Enteric Bacterial Translocation Research Articles

Pathophysiology of the gastrointestinal tract in burn disease

The review of foreign publications resulted in a generalisation of medical reports on the pathological changes of the gastrointestinal tract in burn disease. Burn disease produces an immediate reaction in all organs and systems, which are not always able to maintain homeostasis and frequently suffer pathophysiological and morphological damage. One of those target systems is the gastrointestinal tract. Only in very rare cases do severe (mainly electrical) burns cause direct injury to the abdominal cavity organs, thus resulting in a very severe clinical course and high mortality. Patients of all ages who have experienced a burn injury have an increased overall risk of developing gastrointestinal diseases, which include pathology of the esophagus, stomach, and intestines, as well as lesions of the gallbladder, biliary tract, and pancreas. With a burn area of 40—95%, 5.7% of the victims were diagnosed with pathology of the abdominal organs. Among them, 26.0% had an abdominal catastrophe (infarction or perforation), 37.0% had bleeding from the upper parts of the gastrointestinal tract, 32.0% had paralytic intestinal obstruction, and 5.0% developed pancreatitis and acute necrotizing cholecystitis. Large burns are usually associated with a significant decrease in splanchnic perfusion. After severe burns, intestinal ischemia and hypoxia disrupt the intestinal epithelial barrier and enteric bacterial translocation, leading to serious complications such as systemic inflammatory response syndrome, sepsis, and multiple organ failure. Peritonitis or gastrointestinal bleeding accounted for 88.2% of deaths among patients with gastrointestinal dysfunction. In general, gastrointestinal dysfunction was more common in patients with inhalation injuries, burn shock, large burn areas, and high analgesic requirements.

Prolonged cardiopulmonary bypass time as predictive factor for bloodstream infection

ObjectivesTo evaluate the correlation between patient characteristics, operative variables and the risk of blood stream infection as well as the association of primary blood stream infection and adverse outcomes. MethodsClinical records of 6500 adult patients who underwent open heart surgery between February 2008 and October 2020 were analyzed. The microbiological pattern of the primary BSI and its association with adverse events, such as mortality and major cardiovascular events, were evaluated. ResultsPrimary bloodstream infection was diagnosed in 1.7% (n = 108) of patients following cardiac surgery with the application of cardiopulmonary bypass. Most isolated bacteria were gram-negative bacillus groups, such as the Enterobacteriaceae family with Serrata marcescens in 26.26%, followed by the Enterococcaceae family with the Enterococcus faecalis in 7.39% and Enterococcus faecium in 9.14% as the most frequently identified bacteria. The postprocedural mortality, stroke rate p < 0.001, the incidence of postoperative new renal failure p < 0.001, and the renal replacement therapy p < 0.001 were significantly higher in the primary BSI group. Aortic cross-clamp time >120 min, OR 2.31 95%CI 1.34 to 3.98, perfusion time >120 min, OR 2.45 95%CI 1.63 to 3.67, and duration of the intervention >300min, OR 2.78 95%CI 1.47 to 5.28, were significantly related to the primary BSI. ConclusionThe gram-negative bacillus was the most common microorganism identified in BSI after cardiovascular operations using cardiopulmonary bypass. Patients on dialysis prior to cardiac surgery are at higher risk for having BSI. Enteric bacterial translocation after prolonged cardiopulmonary bypass is a possible mechanism of early primary bloodstream infection in these patients. In patients at high risk, prophylactic use of an antibiotic regimen with broader gram-negative bacteria coverage should be considered, especially in those with prolonged cardiopulmonary bypass and intervention time.

Methanolic Moringa oleifera leaf extract protects against epithelial barrier damage and enteric bacterial translocation in intestinal I/R: Possible role of caspase 3.

