Nonalcoholic fatty liver disease aggravates acute pancreatitis through bacterial translocation and cholesterol metabolic dysregulation in the liver and pancreas in mice

Background:Nonalcoholic fatty liver disease(NAFLD)is an independent risk factor for severe acute pancreatitis(AP).The underlying mechanism remains unclear.We sought to determine how bacterial translocation and cholesterol metabolism in the liver and pancreas affect the severity of AP in NAFLD mice.Methods:C57BL/6N mice were fed on a high-fat diet(HFD)to generate the NAFLD model,and mice in the control group were provided with a normal diet(ND).After being anesthetized with ketamine/xylazine,mice got a retrograde infusion of taurocholic acid sodium into the pancreatic duct to induce AP,and sham operation(SO)was used as control.Serum amylase and Schmidt’s pathological score system were used to evaluate AP severity.Bacterial loads,total cholesterol level,and cholesterol metabolic-associated molecules[low-density lipoprotein receptor(LDLR)and ATP-binding cassette transporter A1(ABCA1)]were analyzed in the liver and pancreas.Results:Compared with the ND-AP group,mice in the HFD-AP group had severer pancreatitis,manifested with higher serum amylase levels and higher AP pathologic scores,especially the inflammation and hemorrhage scores.Compared with the HFD-SO group and ND-AP group,bacterial loads in the liver and pancreas were significantly higher in the HFD-AP group.Mice in the HFD-AP group showed a decreased LDLR expression and an increased ABCA1 expression in the pancreas,although there was no significant difference in pancreas total cholesterol between the HFD-AP group and the ND-AP group.Conclusions:NAFLD aggravates AP via increasing bacterial translocation in the liver and pancreas and affecting pancreas cholesterol metabolism in mice.

Early intrajejunal nutrition: bacterial translocation and gut barrier function of severe acute pancreatitis in dogs

Objective: To evaluate the effect of early intrajejunalnutrition in attenuating bacterial and/or endotoxintranslocation and improving gut barrier function ofsevere acute pancreatitis (SAP) in dogs.Methods: 15 dogs were divided into parenteral nutrition(PN) group(7 dogs)and early intrajejunal nutrition(EIN) group(8). EIN was delivered nutrients via a nee-dle jejunostomy catheter feeding at 48h after operation.SAP model was induced by injecting 1 ml/kg of com-bined solution of 5% sodium taurocholate and 8000-10000 BAEE units trypsin/ml into the pancreas via thepancreatic duct. Systemic blood samples were ob-tained before and 1, 3, 5, 7 d following SAP, and culturedby aerobic as well as anaerobic bacterial growth. Systemicplasma and portal vein endotoxin levels were quantifiedby the chromogenic limulus amebocyte lysate (LAL)technique. Portal vein blood and specimens of tissuefrom the mesenteriolum and mesocolon lymph nodes,lung, pulmonary portal lymph nodes, pancreatitis tissueand periopancreas tissue were adopted before the experi-ment was finished. Aliquots of the homogenata were cul-tured as blood mentioned above to determine the magnitudeof the bacteria DNA, protein and the villi, the thickness ofmucosa, and the whole bowel wall of the ileum and trans-verse colon were measured.Results: The study showed that the levels of systemicplasma endotoxin and the magnitude of bacterialtranslocation to the portal and systemic blood and dis-tant organ were reduced significantly in the EINgroup as compared with the TPN group. The contentsof protein and DNA, the height of villi, the thicknessof mucosa and whole bowel wall of the ileum andtransverse colon in the EIN group were higher thanthose in the PN group.Conclusion: Our results suggested that EIN is safe andeffective to be adopted by intrajejunal delivery of nu-trients in SAP, decreases the occurrence of gut bacterialtranslocation, and improves the gut barrier function.

