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

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

Effects of nutritional therapy on gastrointestinal microbial digestion and barrier defense markers in elderly patients with diabetes.

OBJECTIVE: We sought to investigate the effects of gastrointestinal nutrition therapy on gastrointestinal microbial digestion and barrier defense markers in elderly patients with diabetes. METHODS: A total of 120 elderly patients with type 2 diabetes were enrolled at our hospital between January 2020 and December 2022. The participants in this study were randomly allocated into either the nutritional group (n = 60) who underwent gastrointestinal nutrition therapy or the control group (n = 60) who underwent conventional T2DM diet management for a period of 12 weeks. Clinical data, as well as small intestinal permeability measured by the lactulose-mannitol urine test, plasma circulating IL-6 and zonulin levels measured by ELISA, and expressions of ZO-1 and Claudin-3 in blood analyzed through Western blotting were collected. RESULTS: The nutrition group demonstrated a higher proportion of patients achieving HbA1c < 7% compared to the control group (P < 0.05). Moreover, the nutrition group exhibited a greater reduction in fasting and postprandial blood glucose levels compared to the control group (P < 0.05). The concentrations of formate-tetrahydrofolate ligase and acetic CoA transferase were significantly increased in the nutrition group compared to the control group (P < 0.05). Fecal analysis revealed higher levels of acetic acid and butyric acid in the nutrition group compared to the control group (P < 0.05). The ratio of lactulose to mannitol was higher in the nutrition group compared to the control group (P < 0.05). Furthermore, the nutrition group showed lower levels of IL-6 and zonulin compared to the control group (P < 0.05). CONCLUSION: Personalized gastrointestinal nutrition therapy was found to enhance the production of short-chain fatty acids and preserve intestinal permeability, leading to improved gastrointestinal microbial digestion and barrier defense in elderly patients with diabetes.

The Effects of a Very-Low-Calorie Ketogenic Diet on the Intestinal Barrier Integrity and Function in Patients with Obesity: A Pilot Study.

The very-low-calorie ketogenic diet (VLCKD) is effective and safe for obese individuals, but limited information exists on its impact on the intestinal barrier. This study analyzed the effects of 8 weeks of VLCKD on 24 obese patients (11M/13F). Carbohydrate intake was fixed at 20-50 g/day, while protein and lipid intake varied from 1-1.4 g/kg of ideal body weight and 15-30 g per day, respectively. Daily calorie intake was below 800 kcal. The lactulose-mannitol absorption test assessed small intestinal permeability. Multiple markers, such as serum and fecal zonulin, fatty acid-binding protein, diamine oxidase concentrations, urinary dysbiosis markers (indican and skatole), and circulating lipopolysaccharide levels, were analyzed. Inflammation markers (serum interleukin 6, 8, 10, and tumor necrosis factor-α concentrations) were also evaluated. The results showed significant reductions in weight, BMI, and waist circumference post-diet. However, the lactulose-mannitol ratio increased by 76.5%, and a significant increase in dysbiosis markers at the end of the diet occurred. This trend was particularly evident in a subgroup of patients. Despite initial benefits, the VLCKD might negatively affect the intestinal barrier function in obese patients, potentially worsening their compromised intestinal balance.

Prevention of dextran sulfate sodium (DSS)-induced ulcerative colitis in mice by a synbiotic approach using probiotic and lactulose.

In this research, the synbiotic effects of the probiotic Lactiplantibacillus plantarum YW11 and lactulose on intestinal morphology, colon function, and immune activity were evaluated in a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed that L. plantarum YW11 in combination with lactulose decreased the severity of colitis in mice and improved the structure of the damaged colon, as assessed using colon length and disease condition. Moreover, colonic levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-12, TNF-α, and IFN-γ) were significantly lower and anti-inflammatory factors (IL-10) were significantly higher following the synbiotic supplementation. The synbiotic also exerted antioxidant effects by up-regulating SOD and CAT levels and down-regulating MDA levels in colon tissue. It could also reduce the relative expression of iNOS mRNA and increase the relative expression of nNOS and eNOS mRNA. Western blot confirmed the increased expression of c-Kit, IκBα, and SCF and significantly reduced expression of the NF-κB protein. Therefore, the combination of L. plantarum YW11 and lactulose exerted therapeutic effects mainly through the NF-κB anti-inflammatory pathway, which represented a novel synbiotic approach in the prevention of colonic inflammation.