Background: Activation of caspase 3 has been implicated in the pathogenesis of I/R injury in various organs, but there is a paucity of data on its role in IIRI. Also, no reports were found on the beneficial role of methanolic Moringa oleifera leaf extract (MMOLE) in IIRI. This study investigated the involvement of caspase 3 in IIRI, and the impact of MMOLE in IIRI. Methods: Male Wistar rats were randomized into five groups; the sham-operated group that was sham-operated and received 0.5 ml of distilled water for 7 days prior to sham surgery, and the IIRI, febuxostat (FEB) +IIRI, low dose MMOLE (LDMO)+IIRI, and high dose MMOLE (HDMO)+IIRI groups that underwent I/R and also received 0.5 ml of distilled water, 10 mg/kg of febuxostat, 200 mg/kg of MMOLE, and 400 mg/kg of MMOLE respectively for 7 days prior to I/R. Markers of hepatic function, oxidative stress, and inflammation as well as enteric bacterial translocation and histoarchitecture integrity of intestinal and hepatic tissues were evaluated. The bioactive components of MMOLE were also determined by GC-MS. Results: As revealed by GC-MS, the active bioactive components of MMOLE were thiosemicarbazone, hydrazine, 1,3-dioxolane, octanoic acid, 1,3-benzenediamine, 9-octadecenoic acid, oleic acid, nonadecanoic acid, 3-undecanone, phosphonic acid, and cyclopentanecarboxylic acid. MMOLE alleviated IIRI-induced rise in intestinal and hepatic injury markers, malondialdehyde, TNF-α, IL-6, and myeloperoxidase activities. MMOLE improved IIRI-induced suppression of reduced glutathione, thiol and non-thiol proteins, and superoxide dismutase, catalase and glutathione peroxidase activities. These were associated with suppression of IIRI-induced caspase 3 activity and bacterial translocation. Histopathological evaluation revealed that MMOLE attenuated IIRI-induced alterations in intestinal and hepatic histoarchitecture integrity. MMOLE also militated against increased absolute and relative intestinal and hepatic weight, intestinal and hepatic injuries, epithelial mucosal barrier dysfunction, and enteric bacterial translocation associated with IIRI by downregulating oxidative stress-mediated activation of caspase 3. Conclusion: IIRI is associated with a rise in caspase 3 activity. Also, MMOLE confers protection against IIRI, possibly due to its constituent bioactive molecules, especially hydrazine, 9-octadecenoic acid, 1,3-dioxolane, oleic acid, and nonadecanoic acid.

Mammary tumors alter the fecal bacteriome and permit enteric bacterial translocation

BackgroundCancer patients experience gastrointestinal and behavioral symptoms, and are at increased risk of systemic infection and inflammation. These conditions are a major source of morbidity and decreased quality of life prior to cancer treatment, but poorly defined etiologies impede successful treatment. The gastrointestinal microbiota shape inflammation, influence cancer progression and treatment, and colonize tumors. However, research has not directly determined if peripheral tumors influence the microbiome and intestinal physiology, thus influencing gastrointestinal and behavioral symptoms. Therefore, the purpose of this study was to examine consequences of orthotopic, syngeneic mammary tumor implantation, growth, and resection on fecal bacteriome composition and intestinal barrier function in relation to systemic inflammation and enteric bacterial translocation in mice.MethodsFemale mice were randomized to 3 experimental groups: sham surgical control, tumor recipients, and tumor recipients later receiving tumor-resection. Mice were sacrificed three weeks after tumor implantation or resection for collection of stool, colon, spleen, and brain tissue and analysis.ResultsTumor-bearing mice exhibited several markers of colonic barrier disruption, including dampened expression of tight junction proteins (Cldn1 and Ocln) and elevated circulating lipopolysaccharide binding protein (LBP). Compromised colonic barrier integrity was associated with altered fecal bacterial profiles in tumor-mice, including lower relative abundance of Lactobacillus, but higher Bacteroides. Consistent with colonic barrier disruption and altered microbiomes, tumor-mice displayed markers of systemic inflammation including splenomegaly, higher splenic bacterial load, and elevated splenic and brain pro-inflammatory cytokines. Several bacteria cultured from spleens had 16S rRNA gene amplicons matching those in fecal samples, suggesting they were of intestinal origin. Fecal Lactobacillus was highly-interrelated to physiological parameters disrupted by tumors via correlation network analysis. Tumor resection ameliorated circulating LBP, splenomegaly, and splenic cytokines, but not other parameters associated with loss of colonic barrier integrity and bacterial translocation.ConclusionsOrthotopic mammary tumors alter the microbiome, reduce intestinal barrier function, increase translocation of enteric bacteria, and alter systemic inflammation. This provides insight into how tumors commence gastrointestinal and behavioral symptoms prior to treatment, and identify targets for future therapeutics, such as probiotic Lactobacillus supplementation.

POS-636 Risk of Peritonitis after Gastroscopy in Peritoneal Dialysis Patients

Peritonitis is a common infective complication of peritoneal dialysis (PD), which causes serious adverse sequelae including peritoneal membrane failure, necessitating conversion to hemodialysis and even mortality. Peritonitis could be secondary to enteric bacterial translocation during gastrointestinal endoscopic procedure. Although gastroscopy is often regarded as having a low infective risk, peritonitis after gastroscopy had been described previously. Owing to the limitation of small sample size in previous series, the risk of peritonitis after gastroscopy is not yet well characterized.

