D-lactate Levels Research Articles

Amelioration of intestinal barrier function and reduction of blood lead level in adult women with recurrent spontaneous abortion by a novel product of dietary fiber mixture, Holofood

BackgroundThe elevated circulating toxins secondary to the impairment of intestinal barrier integrity commonly elicit a chronic inflammatory response and finally contribute to multiple diseases. These toxins, including bacterial by-products and heavy metals, are the potent risk factors for the development of recurrent spontaneous abortion (RSA). Preclinical evidence suggests that several dietary fibers can restore intestinal barrier function and decrease the accumulation of heavy metals. However, it is uncertain whether treatment with a newly developed blend of dietary fibers product (Holofood) benefits patients with RSA.MethodsIn this trial, we enrolled 70 adult women with RSA, who were randomly assigned into the experiment group and the control group in a 2:1 ratio. Upon the basis of conventional therapy, subjects in the experiment group (n = 48) received 8 weeks oral administration with Holofood three times daily at a dose of 10 g each time. Subjects without Holofood consumption were set as the control (n = 22). Blood samples were collected for the determinations of metabolic parameters, heavy mental lead, and the indices related to intestinal barrier integrity (d-lactate, bacterial endotoxin, and diamine oxidase activity).ResultsThe reduction amplitude in blood lead from baseline to week 8 was 40.50 ± 54.28 (μg/L) in the experiment group as compared with 13.35 ± 36.81 (μg/L) in the control group (P = 0.037). The decreased level of serum d-lactate from baseline to week 8 was 5.58 ± 6.09 (mg/L) in the experiment group as compared with − 2.38 ± 8.90 (mg/L, P < 0.0001) in the control group. The change in serum DAO activity from baseline to week 8 was 3.26 ± 2.23 (U/L) in the experiment group as compared with − 1.24 ± 2.22 (U/L, P < 0.0001) in the control group. Participants who received Holofood had a greater decline in blood endotoxin from baseline to week 8 than those in the control group. Moreover, by comparing with the self-baseline, Holofood consumption significantly decreased the blood levels of lead, d-lactate, bacterial endotoxin, and DAO activity.ConclusionOur results suggest that Holofood affords a clinically relevant improvements in blood lead level and intestinal barrier dysfunction in patients with RSA.

The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease.

Kawasaki disease (KD), an acute febrile systemic vasculitis in children, has become the leading cause of acquired heart disease in developed countries. Recently, the altered gut microbiota was found in KD patients during the acute phase. However, little is known about its characteristics and role in the pathogenesis of KD. In our study, an altered gut microbiota composition featured by the reduction in SCFAs-producing bacteria was demonstrated in the KD mouse model. Next, probiotic Clostridium butyricum (C. butyricum) and antibiotic cocktails were respectively employed to modulate gut microbiota. The use of C. butyricum significantly increased the abundance of SCFAs-producing bacteria and attenuated the coronary lesions with reduced inflammatory markers IL-1β and IL-6, but antibiotics depleting gut bacteria oppositely deteriorated the inflammation response. The gut leakage induced by dysbiosis to deteriorate the host's inflammation was confirmed by the decreased intestinal barrier proteins Claudin-1, Jam-1, Occludin, and ZO-1, and increased plasma D-lactate level in KD mice. Mechanistically, SCFAs, the major beneficial metabolites of gut microbes to maintain the intestinal barrier integrity and inhibit inflammation, was also found decreased, especially butyrate, acetate and propionate, in KD mice by gas chromatography-mass spectrometry (GC-MS). Moreover, the reduced expression of SCFAs transporters, monocarboxylate transporter 1 (MCT-1) and sodium-dependent monocarboxylate transporter 1 (SMCT-1), was also shown in KD mice by western blot and RT-qPCR analyses. As expected, the decrease of fecal SCFAs production and barrier dysfunction were improved by oral C. butyricum treatment but was deteriorated by antibiotics. In vitro, butyrate, not acetate or propionate, increased the expression of phosphatase MKP-1 to dephosphorylate activated JNK, ERK1/2 and p38 MAPK against excessive inflammation in RAW264.7 macrophages. It suggests a new insight into probiotics and their metabolites supplements to treat KD.

MicroRNA-1-3p and T-synthase mRNA have high diagnostic efficacy on intestinal mucosal barrier dysfunction in patients with severe acute pancreatitis.