Intestinal permeability in patients undergoing stem cell transplantation correlates with systemic acute phase responses and dysbiosis.

Intestinal permeability may correlate with adverse outcomes during hematopoietic stem cell transplantation (HSCT), but longitudinal quantification with traditional oral mannitol and lactulose is not feasible in HSCT recipients because of mucositis and diarrhea. A modified lactulose:rhamnose (LR) assay is validated in children with environmental enteritis. Our study objective was to quantify peri-HSCT intestinal permeability changes using the modified LR assay. The LR assay was administered before transplant, at day +7 and +30 to 80 pediatric and young adult patients who received allogeneic HSCT. Lactulose and rhamnose were detected using urine mass spectrometry and expressed as an L:R ratio. Metagenomic shotgun sequencing of stool for microbiome analyses and enzyme-linked immunosorbent assay analyses of plasma lipopolysaccharide binding protein (LBP), ST2, REG3α, claudin1, occludin, and intestinal alkaline phosphatase were performed at the same timepoints. L:R ratios were increased at day +7 but returned to baseline at day +30 in most patients (P = .014). Conditioning regimen intensity did not affect the trajectory of L:R (P = .39). Baseline L:R ratios did not vary with diagnosis. L:R correlated with LBP levels (r2 = 0.208; P = .0014). High L:R ratios were associated with lower microbiome diversity (P = .035), loss of anaerobic organisms (P = .020), and higher plasma LBP (P = .0014). No adverse gastrointestinal effects occurred because of LR. Intestinal permeability as measured through L:R ratios after allogeneic HSCT correlates with intestinal dysbiosis and elevated plasma LBP. The LR assay is well-tolerated and may identify transplant recipients who are more likely to experience adverse outcomes.

Gastrointestinal structure and function of preweaning dairy calves fed a whole milk powder or a milk replacer high in fat.

The composition of milk replacer (MR) for calves greatly differs from that of bovine whole milk, which may affect gastrointestinal development of young calves. In this light, the objective of the current study was to compare gastrointestinal tract structure and function in response to feeding liquid diets having a same macronutrient profile (e.g., fat, lactose, protein) in calves in the first month of life. Eighteen male Holstein calves (46.6 ± 5.12 kg; 1.4 ± 0.50 d of age at arrival; mean ± standard deviation) were housed individually. Upon arrival, calves were blocked based on age and arrival day, and, within a block, calves were randomly assigned to either a whole milk powder (WP; 26% fat, DM basis, n = 9) or a MR high in fat (25% fat, n = 9) fed 3.0 L 3 times daily (9 L total per day) at 135 g/L through teat buckets. On d 21, gut permeability was assessed with indigestible permeability markers [chromium (Cr)-EDTA, lactulose, and d-mannitol]. On d 32 after arrival, calves were slaughtered. The weight of the total forestomach without contents was greater in WP-fed calves. Furthermore, duodenum and ileum weights were similar between treatment groups, but jejunum and total small intestine weights were greater in WP-fed calves. The surface area of the duodenum and ileum did not differ between treatment groups, but the surface area of the proximal jejunum was greater in calves fed WP. Urinary lactulose and Cr-EDTA recoveries were greater in calves fed WP in the first 6 h post marker administration. Tight junction protein gene expression in the proximal jejunum or ileum did not differ between treatments. The free fatty acid and phospholipid fatty acid profiles in the proximal jejunum and ileum differed between treatments and generally reflected the fatty acid profile of each liquid diet. Feeding WP or MR altered gut permeability and fatty acid composition of the gastrointestinal tract and further investigation are needed to understand the biological relevance of the observed differences.

Consumption of a multi-deficient diet causes dynamic changes in the intestinal morphofunctional barrier, body composition and impaired physical development in post-weaning mice.

