CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut.

The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites. Consequent impairment of the outer blood retinal barrier and colonic intestinal epithelial barrier in Rd8 mice led to the translocation of intestinal bacteria from the lower gastrointestinal (GI) tract to the retina, resulting in secondary retinal degeneration. Either the depletion of bacteria systemically or the reintroduction of normal Crb1 expression colonically rescued Rd8-mutation-associated retinal degeneration without reversing the retinal barrier breach. Our data elucidate the pathogenesis of Crb1-mutation-associated retinal degenerations and suggest that antimicrobial agents have the potential to treat this devastating blinding disease.

Capsaicin shapes gut microbiota and pre-metastatic niche to facilitate cancer metastasis to liver.

Dietary factors are fundamental in tumorigenesis throughout our lifetime. A spicy diet has been ambiguous on the development of cancers, especially in the study of colon cancer metastasis. Here, we utilized a mouse metastasis model to test the potential role of capsaicin in influencing metastasis. Long-term continuous administration of capsaicin diet (300 mg/kg) to mice promotes the formation of liver pre-metastatic niche to facilitate the metastasis of colon cancer cells. Bacteria translocation to liver is clearly observed. Capsaicin increases intestinal barrier permeability and disrupts gut vascular barrier by altering the composition of gut microbiota. Capsaicin not only changes the abundance of mucin-related bacteria like Akkermanisa and Muribaculaceae, but also bacteria involved in bile acids metabolism. Dysregulated bile acids profile is related to the recruitment of natural killer T (NKT) cells in pre-metastatic niche, primary bile acid α-Muricholic acid can enhance the recruitment of NKT cells, while secondary bile acids Glycoursodeoxycholic acid and Taurohyodeoxycholic acid impair the recruitment of NKT cells. These findings reveal long term consumption of capsaicin increases the risk of cancer metastasis through modulating the gut microbiota. Capsaicin (300 mg/kg) disrupts gut barrier and promotes the translocation of bacteria to liver, while altered bile acids metabolism affects the recruitment of NKT cells in liver, forming a pre-metastatic niche and promoting cancer metastasis.

Heart-gut microbiota communication determines the severity of cardiac injury after myocardial ischaemia/reperfusion.

AIMS: Recent studies have suggested a key role of intestinal microbiota in pathological progress of multiple organs via immune modulation. However, the interactions between heart and gut microbiota remain to be fully elucidated. The aim of the study is to investigate the role of gut microbiota in the post-ischaemia/reperfusion (I/R) inflammatory microenvironment. METHODS AND RESULTS: Here, we conducted a case-control study to explore the association of gut bacteria translocation products with inflammation biomarkers and I/R injury severity in ST-elevation myocardial infarction patients. Then, we used a mouse model to determine the effects of myocardial I/R injury on gut microbiota dysbiosis and translocation. Blooming of Proteobacteria was identified as a hallmark of post-I/R dysbiosis, which was associated with gut bacteria translocation. Abrogation of gut bacteria translocation by antibiotic cocktail alleviated myocardial I/R injury via mitigating excessive inflammation and attenuating myeloid cells mobilization, indicating the bidirectional heart-gut-microbiome-immune axis in myocardial I/R injury. Glucagon-like peptide 2 (GLP-2), an endocrine peptide produced by intestinal L-cells, was used in the experimental myocardial I/R model. GLP-2 administration restored gut microbiota disorder and prevented bacteria translocation, eventually attenuated myocardial I/R injury through alleviating systemic inflammation. CONCLUSION: Our work identifies a bidirectional communication along the heart-gut-microbiome-immune axis in myocardial I/R injury and demonstrates gut bacteria translocation as a key regulator in amplifying inflammatory injury. Furthermore, our study sheds new light on the application of GLP-2 as a promising therapy targeting gut bacteria translocation in myocardial I/R injury.

Creeping fat formation and interaction with intestinal disease in Crohn's disease.

