Intestinal barrier dysfunction always accompanies cirrhosis in patients with advanced liver disease and is an important contributor facilitating bacterial translocation (BT), which has been involved in the pathogenesis of cirrhosis and its complications. Several studies have demonstrated the protective effect of Vitamin D on intestinal barrier function. However, severe cholestasis leads to vitamin D depletion. This study was designed to test whether vitamin D therapy improves intestinal dysfunction in cirrhosis. Rats were subcutaneously injected with 50% sterile CCl₄ (a mixture of pure CCl₄ and olive oil, 0.3 mL/100 g) twice a week for 6 weeks. Next, 1,25(OH)₂D₃(0.5 µg/100 g) and the vehicle were administered simultaneously with CCl₄ to compare the extent of intestinal histologic damage, tight junction protein expression, intestinal barrier function, BT, intestinal proliferation, apoptosis, and enterocyte turnover. Intestinal heme oxygenase-1 (HO-1) expression and oxidative stress were also assessed. We found that vitamin D could maintain intestinal epithelial proliferation and turnover, inhibit intestinal epithelial apoptosis, alleviate structural damage, and prevent BT and intestinal barrier dysfunction. These were achieved partly through restoration of HO-1 and inhibition of oxidative stress. Taken together, our results suggest that vitamin D ameliorated intestinal epithelial turnover and improved the integrity and function of intestinal barrier in CCl₄-induced liver cirrhotic rats. HO-1 signaling activation was involved in these above beneficial effects.
Animals ; Apoptosis ; Bacterial Translocation ; Cholestasis ; Enterocytes ; Fibrosis ; Heme Oxygenase-1 ; Heme ; Humans ; Liver ; Liver Diseases ; Olive Oil ; Oxidative Stress ; Rats ; Tight Junctions ; Vitamin D ; Vitamins

OBJECTIVE: To investigate the protective effects of shen-mai injection on intestinal barrier function in the early stage of 30% 3° scald, and to provide experimental basis for the prevention and control of enterogenic infection. METHODS: A total of 60 Wistar rats were randomly divided into 6 groups: normal control group (without treatment), model control group (with 30% total body surface area (TBSA) fully thickness burn on the back), hexadecadrol (5 mg/kg) group, Shenmai injection (5, 10, 15 mg/kg) groups, with 10 rats in each group. After burned by scald apparatus, rats in each group were treated with drugs immediately by intraperitoneal injection once a day. At 72 hours after burned, the levels of plasma endotoxin, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-α), interleukins-6(IL-6) in all rats were detected and the mesenteric lymph nodes, liver and spleen were homogenized to culture for bacteria. The change of secretory immunoglobulin A (sIgA) in intestinal mucosa was measured. RESULTS: Compared with normal control group, bacterial translocation quantity in mesenteric lymph nodes(MLN), liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in model control group were increased significantly (P＜0.01); compared with model control group, bacterial translocation quantity in MLN, liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in hexadecadrol (5 mg/kg) group and shen-mai injection (5, 10, 15 mg/kg) groups were decreased significantly (P＜0.05 or P＜0.01). CONCLUSION Shen-mai injection can alleviate intestinal mucosa injury caused by severe scald, and the effects are similar with those of dexamethasone, and the effect is better in the high-dose group.
Animals ; Bacterial Translocation ; drug effects ; Burns ; complications ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Intestinal Mucosa ; drug effects ; pathology ; Random Allocation ; Rats ; Rats, Wistar

Chronic high-salt diet-associated renal injury is a key risk factor for the development of hypertension. However, the mechanism by which salt triggers kidney damage is poorly understood. Our study investigated how high salt (HS) intake triggers early renal injury by considering the ‘gut-kidney axis’. We fed mice 2% NaCl in drinking water continuously for 8 weeks to induce early renal injury. We found that the ‘quantitative’ and ‘qualitative’ levels of the intestinal microflora were significantly altered after chronic HS feeding, which indicated the occurrence of enteric dysbiosis. In addition, intestinal immunological gene expression was impaired in mice with HS intake. Gut permeability elevation and enteric bacterial translocation into the kidney were detected after chronic HS feeding. Gut bacteria depletion by non-absorbable antibiotic administration restored HS loading-induced gut leakiness, renal injury and systolic blood pressure elevation. The fecal microbiota from mice fed chronic HS could independently cause gut leakiness and renal injury. Our current work provides a novel insight into the mechanism of HS-induced renal injury by investigating the role of the intestine with enteric bacteria and gut permeability and clearly illustrates that chronic HS loading elicited renal injury and dysfunction that was dependent on the intestine.
Animals ; Bacteria ; Bacterial Translocation ; Blood Pressure ; Drinking Water ; Dysbiosis ; Enterobacteriaceae ; Gastrointestinal Microbiome ; Gene Expression ; Hypertension ; Intestines ; Kidney ; Mice* ; Microbiota ; Permeability ; Risk Factors