Acute pancreatitis (AP) is an inflammatory disorder of the pancreas that can be complicated by intestinal mucosal barrier dysfunction (SAP&IBD). The current study sought to examine the diagnostic efficacy of miR-1-3p and T-synthase mRNA in SAP&IBD patients. First, SAP patients were assigned to SAP&IBD and SAP groups. Serum miR-1-3p expression and T-synthase mRNA expression patterns in peripheral blood B lymphocytes were measured using RT-qPCR. Pearson tests, ROC curve analysis, and multivariate logistic regression were used to analyze the correlation between miR-1-3p/T-synthase mRNA and clinical data, their diagnostic efficiency, and independent risk factors for SAP&IBD patients, respectively. The results showed that serum miR-1-3p in the SAP&IBD group was elevated, and T-synthase mRNA expression in peripheral blood B lymphocytes was diminished. Additionally, serum miR-1-3p expression in SAP&IBD patients was negatively correlated with T-synthase mRNA expression, and positively correlated with their Ranson score, CRP, IL-6, DAO, and D-Lactate levels. Meanwhile, T-synthase mRNA level was negatively correlated with IL-6, DAO, and D-Lactate levels. Both, serum miR-1-3p, T-synthase mRNA, and their combination were found to exhibit diagnostic efficiency for SAP&IBD patients, and were independently associated with IBD in SAP patients. Collectively, our findings suggest that miR-1-3p and T-synthase serve as independent risk factors for SAP&IBD patients and can aid the diagnosis of IBD in SAP patients.

Gut barrier protein levels in serial blood samples from critically ill trauma patients during and after intensive care unit stay.

In an effort to better manage critically ill patients hospitalised in the intensive care unit (ICU) after experiencing multiple traumas, the present study aimed to assess whether plasma levels of intestinal epithelial cell barrier proteins, including occludin, claudin-1, junctional adhesion molecule (JAM-1), tricellulin and zonulin, could be used as novel biomarkers. Additional potential markers such as intestinal fatty acid-binding protein (I-FABP), D-lactate, lipopolysaccharide (LPS) and citrulline were also evaluated. We also aimed to determine the possible relationships between the clinical, laboratory, and nutritional status of patients and the measured marker levels. Plasma samples from 29 patients (first, second, fifth and tenth days in the ICU and on days 7, 30 and 60 after hospital discharge) and 23 controls were subjected to commercial enzyme-linked immunosorbent assay (ELISA) testing. On first day (admission) and on the second day, plasma I-FABP, D-lactate, citrulline, occludin, claudin-1, tricellulin and zonulin levels were high in trauma patients and positively correlated with lactate, C-reactive protein (CRP), number of days of ICU hospitalisation, Acute Physiology and Chronic Health Evaluation II (APACHE II) score and daily Sequential Organ Failure Assessment (SOFA) scores (P < 0.05-P < 0.01). The results of the present study showed that occludin, claudin-1, tricellulin and zonulin proteins, as well as I-FABP, D-lactate and citrulline, may be used as promising biomarkers for the evaluation of disease severity in critically ill trauma patients, despite the complexity of the analysis of various barrier markers. However, our results should be supported by future studies.

Early detection of plasma d-lactate: Toward a new highly-specific biomarker of bacteraemia?

BackgroundBloodstream infections are a leading cause of mortality. Their detection relies on blood cultures (BCs) but time to positivity is often between tens of hours and days. d-lactate is a metabolite widely produced by bacteria but very few in human. We aimed to evaluate d-lactate, d-lactate/l-lactate ratio and d-lactate/total lactate ratio in plasma as potential early biomarkers of bacteraemia on a strictly biological standpoint. MethodsA total of 228 plasma specimens were collected from patients who had confirmed bacteraemia (n = 131) and healthy outpatients (n = 97). Specific l-lactate and d-lactate analyses were performed using enzymatic assays and analytical performances of d-lactate, d-lactate/total lactate and d-lactate/l-lactate ratios for the diagnosis of bacteraemia were assessed. ResultsA preliminary in vitro study confirmed that all strains of Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus were able to produce d-lactate at significant levels. In patients, plasma d-lactate level was the most specific biomarker predicting a bacteraemia profile with a specificity and predictive positive value of 100% using a cut-off of 131 μmol.L−1. However, sensitivity and negative predictive value were rather low, estimated at 31% and 52%, respectively. d-lactate displayed an Area Under Receiver Operating Characteristic (AUROC) curve of 0.696 with a P value < 0.0001. There was no difference of d-lactate levels between BCs bottles positive for Gram-positive or Gram-negative bacteria (p = 0.55). Conclusiond-lactate shows promise as a specific early biomarker of bacterial metabolism. The development of rapid automated assays could raise clinical applications for infectious diseases diagnosis including early bacteraemia prediction.