Creeping fat (CrF), also known as fat wrapping, is a significant disease characteristic of Crohn's disease (CD). The transmural inflammation impairs intestinal integrity and facilitates bacteria translocation, aggravating immune response. CrF is a rich source of pro-inflammatory and pro-fibrotic cytokines with complex immune microenvironment. The inflamed and stricturing intestine is often wrapped by CrF, and CrF is associated with greater severity of CD. The large amount of innate and adaptive immune cells as well as adipocytes in CrF promote fibrosis in the affected intestine by secreting large amount of pro-fibrotic cytokines, adipokines, growth factors and fatty acids. CrF is a potential therapeutic target for CD treatment and a promising bio-marker for predicting response to drug therapy. This review aims to summarize and update the clinical manifestation and application of CrF and the underlying molecular mechanism involved in the pathogenesis of intestinal inflammation and fibrosis in CD.

The Gut Microbiota Metabolite Succinate Promotes Adipose Tissue Browning in Crohn's Disease.

BACKGROUND AND AIMS: Crohn's disease [CD] is associated with complex microbe-host interactions, involving changes in microbial communities, and gut barrier defects, leading to the translocation of microorganisms to surrounding adipose tissue [AT]. We evaluated the presence of beige AT depots in CD and questioned whether succinate and/or bacterial translocation promotes white-to-beige transition in adipocytes. METHODS: Visceral [VAT] and subcutaneous [SAT] AT biopsies, serum and plasma were obtained from patients with active [n = 21] or inactive [n = 12] CD, and from healthy controls [n = 15]. Adipose-derived stem cells [ASCs] and AT macrophages [ATMs] were isolated from VAT biopsies. RESULTS: Plasma succinate levels were significantly higher in patients with active CD than in controls and were intermediate in those with inactive disease. Plasma succinate correlated with the inflammatory marker high-sensitivity C-reactive protein. Expression of the succinate receptor SUCNR1 was higher in VAT, ASCs and ATMs from the active CD group than from the inactive or control groups. Succinate treatment of ASCs elevated the expression of several beige AT markers from controls and from patients with inactive disease, including uncoupling protein-1 [UCP1]. Notably, beige AT markers were prominent in ASCs from patients with active CD. Secretome profiling revealed that ASCs from patients with active disease secrete beige AT-related proteins, and co-culture assays showed that bacteria also trigger the white-to-beige switch of ASCs from patients with CD. Finally, AT depots from patients with CD exhibited a conversion from white to beige AT together with high UCP1 expression, which was corroborated by in situ thermal imaging analysis. CONCLUSIONS: Succinate and bacteria trigger white-to-beige AT transition in CD. Understanding the role of beige AT in CD might aid in the development of therapeutic or diagnostic interventions.

[Electroacupuncture at "Zusanli"(ST36) protects intestinal mucosal immune barrier by suppre-ssing apoptosis of intestinal lymphocytes and regulating expression of Bcl-2 and Bax in sepsis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) on apoptosis of intestinal T lymphocytes, translocation of intestinal bacteria and expression of intestinal Bcl-2 and Bax proteins and intestinal mucosal immune barrier in sepsis rats, so as to explore its underlying mechanism in relieving sepsis. METHODS: SD rats were randomly divided into sham operation (n=6), model (n=15), non-meridian and non-acupoint (non-acupoint, n=15) and acupoint EA(n=15) groups by using random number table method. The sepsis model was established by using cecal ligation and perforation(CLP) method. EA (2 Hz, 2 mA) was applied to bilateral ST36 or non-acupoint for 30 min one hour after modeling, once every day for 3 days. The rats' general conditions and fatality rate in 3 days after modeling were recorded. The liver, spleen and mesenteric lymph nodes were taken for bacterial culture to detect the translocation rate of intestinal bacteria. The small intestinal tissue was taken for observing histopathological changes (Chiu's score: 0-5 points) after HE staining, and for determining the expression levels of Bcl-2 and Bax proteins using Western blot. The intestinal mucosa was sampled for detecting the apop-tosis (apoptotic index) of lymphocytes by using terminal deoxynucleoitidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) assay, and the counts of CD4+ and CD8+T cells using flow cytometry. The contents of IL-4 in the small intestine and that of secretory IgA (sIgA) in the small intestinal mucus were determined by using ELISA. RESULTS: After modeling, of the 15 rats in each of the 3 groups, 7, 7 and 2 in the model, non-acupoint and EA groups were dead in the first 3 days, with the fatality rate being 46.67% (7/15), 46.67% (7/15) and 13.33% (2/15), respectively (being obviously lower in the EA group than in the former two groups, P<0.05). Compared with the sham operation group, the incidence of intestinal bacterial translocation, apoptotic index, Chiu's score, and Bax expression were significantly increased (P<0.05), and the percentages of CD4+ and CD8+T cells, IL-4 and sIgA contents and Bcl-2 expression considerably decreased (P<0.05) in the model group. In comparison with the model group, modeling-induced increase of incidence of bacterial translocation, apoptotic index and Bax expression, and decrease of percentages of CD4+ and CD8+T cells, IL-4 and sIgA contents and Bcl-2 expression were reversed (P<0.05) in the EA group. CONCLUSION: EA at ST36 can reduce death rate and intestinal bacteria translocation incidence in sepsis rats, which may be related to its functions in regulating the expression of intestinal Bcl-2 and Bax proteins and inhibiting the apoptosis of intestinal mucosal T lymphocytes, thereby protecting the immune barrier function of intestinal mucosa to reduce the intestinal permeability.