Few studies have focused on nutrient-deficient diets and associated pathobiological dynamics of body composition and intestinal barrier function. This study evaluated the impact of a nutrient-deficient diet on physical development and intestinal morphofunctional barrier in mice. C57BL/6 (21 days of age) mice were fed a Northeastern Brazil regional basic diet (RBD) or a control diet for 21 d. The animals were subjected to bioimpedance analysis, lactulose test, morphometric analysis and quantitative reverse transcription-PCR to evaluate tight junctions and intestinal transporters. RBD feeding significantly reduced weight (P < 0·05) from day 5, weight gain from day 3 and tail length from day 14. The intake of RBD reduced total body water, extracellular fluid, fat mass and fat-free mass from day 7 (P < 0·05). RBD induced changes in the jejunum, with an increase in the villus:crypt ratio on day 7, followed by reduction on days 14 and 21 (P < 0·05). Lactulose:mannitol ratio increased on day 14 (P < 0·05). Changes in intestinal barrier function on day 14 were associated with reductions in claudin-1 and occludin, and on day 21, there was a reduction in the levels of claudin-2 and occludin. SGLT-1 levels decreased on day 21. RBD compromises body composition and physical development with dynamic changes in intestinal barrier morphofunctional. RBD is associated with damage to intestinal permeability, reduced levels of claudin-1 and occludin transcripts and return of bowel function in a chronic period.

Efficacy evaluation of probiotics combined with prebiotics in patients with clinical hypothyroidism complicated with small intestinal bacterial overgrowth during the second trimester of pregnancy.

Objective: To explore the effect of probiotics combined with prebiotics on clinical hypothyroidism during pregnancy combined with small intestinal bacterial overgrowth. Methods: (1) In total, 441 pregnant women were included in this study. A total of 231 patients with clinical hypothyroidism during the second trimester of pregnancy and 210 normal pregnant women were enrolled in the lactulose methane-hydrogen breath test. The positive rate of intestinal bacterial overgrowth (SIBO), gastrointestinal symptoms, thyroid function and inflammatory factors were compared between the two groups by chi-square test and two independent sample t-test. (2) SIBO-positive patients in the clinical hypothyroidism group during pregnancy (n=112) were treated with probiotics combined with prebiotics based on conventional levothyroxine sodium tablets treatment. The changes in the methane-hydrogen breath test, gastrointestinal symptoms, thyroid function and inflammatory factors were compared before treatment (G0) and 21 days after treatment (G21) by chi-square test and paired sample t test. Results: (1) The positive rates of SIBO in pregnant women in the clinical hypothyroidism group and control group were 48.5% and 24.8%, respectively. (2) The incidence of abdominal distention and constipation in the clinical hypothyroidism group was significantly higher than that in the control group, and the risk of abdominal distention and constipation in SIBO-positive pregnant women was higher than that in SIBO-negative pregnant women. (3) The serum levels of hypersensitive C-reactive protein (hsCRP), IL-10, IL-6, TNF-α, low-density lipoprotein (LDL), total cholesterol (TC), free fatty acids (FFAs) and apolipoprotein B (ApoB) in the hypothyroidism group during pregnancy were higher than those in the control group. (4) After 21 days of probiotics combined with prebiotics, the incidence of pure methane positivity in the methane-hydrogen breath test in the G21 group was significantly reduced, and the average abundance of hydrogen and methane at each time point in the G21 group was lower than that in the G0 group. (5) The incidence of constipation in the G21 group was significantly lower than before treatment. (6) The levels of serum TSH, hsCRP, IL-6, TNF-α, TC and LDL in pregnant women after probiotics combined with prebiotics were lower than those before treatment. Conclusion: Probiotics combined with prebiotics are effective in the treatment of pregnant patients with clinical hypothyroidism complicated with SIBO, providing a new idea to treat pregnant patients with clinical hypothyroidism complicated with SIBO.

The potential role of lactulose pharmacotherapy in the treatment and prevention of diabetes.