Inhibitory Effects of Lactulose on Enteric Bacterial Dynamics and Gut Permeability in Bile-Duct Ligated Rats

Background and Aim: The prebiotic potential of lactulose is well known, but its effect to inhibit enteric bacterial dynamics and gut permeability has not yet been investigated in experimental studies. The present study aims to assess the effects of lactulose on the enteric bacterial dynamics gut permeability in a model of bile duct ligation in Wistar rats. Methods: Wistar rats were assigned into 3 groups, the Sham-operated control, bile duct ligated (BDL) and BDL+ Lac group on the 28th day of bile duct ligation. Animals of BDL + Lac groups were treated with lactulose (1.0 g/kg), administrated by gavage, once a day for 7 days. Bacterial translocation into the organs and bacterial overgrowth as the indicators of the enteric bacterial dynamics and the levels of DAO and D-lactate as the biochemical makers of the gut permeability were measured in each group. Results: The bacterial colony forming units (CFU) in spleen and liver of BDL+Lac group was significantly decreased compared with BDL model group (P&lt;0.01) and significant decrease of bacterial CFU was seen in the intestinal lavage in BDL+Lac group compared to BDL group (P&lt;0.01). On the other hand, Lactulose revealed significant inhibitory effect as evidence by decreasing plasma DAO activity and D-lactate levels (P&lt;0.01) in this model. Conclusion: These results indicate that lactulose can inhibit the enteric bacterial overgrowth, bacterial translocation (BT) and increasing gut permeability by opening the mucosa tight junction in ductal obstruction and obviate even systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) induced by obstructive jaundice.

Effects of Equol Supplementation on Growth Performance, Redox Status, Intestinal Health and Skeletal Muscle Development of Weanling Piglets with Intrauterine Growth Retardation.

Animals with intrauterine growth retardation (IUGR) usually undergo injured postnatal growth and development during the early period after birth. Equol (Eq), an isoflavan produced by gut bacteria in response to daidzein intake, has various health benefits. Therefore, the objective of this study was to evaluate whether Eq supplementation can influence the growth performance, redox status, intestinal health and skeletal muscle development of weanling piglets with IUGR. A total of 10 normal-birth-weight (NBW) newborn female piglets and 20 newborn female piglets with IUGR were selected. After weaning at the age of 21 d, 10 NBW piglets and 10 IUGR piglets were allocated to the NBW group and IUGR group, respectively, and offered a basal diet. The other 10 IUGR piglets were allocated to the IUGR + Eq group and offered a basal diet with 50 mg of Eq per kg of diet. The whole trial lasted for 21 d. At the end of the feeding trial, all piglets were sacrificed for the collection of serum, intestinal tissues and skeletal muscles. Supplementation with Eq increased the average daily gain (ADG), average daily feed intake (ADFI), duodenal villus height to crypt depth ratio (V/C), jejunal villus height and V/C, but reduced the duodenal crypt depth in neonatal piglets with IUGR. Meanwhile, Eq supplementation elevated the activities of superoxide dismutase (SOD) and catalase (CAT) in the serum and duodenum and the activity of SOD in the jejunum, but lowered malondialdehyde (MDA) content in the serum, jejunum and ileum of piglets with IUGR. In addition, supplementation with Eq reduced diamine oxidase (DAO) activity and the levels of D-lactate and endotoxin in serum, and the tumor necrosis factor-α (TNF-α) level in jejunum and ileum, whereas the concentration of serum immunoglobulin G (IgG) and the mRNA levels of intestinal barrier-related markers in jejunum and ileum of IUGR piglets were increased. Furthermore, supplementation with Eq elevated the percentage of fast-fibers and was accompanied with higher mRNA expression of myosin heavy chain IIb (MyHC IIb) and lower mRNA levels in MyHC I in the longissimus thoracis (LT) muscle of IUGR piglets. In summary, Eq supplementation can promote antioxidant capacity, maintain intestinal health and facilitate skeletal muscle development, thus resulting in the higher growth performance of IUGR piglets.

Microbiota-derived tryptophan metabolites indole-3-lactic acid is associated with intestinal ischemia/reperfusion injury via positive regulation of YAP and Nrf2