Colonic inflammation accelerates the progression of liver disease: A protective role of dipotassium glycyrrhizate.

BACKGROUND: The incidence of non-alcoholic fatty liver disease (NAFLD) and its more severe and progressive form, non-alcoholic steatohepatitis (NASH) is increasing worldwide. Gut inflammation seems to concur to the pathogenesis of NASH. No drugs are currently approved for NASH treatment. AIMS: To investigate if inflamed gut directly contributes to the progression of NASH through gut epithelial and vascular barrier impairment and to evaluate the efficacy of dipotassium glycyrrhizate (DPG) to improve the liver disease. METHODS: A NASH model was set up by feeding mice, for 8 and 13 weeks, with high fat diet with high fructose and glucose (HFD-FG) supplemented periodically with dextran sulfate sodium (DSS) in drinking water. A group was also treated with DPG by gavage. Histological, immunohistochemical and molecular analysis were performed. RESULTS: DSS-induced colitis increased steatosis, inflammatory (IL-6, TNFα, NLRP3, MCP-1) as well as fibrotic (TGF-ß, α-SMA) mediator expression in HFD-FG mice. Beneficial effect of DPG was associated with restoration of intestinal epithelial and vascular barriers, evaluated respectively by ZO-1 and PV-1 expression, that are known to limit bacterial translocation. CONCLUSION: Colonic inflammation strongly contributes to the progression of NASH, likely by favouring bacterial translocation. DPG treatment could represent a novel strategy to reduce liver injury.

Preterm Birth Is Correlated With Increased Oral Originated Microbiome in the Gut.

Background: Preterm birth is one of the leading causes of perinatal morbidity and mortality. Gut microbiome dysbiosis is closely related to adverse pregnancy outcomes. However, the role of the gut microbiome in the pathogenesis of preterm birth remains poorly studied. Method: We collected fecal samples from 41 women (cases presenting with threatened preterm labor =19, 11 of which delivered preterm; gestational age-matched no-labor controls, all of which delivered at term = 22) were recruited for the study. We performed 16S rRNA amplicon sequencing to compare the composition of the gut microbiome in threatened preterm labor cases and controls and among women who delivered preterm and at term. By annotating taxonomic biomarkers with the Human Oral Microbiome Database, we observed an increased abundance of potential oral-to-gut bacteria in preterm patients. Results: Patients with preterm birth showed a distinct gut microbiome dysbiosis compared with those who delivered at term. Opportunistic pathogens, particularly Porphyromonas, Streptococcus, Fusobacterium, and Veillonella, were enriched, whereas Coprococcus and Gemmiger were markedly depleted in the preterm group. Most of the enriched bacteria were annotated oral bacteria using the Human Oral Microbiome Database. These potential oral-to-gut bacteria were correlated with clinical parameters that reflected maternal and fetal status. Conclusions: This study suggests that patients who deliver preterm demonstrate altered gut microbiome that may contain higher common oral bacteria.

Gut Alterations in Septic Patients: A Biochemical Literature Review.

