α-receptors I and II, soluble CD163, inflammatory monocytes, and activated CD4+ lymphocytes in adjusted models. HIV status tended to modify the effect between heroin use and LBP, BDG, hsCRP, patrolling monocytes, and activated CD4+ lymphocytes (P < 0.15 for interactions); however, it was not as expected. The effect of heroin on these markers (except patrolling monocytes) was greatest among those without HIV rather than among those with HIV.Conclusions:Heroin use is associated with heightened microbial translocation, systemic inflammation, and immune activation. Concurrent HIV infection in virologically suppressed individuals does not seem to substantially worsen the effects heroin has on these markers.

80. Heme Oxygenase-1 Gene promoter and associations with inflammation and subclinical vascular disease in Ugandan adolescents with and without HIV

Abstract Background Heme oxygenase-1 (HO-1) is a cytoprotective enzyme with potent anti-inflammatory, and anti-oxidant effects. The HO-1 response is modulated by functional polymorphisms (a dinucleotide (GT)n repeat length variation) in the HO-1 gene promoter region which have been associated with cardiovascular disease (CVD) susceptibility in adults. HO-1 polymorphisms and their associations with markers of inflammation and CVD in Ugandan adolescents with (HIV+) and without HIV (HIV-) have not been investigated. Methods We included 177 children (92 HIV+, 85 HIV-) enrolled in an ongoing observational cohort study at the Joint Clinical Research Center, Kampala, Uganda. All HIV+ participants were on ART. HO-1 (GT)n allele genotypes were determined by PCR of the (GT)n repeat region followed by fragment size determination on a capillary sequencer in DNA extracted from blood samples. Allele designations were assigned by number of (GT)n repeats: S &amp;lt; 27, M 27-34, or L &amp;gt; 34 repeats. We measured mean common carotid artery intima-media thickness (IMT) as a marker of CVD, markers of systemic inflammation (hsCRP, IL6, sTNFRI), monocyte activation (sCD14 and sCD163), and T-cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+) , oxidized lipids, markers of gut integrity and fungal translocation (BDG). Results Median age (IQR) was 13 (11, 14), 44% were females, 86% had viral load &amp;lt; 20 copies/mL. 19% had a short allele genotype, 37% had a medium allele genotype and 44% had a long allele genotype (Figure). The shortest and longest allele length correlated with lower IMT in HIV- only (r=-0.36 and -0.30, respectively, p≤ 0.01 for both). Among biomarkers, only the medium allele correlated with oxidized lipids in HIV+ and with hsCRP and BDG in HIV- (p≤ 0.05). After adjusting for age, sex, and BMI, the presence of a long allele was associated with lower IMT. This was no longer significant after adjusting for markers of inflammation or oxidized lipids (Table). Heme Oxygenase-1 genotype allele length frequency in Ugandan cohort of HIV+ and HIV- youth 1: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2) and HIV status (positive vs negative) 2: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2), sCD14 (pg/mL) and HIV status (positive vs negative) 3: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2), high sensitivity C reactive protein (ng/mL) and HIV status (positive vs negative) 4: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2), oxidized lipids and HIV status (positive vs negative) Conclusion These findings underscore the potential of the HO pathways in modulating future risk for CVD in adolescents through inflammation. HIV status in this setting, likely influences the associations with the genotype with the risk of CVD. Further studies to validate our findings in this population are required. Disclosures Grace A. McComsey, MD, Gilead (Consultant, Advisor or Review Panel member)Janssen (Consultant, Advisor or Review Panel member)Merck (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Redhill (Research Grant or Support)Roche (Grant/Research Support)Tetraphase, Astellas (Research Grant or Support)Theratechnologies (Consultant)Vanda (Grant/Research Support)ViiV/GSK (Scientific Research Study Investigator, Advisor or Review Panel member)

Assessment of Markers of Gut Integrity and Inflammation in Non-Celiac Gluten Sensitivity After a Gluten Free-Diet.