The non-absorbable disaccharide lactulose is mostly used in the treatment of various gastrointestinal disorders such as chronic constipation and hepatic encephalopathy. The mechanism of action of lactulose remains unclear, but it elicits more than osmotic laxative effects. As a prebiotic, lactulose may act as a bifidogenic factor with positive effects in preventing and controlling diabetes. In this review, we summarized the current evidence for the effect of lactulose on gut metabolism and type 2 diabetes (T2D) prevention. Similar to acarbose, lactulose can also increase the abundance of the short-chain fatty acid (SCFA)-producing bacteria Lactobacillus and Bifidobacterium as well as suppress the potentially pathogenic bacteria Escherichia coli. These bacterial activities have anti-inflammatory effects, nourishing the gut epithelial cells and providing a protective barrier from microorganism infection. Activation of peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP1) can influence secondary bile acids and reduce lipopolysaccharide (LPS) endotoxins. A low dose of lactulose with food delayed gastric emptying and increased the whole gut transit times, attenuating the hyperglycemic response without adverse gastrointestinal events. These findings suggest that lactulose may have a role as a pharmacotherapeutic agent in the management and prevention of type 2 diabetes via actions on the gut microbiota.

Intestinal Barrier Permeability in Obese Individuals with or without Metabolic Syndrome: A Systematic Review.

Altered intestinal barrier permeability has been associated with obesity and its metabolic and inflammatory complications in animal models. The purpose of this systematic review is to assess the evidence regarding the association between obesity with or without Metabolic Syndrome (MetS) and alteration of the intestinal barrier permeability in humans. A systematic search of the studies published up until April 2022 in Latin America & Caribbean Health Sciences Literature (LILACS), PubMed, Scopus, Embase, and ScienceDirect databases was conducted. The methodological quality of the studies was assessed using the Newcastle-Ottawa scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) checklist. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the quality of the evidence. Eight studies were included and classified as moderate to high quality. Alteration of intestinal barrier permeability was evaluated by zonulin, lactulose/mannitol, sucralose, sucrose, lactulose/L-rhamnose, and sucralose/erythritol. Impaired intestinal barrier permeability measured by serum and plasma zonulin concentration was positively associated with obesity with MetS. Nonetheless, the GRADE assessment indicated a very low to low level of evidence for the outcomes. Thus, clear evidence about the relationship between alteration of human intestinal barrier permeability, obesity, and MetS was not found.

Enteropathy Markers in Early Life Were Associated with Adipokine, Apolipoprotein, and Cytokine Profiles Consistent with an Adverse Cardiometabolic Disease Risk Profile Later in Childhood in a Peruvian Birth Cohort.

Metabolic syndrome is a cluster of risk factors for cardiovascular disease afflicting more than 1 billion people worldwide and is increasingly being identified in younger age groups and in socioeconomically disadvantaged settings in the global south. Enteropathogen exposure and environmental enteropathy in infancy may contribute to metabolic syndrome by disrupting the metabolic profile in a way that is detectable in cardiometabolic markers later in childhood. A total of 217 subjects previously enrolled in a birth cohort in Amazonian Peru were monitored annually from ages 2 to 5 years. A total of 197 blood samples collected in later childhood were analyzed for 37 cardiometabolic biomarkers, including adipokines, apolipoproteins, cytokines, which were matched to extant early-life markers of enteropathy ascertained between birth and 2 years. Multivariate and multivariable regression models were fitted to test for associations, adjusting for confounders. Fecal and urinary markers of intestinal permeability and inflammation (myeloperoxidase, lactulose, and mannitol) measured in infancy were associated with later serum concentrations of soluble CD40-ligand, a proinflammatory cytokine correlated with adverse metabolic outcomes. Fecal myeloperoxidase was also associated with later levels of omentin-1. Enteric protozoa exposure showed stronger associations with later cardiometabolic markers than viruses, bacteria, and overall diarrheal episodes. Early-life enteropathy markers were associated with altered adipokine, apolipoprotein, and cytokine profiles later in childhood consistent with an adverse cardiometabolic disease risk profile in this cohort. Markers of intestinal permeability and inflammation measured in urine (lactulose, mannitol) and stool (myeloperoxidase, protozoal infections) during infancy may predict metabolic syndrome in adulthood.

Lactulose production from lactose isomerization by chemo-catalysts and enzymes: Current status and future perspectives.