BACKGROUND: Sepsis is a life-threatening organ dysfunction with high mortality and morbidity rate and with the disease progression many alterations are observed in different organs. The gastrointestinal tract is often damaged during sepsis and septic shock and main symptoms are related to increased permeability, bacterial translocation and malabsorption. These intestinal alterations can be both cause and effect of sepsis. OBJECTIVE: The aim of this review is to analyze different pathways that lead to intestinal alteration in sepsis and to explore the most common methods for intestinal permeability measurement and, at the same time to evaluate if their use permit to identify patients at high risk of sepsis and eventually to estimate the prognosis. MATERIAL AND METHODS: The peer-reviewed articles analyzed were selected from PubMed databases using the keywords "sepsis" "gut alteration", "bowel permeability", "gut alteration", "bacterial translocation", "gut permeability tests", "gut inflammation". Among the 321 papers identified, 190 articles were selected, after title - abstract examination and removing the duplicates and studies on pediatric population,only 105 articles relating to sepsis and gut alterations were analyzed. RESULTS: Integrity of the intestinal barrier plays a key role in the preventing of bacterial translocation and gut alteration related to sepsis. It is obvious that this dysfunction of the small intestine can have serious consequences and the early identification of patients at risk - to develop malabsorption or already malnourished - is very recommended to increase the survivor rate. Until now, in critical patients, the dosage of citrullinemia is easily applied test in clinical setting, in fact, it is relatively easy to administer and allows to accurately assess the functionality of enterocytes. CONCLUSION: The sepsis can have an important impact on the gastrointestinal function. In addition, the alteration of the permeability can become a source of systemic infection. At the moment, biological damage markers are not specific, but the dosage of LPS, citrulline, lactulose/mannitol test, FABP and fecal calprotectin are becoming an excellent alternative with high specificity and sensitivity.

Effect of Tanshinone ⅡA injection on intestinal mucosal tight junction protein in severe rat septic models / 中国中西医结合急救杂志

Objective To discuss the influence of Tanshinone ⅡA on the tight junction protein of intestinal mucosal epithelial cells in rat severe septic models. Methods Seventy-five Sprague-Dawley (SD) rats were randomly divided into sham operation group, model group and Tanshinone ⅡA injection high (20 mg/kg), medium (10 mg/kg) and low (5 mg/kg) dose groups, each group 15 rats. Sepsis rat models were established by cecal ligation and puncture (CLP) method, in sham operation group, only switched abdominal surgery was performed without CLP. In Tanshinone ⅡA injection groups, different doses of Tanshinone ⅡA were injected intraperitoneally after modeling for 10 minutes and 6 hours; in sham operation and model groups, equal volume of normal saline was injected intraperitoneally at the same times as above. After operation, 3 L/kg of normal saline was injected into the caudal vein in all rats for fluid resuscitation.Twelve hours after operation, the rats were killed, the abdominal lymph nodes, liver, spleen and kidney tissues were taken for bacterial culture and calculating the rate of bacterial translocation; under