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

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国际肝胆胰疾病杂志:英文版 2023年第5期22卷 504-511页

作者： Tian-Yu Lin Yi-Fan Zhang Yang Wang Yun Liu Jun Xu Yu-Lan Liu Department of Gastroenterology Peking University People’s HospitalBeijing 100044China Clinical Center of Immune-Mediated Digestive Diseases Peking University People’s HospitalBeijing 100044China Central Laboratory&Institute of Clinical Molecular Biology Peking University People’s HospitalBeijing 100044China

Background:Nonalcoholic fatty liver disease(NAFLD)is an independent risk factor for severe acute pancreatitis(AP).The underlying mechanism remains *** sought to determine how bacterial translocation and cholesterol metabolism in the liver and pancreas affect the severity of AP in NAFLD ***: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 *** amylase and Schmidt’s pathological score system were used to evaluate AP *** 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 ***: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 *** with the HFD-SO group and ND-AP group,bacterial loads in the liver and pancreas were significantly higher in the HFD-AP *** 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 ***:NAFLD aggravates AP via increasing bacterial translocation in the liver and pancreas and affecting pancreas cholesterol metabolism in mice.

关键词： Nonalcoholic fatty liver disease Acute pancreatitis bacterial translocation Cholesterol metabolism

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bacterial translocation and Change in Intestinal Permeability in Patients after Abdominal Surgery

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2009年第4期29卷 486-491页

作者：乔治黎沾良李基业陆连荣吕艺黎君友 Department of General Surgery the First Affiliated Hospital of Chinese PLA General Hospital Research Department of Burn Institute the First Affiliated Hospital of Chinese PLA General Hospital

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.

关键词： bacterial translocation intestinal permeability abdominal surgery polymerase chain reaction (PCR)

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Effects of glutamine and curcumin on bacterial translocation in jaundiced rats

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World Journal of Gastroenterology 2010年第34期16卷 4313-4320页

作者： Oguzhan Karatepe Ersin Acet Muharrem Battal Gokhan Adas Ahu Kemik Merih Altiok Gulcin Kamali Safiye Koculu Atahan Catay Sedat Kamali Servet Karahan Department of Surgery Okmeydani Education and Research Hospital Department of Biochemistry Istanbul Faculty of Medicine Istanbul 34725 Turkey Department of Infectious Disease Istanbul Faculty of Medicine Istanbul 34715 Turkey

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.

关键词： Obstructive jaundice bacterial translocation Oxidative damage Glutamine Curcumin

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

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Neural Regeneration Research 2010年第6期5卷 456-460页

作者： Kai Cao Lu Huang Jianwei Liu Hong An Yong Shu Zhimin Han Department of Orthopedics First Affiliated Hospital' Nanchang University Nanchang 330006 Jiangxi Province China Department of Child Care Jiangxi Maternal and Child Health Hospital Nanchang 330006 Jiangxi Province China Department of Orthopedics Third People's Hospital of Zigong City Zigong 643000 Sichuan Province China Department of Orthopedics First Affiliated Hospital Chongqing University of Medical Sciences Chongqing 400016 China

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

关键词： methylprednisolone spinal cord injury bacterial translocation endotoxemia

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

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Chinese Medical Journal 2003年第5期116卷 767-771页

作者：张顺财王唯任卫英戴茜贺伯明周康 Department of Gastroenterology Zhongshan Hospital Shanghai Medical University Shanghai 200032 China Institute of Materia Medica Chinese Academy of Science Shanghai 200032 China

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.

关键词： bacterial translocation · cirrhosis · intestinal permeability · lactulose · endotoxin

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

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World Journal of Gastrointestinal Pathophysiology 2021年第6期12卷 106-114页

作者： Christos Doudakmanis Konstantinos Bouliaris Christina Kolla Matthaios Efthimiou Georgios D Koukoulis Department of General Surgery General Hospital of LarissaLarisa 41221Greece

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

关键词： bacterial translocation Major gastrointestinal surgery Postoperative sepsis Intestinal permeability Microbiota

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

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Hepatobiliary & Pancreatic Diseases International 2002年第1期1卷 150-154页

作者： Huan-Long Qin Zhen-Dong Su Qi Gao Qing-Tian Lin From the Department of Surgery, Shanghai Sixth People’s Hospital, Shanghai, 200233, China Department of Surgery Shanghai Sixth People's Hospital Shanghai 200233 China

Objective: To evaluate the effect of early intrajejunalnutrition in attenuating bacterial and/or endotoxintranslocation and improving gut barrier function ofsevere acute pancreatitis (SAP) in ***: 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 *** 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 ***: 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 ***: 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.

关键词： early intrajejunal nutrition parenteral nutrition severe acute pancreatitis bacterial translocation barrier function

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Liver Cirrhosis and Intestinal bacterial translocation

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国际感染病学（电子版） 2014年第3期3卷 133-138页

作者： Tao Lan Bao-chun Chen Li-ping Fu Zhi-juan Li Xiang-jun Wu Nai-qiang Cui Graduate School of Tianjin University of Traditional Chinese Medicine Cangzhou People's Hospital Affiliated to Southern Medical University

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.