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

BackgroundGut 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.MethodsAn 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.ResultsOur 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-1β and 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-1β and 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.ConclusionsCollectively, the present study illustrated that CFTR and downstream signaling were critical in modulating the intestinal epithelial junction and EBT post severe burn.

Non-selective beta-blocker use in cirrhotic patients is associated with a reduced likelihood of hospitalisation for infection.

Non-selective beta-blockers (NSBBs) reduce enteric bacterial translocation rates and the frequency of spontaneous bacterial peritonitis (SBP) in animal models. To evaluate the effect of NSBBs on infection-related admissions. We performed a case-control study of cirrhotic patients' first in-patient admission between 1 January 2011 and 31 December 2016. We examined NSBB use and the development of infection. We performed a propensity score-matched analysis in those with NSBB use vs no use and calculated odds ratios on this matched cohort to determine the odds of outcomes based on NSBB use. We identified 2165 cirrhotic patients who met our inclusion criteria. Most patients were Caucasian (69%), male (62%). Admission Model for End stage Liver Disease (MELD) score, Charlson comorbidity index and Child-Pugh score were 12±1, 4±2, and 8±2, respectively. Ascites was the most common complication of portal hypertension (44%); 23% of patients used NSBBs at home. Infections occurred in 33% of admissions. In the propensity score-matched cohort, the use of NSBBs at home was associated with lower overall, and specific, infections. The effect was similar in patients taking NSBBs for either primary or secondary oesophageal variceal prophylaxis and for those on NSBBs for other indications. Patients not on NSBBs had higher odds of infection (OR=2.5), SBP (OR=4.0), and bacteraemia (OR=6.0). Home use of NSBBs by patients with cirrhosis was associated with fewer infection-related admissions. The data suggest that NSBBs in this group of patients reduce the risk of infection.

Impact of uric acid on liver injury and intestinal permeability following resuscitated hemorrhagic shock in rats.

Multiorgan failure is a consequence of severe ischemia-reperfusion injury after traumatic hemorrhagic shock (HS), a major cause of mortality in trauma patients. Circulating uric acid (UA), released from cell lysis, is known to activate proinflammatory and proapoptotic pathways and has been associated with poor clinical outcomes among critically ill patients. Our group has recently shown a mediator role for UA in kidney and lung injury, but its role in liver and enteric damage after HS remains undefined. Therefore, the objective of this study was to evaluate the role of UA on liver and enteric injury after resuscitated HS. A murine model of resuscitated HS was treated during resuscitation with a recombinant uricase, a urate oxidase enzyme (rasburicase; Sanofi-Aventis, Canada Inc, Laval, Canada), to metabolize and reduce circulating UA. Biochemical analyses (liver enzymes, liver apoptotic, and inflammatory markers) were performed at 24 hours and 72 hours after HS. Physiological testing for enteric permeability and gut bacterial product translocation measurement (plasma endotoxin) were performed 72 hours after HS. In vitro, HT-29 cells were exposed to UA, and the expression of intercellular adhesion proteins (ZO-1, E-cadherin) was measured to evaluate the influence of UA on enteric permeability. The addition of uricase to resuscitation significantly reduced circulating and liver UA levels after HS. It also prevented HS-induced hepatolysis and liver apoptotic/inflammatory mediators at 24 hours and 72 hours. Hemorrhagic shock-induced enteric hyperpermeability and endotoxemia were prevented with uricase. After resuscitated HS, UA is an important mediator in liver and enteric injury. Uric acid represents a therapeutic target to minimize organ damage in polytrauma patients sustaining HS.

Gut microbiome in primary sclerosing cholangitis: A review.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by biliary inflammation and stricturing. Exploration of the pathogenesis of PSC in light of its association with inflammatory bowel disease (IBD) and the “gut-liver” axis is an emerging area of interest. A growing number of studies have begun to elucidate the role of the gut microbiota, its metabolites and its influence on host immune responses in the development of PSC and PSC-IBD. Studies of the fecal microbiota have highlighted enriched levels of certain species, including Veillonella, Streptococcus and Enterococcus, among others. A heightened immune response to enteric dysbiosis and bacterial translocation have also been implicated. For example, Klebsiella pneumoniae strains derived from gnotobiotic mice transplanted with PSC-IBD microbiota were found to induce pore formation in human intestinal epithelial cells and enhanced Th17 responses. Gut microbes have additionally been hypothesized to be implicated in PSC pathogenesis through their role in the synthesis of various metabolites, including bile acids (BAs), which function as signaling molecules with important gut and hepatic effects. An expanded knowledge of the gut microbiome as it relates to PSC offers critical insight into the development of microbe-altering therapeutic interventions, such as antibiotics, nutritional interventions and fecal microbial transplantation. Some of these have already shown some preliminary evidence of benefit. Despite exciting progress in the field, much work remains to be done; areas that are particularly lacking include functional characterization of the microbiome and examination of pediatric populations. In this review, we summarize studies that have investigated the microbiome in PSC and PSC-IBD as well as putative mechanisms, including the potential role of metabolites, such as BAs. We then briefly review the evidence for interventions with microbe-altering properties for treating PSC.