BackgroundLactobacillus has been demonstrated to serve a protective role in intestinal injury. However, the relationship between Lactobacillus murinus (L. murinus)-derived tryptophan metabolites and intestinal ischemia/reperfusion (I/R) injury yet to be investigated. This study aimed to evaluate the role of L. murinus-derived tryptophan metabolites in intestinal I/R injury and the underlying molecular mechanism.MethodsLiquid chromatograph mass spectrometry analysis was used to measure the fecal content of tryptophan metabolites in mice undergoing intestinal I/R injury and in patients undergoing cardiopulmonary bypass (CPB) surgery. Immunofluorescence, quantitative RT-PCR, Western blot, and ELISA were performed to explore the inflammation protective mechanism of tryptophan metabolites in WT and Nrf2-deficient mice undergoing intestinal I/R, hypoxia-reoxygenation (H/R) induced intestinal organoids.ResultsBy comparing the fecal contents of three L. murinus-derived tryptophan metabolites in mice undergoing intestinal I/R injury and in patients undergoing cardiopulmonary bypass (CPB) surgery. We found that the high abundance of indole-3-lactic acid (ILA) in the preoperative feces was associated with better postoperative intestinal function, as evidenced by the correlation of fecal metabolites with postoperative gastrointestinal function, serum I-FABP and D-Lactate levels. Furthermore, ILA administration improved epithelial cell damage, accelerated the proliferation of intestinal stem cells, and alleviated the oxidative stress of epithelial cells. Mechanistically, ILA improved the expression of Yes Associated Protein (YAP) and Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) after intestinal I/R. The YAP inhibitor verteporfin (VP) reversed the anti-inflammatory effect of ILA, both in vivo and in vitro. Additionally, we found that ILA failed to protect epithelial cells from oxidative stress in Nrf2 knockout mice under I/R injury.ConclusionsThe content of tryptophan metabolite ILA in the preoperative feces of patients is negatively correlated with intestinal function damage under CPB surgery. Administration of ILA alleviates intestinal I/R injury via the regulation of YAP and Nrf2. This study revealed a novel therapeutic metabolite and promising candidate targets for intestinal I/R injury treatment.

Bile Acid Derivatives Effectively Prevented High-Fat Diet-Induced Colonic Barrier Dysfunction.

Bile acids (BAs) have recently emerged as important regulators of many physiological and pathological processes. However, the change of colonic BAs induced by high-fat diet (HFD) and their effects on colonic barrier function remain to be further elucidated. C57BL/6 mice are divided into two groups and feed 12weeks with diets differing for fat content. Higher levels of serum diamine oxidase (DAO) activity, endotoxin (ET), and d-lactate (d-LA) are observed in HFD-fed mice, indicating an increase in intestinal permeability. Real-time quantitative PCR and western blot analyses demonstrate that HFD downregulates tight junction proteins (TJs, including zonula-occludens 1 [ZO-1], Occludin, and Claudin1) and Muc2 expression in the colon. The colonic BA profiles are analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). HFD induces an increase in primary BAs but a decrease in secondary BAs. In human colonic cell line Caco-2, secondary BAs (deoxycholic acid [DCA], lithocholic acid [LCA], their 3-oxo- and iso- derivates) upregulate the expression of TJs and counteract DSS-induced increase in intestinal permeability at physiological concentrations. IsoDCA and isoLCA are the most effective ones. Moreover, supplementation of isoDCA or isoLCA also effectively prevents HFD-induced colonic barrier dysfunction in mice. These results demonstrate that secondary BAs (especially isomerized derivatives) may be important protectors for the colonic barrier function.

Early-onset gout and rare deficient variants of the lactate dehydrogenase D gene.

To investigate whether the lactate dehydrogenase D (LDHD) gene deficiency causes juvenile-onset gout. We used whole-exome sequencing for two families and a targeted gene-sequencing panel for an isolated patient. d-lactate dosages were analysed using ELISA. We demonstrated linkage of juvenile-onset gout to homozygous carriage of three rare distinct LDHD variants in three different ethnicities. In a Melanesian family, the variant was (NM_153486.3: c.206C>T; rs1035398551) and, as compared with non-homozygotes, homozygotes had higher hyperuricaemia (P = 0.02), lower fractional clearance of urate (P = 0.002), and higher levels of d-lactate in blood (P = 0.04) and urine (P = 0.06). In a second, Vietnamese, family, very severe juvenile-onset gout was linked to homozygote carriage of an undescribed LDHD variant (NM_153486.3: c.1363dupG) leading to a frameshift followed by a stop codon, p.(AlaGly432fsTer58). Finally, a Moroccan man, with early-onset and high d-lactaturia, whose family was unavailable for testing, was homozygous for another rare LDHD variant [NM_153486.3: c.752C>T, p.(Thr251Met)]. Rare, damaging LDHD variants can cause autosomal recessive early-onset gout, the diagnosis of which can be suspected by measuring high d-lactate levels in the blood and/or urine.