关键词： Cirrhosis Intestinal barrier bacterial translocation Endotoxemia

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Bacteroides ovatus-mediated CD27^(−)MAIT cell activation is associated with obesity-related T2D progression

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Cellular & Molecular Immunology 2022年第7期19卷 791-804页

作者： Yue Li Yi Yang Jin Wang Peihong Cai Mei Li Xixiang Tang Ying Tan Yuchan Wang Fan Zhang Xiaofeng Wen Qiaoxing Liang Yuanpeng Nie Tufeng Chen Xiang Peng Xuemin He Yanhua Zhu Guojun Shi Wai WCheung Lai Wei Yanming Chen Yan Lu Department of Endocrinology&Metabolism Guangdong Provincial Key Laboratory of DiabetologyThe Third Affliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Clinical Immunology The Third Affliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China VIP Medical Service Center The Third Affliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Department of Gastrointestinal Surgery The Third Affliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Rheumatology The Sixth Affliated Hospital of Guangzhou Medical UniversityQingyuan People's HospitalQingyuan 511518China Division of Pediatric Nephrology Rady Children's HospitalUniversity of CaliforniaSan DiegoCA 92093-0831USA

Type 2 diabetes(T2D)is highly associated with ***,the factors that drive the transition from excessive weight gain to glucose metabolism disruption are still uncertain and seem to revolve around systemic immune ***-associated invariant T(MAIT)cells,which are innate-like T cells that recognize bacterial metabolites,have been reported to be altered in obese people and to lead to metabolic dysfunction during *** studying the immunophenotypes of blood MAIT cells from a cross-sectional cohort of obese participants with/without T2D,we found an elevation in CD27^(-)negative(CD27−)MAIT cells producing a high level of IL-17 under T2D obese conditions,which could be positively correlated with impaired glucose metabolism in obese *** further explored microbial translocation caused by gut barrier dysfunction in obese people as a triggering factor of MAIT cell ***,accumulation of the bacterial strain Bacteroides ovatus in the peripheral blood drove IL-17^(-)producing CD27−MAIT cell expansion and could be associated with T2D risk in obese ***,these results suggest that an aberrant gut microbiota–immune axis in obese people may drive or exacerbate ***,CD27−MAIT cell subsets and Bacteroides ovatus could represent targets for novel interventional *** findings extend current knowledge regarding the clinical relevance of body mass index(BMI)-associated variation in circulating MAIT cells to reveal the role of these cells in obesity-related T2D progression and the underlying cellular mechanisms.

关键词： type 2 diabetes obesity MAIT cells Bacteroides ovatus bacterial translocation

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translocation of gut microbes to epididymal white adipose tissue drives lipid metabolism disorder under heat stress

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Science China(Life Sciences) 2023年第12期66卷 2877-2895页

作者： Zhang-Chao Deng Jia-Cheng Yang Yu-Xuan Huang Ling Zhao Jinshui Zheng Qing-Biao Xu Leluo Guan Lv-Hui Sun State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryFrontiers Science Center for Animal Breeding and Sustainable ProductionCollege of Animal Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China Department of Agricultural Food and Nutritional ScienceUniversity of AlbertaEdmonton AB T6G 2P5Canada

Heat stress induces multi-organ damage and serious physiological dysfunction in mammals,and gut bacteria may translocate to extra-intestinal tissues under heat stress ***,whether gut bacteria translocate to the key metabolic organs and impair function as a result of heat stress remains *** a heat stress-induced mouse model,heat stress inhibited epididymal white adipose tissue(eWAT)expansion and induced lipid metabolic disorder but did not damage other organs,such as the heart,liver,spleen,or *** profiling analysis revealed that heat stress shifted the bacterial community in the cecum and eWAT but not in the inguinal white adipose tissue,blood,heart,liver,spleen,or ***,gut-vascular barrier function was impaired,and the levels of some bacteria,particularly Lactobacillus,were higher in the eWAT,as confirmed by catalyzed reporter deposition fluorescence in situ hybridization(CARD-FISH)staining when mice were under heat ***,integrated multi-omics analysis showed that the eWAT microbiota was associated with host lipid metabolism,and the expression of genes involved in the lipid metabolism in eWAT was upregulated under heat stress.A follow-up microbial supplementation study after introducing Lactobacillus plantarum to heat-stressed mice revealed that the probiotic ameliorated heat stress-induced loss of eWAT and dyslipidemia and reduced gut bacterial translocation to the eWAT by improving gut barrier ***,our findings suggest that gut bacteria,particularly Lactobacillus spp.,play a crucial role in heat stress-induced lipid metabolism disorder and that there is therapeutic potential for using probiotics,such as Lactobacillus plantarum.

关键词： heat stress gut microbiome bacterial translocation Lactobacillus host metabolism

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