42 CFTR Mediates Enteric Bacterial Translocation Post Severe Burn via ERK and Inflammatory Signaling

Abstract Introduction This research was to investigate the role of cystic fibrosis transmembrane conductance regulator (CFTR) in mediating enteric bacterial translocation (EBT) post severe burn as well as the signaling pathways involved. Methods A hypoxia treatment model of Caco-2 in vitro and a 30% TBSA full-thickness dermal burn mice model in vivo were established to explore the effect of major burn injury on intestinal epithelial barrier and the expression of CFTR and tight junction proteins. In addition, the DF508 mice (mice with F508del CFTR gene mutation) were used to analyze bacterial counts in extraintestinal organs and the expression of ZO-1, OCLN and E-cadherin. And CFTR specific inhibitor or down-regulation of CFTR in Caco-2 cells were used to explore the effect of CFTR on tight junction of intestinal cells. Furthermore, in the models above, MAPK pathway and inflammatory factors were detected to explore the mechanism. Finally, Vitamin D3 was used to pretreat mice before severe burn or Caco-2 cells before hypoxia. Bacterial counts in extraintestinal organs and the expression of CFTR, ZO-1, OCLN and P-ERK as well as the concentrations of inflammatory factors were detected. Results Our data showed a decrease of CFTR, concomitant with activation of ERK signaling, elevation of inflammatory factors (TNF-α, IL-1β and IL-8) and declined expression of ZO-1, occludin and E-cadherin, and a cellular mislocation of ZO-1 and OCLN post hypoxia. Furthermore, either administration of CFTR specific inhibitor or down-regulation of CFTR caused similar alterations as hypoxia did. Ileum of DF508 -/- and +/- mice exhibited increased inflammation, declined ZO-1, occludin and E-cadherin and EBT compared to +/+ mice. Moreover, vitamin D3 could reverse the junctional damage induced by hypoxia, thus preventing occurrence of EBT, possibly via up-regulating CFTR. Conclusions CFTR/ERK/inflammatory factors signaling was critical in modulating intestinal epithelial junction, accordingly regulating EBT. Vitamin D3 can protect intestinal epithelial barrier after severe burn, which may be associated with the up-regulation of CFTR, the inhibition of ERK pathway and decreased pro-inflammatory cytokine. Applicability of Research to Practice This research may be used in practice in the future to regulate the metabolism after severe burns.

Severe neonatal anemia increases intestinal permeability by disrupting epithelial adherens junctions.

Anemia is a frequent diagnosis in critically ill infants, but the clinical implications of severe anemia in these patients remain unclear. In this study, we examined preweaned mice to investigate the effects of severe anemia during early infancy on gut mucosal permeability. C57BL/6 mice were subjected to timed phlebotomy between postnatal days (P) 2-10 to induce severe anemia (hematocrits 20%-24%), and intestinal permeability was tracked longitudinally between P10 and P20 as intestine-to-plasma translocation of enteral macromolecules and bacterial translocation. Epithelial junctions were evaluated by electron microscopy, polymerase chain reactions, immunohistochemistry, and/or enzyme immunoassays on intestinal tissues, Caco-2 intestinal epithelial-like cells, and colonic organoids. Preweaned mouse pups showed an age-related susceptibility to severe anemia, with increased intestinal permeability to enteral macromolecules (dextran, ovalbumin, β-lactoglobulin) and luminal bacteria. Electron micrographs showed increased paracellular permeability and ultrastructural abnormalities of the adherens junctions. These findings were explained by the loss of E-cadherin in epithelial cells, which was caused by destabilization of the E-cadherin (Cdh1) mRNA because of microRNA let-7e-5p binding to the 3'-untranslated region. Severe anemia resulted in a disproportionate and persistent increase in intestinal permeability in preweaned mice because of the disruption of epithelial adherens junctions. These changes are mediated via microRNA let-7e-mediated depletion of Cdh1 mRNA.NEW & NOTEWORTHY This research article shows that newborn infants with severe anemia show an age-related susceptibility to developing increased intestinal permeability to ingested macromolecules. This abnormal permeability develops because of abnormalities in intestinal epithelial junctions caused by a deficiency of the molecule E-cadherin in epithelial cells. The deficiency of E-cadherin is caused by destabilization of its mRNA precursor because of increased expression and binding of another molecule, the microRNA let-7e-5p, to the E-cadherin mRNA.