Effects of glutamine and curcumin on bacterial translocation in jaundiced rats

AIM: To investigate the effect of curcumin on bacterial translocation and oxidative damage in an obstructive jaundice model and compare the results to glutamine, an agent known to be effective and clinically used. METHODS: Twenty-four female Wistar-Albino rats, weighing 200-250 g, were randomly divided into three groups (8 in each group). After ligation of the common bile duct in all animals, GroupⅠ received oral normal saline, Group Ⅱ received oral glutamine and Group Ⅲ received oral curcumin for seven days. Blood samples via cardiac puncture, tissue samples (terminal ileum, liver and mesenteric lymph node) and peritoneal fluid were obtained from the animals at the time of death to investigate bacterial translocation and oxidative damage. RESULTS: We observed that both glutamine and curcumin reduced bacterial translocation in blood, hepatocellular damage, plasma cytokine levels, oxidative tissue damage and apoptosis significantly compared to the control group. Additionally, glutamine showed protective effects on ileal epithelium and reduced villus atrophy. CONCLUSION: On the basis of these findings, both curcumin and glutamine are thought to be effective in preventing or reducing bacterial translocation and oxidative damage in obstructive jaundice.

Bacterial Translocation and Change in Intestinal Permeability in Patients after Abdominal Surgery

The purpose of this study was to investigate bacterial translocation and change in intestinal permeability in patients after abdominal surgery. Sixty-three patients undergoing elective abdominal surgery were enrolled in the study. Blood samples were collected prior to operation and 2, 24, 48 h after surgery for bacterial culture, microbial DNA extraction, plasma D-lactate and endotoxin measurement. PCR analysis was performed after DNA extraction, with β-lactosidase gene of E. coli and 16S rRNA gene as target genes. All patients were observed for a period of 30 days for infectious complications. Our results showed that no bacterial DNA was detected before surgery, but after operation it was found in 12 patients （19.0%）. Bacterial DNA was detected in 41.7% （10/24） of SIRS patients and 5.1% （2/39） of non-SIRS patients （P〈0.01）. About 83.3% of PCR-positive patients developed systemic inflammatory response syndrome （SIRS）, but only 27.5% of PCR-negative patients did so （P〈0.01）. Two thirds of PCR-positive patients developed infectious complications, while none of PCR-negative patients did （P〈0.01）. The blood culture was positive only in 3 patients （4.8%）, who were all PCR-positive. E. coli DNA was found in 66.7% of the PCR-positive patients. The plasma levels of D-lactate and endotoxin were elevated significantly 2, 24 and 48 h after operation in PCR-positive patients, with a significant positive correlation found between them （r=0.91, P〈0.01）. It is concluded that increased intestinal permeability was closely related with bacterial translocation. Intestinal bacterial translocation （most commonly E. coli） might occur at early stage （2 h） after abdominal surgery. Postoperative SIRS and infection might bear a close relationship with bacterial translocation.

Liver Cirrhosis and Intestinal Bacterial Translocation

Intestinal barrier dysfunction, facilitating translocation of bacteria and bacterial products, plays an important role in the pathophysiology of liver cirrhosis and its complications. Intestinal defense system including microbial barrier, immunologic barrier, mechanical barrier, chemical barrier, plays an important role in the maintenance of intestinal function. Under normal circumstances, the intestinal barrier can prevent intestinal bacteria through the intestinal wall from spreading to the body. Severe infection, trauma, shock, cirrhosis, malnutrition, immune suppression conditions, intestinal bacteria and endotoxin translocation, can lead to multiple organ dysfunction. The intestinal microflora is not only involved in the digestion of nutrients, but also in local immunity, forming a barrier against pathogenic microorganisms. The derangement of the gut microflora may lead to microbial translocation, defined as the passage of viable microorganisms or bacterial products from the intestinal lumen to the mesenteric lymph nodes and other extraintestinal sites. In patients with cirrhosis, primary and intestinal flora imbalance, intestinal bacterial overgrowth, intestinal mucosal barrier dysfunction, endotoxemia is associated with weakened immunity.