PurposeMarkers for gut integrity and inflammation have received increasing interest as intestinal permeability and innate immune system activation are suggested as possible pathophysiological mechanisms in non-celiac gluten sensitivity (NCGS). We aimed to assess relevant biomarkers in NCGS by analyzing serum levels of gut integrity and permeability markers, pro-inflammatory cytokines and antigliadin IgG in patients with suspected NCGS on a gluten-free diet (GFD), and compare them to serum levels in patients with irritable bowel syndrome (IBS) and healthy controls (HC).Patients and MethodsSerum samples collected from patients with suspected NCGS on a GFD (n=20, 14 women, 21–62 years), IBS (n=20, 16 women, 24–67 years) and HC (n=20, 14 women, 21–54 years) were analyzed. IBS severity scoring system (IBS-SSS) was applied to evaluate gastrointestinal symptoms.ResultsThe IBS-SSS score was higher in subjects with suspected NCGS and IBS patients compared to HC (p<0.0001). No significant differences were found in the serum levels of any of the gut integrity and permeability markers, cytokines or antigliadin IgG antibodies between the three groups. However, positive correlations were observed between claudin-1 and i-FABP, and between claudin-1 and antigliadin IgG antibodies.ConclusionNo differences in serum levels of gut integrity and permeability markers, pro-inflammatory cytokines or antigliadin IgG antibodies were found among patients with suspected NCGS on a GFD, IBS and HC.

A Low to Medium-Shear Extruded Kibble with Greater Resistant Starch Increased Fecal Oligosaccharides, Butyric Acid, and Other Saccharolytic Fermentation By-Products in Dogs.

The objective of this study was to assess whether diets with increased resistant starch (RS) had a positive effect on markers of colonic health in dogs. Three identical diets were extruded with high, medium and low shear (HS, MS and LS) to incrementally increase RS, and fed to 24 dogs in a replicated 3 × 3 William’s Latin square design for 28-day periods. Fasting blood and fresh feces were collected on the last week of each period. Fecal quality was maintained among treatments. Gut integrity markers were measured by ELISA. Fecal short-chain fatty acids (SCFAs) were measured by LC MS/MS. In addition, the microbiota of dogs was determined from fresh feces by 16s rRNA high throughput sequencing. Untargeted metabolomics of both feces and serum were determined by UPLC. Data were analyzed using mixed models. There were no treatment effects on satiety hormones or gut integrity markers. Dogs fed LS or MS diets had marginal evidence (p < 0.10) for decreased fecal pH and for higher concentration (p < 0.05) of butyric acid and fecal oligosaccharides, succinate and lactate. Also, dogs fed the MS or LS diets had a shift towards more saccharolytic bacteria.

Wheat Germ Supplementation Improves Glucose Homeostasis Markers of Overweight Adults Independent of Gut Microbial Modulation

Abstract Objectives This study investigated the effects of wheat germ (WG) supplementation on inflammation, metabolic, and gut health markers in overweight adults. Methods Forty overweight (BMI = 25.0–30 kg/m2) adults between 18–45 y old were recruited to this single-blinded randomized placebo-controlled study. Qualified participants were asked to maintain their normal diet and physical activity and consume energy balls containing 30 g of either WG or cornmeal (control) daily for 4 wks. Anthropometric and metabolic parameters, as well as dietary (3-d food record), medical history, physical activity (Yale Physical Activity Survey), stool measures (Bristol Stool Chart and the Cleveland Clinic Constipation Scoring System), gut integrity markers, and fecal bacterial population were assessed at baseline and at the end of the supplementation period. Results Thirty-nine participants completed the 4-week study (n = 20 and 19 for the WG and control group, respectively). There were no differences in the lipid profile, but glycated hemoglobin (P = 0.04), insulin (P = 0.03), and homeostatic model assessment of insulin resistance (HOMA-IR; P = 0.04) were significantly decreased in the WG but not the control group. Similarly, the adipokine resistin was also significantly reduced (P = 0.03) by WG but not the control. There were no changes in stool characteristics between the two groups before and after supplementation. Similarly, there were no changes in gut bacterial population due to WG supplementation but the phyla Bacteroidetes (P = 0.03) and Proteobacteria (P = 0.048) and the genus Bacteroides (P = 0.03) were significantly decreased in the control group. No significant changes were observed in plasma inflammatory markers, fecal short-chain fatty acid (SCFA) concentrations, and markers of gut integrity in both groups. Conclusions Four weeks of WG supplementation improved markers of glucose homeostasis, which can partly be attributed to the reduction of the pro-inflammatory adipokine resistin and not due to changes within the gut (i.e., bacterial population, gut integrity markers, and SCFA production). Our findings indicate that WG may be a safe, effective, and economical approach to improve glucose homeostasis. Funding Sources USDA Award #2019–67,018-29,260 and the Jim and Lynn Williams Professorship.