Lactulose, a semisynthetic nondigestive disaccharide with versatile applications in the food and pharmaceutical industries, has received increasing interest due to its significant health-promoting effects. Currently, industrial lactulose production is exclusively carried out by chemical isomerization of lactose via the Lobry de Bruyn-Alberda van Ekenstein (LA) rearrangement, and much work has been directed toward improving the conversion efficiency in terms of lactulose yield and purity by using new chemo-catalysts and integrated catalytic-purification systems. Lactulose can also be produced by an enzymatic route offering a potentially greener alternative to chemo-catalysis with fewer side products. Compared to the controlled trans-galactosylation by ß-galactosidase, directed isomerization of lactose with high isomerization efficiency catalyzed by the most efficient lactulose-producing enzyme, cellobiose 2-epimerase (CE), has gained much attention in recent decades. To further facilitate the industrial translation of CE-based lactulose biotransformation, numerous studies have been reported on improving biocatalytic performance through enzyme mediated molecular modification. This review summarizes recent developments in the chemical and enzymatic production of lactulose. Related catalytic mechanisms are also highlighted and described in detail. Emerging techniques that aimed at advancing lactulose production, such as the boronate affinity-based technique and molecular biological techniques, are reviewed. Finally, perspectives on challenges and opportunities in lactulose production and purification are also discussed.

Colonic Lactulose Fermentation Has No Impact on Glucagon-like Peptide-1 and Peptide-YY Secretion in Healthy Young Men.

CONTEXT: The colon houses most of humans' gut microbiota, which ferments indigestible carbohydrates. The products of fermentation have been proposed to influence the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) from the many endocrine cells in the colonic epithelium. However, little is known about the colonic contribution to fasting or postprandial plasma levels of L-cell products. OBJECTIVE: To determine the impact of colonic lactulose fermentation on gut peptide secretion and to evaluate whether colonic endocrine secretion contributes to gut hormone concentrations measurable in the fasting state. METHODS: Ten healthy young men were studied on 3 occasions after an overnight fast. On 2 study days, lactulose (20 g) was given orally and compared to water intake on a third study day. For 1 of the lactulose visits, participants underwent a full colonic evacuation. Over a 6-h study protocol, lactulose fermentation was assessed by measuring exhaled hydrogen, and gut peptide secretion, paracetamol, and short-chain fatty acid levels were measured in plasma. RESULTS: Colonic evacuation markedly reduced hydrogen exhalation after lactulose intake (P = 0.013). Our analysis suggests that the colon does not account for the measurable amounts of GLP-1 and PYY present in the circulation during fasting and that fermentation and peptide secretion are not acutely related. CONCLUSION: Whether colonic luminal contents affect colonic L-cell secretion sufficiently to influence circulating concentrations requires further investigation. Colonic evacuation markedly reduced lactulose fermentation, but hormone releases were unchanged in the present study.

The clinical value of breath ammonia determination in patients with irritable bowel syndrome.

Gastrointestinal tract is the major source of ammonia (NH3). NH3 is produced by bacterial hydrolysis of urea as well as by bacterial protein deamination. The intensity of this process depends on protein intake and the amount of gut bacteria. AIM: The aim of the study was to assess the level of the fasting breath ammonia in patients with irritable bowel syndrome (IBS) in relation to the results of lactulose hydrogen breath test (LHBT) and to clinical form of this syndrome before and after 14-days rifaximin treatment at daily dose of 1200 mg. MATERIALS AND METHODS: The study was conducted in 120 subjects, including 40 healthy people (Controls, group I), 40 patients with IBS and predominant diarrhea (group II, IBS-D), and 40 patients with IBS and predominant constipation (group III, IBS-C). The lactulose breath test (LHBT) and ammonia breath test (ABT) were performed. Diagnosis of IBS was based on Rome IV Criteria. The severity of abdominal symptoms was assessed using the Gastrointestinal Symptom Rating Scale (GSRS-IBS). RESULTS: The basic level of ammonia in expired air in control group I was 5.2 ± 1.6 ppm, in group II - 20.8 ± 5.1 ppm (p< 0.001), and in group III - 10.4 ± 3.2 ppm (p< 0.001). Positive correlation was found between breath ammonia level and the results of LHBT in both groups with IBS. After 14-days rifaximin treatment at daily dose of 1200 mg the results of LHBT and breath ammonia significantly decreased in both groups. At the same time abdominal ailments subsided or significantly reduced. CONCLUSIONS: The determination of breath ammonia may be useful as biomarker of dysbiosis in patients with irritable bowel syndrome, especially in questionable results of hydrogen breath test.

Higher doses of ascorbic acid may have the potential to promote nutrient delivery via intestinal paracellular absorption.