Bacterial translocation in patients undergoing major gastrointestinal surgery and its role in postoperative sepsis

Bacteria of the human intestinal microflora have a dual role.They promote digestion and are part of a defense mechanism against pathogens.These bacteria could become potential pathogens under certain circumstances.The term“bacterial translocation”describes the passage of bacteria of the gastrointestinal tract through the intestinal mucosa barrier to mesenteric lymph nodes and other organs.In some cases,the passage of bacteria and endotoxins could result in blood stream infections and in multiple organ failure.Open elective abdominal surgery more frequently results in malfunction of the intestinal barrier and subsequent bacterial translocation and blood stream infections than laparoscopic surgery.Postoperative sepsis is a common finding in patients who have undergone non-elective abdominal surgeries,including trauma patients treated with laparotomy.Postoperative sepsis is an emerging issue,as it changes the treatment plan in surgical patients and prolongs hospital stay.The association between bacterial translocation and postoperative sepsis could provide novel treatment options.

Inhibitory effects of high-dose methylprednisolone on bacterial translocation from gut and endotoxin release following acute spinal cord injury-induced paraplegia in rats

BACKGROUND： Previous studies have shown that autonomic dysfunction results in gastrointestinal motility disorders and ultimately results in bacterial translocation following acute spinal cord injury （SCI）. Intensive methylprednisolone dosing improves neurological recovery in SCI patients. However, it remains uncertain whether high-dose methylprednisolone inhibits bacterial translocation and endotoxin release following acute SCI. OBJECTIVE： To investigate the inhibitory effect of methylprednisolone on bacterial translocation and endotoxin release from the gut in paraplegic rats. DESIGN, TIME AND SETTING： The randomized, controlled study was performed at the Orthopedic Lab, First Affiliated Hospital, Nanchang University, China, from April to December 2008. MATERIALS： Methylprednisolone （Pfizer, USA）, automatic microbial identification instrument ATB Expression and reagent ID 32 system （BioMerieux, France）, Limulus test kit （ACC, USA）, and optical microscope （Olympus, Japan） were used in this study. METHODS： A paraplegia model was established following SCI in 48 Wistar rats, aged 7 weeks. The rats were equally and randomly assigned to saline and methylprednisolone groups. Immediately post-injury, the methylprednisolone group was administered 30 mg/kg methylprednisolone via caudal intravenous infusion, followed by a 23-hour infusion of 5.4 mg/kg per hour. The saline group received an equal volume of saline as placebo. MAIN OUTCOME MEASURES： At 24 hours, 72 hours, and 1 week after SCI, blood samples were collected for bacterial cultures, and bacteria and endotoxin were identified using ATB Expression and Limulus test kits. In addition, mesenteric lymph node, spleen, and liver samples were collected for bacterial cultures. Histological examinations of mesenteric lymph node, spleen, liver, jejunum, and ileum were performed 1 week post-injury. Locomotor function in the hind limb was evaluated using the Basso, Beattie, and Bresnahan score at pre-injury time point, as well as 24 hours, 72 hours, and 1 week post-injury. RESULTS： Endotoxemia and bacterial growth were identified at 24 hours post-injury in both groups. However, plasma endotoxin levels were significantly decreased in the methylprednisolone group compared with the saline group at 72 hours and 1 week post-injury （P 〈 0.05）. Translocated bacteria mainly comprised Bacillus coli, Enterobacter cloacae, Escherichia coli, Proteus vulgaris, and Enterococcus faecalis following SCI combined with paraplegia. Histological changes were not as severe in the methylprednisolone group compared with the saline group 1 week after injury. Basso, Beattie, and Bresnahan scores were significantly better in the methylprednisolone group compared with the saline group 1 week after injury （P 〈 0.05）. CONCLUSION： High-dose methylprednisolone inhibited bacterial translocation from the gut and endotoxin release in rats with SCI.