microscope, the histopathological changes of ileum mucosal tissues were examined and Chiu scoring was carried out; TdT-mediated dUTP nick end labeling (TUNEL) was applied to detect the ileum mucosal epithelial cell apoptosis and calculating the index (AI);fluorescence immunoassay and Western Blot methods were used to measure the contents and protein expression levels of tight junction protein, junctional adhesion molecule-1 (JAM), Claudin-1, Zonula occludens-1 (ZO-1), Occludin, c-Fos and Tryptase. Results ① In bacterial cultures of abdominal lymph node, liver, spleen and kidney, the positive rate of mesenteric lymph node was the highest, followed by liver and spleen, mainly Escherichia coli, Proteus mirabilis, etc. The highest positive rate of bacterial culture was in model group (38.8%), followed by low dose of Tanshinone ⅡA injection group (35.0%), and the lowest was 16.6% in high dose Tanshinone ⅡA injection group, the differences being statistically significant in comparisons between any pair of groups (all P < 0.05). ② Pathological examination showed that the pathological changes of ileum mucosa were obvious and the Chiu score (4.17±0.98 vs. 0) and AI (11.70±2.87 vs. 2.17±0.80) in model group were significantly higher than those in sham group (all P < 0.05); with the increase of dosage of Tanshinone ⅡA injection, the pathological changes of rat ileum mucosa were improved gradually, the Chiu score and AI were decreased gradually, and the degrees of decrease in high dose Tanshinone ⅡA group were more significant than those in model group (Chiu score: 1.12±0.79 vs. 4.17±0.98, AI: 3.65±1.98 vs. 11.70±2.87, both P < 0.05).③ Immunofluorescence staining showed that the positive staining of protein JAM, ZO-1 and c-Fos were all green in color, Claudin-1, Occludin and Tryptase were all red in color, the localizations of all of them were in the cytoplasm, the protein expression of JAM, Claudin-1, ZO-1, Occludin from strong to weak in turn were Sham group, high, medium, low dose Tanshinone ⅡA group and model group, the expression of c-Fos, Tryptase from strong to weak in turn were model group, low, medium, high dose Tanshinone ⅡA group and Sham group. ④ Western Blot showed that the expressions of ileum tissue JAM, Claudin-1, ZO-1 and Occludin in model group were all significantly lower than those of the sham group, while the expressions of c-Fos, Tryptase were obviously higher than those of the sham group, with the increase of dosage of Tanshinone ⅡA, the expressions of JAM, Claudin-1, ZO-1 and Occludin were increased gradually and the protein expressions of c-Fos and Tryptase were gradually decreased, and the changes in high dosage group of Tanshinone ⅡA were more significant than those in low and moderate groups [JAM (gray value): 25.39±1.82 vs. 12.41±1.34, 19.45±1.66, Claudin-1 (gray value): 28.44±1.56 vs.17.26±1.46, 21.23±1.34, ZO-1 (gray value): 28.84±1.59 vs. 16.45±1.21, 24.22±1.46, Occludin (gray value): 25.49±1.63 vs. 13.34±1.45, 19.45±1.37, c-Fos (gray value):15.76±1.36 vs. 27.84±1.36, 21.22±1.73, Tryptase (gray value): 14.44±1.41 vs. 28.14±1.38, 22.32±1.57], all the above comparisons of different dosage groups were statistically significant (all P < 0.05). Conclusion Tanshinone ⅡA injection may improve intestinal wall structure and reduce bacterial translocation by improving the intestinal mucosal tight junction protein in sepsis model rats, and this effect is positively correlated to Tanshinone ⅡA dosage.