The significance of plasma ascorbic acid (AA) is underscored by its enzymatic and antioxidant properties as well as involvement in many aspects of health including the synthesis of biomolecules during acute illness, trauma and chronic health conditions. Dietary intake supports maintenance of optimal levels with supplementation at higher doses more likely pursued. Transient increased intestinal paracellular permeability following high dose AA may be utilised to enhance delivery of other micronutrients across the intestinal lumen. The potential mechanism following dietary intake however needs further study but may provide an avenue to increase small intestinal nutrient co transport and absorption, including in acute and chronic illness.

New alkali tolerant ß-galactosidase from Paracoccus marcusii KGP - A promising biocatalyst for the synthesis of oligosaccharides derived from lactulose (OsLu), the new generation prebiotics.

The enzyme ß-galactosidase can synthesise novel prebiotics such as oligosaccharides derived from lactulose (OsLu) which can be added as a supplement in infant food formula. In this study, the intracellular ß-galactosidase produced by the alkaliphilic bacterium Paracoccus marcusii was extracted and purified to homogeneity using hydrophobic and metal affinity chromatography. The purification resulted in 18 U/mg specific activity, with a yield of 8.86% and an 18-fold increase in purity. The purified enzyme was a monomer with an 86 kDa molecular weight as determined by SDS PAGE and Q-TOF-LC/MS. ß-Galactosidase was highly active at 50 °C and pH 6-8. The enzyme displayed an alkali tolerant nature by maintaining more than 90% of its initial activity over a pH range of 5-9 after 3 h of incubation. Furthermore, the enzyme activity was enhanced by 37% in the presence of 5 M NaCl and 3 M KCl, indicating its halophilic nature. The effects of metal ions, solvents, and other chemicals on enzyme activity were also studied. The kinetic parameters KM and Vmax of ß-galactosidase were 1 mM and 8.56 µmoles/ml/min and 72.72 mM and 11.81 µmoles/ml/min on using oNPG and lactose as substrates. P. marcusii ß-galactosidase efficiently catalysed the transgalactosylation reaction and synthesised 57 g/L OsLu from 300 g/L lactulose at 40 °C. Thus, in this study we identified a new ß-galactosidase from P. marcusii that can be used for the industrial production of prebiotic oligosaccharides.

Short intense psychological stress induced by skydiving does not impair intestinal barrier function.

BACKGROUND AND AIM: Psychological stress has been shown to increase intestinal permeability and is associated with the development of gastrointestinal disorders. This study aimed to investigate skydiving as an alternative model to analyse the effect of acute psychological stress on intestinal barrier function. MATERIALS AND METHODS: Twenty healthy subjects participated in a tandem skydive followed by a negative control visit, of which 19 (9 females and 10 males, 25.9 ± 3.7 years) were included in the study. Intestinal permeability was assessed by a multi-sugar urinary recovery test. Sucrose recovery and lactulose/rhamnose ratio in 0-5h urine indicated gastroduodenal and small intestinal permeability, respectively, and sucralose/erythritol ratio in 5-24h urine indicated colonic permeability. Blood samples were taken to assess markers associated with barrier function. This study has been registered at ClinicalTrials.gov (NCT03644979) on August 23, 2018. RESULTS: Skydiving resulted in a significant increase in salivary cortisol levels directly after skydiving compared to the control visit. Cortisol levels were still increased two hours after landing, while cortisol levels before skydiving were not significantly different from the baseline at the control visit. Skydiving did not induce a significant increase in gastroduodenal, small intestinal or colonic permeability. There was also no significant increase in plasma intestinal and liver fatty acid-binding proteins, suggesting no damage to the enterocytes. DISCUSSION: These results show that the acute intense psychological stress induced by skydiving does not affect intestinal permeability in healthy subjects. Future models aiming to investigate the effect of stress on human intestinal barrier function should consider a more sustained exposure to the psychological stressor.

Effect of Early Feeding on Intestinal Permeability and Inflammation Markers in Infants with Genetic Susceptibility to Type 1 Diabetes: A Randomized Clinical Trial.