Molecular mechanism mediating enteric bacterial translocation after severe burn:the role of cystic fibrosis transmembrane conductance regulator

Background:Gut ischemia and hypoxia post severe burn leads to breakdown of intestinal epithelial barrier and enteric bacterial translocation(EBT),resulting in serious complications,such as systemic inflammatory response syndrome,sepsis and multiple organ failure.Cystic fibrosis transmembrane conductance regulator(CFTR)is known to be downregulated by hypoxia and modulate junctional complexes,which are crucial structures maintaining the intestinal barrier.This study aimed to investigate whether CFTR plays a role in both regulating the intestinal barrier and mediating EBT post severe burn,as well as the signaling pathways involved in these processes.Methods:An in vitro Caco-2 cell model subjected to hypoxic injury and an in vivo mouse model with a 30%total body surface area full-thickness dermal burn were established.DF 508 mice(mice with F508del CFTR gene mutation)were used as an in vivo model to further demonstrate the role of CFTR in maintaining normal intestinal barrier function.QRT-PCR,western blot,ELISA,TER assay and immunofluorescence staining were used to detect the expression and localization of CFTR and tight junction proteins,as well as the function of tight junctions.Results:Our data indicated that,in Caco-2 cells,the hypoxia condition significantly reduced CFTR expression;activated extracellular signal-regulated kinase and nuclear factor-κB signaling;elevated secretion of inflammatory factors(tumor necrosis factor-α,interleukin-1βand interleukin-8);downregulated zonula occludens-1,occludin and E-cadherin expression;decreased transepithelial electrical resistance values;and led to a cellular mislocation of ZO-1.More importantly,knockdown of CFTR caused similar alterations.The upregulation of inflammatory factors and downregulation of tight junction proteins(ZO-1 and occludin)induced by knockdown of CFTR could be reversed by specific extracellular signal-regulated kinase or nuclear factor-κB inhibition.In support of the in vitro data,exuberant secretion of pro-inflammatory mediators and EBT was observed in the intestine of severely burnt mice in vivo.EBT occurred in DF508 mice(mice with the F508del CFTR gene mutation),accompanied by augmented tumor necrosis factor-α,interleukin-1βand interleukin-8 levels in the ileum compared to wildtype mice.In addition,vitamin D3 was shown to protect the intestinal epithelial barrier from hypoxic injury.Conclusions:Collectively,the present study illustrated that CFTR and downstream signaling were critical in modulating the intestinal epithelial junction and EBT post severe burn.

Prophylactic treatment with growth hormone improves intestinal barrier function and alleviates bacterial translocation in stressed rats

Background Damage to the gut barrier often occurs during critical illnesses. In such cases, it is very important to alleviate impairment of the intestinal barrier and protect intestinal barrier function. This study investigated the protective effect of growth hormone on intestinal barrier function in rats under stress.Methods This study consisted of prospective, randomized, and controlled animal experiments. Twenty-five Sprague-Dawley rats served as total parenteral nutrition (TPN) models and were divided into three groups: TPN group, sepsis (Sep) group, and growth hormone (GH) group. Another 8 rats served as normal controls. Each group received different stress stimuli. Rats were fed for 7 days, and samples were taken for examination 24 hours after gavaging with dual saccharides.Results The architecture of the small intestinal mucosa in the Sep group showed the most severe damage among all groups. Nitric oxide levels in blood plasma and immunoglobulin A levels in the intestinal mucosa of the GH group were significantly lower than in the Sep group (P<0. 02). There were no significant changes in CD3 counts and in the CD4/CD8 ratio between the four groups. Dual sugar tests and bacteriological examinations revealed that intestinal permeability and rate of bacterial translocation in the GH group were lower than in the Sep group (P<0. 01, respectively).Conclusion Prophylactic treatment with growth hormone can alleviate damage to intestinal barrier function caused by trauma and endotoxemia in rats under stress.