BACKGROUND/AIMS: Non-selective beta blockers (NSBBs) are currently the only accepted regimen for preventing portal hypertension (PHT)-related complications. However, the effect of NSBBs is insufficient in many cases. Bacterial translocation (BT) is one of the aggravating factors of PHT in cirrhosis; therefore, selective intestinal decontamination by rifaximin is a possible therapeutic option for improving PHT. We investigated whether the addition of rifaximin to propranolol therapy can improve hepatic venous pressure gradient (HVPG) response. METHODS: Sixty-four cirrhosis patients were randomly assigned to propranolol monotherapy (n=48) versus rifaximin and propranolol combination therapy (n=16). Baseline and post-treatment HVPG values, BT-related markers (lipopolysaccharide [LPS], LPS-binding protein [LBP], interleukin-6 [IL-6], and tumor necrosis factor α [TNF-α]), serological data, and adverse event data were collected. HVPG response rate was the primary endpoint. RESULTS: Combination therapy was associated with better HVPG response rates than monotherapy (56.2% vs 87.5%, p=0.034). In combination therapy, posttreatment BT-related markers were significantly decreased (LPS, p=0.005; LBP, p=0.005; IL-6, p=0.005; TNF-α, p=0.047). CONCLUSIONS: Rifaximin combination therapy showed an additive effect in improving PHT compared to propranolol monotherapy. These pilot data suggest that the addition of rifaximin to NSBBs could be a good therapeutic option for overcoming the limited effectiveness of NSBBs.
Bacterial Translocation ; Decontamination ; Fibrosis ; Humans ; Hypertension, Portal ; Interleukin-6 ; Pilot Projects* ; Portal Pressure* ; Propranolol* ; Tumor Necrosis Factor-alpha ; Venous Pressure

Acute cholecystitis after colonoscopy is very rare, and has not been extensively studied. A 51-year-old male with history of acute cholecystitis caused by common bile duct stones 1 year ago underwent screening colonoscopy. Colonoscopy was performed without difficulty and showed normal findings. Two days after colonoscopy, right upper quadrant abdominal pain and fever were developed. Abdominal computed tomography showed an enlargement of gallbladder with diffuse wall thickening and gallstones in the neck of gallbladder. The findings were consistent with that of acute cholecystitis as post-colonoscopy complication. Although its pathophysiology is uncertain, possible causes including dehydration of patient, concentration of bile and bacterial translocation were suggested in previous reports. Due to its rarity, it is hard to suspect an acute cholecystitis as primary complication of colonoscopy. Thus acute cholecystitis should be considered in differential diagnosis of patients with abdominal pain and fever after colonoscopy, particularly those who with history of gallstones.
Abdominal Pain ; Bacterial Translocation ; Bile ; Cholecystectomy ; Cholecystitis ; Cholecystitis, Acute* ; Colonoscopy* ; Common Bile Duct ; Dehydration ; Diagnosis, Differential ; Fever ; Gallbladder ; Gallstones ; Humans ; Male ; Mass Screening* ; Middle Aged ; Neck