Lafutidine Ameliorates Indomethacin-Induced Small Intestinal Damage in Rats by Modifying the Intestinal Mucosal Barrier, Inflammation, and Microbiota

Introduction: Nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage is a serious and escalating clinical problem without effective treatment. Lafutidine (LAF) is a novel histamine H2 receptor antagonist with a mucosal protective action. This study aimed to investigate the protective effect of LAF on indomethacin (IND)-induced enteropathy in rats. Methods: Rats were treated with LAF for 10 days with concomitant IND treatment on the final 5 days. Changes in metabolism and hematological and biochemical parameters were measured, and intestinal damage was blindly scored. Intestinal mucosal tissue and luminal contents were collected for transcriptome and microbiota sequencing. Intestinal inflammation and barrier function were also evaluated. Results: LAF treatment prevented anorexia and weight loss in rats and ameliorated reductions in hemoglobin, hematocrit, total protein, and albumin levels. LAF reduced the severity of IND-induced intestinal damage including macroscopic and histopathological damage score. Transcriptome sequencing results indicated that LAF might have positive effects on intestinal inflammation and the intestinal mucosal barrier. Further research revealed that LAF decreased neutrophil infiltration, and IL-1β and TNF-α expression in intestinal tissue. Besides, the treatment increased mucus secretion, MUC2, Occludin, and ZO-1 expression, and decreased serum D-lactate levels. LAF treatment also ameliorates microbial dysbiosis in small intestine induced by IND and increased the abundance of Lactobacillus acidophilus. Conclusion: LAF may protect against NSAID enteropathy via enhancing the intestinal mucosal barrier, inhibiting inflammation, and regulating microbiota.

Bacterial lipopolysaccharide with different administration routes affects intestinal mucosal morphological, immunological, and microbial barrier functions in goslings

The current study was conducted to evaluate the effects of different administration routes of bacterial lipopolysaccharide (LPS) on intestinal mucosal morphological, immunological, and microbial barrier functions in goslings. First, we compared intestinal villi morphology of goslings under intraperitoneal or oral LPS treatment through hematoxylin and eosin staining. Then, we determined the signatures of the microbiome in the ileum mucosa of goslings subjected to oral LPS treatment at 0, 2, 4, and 8 mg/kg BW by 16S sequencing, and analyzed the changes in intestinal barrier functions and permeability, levels of LPS in the ileum mucosa, plasma, and liver tissue, and the induced inflammatory response of Toll-like receptor 4 (TLR4). As a result, intraperitoneal LPS injection resulted in a thicker intestinal wall in the ileum within a short time, whereas villus height was less affected; in contrast, oral LPS treatment exerted a stronger influence on villus height but not on intestinal wall thickness. We also found that oral LPS treatment affected the structure of the intestinal microbiome, reflected by changes in the clustering of intestinal microbiota. The average abundance of Muribaculaceae showed an increasing trend with increasing LPS levels, and that of the genus Bacteroides decreased, compared with the control group. In addition, oral LPS treatment with 8 mg/kg BW affected the intestinal epithelial morphology, damage the mucosal immune barrier, downregulated the expression of tight junction proteins, increased circulating D-lactate levels, and stimulated the secretion of various inflammatory mediators and activation of the TLR4/MyD88/NFκB pathway. This study presented the injuries of intestinal mucosal barrier function induced by LPS challenges in goslings and provided a scientific model for searching the novel strategies to attenuate the immunological stress and gut injury caused by LPS.

Evaluation of Methanotroph (Methylococcus capsulatus, Bath) Bacteria Protein as an Alternative to Fish Meal in the Diet of Juvenile American Eel (Anguilla rostrata).

This study was conducted to evaluate the effects of replacing fish meal (FM) with methanotroph (Methylococcus capsulatus, Bath) bacteria protein (MBP) in the diets of the juvenile American eel (Anguilla rostrata). Trial fish were randomly divided into the MBP0 group, MBP6 group, MBP12 group, and MBP18 group fed the diets with MBP replacing FM at levels of 0, 6%, 12%, and 18%, respectively. The trial lasted for ten weeks. There were no significant differences in weight gain or feed utilization among the MBP0, MBP6, and MBP12 groups (except for the feeding rate in the MBP12 group). Compared with the MBP0 group, the D-lactate level and diamine oxidase activity in the serum were significantly elevated in the MBP12 and MBP18 groups. In terms of non-specific immunity parameters in serum, the alkaline phosphatase activity was significantly decreased in the MBP18 group, and the complement 3 level was significantly elevated in the MBP12 and MBP18 groups. The activities of lipase and protease in the intestine were significantly decreased in the MBP12 and MBP18 groups. Compared with the MBP0 group, the total antioxidant capacity and activities of superoxide dismutase, catalase, and glutathione peroxidase in the intestine were significantly decreased in the MBP18 group, while the malondialdehyde level was significantly increased. The villus height, muscular thickness, and microvillus density were significantly decreased in the MBP12 and MBP18 groups. There were no significant differences in the foresaid parameters between the MBP0 group and the MBP6 group. The intestinal microbiota of the MBP6 group was beneficially regulated to maintain similar growth and health status with the MBP0 group. The adverse effects on the intestinal microbiota were reflected in the MBP18 group. In conclusion, MBP could successfully replace 6% of FM in the diet without adversely affecting the growth performance, serum biochemical parameters, and intestinal health of juvenile American eels.