Role of granulocyte colony-stimulating factor in paclitaxel-induced intestinal barrier breakdown and bacterial translocation in rats

Background Chemotherapy causes breakdown of the intestinal barrier, which may lead to bacterial translocation. Paclitaxel, an anti-tubulin agent, has many side effects; however, its effect on the intestinal barrier is unknown. Previous studies show that granulocyte colony-stimulating factor （G-CSF） plays an important role in modulating intestinal barrier function, but these studies are not conclusive. Here, we investigated the effects of paclitaxel on the intestinal barrier, and whether G-CSF could prevent paclitaxel-induced bacterial translocation. Methods Twenty-four male Sprague-Dawley rats were divided into three groups： control group, paclitaxel group and paclitaxel ＋ G-CSF group. Intestinal permeability was measured by the urinary excretion rates of lactulose and mannitol administered by gavage. The mesenteric lymph nodes, spleen and liver were aseptically harvested for bacterial culture. Endotoxin levels and white blood cell （WBC） counts were measured and bacterial quantification performed using relative real-time PCR. Jejunum samples were also obtained for histological observation. Intestinal apoptosis was evaluated using a fragmented DNA assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate （dUTP）-biotin nick end-labeling staining. One-way analysis of variance and Fisher＇s exact test were used to compare differences between groups. Results Paclitaxel induced apoptosis in 12.5% of jejunum villus cells, which was reduced to 3.8% by G-CSF treatment. Apoptosis in the control group was 0.6%. Paclitaxel treatment also resulted in villus atrophy, increased intestinal permeability and a reduction in the WBC count. G-CSF treatment resulted in increased villus height and returned WBC counts to normal levels. No bacterial translocation was detected in the control group, whereas 6/8, 8/8, and 8/8 rats in the paclitaxel group were culture-positive in the liver, spleen and mesenteric lymph nodes, respectively. Bacterial translocation was partially inhibited by G-CSF. Conclusions Paclitaxel disrupts the intestinal barrier, resulting intestinal barrier, prevents bacterial translocation, and attenuates n bacterial translocation. G-CSF treatment protects the paclitaxel-induced intestinal side-effects.

Effects of lactulose on intestinal endotoxin and bacterial translocation in cirrhotic rats

Objective To investigate the effects of lactulose on intestinal bacterial overgrowth (IBO), bacterial translocation (BT), intestinal transit and permeability in cirrhotic rats. Methods BT in all animals was assessed by bacterial culture of mesenteric lymph node (MLN), liver and spleen, and IBO was assessed by a jejunal bacterial count of the specific organism. Intestinal permeability was determined by the 24-hour urinary 99mTc-diethylenetriamine pentaacetatic acid ( 99mTc-DTPA) excretion, and intestinal transit was determined by measuring the distribution of 51Cr in the intestine. Results BT and IBO were found in 48% and 80% of the cirrhotic rats, respectively, while not in the control rats. Cirrhotic rats with IBO had significantly higher levels of intestinal endotoxin higher rates of bacterial translocation, shorter intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT were closely associated with IBO and injury of the intestinal barrier. Compared with the placebo group, lactulose-treated rats had lower rates of BT and IBO, which were closely associated with increased intestinal transit and improved intestinal permeability by lactulose. Conclusions Our study indicate that endotoxin and bacterial translocation in cirrhotic rats may attribute to IBO and increased intestinal permeability. Lactulose that accelerates intestinal transit and improves intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.

Role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxin translocation and the effect of bifidobacterial supplement on gut barrier function following burns

Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this studywas to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxintranslocation following burns and the effects of bifidohacterial supplement on gut barrier.Methods:Wistar rats wererandomly divided into burn group(Burn,n=60),sham burn g...

Effects of Salvia miltiorrhiza on intestinal microflora in rats with ischemia/reperfusion liver injury