Acute cholecystitis after colonoscopy is very rare, and has not been extensively studied. A 51-year-old male with history of acute cholecystitis caused by common bile duct stones 1 year ago underwent screening colonoscopy. Colonoscopy was performed without difficulty and showed normal findings. Two days after colonoscopy, right upper quadrant abdominal pain and fever were developed. Abdominal computed tomography showed an enlargement of gallbladder with diffuse wall thickening and gallstones in the neck of gallbladder. The findings were consistent with that of acute cholecystitis as post-colonoscopy complication. Although its pathophysiology is uncertain, possible causes including dehydration of patient, concentration of bile and bacterial translocation were suggested in previous reports. Due to its rarity, it is hard to suspect an acute cholecystitis as primary complication of colonoscopy. Thus acute cholecystitis should be considered in differential diagnosis of patients with abdominal pain and fever after colonoscopy, particularly those who with history of gallstones.
Abdominal Pain ; Bacterial Translocation ; Bile ; Cholecystectomy ; Cholecystitis ; Cholecystitis, Acute* ; Colonoscopy* ; Common Bile Duct ; Dehydration ; Diagnosis, Differential ; Fever ; Gallbladder ; Gallstones ; Humans ; Male ; Mass Screening* ; Middle Aged ; Neck

This paper is to explore changes of intestinal mucosal barrier, intestinal flora, and bacterial translocation in rats with severe acute pancreatitis (SAP). Twenty four male SD rats were randomly divided into the control group (n = 10) and the experimental group (n = 14). The model of severe acute pancreatitis of rats was induced by the method of injecting adversely 5% sodium taurocholate into the common biliary-pancreatic duct. All of the rats were killed after 24 hours and the level of the serum amylase and the plasma endotoxin was determined after that. The pathological changes of pancreas and small intestine were observed through hematoxylin-eosin staining (HE staining) and the abdominal viscera bacterial translocation rates were tested. With the method of real-time polymerase chain reaction (RT-PCR) the quantity of the intestinal flora was analyzed. In the control group, the level of Escherichia coli, Lactobacillus and Bifidobacterium were 2.08 ± 1.29, 11.04 ± 7.55 and 12.21 ± 4.95, respectively. On the contrast, the level of Escherichia coli in the cecum contents was much higher (9.72 ± 3.58, P < 0.01), while the Lactobacillus number was decreased significantly (0.67 ± 0.34, P < 0.01), and the Bifidobacterium number was also decreased (4.59 ± 3.42, P < 0.05) in the experimental group, so the ratio of Bifidobacterium/Escherichia coli was reversed. Besides, in the experimental group, the plasma endotoxin positive rates and the bacterial translocation rates were much higher (P < 0.01 or P < 0.05) and the pathology scores of pancreas and small intestines were also significantly higher (P < 0.01) than those in the control group. These results indicated that in severe acute pancreatitis rats, the intestinal mucosal barrier was severely damaged and the dysbacteriosis occurs in the intestinal canal. And these might relate to the occurrence and development of multiple organ infection.
Animals ; Bacterial Translocation ; Endotoxins ; Intestinal Mucosa ; pathology ; Intestines ; microbiology ; Male ; Pancreas ; pathology ; Pancreatitis ; microbiology ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effect of Modified Dachengqi Decoction (MDD) as whole course therapy on mediators of inflammation in severe acute pancreatitis (SAP) model rats, and to compare interventional advantages over intestinal mucosal barrier (IMB) of SAP rats between whole course therapy of MDD and early stage therapy of MDD.

METHODSTotally 190 SD rats were divided into five groups according to random digit table, i.e., the sham-operation group, the model group, the octreotide (OT) group, the early stage MDD treatment group, the whole course MDD treatment group, 38 in each group. SAP models were established with retrograde injection of 5% sodium taurocholate into the pancreaticobiliary duct. Three hours after modeling normal saline (NS) was administered to rats in the sham-operation group and the model group by gastrogavage, once per 12 h.1.35 µg/100 g OT was subcutaneously injected to rats in the OT group, once every 8 h. 0.4 mL/100 g MDD was administered to rats in the early stage MDD treatment group, and 6 h later changed to NS (once per 12 h).0.4 mL/100 g MDD was administered to rats in the whole course MDD treatment group, once every 12 h. The accumulative survival rate and morphological manifestations of pancreas and small intestine were observed under microscope 48 h after modeling. Pathologic scores of the pancreas and small intestine were conducted at 4, 6, 24, and 48 h after modeling. Contents of serum amylase (AMY), alanine transaminase (ALT), and TNF-α were also detected. The expression of high mobility group box protein 1 (HMGB1) in the small intestine tissue was also detected by Western blot. The positive rate of bacterial translocation in mesenteric lymph nodes (MLNs) was observed within 48 h. Correlations between serum TNF-α or HMGB1 in small intestinal tissue and pathological scores of the pancreas or the small intestine were analyzed.