Rice Water-Fried Atractylodis Rhizoma Relieves Spleen Deficiency Diarrhea by Regulating the Intestinal Microbiome.

Spleen deficiency diarrhea (SDD) is a common Traditional Chinese Medicine (TCM) gastrointestinal condition, the causes of which include dysfunction of the intestinal barrier and microbiota. Rice water-fried Atractylodis Rhizoma (RAR) is a commonly used drug to treat this condition, but its mechanism remains unclear. This study explored the related mechanisms of ethanolic extract of rice water-fried Atractylodis Rhizoma (EAR) in the treatment of SDD by examining changes in the intestinal microbiota. Wistar rats were randomly divided into 4 groups including the control, model, EAR low, and high-dose groups, 6 rats in each group. All rats, except the control group, were induced to develop SDD by a bitter-cold purgation method with rhubarb. The therapeutic effect of EAR on SDD was evaluated by pathological sections, inflammatory indicators (TNF-α, IL-1β, and IL-10), gastrointestinal-related indicators (GAS, DAO, D-lactate, VIP, and SIgA), and intestinal flora (bacteria and fungi) analysis. The results showed that the developed SDD rat model (model group) showed weight loss, decreased food intake, and increased fecal moisture content. Compared with those of the control group, the levels of TNF-α, IL-1β, DAO, D-lactate, and VIP in the model group were significantly increased, but the levels of IL-10, GAS and SIgA were significantly decreased (p < 0.05). However, the indicators were significantly improved after EAR treatment, indicating that EAR maintained the balance of pro- and anti-inflammatory cytokines and reduced gastric emptying, thereby protecting intestinal barrier function, alleviating intestinal mucosal injury, and relieving SDD by regulating the release of neurotransmitters. EAR was also shown to prevent infection by promoting the accumulation of noninflammatory immunoglobulin SIgA and improving intestinal mucosal immunity to inhibit the adhesion of bacteria, viruses, and other pathogens. Intestinal microbiome analysis showed that the intestinal bacteria and fungi of SDD model rats changed greatly compared with the control group, resulting in intestinal microecological imbalance. The reversal in the composition of the flora after EAR treatment was mainly characterized by a large enrichment of beneficial bacteria represented by Lactobacillus and a decrease in the abundance of potentially pathogenic fungi represented by Aspergillus. Thus, it was speculated that EAR primarily functions to alleviate SDD by increasing the abundance of beneficial bacteria and reducing the abundance of potentially pathogenic fungi. The strong therapeutic effect of EAR on SDD suggests that it is a promising treatment for this condition.

PLK1 protects intestinal barrier function in sepsis: A translational research.

Sepsis and its related complications are very challenging in the intensive care unit, among which intestinal barrier injury is a general manifestation. Polo-like kinase 1 (PLK1) is widely studied in cancer, while its role in sepsis is poorly understood. In this study, the efficiency of PLK1 as a marker of intestinal barrier function as well as a predictor of mortality in sepsis was evaluated. The level of serum PLK1 was measured in septic patients (n=51) and controls (n=20); subsequently, its correlation with serum diamine oxidase (DAO), d-lactate, and endotoxin levels and its ability topredict mortality were analysed. The survival rate and barrier injury degree were also assessed in septic mice. Serum PLK1 levels were elevated in septic patients, were negatively correlated with serum DAO, d-lactate, and endotoxin levels, and had a high predictive value for 28-day mortality in patients. The serum PLK1 level in non-survivors was lower. The expression of PLK1 in the intestine was decreased in septic mice, and overexpression or inhibition of PLK1 alleviated or aggravated intestinal barrier injury, respectively, as evaluated by Chiu's score, serum levels of DAO and d-lactate, and expression of tight junction proteins. Overexpressing PLK1 also decreased the 72-hour death rate of septic mice. Further study also revealed the negative correlation of PLK1 and IL-6 in patients, and increasing or interfering with PLK1 expression reduced or increased the serum IL-6 level in mice. PLK1 plays a critical role in intestinal barrier function during sepsis, providing a novel perspective for sepsis therapy in the clinic.

Effect of Intestinal Microbiota Transplantation on Intestinal Flora and Inflammatory Factor Levels in Patients with Ulcerative Colitis.