BACKGROUND: Hepatic ischemia/reperfusion injury may induce intestinal microflora imbalance. Salvia miltiorrhiza is effective in promoting blood circulation and counteracting peroxidation in tissues. The aim of the present study was to determine the effects of Salvia miltiorrhiza on intestinal mi- croflora, endotoxemia, and bacterial translocation in rats with hepatic I/R injury. METHODS: Sprague-Dawley rats in specific pathogen free grade were divided into 3 groups: group I(n =6) for sham operation: groups ( n = 7) for liver ische- mia for 20 minutes and reperfusion for 22 hours. Group was also pretreated with 4 ml/day of Salvia miltiorrhiza solu- tion (250 mg/kg) by daily gavage for 7 days. The levels of serum alanine aminotransferase (ALT), aspartate amino- transferase (AST), malondialdehyde ( MDA) and supero- xide dismutase ( SOD ) in liver tissues, serum endotoxin, intestinal bacterial counts, intestinal mucosal histology and bacterial translocation were studied. RESULTS: The levels of ALT, AST, plasma endotoxin and MDA in liver tissues were decreased more markedly in group (57.57 ± 18.08 U/L, 147.57 ±40.84 U/L, 0.42 ± 0.144 EU/ml and 0. 52 ±0.19 nmol/mg-prot respectively) in group 295.9±216.92 U/L, 0.80± 0.262 EU/ml and 0.72±0.12 nmol/mg-prot; P <0.05-0.01 respectively). Liver SOD activity was increased more sig- nificantly in group (318.47±64.62 U/mg-prot) than in group U/mg-prot, P<0.05). The counts of Bifidobacteria and Bacteroides increased more significantly in group than in group but were similar to those in group I. Bacterial translocation to the kidney in group was 50% (5/10), whereas no bacterial translocation to the kidney occurred in the other two groups (P <0. 01). Ileal mucosal structure was markedly ameliorated in group as compared with group CONCLUSIONS: Salviae miltiorrhiza could partially restore intestinal microflora balance, improve intestinal mucosal integrity, and reduce bacterial translocation and plasma en- dotoxin in rats with hepatic ischemia/reperfusion injury.

Enteral supplementation with glycyl-glutamine improves intestinal barrier function after liver transplantation in rats

BACKGROUND:Most patients after liver transplantation (LT) suffer from intestinal barrier dysfunction.Glycyl-glutamine (Gly-Gln) by parenteral supplementation is hydrolyzed to release glutamine,which improves intestinal barrier function in intestinal injury.This study aimed to investigate the effect of GlyGln by enteral supplementation on intestinal barrier function in rats after allogenetic LT under immunosuppressive therapy.METHODS:Twelve inbred Lewis rats were selected randomly as donors,and 24 inbred Brown Norway (BN) rats as recipients of allogenetic LT.The recipients were divided into a control group (Ala,n=12) and an experimental group (Gly-Gln,n=12).In each group,6 normal BN rats were sampled for normal parameters on preoperative day 3.The 6 recipients in the control group received alanine (Ala) daily by gastric perfusion for 3 preoperative days and 7 postoperative days,and the 6 recipients in the experimental group were given Gly-Gln in the same manner.The 12 BN recipients underwent orthotopic LT under sterile conditions after a 3-day fast and were given immunosuppressive therapy for 7 days.They were harvested for sampling on postoperative day 8.The following parameters were assessed:intestinal mucosal protein content,mucosal ultrastructure,ileocecal sIgA content,portal plasma levels of endotoxin and TNF-α,and bacterial translocation.RESULTS:All recipients were alive after LT.On preoperative day 3,all parameters were similar in the two groups.On postoperative day 8,all parameters in the two groups were remarkably changed from those on preoperative day 3.However,compared to the Ala group,supplementation withGly-Gln increased the levels of intestinal mucosal protein and ileocecal sIgA,improved mucosal microvilli,and decreased portal plasma levels of endotoxin and TNF-α as well as bacterial translocation.CONCLUSION:Enteral supplementation with Gly-Gln improved intestinal barrier function after allogenetic LT in rats.

Gut-liver axis in cirrhosis:Are hemodynamic changes a missing link?

Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several links.Gut dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic inflammation.Systemic inflammation further causes vasodilation,arterial hypotension,and hyperdynamic circulation,leading to the aggravation of portal hypertension,which contributes to the development of complications of cirrhosis,resulting in a poorer prognosis.The majority of the data underlying this model were obtained initially from animal experiments,and most of these correlations were further reproduced in studies including patients with cirrhosis.However,despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development,the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly studied.They remain a missing link in the gut-liver axis and a challenge for future research.