RESULTSThe accumulative survival rate was 100. 0% in the sham-operation group, 79. 2% in the whole course MDD treatment group, 70. 8% in the OT group, 45. 8% in the early stage MDD treatment group, and 37.5% in the model group. At 6 h after modeling, pathological scores decreased more in the whole course MDD treatment group, the early stage MDD treatment group, the OT group than in the model group (P < 0.05). At 24 and 48 h after modeling, pathological scores of the pancreas and the small intestine decreased more in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group (P <0. 05). At 6, 24, and 48 h after modeling, serum contents of AMY and ALT both decreased more in the whole course MDD treatment group, the early stage MDD treatment group, the OT group than in the model group (P < 0.05). At 48 h after modeling serum contents of AMY and ALT both decreased more in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group (P < 0.05). At 6 h after modeling serum TNF-α levels decreased more in the whole course MDD treatment group, the early stage MDD treatment group, the OT group than in the model group (P < 0.05). At 6, 24, and 48 h after modeling the level of HMGB1 in the small intestinal tissue decreased more in the whole course MDD treatment group, the early stage MDD treatment group, the OT group than in the model group (P < 0.05). Of them, HMGB1 levels at 24 and 48 h were lower in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group (P < 0.05). The number of MLNs bacterial translocation at 48 h after modeling was lower in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group and the model group (P < 0.05). Serum TNF-α contents within 6 h were positively correlated with pathological scores of pancreas (r = 0.579, P < 0.01). ROC curve showed that serum TNF-α contents could predict the severity of SAP (ROC = 0.990, 95% Cl: 0.971 to 1.000). HMGB1 in the small intestine was positively correlated with pathological scores of the small intestine (r = 0.620, P < 0.01).

CONCLUSIONSEarly stage use of MDD could effectively reduce the release of TNF-α, while whole course use of MDD could effectively inhibit the expression of HMGB1. The latter could preferably attenuate injuries of the pancreas and the small intestine, lower MLNs bacterial translocation, and elevate the survival rate.

Animals ; Bacterial Translocation ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; HMGB1 Protein ; Intestinal Mucosa ; drug effects ; Octreotide ; Pancreas ; Pancreatitis ; drug therapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Taurocholic Acid ; Tumor Necrosis Factor-alpha

Animals ; Bacterial Translocation ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Insulin Resistance ; Obesity ; microbiology ; therapy ; Probiotics ; therapeutic use

OBJECTIVETo observe the ultrastructural change of the route of gut bacterial translocation in a rat with spinal cord injury (SCI).

METHODSForty Wistar rats were divided into the following groups: control group and 3 SCI groups (10 in each group). The rats in the SCI groups were established SCI model at 24 h, 48 h, and 72 h after SCI. Small intestine mucous membrane tissue was identified and assayed by transmission electron microscope, scanning electron microscope and immunofluorescence microscopy.

RESULTSSmall intestine mucous membrane tissue in control group was not damaged significantly, but those in SCI groups were damaged significantly. Proliferation bacteria in gut lumen attached on microvilli. The extracellular bacteria torn the intestinal barrier and perforated into the small intestinal mucosal epithelial cell. The bacteria and a lot of particles of the seriously damaged region penetrated into the lymphatic system and the blood system directly. Some bacteria were internalized into the goblet cell through the apical granule. Some bacteria and particles perforated into the submucosa of the M cell running the long axis of M cells through the tight junctions. In the microcirculation of mucosa, the bacteria that had already broken through the microvilli into blood circulation swim accompanying with erythrocytes.

CONCLUSIONThe routes of bacterial translocation interact and format a vicious circle. At early step, the transcellular pathway of bacterial translocation is major. Following with the destroyed small intestine mucous, the routes of bacterial translocation through the lymphatic system and the blood system become direct pathways. The goblet cell-dendritic cell and M cell pathway also play an important role in the bacterial translocation.

Animals ; Bacteria ; Bacterial Translocation ; Epithelial Cells ; microbiology ; Goblet Cells ; microbiology ; Intestinal Mucosa ; microbiology ; pathology ; ultrastructure ; Intestine, Small ; microbiology ; pathology ; ultrastructure ; Microvilli ; microbiology ; Rats ; Rats, Wistar ; Spinal Cord Injuries ; microbiology