The present study was performed to evaluate the effect of intestinal microbiota transplantation (IMT) on intestinal flora and inflammatory factor levels in patients with ulcerative colitis (UC). In this study, 94 UC patients who attended the Department of Proctology or the Department of Gastroenterology departments of Sinopharm Dongfeng General Hospital between April 2021 and April 2022 were identified as research participants and were assigned to the control or Research Groups via the random number table method, with 47 cases in each group. Interventions included oral mesalamine for patients in the control group and oral mesalamine plus IMT for those in the research group. Outcome measures included clinical efficacy, intestinal microbiota score, enteroscopy score, Sutherland index, inflammatory factor level, intestinal mucosal barrier function level, and adverse reactions. Mesalamine plus IMT was associated with significantly higher treatment efficiency (97.8%) versus mesalamine alone (80.85%) (P<0.05). Mesalamine plus IMT provided a better intestinal microbiota balance and milder disease symptoms versus mesalamine, as evidenced by the significantly lower intestinal microbiota scores, colonoscopy scores, and Sutherland index (P<0.05). In post-treatment, patients with IMT exhibited more mitigated inflammatory responses than those without, as shown by the higher levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-17 (IL-17), and interleukin-23 (IL-23) (P<0.05). Significantly lower D-lactate and serum diamine oxidase (DAO) levels were observed after IMT intervention than those with mesalamine alone (P<0.05). IMT features no significant increase in adverse effects than the control group (P>0.05). IMT efficiently ameliorates the intestinal microbiota conditions of UC patients, mitigates inflammatory responses in the body, and facilitates the restoration of intestinal mucosal barrier function with no significant increase in adverse effects.

Features of assessing the intestinal barrier permeability in chronic kidney disease

Numerous studies have shown that changes in the intestinal microbial-tissue complex are a risk factor for the progression of chronic kidney disease (CKD) to end-stage renal disease and, therefore, a potential target for new therapeutic interventions. Thus, reliable and sensitive diagnostic tools for measuring intestinal permeability in the clinical setting are necessary. Modern genome sequencing and multi-omics technologies have established that patients with CKD are characterized by a specific imbalance between the saccharolytic and proteolytic microbiota, contributing to the accumulation of numerous toxic microbial products, such as indoxyl sulphate, p-cresyl sulphate, trimethylamine-N-oxide. Progressive kidney function decline leads to compensatory urea accumulation in the gastrointestinal tract. In the intestinal lumen, urea is hydrolyzed by microbial urease, forming a large amount of ammonium hydroxide, which may be accompanied by disruption of the epithelial barrier integrity with an increase in intestinal permeability for microbial molecules that initiate systemic inflammation. Experimental approaches to studying the intestinal barrier in CKD include the assessment of electrophysiological parameters of the intestinal epithelium and the transport of fluorescently labelled tracers in the Ussing chamber. Actively improving various cell-based in vitro methods, which may be useful for studying the effect of microbiota on the barrier functions of the intestinal epithelium. Gene expression and protein content of tight junctions are estimated using polymerase chain reaction, immunohistochemical methods and Western blotting. Using various biomolecular methods, it was found that renal failure is characterized by the presence of inflammatory and atrophic changes throughout the gastrointestinal tract, destruction of the mucin layer, damage to tight junctions with a decrease in the amount of claudine-1, occludin and ZO-1 as well as a decrease in transepithelial electrical resistance. Clinical examination of intestinal permeability by methods based on the urine excretion of orally administered sugars, polyethylene glycol polymers and labelled tracers indicate a distortion of the results in patients with CKD due to altered renal clearance. Alternatively, quantitative determination of bacterial DNA and D-lactate levels in the blood is considered. Identification of serum non-coding microRNAs, confocal laser endomicroscopy and impedance spectroscopy have the potential to be used as methods for assessing intestinal barrier function.

A blend of formic acid, benzoic acid, and tributyrin alleviates ETEC K88-induced intestinal barrier dysfunction by regulating intestinal inflammation and gut microbiota in a murine model