Serum zonulin levels in patients with liver cirrhosis:Prognostic implications

BACKGROUND Increased gut permeability and bacterial translocation play an important role in liver cirrhosis.Zonulin is a recently recognized protein involved in the disintegration of the intestinal barrier.AIM To investigate possible differences in serum zonulin levels among patients with different cirrhosis stages and their potential prognostic implications.METHODS Consecutive cirrhotic patients who attended our liver clinic were included in the study.Serum zonulin levels,clinical,radiological and biochemical data were collected at baseline.Patients who accepted participation in a regular surveillance program were followed-up for at least 12 mo.RESULTS We enrolled 116 cirrhotics[mean Child-Turcotte-Pugh(CTP)score:6.2±1.6;model for end-stage liver disease score:11±3.9].The causes of cirrhosis were viral hepatitis(39%),alcohol(30%),non-alcoholic fatty liver disease(17%),and other(14%).At baseline,53% had decompensated cirrhosis,48% had ascites,and 32% had history of hepatic encephalopathy.Mean zonulin levels were significantly higher in patients with CTP-B class than CTP-A class(4.2±2.4 ng/dL vs 3.5±0.9 ng/dL,P=0.038),with than without ascites(P=0.006),and with than without history of encephalopathy(P=0.011).Baseline serum zonulin levels were independently associated with the probability of decompensation at 1 year(P=0.039),with an area under the receiving operating characteristic of 0.723 for predicting hepatic decompensation.Higher CTP score(P=0.021)and portal vein diameter(P=0.022)were independent predictors of mortality.CONCLUSION Serum zonulin levels are higher in patients with more advanced chronic liver disease and have significant prognostic value in identifying patients who will develop decompensation.

Effects of Salmonella infection on hepatic damage following acute liver injury in rats

BACKGROUND： Acute liver injury is a common clinical disorder associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The purpose of this study was to address this unanswered question using a rat model. METHODS： Oral supplementation with Salmonella enterica serovar enteritidis（S. enteritidis） was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver injury.RESULTS： The levels of liver damage and endotoxin were significantly increased in the Salmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury（P〈0.01）; The peyer＇s patch CD3＋ T cell counts were increased significantly when the Salmonella infection with severe injury group was compared with the normal group（P〈0.05）. S. enteritidis pretreatment enhanced intestinal barrier impairment and bacterial translocation.CONCLUSIONS： Oral S. enteritidis administration exacerbates acute liver injury, especially when injury was severe.Major factors of the exacerbation include inflammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.

Autoimmune enteropathy and primary biliary cholangitis after proctocolectomy for ulcerative colitis:A case report and review of the literature

BACKGROUND Autoimmune enteropathy(AIE)and primary biliary cholangitis(PBC)are both immune-mediated diseases.AIE or PBC complicated with ulcerative colitis(UC)are rare.There are no cases of AIE and PBC diagnosed after proctocolectomy for UC reported before,and the pathogenesis of these comorbidities has not been revealed.CASE SUMMARY A middle-aged woman diagnosed with UC underwent subtotal colectomy and ileostomy due to the steroid-resistant refractory disease,and a restorative proctectomy with ileal pouch-anal anastomosis and proximal neoileostomy was postponed due to active residual rectal inflammation in January 2016.A few months after the neoileostomy,she began to suffer from recurrent episodes of watery diarrhea.She was diagnosed with postcolectomy enteritis and stoma closure acquired a good therapeutic effect.However,her symptoms of diarrhea relapsed in 2019,with different histological features of endoscopic biopsies compared with 2016,which showed apoptotic bodies,a lack of goblet and Paneth cells,and villous blunting.A diagnosis of AIE was established,and the patient’s stool volume decreased dramatically with the treatment of methylprednisolone 60 mg/d for 1 wk and tacrolimus 3 mg/d for 4 d.Meanwhile,her constantly evaluated cholestatic enzymes and high titers of antimitochondrial antibodies indicated the diagnosis of PBC,and treatment with ursodeoxycholic acid(16 mg/kg per day)achieved satisfactory results.CONCLUSION Some immune-mediated diseases may be promoted by operation due to microbial alterations in UC patients.Continuous follow-up is essential for UC patients with postoperative complications.