Effects of ω-3 PUFA on inflammatory response of intestine and bacteria translocation in rats with traumatic shock / 中华急诊医学杂志

Objective To investigate the effects of ω-3 polyunsaturated fatty acids (ω-3 PUFA) on inflammatory response of intestine and bacteria translocation in rats with traumatic shock (TS) in order to explore the underlying mechanism.Methods A total of 36 male Wistar rats provided by Academy of Military Medical Sciences Animal Center were assigned randomly (random number) into 3 groups (n =12 in each group):sham operation group,TS model group and PUFA pretreatment group.Rat models of IS were established by comminuted fracture of femur and depletion of blood,and 2 mg/kg ω-3 PUFA or normal saline were injected 12 hours and 2 hours before modeling.Blood specimens were collected and intestinal tissue samples were obtained 120 min after modeling.The serum levels of tumor necrosis factor-o (TNF-α),IL-1β,IL-10 and 8-iso-prostaglandin F 2α (8-iso-PGF2α) were measured with ELISA.Light microscopic examination was carried out for histopathological assessment of the intestina tissue and the intestinal mucosa damage index ( IMDI ) was calculated.The number of marked bacilli found in mesenteric lymph nodes,lung,liver,spleen,and kidney tissues were counted under a fluorescent microscope.The percentages for categorical variables and mean ± SD for continuous variables were expressed. Chi-square test and unpaired t-test were used for comparisons among groups,and statistical significance defined as P ＜ 0.05.Results The levels of TNF-α,IL-1β,IL-10 and 8-iso-PGF2α,the IMDI and the positive rates of bacteria translocation in TS model group were [ (325.14 ±21.17) ng/ml,(26.93 +2.58) μg/L,(7.59 ± 1.26) μg/L,(259.73 +61.32) pg/ml,(4.15 +0.37) and 58.33％,respectively] and those in PUFA group were [ (251.47 + 19.16) ng/ml,(17.81±1.94) μg/L,(9.44±1.85) μg/L,(171.44±39.25) pg/ml,(3.28±0.43) and 36.67％,respectively ].And those biomarkers in both TS group and PUFA group were higher obviously than those in sham group [ (37.02 ±5.54) ng/ml,(2.49 ±0.67) μg/L,(2.93 ±0.74) μg/L,(81.26 ± 15.18) pg/ml,(0.33 ±0.12) and 6.67％,respectively,P＜0.01].Compared with TS model group,the levels of TNF-α,IL-1β and 8-iso-PGF2α,the IMDI and the positive rates of bacteria translocation were lower,and the levels of IL-10 were higher in PUFA group ( P ＜ 0.01 or P ＜ 0.05 ).Conclusions The supplementation of ω-3 PUFA lessens the injury of intestina mucosa after traumatic shock,and it may be associated with the inhibition of inflammatory response by intestine and bacteria translocation.was carried out for histopathological assessment of the intestina tissue and the intestinal mucosa damage index ( IMDI ) was calculated.The number of marked bacilli found in mesenteric lymph nodes,lung,liver,spleen,and kidney tissues were counted under a fluorescent microscope.The percentages for categorical variables and mean ± SD for continuous variables were expressed. Chi-square test and unpaired t-test were used for comparisons among groups,and statistical significance defined as P ＜ 0.05.Results The levels of TNF-α,IL-1β,IL-10 and 8-iso-PGF2α,the IMDI and the positive rates of bacteria translocation in TS model group were [ (325.14 ±21.17) ng/ml,(26.93 +2.58) μg/L,(7.59 ± 1.26) μg/L,(259.73 +61.32) pg/ml,(4.15 +0.37) and 58.33％,respectively] and those in PUFA group were [ (251.47 + 19.16) ng/ml,(17.81±1.94) μg/L,(9.44±1.85) μg/L,(171.44±39.25) pg/ml,(3.28±0.43) and 36.67％,respectively ].And those biomarkers in both TS group and PUFA group were higher obviously than those in sham group [ (37.02 ±5.54) ng/ml,(2.49 ±0.67) μg/L,(2.93 ±0.74) μg/L,(81.26 ± 15.18) pg/ml,(0.33 ±0.12) and 6.67％,respectively,P＜0.01].Compared with TS model group,the levels of TNF-α,IL-1β and 8-iso-PGF2α,the IMDI and the positive rates of bacteria translocation were lower,and the levels of IL-10 were higher in PUFA group ( P ＜ 0.01 or P ＜ 0.05 ).Conclusions The supplementation of ω-3 PUFA lessens the injury of intestina mucosa after traumatic shock,and it may be associated with the inhibition of inflammatory response by intestine and bacteria translocation.

Effect of Probiotics on Intestinal Flora Disturbance and Bacteria Translocation of Rats / 上海第二医科大学学报

Objective To investigate the effect of probiotic supplement on the microbiology,bacterial translocation,and gut barrier function of the rats with abdominal infection. Methods After making the models of cecal ligation and perforation,the SD rats were divided into two groups.The rats in the control group were administrated with parenteral nutrition.The rats in the experimental group were administrated with parenteral nutrition and probiotics via the needle jejunostomy and neck vein for 5 d.The feces in the cecum were cultured by anaerobic bacterial growth.The vena cava blood and the homogenated tissues of the lives,hungs and mesenteric lymph nodes were cultured to determine bacterial translocation. Results The quantity of normal intestinal bacteria in the experimental group and the control group had significant difference except Enterobacteriaceae.The quantity of L.acidophilus and Bifidobacteria in the experimental group were higher than those in the control group.The quantity of C.perfrigens,the potential pathogenic germ in the experimental group were lower than those in the control group(P

Gut-derived-infection and biological behavior of intestinal bacteria / 肠外与肠内营养

Currently,the popular notions on the mechanisms of gut-derived-infection are described as follows.The stress may cause the damage of intestinal mucosal barrier and dysfunction of intestinal immune response,which leads to the alteration of intestinal flora,abnormal proliferation of opportunistic pathogen as well as the translocation of alive bacteria and their toxin into systemic compartment.As a result,the proinflammatory cytokines are released to induce the outbreak of intestinal inflammation or systemic inflammatory response syndrome,even the MODS.This review focuses on the relationship between biological behavior of intestinal bacteria and gut-derived-infection.