Montmorency Tart Cherry Supplementation Has Modest Effects on the Gut Microbiome and Markers of Gut Integrity and Insulin Resistance in Mice Fed Western Diet

Abstract Objectives This study investigated the dose-dependent effects of freeze-dried Montmorency tart cherry (TC) supplementation on gut health and metabolic parameters in mice fed a western diet (WD). Methods Six-week-old male C57BL/6 mice were randomly assigned to dietary treatment groups in a 2 × 3 factorial design with diet (control [AIN-93M] or WD, 45% fat kcal and 26% sucrose kcal) and TC (0, 5, 10% wt/wt) as factors for 12 wks. At the end of dietary treatment, body composition was assessed by dual energy xray absorptiometry, and tissues were collected to evaluate metabolic parameters and markers of gut health. Cecal content was used for bacterial and short chain fatty acid analyses (SCFAs). Results TC at the 10% dose significantly increased the abundance of the beneficial bacterial phylum, Actinobacteria, relative to the unsupplemented groups (P = 0.018 and 0.010 vs control and WD, respectively). Relative cecal weight (P = 0.007) and SCFAs were significantly increased (P &amp;lt; 0.05) with TC supplementation (∼20% and 2-fold for relative cecal weight and SCFAs, respectively). Histological evaluation revealed reduced ileal villi height (P = 0.0348), width (P = 0.0042) and area (P = 0.0132) with WD, and TC did not alter this response. Overall, the expression of genes related to gut health (i.e barrier integrity marker, mucus layer formation, and inflammatory marker), were unaffected by both WD and TC supplementation. Body weight (P = 0.0012), fat mass (P = 0.007), fasting blood glucose (P = 0.001), serum total cholesterol (P &amp;lt; 0.0001), triglyceride (P = 0.002), leptin (P = 0.0011), plasminogen activator inhibitor 1 (P = 0.0344), and resistin (P = 0.0012) were increased with WD, and TC had no effect on these parameters. Despite modest effects on metabolic parameters, the homeostatic model assessment of insulin resistance, HOMA-IR, a commonly used tool for assessing insulin resistance, was improved by 50% with the 5% TC (P = 0.0003). Conclusions TC supplementation restored some beneficial bacteria and increased SCFAs altered by WD. However, these changes in the gut did not translate to improvement in metabolic outcomes except for HOMA-IR. The mechanism by which TC improves HOMA-IR needs to be investigated in future studies. Funding Sources Cherry Marketing Institute and the Jim and Lynn Williams Professorship.

Effects of High Intakes of Fructose and Galactose, with or without Added Fructooligosaccharides, on Metabolic Factors, Inflammation, and Gut Integrity in a Rat Model.

A high fructose and galactose intake show adverse metabolic effects in animal models and in humans, but it is yet unknown if addition of fermentable dietary fiber can mitigate such effects. This study investigate the effects of high intakes of fructose and galactose, with/without added fructooligosaccharides (FOS), on metabolic factors, inflammation, and gut integrity markers in rats. Rats (n = 6/group) receive different carbohydrates at isocaloric conditions for 12 weeks as follows: 1) starch (control), 2) fructose, 3) galactose, 4) starch + FOS (FOS control), 5) fructose + FOS, and 6) galactose + FOS, together with a high amount of n-6 polyunsaturated fatty acids (n-6 PUFA) in all diets except for in 7) starch + olive oil (negative control). The rats fed the galactose and galactose + FOS diets exhibit lower body weight than other groups. High-galactose diets has more pronounced effects on metabolic factors and gut permeability than high-fructose diets. High-fructose diets show less pronounced effect on these selected markers. No differences in inflammatory markers are detected for any of the diets. The results suggest potential adverse effects of high galactose and fructose on metabolic factors and gut integrity markers, but not on inflammation. However, several mechanisms are at play, and general net effects are difficult to determine conclusively for the conditions tested.

Exercise and intestinal permeability: another form of exercise-induced hormesis?