OBJECTIVES: To assess whether weaning to an extensively hydrolyzed formula (EHF) decreases gut permeability and/or markers of intestinal inflammation in infants with HLA-conferred diabetes susceptibility, when compared with conventional formula. STUDY DESIGN: By analyzing 1468 expecting biological parent pairs for HLA-conferred susceptibility for type 1 diabetes, 465 couples (32 %) potentially eligible for the study were identified. After further parental consent, 332 babies to be born were randomized at 35th gestational week. HLA genotyping was performed at birth in 309 infants. Out of 87 eligible children, 73 infants participated in the intervention study: 33 in the EHF group and 40 in the control group. Clinical visits took place at 3, 6, 9, and 12 months of age. The infants were provided either EHF or conventional formula whenever breastfeeding was not available or additional feeding was required over the first 9 months of life. The main outcome was the lactulose to mannitol ratio (L/M ratio) at 9 months. The secondary outcomes were L/M ratio at 3, 6, and 12 months of age, and fecal calprotectin and human beta-defensin 2 (HBD-2) levels at each visit. RESULTS: Compared with controls, the median L/M ratio was lower in the EHF group at 9 months (.006 vs .028; P = .005). Otherwise, the levels of intestinal permeability, fecal calprotectin, and HBD-2 were comparable between the two groups, although slight differences in the age-related dynamics of these markers were observed. CONCLUSIONS: It is possible to decrease intestinal permeability in infancy through weaning to an extensively hydrolyzed formula. This may reduce the early exposure to dietary antigens. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01735123.

Application of methane and hydrogen-based breath test in the study of gestational diabetes mellitus and intestinal microbes.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a common complication of pregnancy. The purpose of this study was to compare the incidence of small intestinal bacterial overgrowth (SIBO) in patients with GDM and the control group by methane and hydrogen lactulose breath test (LBT), and to explore its relationship with inflammation, vitamins, and the outcomes of maternal and child. METHODS: LBT was detected in 220 GDM patients, 160 pregnancy control patients and 160 pre-pregnancy control patients. The fasting blood glucose, white blood cells, vitamin A, D, E, neonatal weight, neonatal blood glucose and so on were compared and analyzed. RESULTS: There was no statistical significance in the general data of the three groups. The proportion of abdominal distension in the GDM group was higher than that in the other two groups (P < 0.001). The positive rates of SIBO + in GDM group, gestational control group and pre-pregnancy control group were 54.55%, 27.50% and 14.38%, respectively. The average abundance of hydrogen and methane in GDM group was significantly higher than that in control group at each time point. In the GDM group, SIBO + subjects had higher levels of fasting blood glucose, glycoglycated hemoglobin, C-reactive protein, neonatal weight, and lower levels of vitamin D and neonatal blood glucose (P < 0.001). CONCLUSION: Patients with GDM have a high incidence of SIBO, and SIBO may further increase their blood glucose by affecting inflammatory response and vitamin level, and even affect the outcome of mother and child.

Lactulose significantly increased the relative abundance of Bifidobacterium and Blautia in mice feces as revealed by 16S rRNA amplicon sequencing.

BACKGROUND: Lactulose was one of the earliest prebiotics to be identified. To assess the potential risk of large intakes of lactulose to the intestinal microbiota, mice were fed a diet containing lactulose (0%, 5% and 15%, w/w) for 2 weeks and the changes in the fecal microbiota were evaluated by 16S rRNA high-throughput sequencing. RESULTS: Lactulose intervention decreased the α-diversity of the fecal microbiota in both low-dose and high-dose groups. The relative abundance of Actinobacteria was significantly increased, while that of Bacteroidetes was significantly decreased after lactulose intervention. At the genus level, the relative abundance of Bifidobacterium belonging to Actinobacteria was significantly increased, and that of Alistipes belonging to Bacteroidetes was decreased in both low-dose and high-dose groups. The relative abundance of Blautia was significantly increased from 0.2% to 7.9% in the high-dose group and one strain of Blautia producta was isolated from the mice feces. However, the strain could not utilize lactulose. CONCLUSION: Overall, the microbial diversity was decreased after lactulose treatment, with significant increases in the relative abundance of Bifidobacterium. We also provide a strategy to increase the relative abundance of Blautia in the intestine by lactulose feeding at high doses, although the mechanism is not revealed. This will help us understand the prebiotic effect of lactulose on the host health. © 2021 Society of Chemical Industry.