Effect of Glutamine on Immune Function of Rat with Obstructive Jaundice / 中国普外基础与临床杂志

Objective To explore the effect of glutamine on immune function of rat with obstructive jaundice and its possible mechanism. Methods Fifty male Wistar rats were randomly divided into three groups: Control group (n=10), obstructive jaundice group (n=20) and glutamine treatment group (n=20). The serum concentration of TNF-?, IL-10 was detected by using radioimmune method. Liver function was measured through automated biochemistry analyzer. The animal model of obstructive jaundice was established by ligating the rat's common bile duct. Bacteria cultures were performed with the rat's tissues of lung, spleen, liver and kidney respectively. Resu- lts Compared with control group, obstructive jaundice group showed statistically lower serum level of TNF-?, and statistically higher serum level of IL-10, TBIL, ALT and AST during the first and the second week after ligation of common bile duct. During the first and second week after administration of glutamine, the serum TNF-? of glutamine treatment group was statistically higher than that in control group and obstructive jaundice group. Meanwhile, glutamine treatment group showed statistically lower serum level of IL-10, TBIL, ALT and AST than obstructive jaundice group. There were statistically less bacteria translocations in glutamine treatment group than those in obstructive jaundice group. Conclusion Glutamine can increase the immune function by changing serum concentration of TNF-?, IL-10 and decrease the bacteria translocation.

An Experimental Study on Relationship between Cytokines and the Translocation of Intestinal Bacteria and Endotoxin in Severe Acute Pancreatitis Rats / 中国医师杂志

Objective To investigate the relationship between the plasma cytokines and the translocation of intestinal bacteria and endotoxin after gut barrier injury in severe acute pancreatitis (SAP) rats. Methods SD rats were divided randomly into sham operation group(n=36) and SAP group (n=36). The rat model of SAP was set up by retrograde injection of 4% sodium taurocholate in biliopancreatic duct. Morphological changes of pancreas and ileum were observed. The plasma levels of TNF-a,IL-6 and IL-10 were determined by ELISA. The plasma levels of DAO activities and LPS were measured at various time points. The rates of bacterial translocation to abdominal organs were also calculated. Results The plasma levels of TNF-a and IL-6 obviously elevated immediately after SAP induction and reached peak value at 48 hours, and the plasma IL-10 level significantly increased only 6 hours after SAP induction. Plasma DAO activities increased at the early stage of SAP and obviously decreased at 24 hours. Plasma LPS levels also increased significantly at the early stage of SAP and reached peak value at 48 hours. The rates of bacterial translocation to organs sharply increased 24 hours after SAP induction and reached 58.3% at 72 hours. Conclusion The levels of cytokines increased and gut barrier function was injured in the early stage of SAP. Cytokines may impair the intestinal microcirculation and gut barrier function, which could promote the intestinal bacteria and endotoxin translocation. Simultaneously, intestinal bacteria-endotoxin translocation could also induce excessive release of cytokines and aggravate the gut barrier damage, which might cause systemic inflammatory response syndrome and multiple organ disfunction syndrome. There was a close relationship beween cytokines and the translocation of intestinal bacteria and endotoxin in SAP.

Damag to gut mucosal barrier and intestinal bacteria-endotoxin translocation in acute necrotizing pancreatitis rats / 中国普通外科杂志

Objective To observe the changes in gut mucosal barrier and gut-origin bacteria-endotoxin translocation in acute necrotizing pancreatitis (ANP) rats. Methods Wistar rats were divided randomly into normal group (n=6), sham operation group (n=30) and ANP group (n=39). ANP was introduced by infusion of artificial bile into biliopancreatic duct. Morphology of pancreas and intestine were observed and tight junction on ileum epithelia were assessed by cryofracture replicas electroscopy. Plasma levels of D-lactic acid and endotoxin were examined at various time points. The rates of bacterial translocation to abdominal organs were also calculated. Results Mucosal and tight junction damages of the gut were found during early stage of ANP. Simultaneously, plasma D-lactate levels increased and endotoxemia occurred. The rate of bacterial translocation to organs was 59.5% 72h after ANP occurred. Conclusions Gut barrier function can be injured in the early stage of ANP, and resulting in gut origin bacteria-endotoxin translocation, which may be the originator of systemic inflammatory reaction and secondary infection of the pancreas.