Regular aerobic exercise has numerous benefits on human physiology, arguably by serving as a hormetic stressor resulting in positive adaptations over time. It has long been known that aerobic exercise at a variety of intensities and durations induces intestinal permeability, which is a feature of many pathologies of the gastrointestinal tract and metabolic diseases. Given the health benefits of exercise, it seems unlikely that intestinal permeability induced by exercise outweighs the positive adaptations. In fact, a growing body of evidence suggests adoption of exercise regimens lasting weeks to months improves indicators of intestinal permeability. In this brief review, we summarize factors contributing to acute exercise-induced intestinal permeability and what is known about chronic exercise and the gut barrier. Additionally, we outline known and theoretical adaptations of the gut to chronic exercise that may explain emerging reports that exercise improves markers of gut integrity.

Analysis of gut microbiota and intestinal integrity markers of inpatients with major depressive disorder

Previous studies have reported on the relationship between gut microbiota and major depressive disorder (MDD). However, there remain gaps in literature concerning the role of the intestinal barrier and microflora in the pathogenesis of depression. This study analyzes the potential causative relationship between gut microbiota and inflammatory and gut integrity markers and clinical symptoms in inpatients with depressive episodes. Sixteen inpatients (50% females) being treated with escitalopram (5–20 mg daily) in standardized conditions were included in the study. The composition of fecal microbiota was evaluated at baseline and endpoint using 16S rRNA sequencing. A significant correlation between depression severity was found, as measured with HDRS24 (Hamilton Depression Rating Scale-24 item), and the following abundance in bacteria: positive correlation with Paraprevotella (r = 0.80, q = 0.012), strong, negative correlations with Clostridiales (r = −0.70, q = 0.016), Clostridia (r = −0.71, q = 0.026), Firmicutes (r = −0.67. q = 0.032), and the RF32 order (r = −0.70, p = 0.016) in the Alphaproteobacteria (r = −0.66, q = 0.031). After six weeks of treatment, clinical outcomes were found to have a negative correlation with levels of plasma intestinal fatty acid-binding protein (IFABP) at the beginning of the study. Still they had a positive correlation with changes in fecal calprotectin during hospitalization. In conclusion, gut microbiota was associated with the severity of depressive symptoms. However, these findings do not serve as predictors of symptomatic improvement during antidepressant treatment in inpatient treatment for MDD. In turn, intestinal integrity and inflammation markers were associated with the response to treatment of patients with MDD and symptom severity. Additional studies are needed to confirm and extend these findings.

Dietary Fiber from Oat and Rye Brans Ameliorate Western Diet-Induced Body Weight Gain and Hepatic Inflammation by the Modulation of Short-Chain Fatty Acids, Bile Acids, and Tryptophan Metabolism.

Dietary fiber (DF) induces changes in gut microbiota function and thus modulates the gut environment. How this modulation is associated with metabolic pathways related to the gut is largely unclear. This study aims to investigate differences in metabolites produced by the gut microbiota and their interactions with host metabolism in response to supplementation with two bran fibers. Male C57BL/6N mice are fed a western diet (WD) for 17 weeks. Two groups of mice received a diet enriched with 10% w/w of either oat or rye bran, with each bran containing 50% DF. Microbial metabolites are assessed by measuring cecal short-chain fatty acids (SCFAs), ileal and fecal bile acids (BAs), and the expression of genes related to tryptophan (TRP) metabolism. Both brans lowered body weight gain and ameliorated WD-induced impaired glucose responses, hepatic inflammation, liver enzymes, and gut integrity markers associated with SCFA production, altered BA metabolism, and TRP diversion from the serotonin synthesis pathway to microbial indole production. Both brans develop a favorable environment in the gut by altering the composition of microbes and modulating produced metabolites. Changes induced in the gut environment by a fiber-enriched diet may explain the amelioration of metabolic disturbances related to WD.

Increased monocyte and T-cell activation in treated HIV+ Ugandan children: associations with gut alteration and HIV factors.