This study aimed to investigate the effects of an organic acid (OA) blend on intestinal barrier function, intestinal inflammation, and gut microbiota in mice challenged with enterotoxigenic Escherichia coli K88 (ETEC K88). Ninety female Kunming mice (7weeks old) were randomly allotted to five treatments with six replicates per treatment and three mice per replicate. The five treatments were composed of the non-ETEC K88 challenge group and ETEC K88 challenge+OA blend groups (0, 0.6%, 1.2%, and 2.4% OA blend). The OA blend consisted of 47.5% formic acid, 47.5% benzoic acid, and 5% tributyrin. The feeding trial lasted for 15days, and mice were intraperitoneally injected with PBS or ETEC K88 solution on day 15. At 24h post-challenge, one mouse per replicate was selected for sample collection. The results showed that a dosage of 0.6% OA blend alleviated the ETEC K88-induced intestinal barrier dysfunction, as indicated by the elevated villus height and the ratio of villus height to crypt depth of jejunum, and the reduced serum diamine oxidase (DAO) and D-lactate levels, as well as the up-regulated mRNA levels of ZO-1, Claudin-1, and Occludin in jejunum mucosa of mice. Furthermore, dietary addition with 0.6% OA blend decreased ETEC K88-induced inflammation response, as suggested by the decreased TNF-α and IL-6 levels, and the increased IgA level in the serum, as well as the down-regulated mRNA level of TNF-α, IL-6, IL-1β, TLR-4, MyD88, and MCP-1 in jejunum mucosa of mice. Regarding gut microbiota, the beta-diversity analysis revealed a remarkable clustering between the 0.6% OA blend group and the ETEC K88 challenge group. Supplementation of 0.6% OA blend decreased the relative abundance of Firmicutes, and increased the relative abundance of Bacteroidota, Desulfobacterota, and Verrucomicrobiota of colonic digesta in mice. Also, the butyric acid content in the colonic digesta of mice was increased by dietary 0.6% OA blend supplementation. Collectively, a dosage of 0.6% OA blend could alleviate the ETEC K88-induced intestinal barrier dysfunction by regulating intestinal inflammation and gut microbiota of mice.

Influence of goal-directed fluid therapy guided by the Vigileo-FloTracTM system on intestinal mucosal barrier function in elderly patients with colorectal cancer.

Colorectal cancer is a clinically common malignancy arising in the digestive tract. To evaluate the influence of goal-directed fluid therapy (GDFT) guided by the Vigileo-FloTracTM system on intestinal mucosal barrier function in elderly patients with colorectal cancer. A prospective study was conducted on 106 elderly patients with colorectal cancer. They were divided into control and research groups (n = 53) using a random number table, and subjected to conventional fluid therapy and Vigileo-FloTracTM system-guided GDFT, respectively. Their intraoperative indicators, postoperative indicators, and changes of haemodynamics, oxygen metabolism, intestinal mucosal barrier function at different time points, and incidence rates of complications were compared. Compared with the control group, the intraoperative urine volume, colloid fluid volume, crystalloid fluid volume, and total infusion volume were lower, and the first postoperative exhaust time, first postoperative feeding time, and hospital stay were shorter in the research group (p < 0.05). At T1 and T2, mean artery pressure, heart rate, central venous pressure, oxygen consumption, oxygen delivery, and oxygen extraction ratio in the research group were lower than in the control group, but all of them first rose and then fell in the 2 groups (p < 0.05). On the 3rd day after surgery, the levels of serum endothelin, diamine oxidase and D-lactate declined in both groups, and the decline was more obvious in the research group (p < 0.05). GDFT guided by the Vigileo-FloTracTM system is beneficial to the prognosis of patients by effectively decreasing fluid infusion.

Therapeutic effects of paeoniflorin on irritable bowel syndrome in rats.

Irritable bowel syndrome (IBS) is a functional bowel disorder (FBD). To assess the therapeutic effects of paeoniflorin (PF) on IBS in rats. Sixty male Sprague-Dawley rats were randomly divided into normal, model, positive drug, low-dose PF, medium-dose PF and high-dose PF groups (n = 10). After gavage for 2 consecutive weeks, the effect of PF on abdominal pain symptoms was assessed based on the abdominal withdrawal reflex (AWR) score, fecal water content and pathological changes in colon tissues. D-lactate, interleukin-1β (IL-1β), transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay, and phosphorylated nuclear factor kappa B (p-NF-κB) p65 was detected by Western blotting. The abundance and diversity changes of intestinal flora were explored using 16S ribosomal RNA sequencing. In PF groups, the mucosal morphology of colon tissues was intact, and the glands were arranged neatly and structured clearly, without obvious inflammatory cell infiltration. Compared with the model group, PF groups had significantly elevated pain threshold, and mRNA and protein levels of zonula occludens-1 (ZO-1) and occludin, decreased AWR score at 20 mmHg pressure, fecal water content, mRNA levels of IL-1β, TGF-β, and TNF-α, protein level of p-NF-κB p65 and level of serum D-lactate, and reduced levels of serum IL-1β, TGF-β, and TNF-α (p < 0.05, p < 0.01). PF groups had higher abundance of Lactobacillus, Akkermansia, Alistipes, and Bacteroides, but lower abundance of Desulfovibrio, Parasutterella, and Enterococcus than those of the model group. PF exerts therapeutic effects on IBS in rats probably by regulating the intestinal flora, and then up-regulating the expressions of ZO-1 and occludin in colon tissue while down-regulating the levels of IL-1β, TGF-β, TNF-α, D-lactate and p-NF-κB p65.