The pathophysiology of immune activation and its mechanisms in children living with perinatally acquired HIV (PHIV) in sub-Saharan Africa has been understudied. We enrolled 101 children living with PHIV and 96 HIV-negative controls (HIV-). All participants were between 10 and 18 years of age with no known active infections. PHIVs were on ART with HIV-1 RNA level 400 copies/ml or less. We measured plasma and cellular markers of monocyte activation, T-cell activation (expression of CD38 and HLA-DR on CD4 and CD8), oxidized lipids, markers of gut integrity and fungal translocation. Spearman correlations and linear regression models were used. Overall median (Q1; Q3) age was 13 years (11; 15) and 52% were girls. Groups were similar by age, sex and BMI. Median ART duration was 10 years (8; 11). PHIVs had higher monocyte and T-cell activation; higher sCD14 (P = 0.01) and elevated frequencies of nonclassical monocytes (P < 0.001 for both). Markers of systemic inflammation (hsCRP), fungal translocation (BDG), intestinal permeability (zonulin) and oxidized lipids (ox LDL) correlated with monocyte and T-cell activation in PHIV (≤0.05). After adjusting for age, sex, ART duration, protease inhibitor and nonnucleoside reverse transcriptase inhibitor use, a modest association between BDG and activated CD4 T cells was observed (β=0.65, P < 0.01). Oxidized LDL was inversely associated with activated T cells, inflammatory and nonclassical monocytes (P < 0.01). Ugandan children with perinatally acquired HIV with viral suppression have evidence of ongoing immune activation. Intestinal barrier dysfunction and fungal translocation may be involved in chronic immune dysfunction.

Micronutrients, Metabolic Complications, and Inflammation in Ugandan Children With HIV.

Selenium, zinc, and chromium are essential micronutrients. Their alterations have been associated with HIV disease progression, metabolic complications, and mortality. This is a cross-sectional study in children with perinatally acquired HIV (PHIV, n = 57), HIV-exposed uninfected (HEU, n = 59), and HIV-unexposed uninfected (HIV-, n = 56) children aged 2 to 10 years old, age- and sex-matched, enrolled in Uganda. PHIV were on stable antiretroviral therapy (ART) with undetectable viral load. We measured plasma concentrations of selenium, zinc, and chromium as well as markers of systemic inflammation, monocyte activation, and gut integrity. Among PHIV children, 93% had viral load ≤20 copies/mL, median CD4 was 37%, and 77% were receiving a nonnucleotide reserve transcriptase regimen. Median age of all participants was 8 years and 55% were girls. Median selenium concentrations were higher in PHIV compared with the HEU and HIV groups (P < 0.001), 46% of children overall had low zinc status (P = 0.18 between groups). Higher selenium, but not chromium or zinc, was associated with lower IL6, sTNFRI and II, and higher beta d glucan, a marker of fungal translocation, zonulin, a marker of gut permeability, oxidized LDL and insulin resistance (P ≤ 0.01). In this cohort of PHIV on ART in Uganda, there is a high prevalence of low zinc status overall. Higher plasma selenium concentrations were associated with lower systemic inflammation and higher gut integrity markers. Although our findings do not support the use of micronutrient supplementation broadly for PHIV in Uganda, further studies are warranted to assess the role of selenium supplements in attenuating heightened inflammation.

Insulin resistance and intestinal integrity in children with and without HIV infection in Uganda.

The risk of cardiometabolic complications in children with perinatally acquired HIV infection (PHIVs) and in perinatally HIV-exposed but uninfected children (HEUs) and its relationship to systemic inflammation and markers of gut integrity are not well established. In this current study, we assed insulin resitance in PHIV compared to HEUs and HIV unexposed uninfected children and explored potential association with intestinal damage biomarkers. This was a cross-sectional study in PHIVs, HEUs and HIV-unexposed, uninfected children (HUUs) aged 2-10years enrolled in Uganda. PHIVs were on stable antiretroviral therapy (ART) with HIV viral load <400 HIV-1 RNA copies/mL. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). We measured markers of systemic inflammation, monocyte activation and gut integrity. Kruskal-Wallis tests were used to compare markers by HIV status; Pearson correlation and multiple linear regressions were used to assess associations of the HOMA-IR index with biomarkers of intestinal damage and translocation. Overall, 172 participants were enrolled in the study (57 PHIVs, 59 HEUs and 56 HUUs). The median age was 7.8 [interquartile range (IQR) 6.39, 8.84] years, 55% were female and the median body mass index (BMI) was 15 (IQR 14.3, 15.8) kg/m2 . Among PHIVs, the median CD4% was 37%, and 93% had viral load ≤20 copies/mL. PHIVs had higher waist:hip ratio, high-density lipoprotein (HDL) cholesterol, triglycerides and HOMA-IR index than the other groups (P≤0.02). Factors correlated with insulin resistance included higher BMI and HDL cholesterol and lower soluble tumour necrosis factor receptor I (sTNFRI) (P≤0.02). There was no correlation between any of the other inflammatory or gut biomarkers and HOMA-IR index (P≥0.05). After adjusting for age and sTNFRI, BMI remained independently associated with the HOMA-IR index (β=0.16; P<0.01). Despite viral suppression, Ugandan PHIVs have disturbances in glucose metabolism. Higher BMI, and not immune activation or alteration of gut integrity, was associated with insulin resistance in this population.

2528. Inflammation and Plasma Selenium and Chromium in Ugandan Children Living with HIV

BackgroundSelenium deficiency has been reported to be associated with HIV disease progression and chromium deficiency with insulin resistance and hyperlipidemia. Here, we assessed selenium and chromium status in a cohort of Ugandan HIV+, HIV exposed uninfected (HEU) and HIV negative (HIV−) children and their associations with markers of systemic inflammation, immune activation, and gut integrity.MethodsThis is a cross-sectional study in HIV+, HEU and HIV unexposed uninfected (HIV-) children aged 2–10 years old enrolled in Uganda. HIV+ children were on stable ART with undetectable viral load. We measured plasma concentrations of selenium and chromium as well as markers of systemic inflammation, monocyte activation, gut integrity and insulin resistance (HOMA-IR).ResultsAmong HIV+ children (n = 57), 93% had viral load ≤ 20 copies/mL, mean CD4 was 34% and 77% were receiving a non-nucleotide reserve transcriptase regimen. Mean age of all participants was 7 years and 55% were girls. Mean selenium concentrations were higher in the HIV+ group (106 µg/L) compared with the HEU (84 µg/L) and HIV− (98 µg/L) groups (p . Mean chromium concentrations were 1 µg/L; 1 HIV+ child and 6 HEU children had chromium levels > 1 µg/L (p.ConclusionIn this cohort of HIV+ children on ART in Uganda, plasma selenium and chromium concentrations appear sufficient. Higher plasma selenium concentrations were associated with lower systemic inflammation and higher gut integrity markers. Although our findings do not support the use of selenium supplementation broadly for HIV-infected children in Uganda, further studies are warranted to assess the role of selenium supplements in attenuating heightened inflammation.Disclosures All authors: No reported disclosures.

Effects of a Cod Protein Hydrolysate Supplement on Symptoms, Gut Integrity Markers and Fecal Fermentation in Patients with Irritable Bowel Syndrome.

Peptides from fish may beneficially affect several metabolic outcomes, including gut health and inflammation. The effect of fish peptides in subjects with irritable bowel syndrome (IBS) has not previously been investigated, hence this study aimed to evaluate the effect of a cod protein hydrolysate (CPH) supplement on symptom severity, gut integrity markers and fecal fermentation in IBS-patients. A double-blind, randomized parallel-intervention with six weeks of supplementation with 2.5 g CPH (n = 13) or placebo (n = 15) was conducted. The outcomes were evaluated at baseline and the end of the study. The primary outcomes were symptom severity evaluated by the IBS severity scoring system (IBS-SSS) and quality of life. The secondary outcomes included gut integrity markers and pro-inflammatory cytokines in serum, fecal fermentation measured by concentration of short-chain fatty acids (SCFAs) and fecal calprotectin. The groups were comparable at baseline. The total IBS-SSS-scores were reduced in both the CPH-group (298 ± 69 to 236 ± 106, p = 0.081) and the placebo-group (295 ± 107 to 202 ± 103, p = 0.005), but the end of study-scores did not differ (p = 0.395). The concentrations of serum markers and SCFAs did not change for any of the groups. The baseline measures for the whole group showed that the total SCFA concentrations were inversely correlated with the total IBS-SSS-score (r = −0.527, p = 0.004). Our study showed that a low dose of CPH taken daily by IBS-patients for six weeks did not affect symptom severity, gut integrity markers or fecal fermentation when compared to the placebo group.