PROFIT, a PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis: study protocol for a single-blinded trial

IntroductionPatients with advanced cirrhosis have enteric bacterial dysbiosis and translocation of bacteria and their products across the gut epithelial barrier. This culminates in systemic inflammation and endotoxaemia, inducing innate immune...

Enteric dysbiosis-linked gut barrier disruption triggers early renal injury induced by chronic high salt feeding in mice

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.

Distinct cytoprotective roles of pyruvate and ATP by glucose metabolism on epithelial necroptosis and crypt proliferation in ischaemic gut.

Intestinal ischaemia causes epithelial death and crypt dysfunction, leading to barrier defects and gut bacteria-derived septic complications. Enteral glucose protects against ischaemic injury; however, the roles played by glucose metabolites such as pyruvate and ATP on epithelial death and crypt dysfunction remain elusive. A novel form of necrotic death that involves the assembly and phosphorylation of receptor interacting protein kinase 1/3 complex was found in ischaemic enterocytes. Pyruvate suppressed epithelial cell death in an ATP-independent manner and failed to maintain crypt function. Conversely, replenishment of ATP partly restored crypt proliferation but had no effect on epithelial necroptosis in ischaemic gut. Our data argue against the traditional view of ATP as the main cytoprotective factor by glucose metabolism, and indicate a novel anti-necroptotic role of glycolytic pyruvate under ischaemic stress. Mesenteric ischaemia/reperfusion induces epithelial death in both forms of apoptosis and necrosis, leading to villus denudation and gut barrier damage. It remains unclear whether programmed cell necrosis [i.e. receptor-interacting protein kinase (RIP)-dependent necroptosis] is involved in ischaemic injury. Previous studies have demonstrated that enteral glucose uptake by sodium-glucose transporter 1 ameliorated ischaemia/reperfusion-induced epithelial injury, partly via anti-apoptotic signalling and maintenance of crypt proliferation. Glucose metabolism is generally assumed to be cytoprotective; however, the roles played by glucose metabolites (e.g. pyruvate and ATP) on epithelial cell death and crypt dysfunction remain elusive. The present study aimed to investigate the cytoprotective effects exerted by distinct glycolytic metabolites in ischaemic gut. Wistar rats subjected to mesenteric ischaemia were enterally instilled glucose, pyruvate or liposomal ATP. The results showed that intestinal ischaemia caused RIP1-dependent epithelial necroptosis and villus destruction accompanied by a reduction in crypt proliferation. Enteral glucose uptake decreased epithelial cell death and increased crypt proliferation, and ameliorated mucosal histological damage. Instillation of cell-permeable pyruvate suppressed epithelial cell death in an ATP-independent manner and improved the villus morphology but failed to maintain crypt function. Conversely, the administration of liposomal ATP partly restored crypt proliferation but did not reduce epithelial necroptosis and histopathological injury. Lastly, glucose and pyruvate attenuated mucosal-to-serosal macromolecular flux and prevented enteric bacterial translocation upon blood reperfusion. In conclusion, glucose metabolites protect against ischaemic injury through distinct modes and sites, including inhibition of epithelial necroptosis by pyruvate and the promotion of crypt proliferation by ATP.

Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy: a critical role for IL-6/STAT3.

Lipocalin-2 (LCN2) was originally isolated from human neutrophils and termed neutrophil gelatinase-associated lipocalin (NGAL). However, the functions of LCN2 and the cell types that are primarily responsible for LCN2 production remain unclear. To address these issues, hepatocyte-specific Lcn2 knockout (Lcn2(Hep-/-)) mice were generated and subjected to bacterial infection (with Klesbsiella pneumoniae or Escherichia coli) or partial hepatectomy (PHx). Studies of Lcn2(Hep-/-) mice revealed that hepatocytes contributed to 25% of the low basal serum level of LCN2 protein (∼ 62 ng/mL) but were responsible for more than 90% of the highly elevated serum LCN2 protein level (∼ 6,000 ng/mL) postinfection and more than 60% post-PHx (∼ 700 ng/mL). Interestingly, both Lcn2(Hep-/-) and global Lcn2 knockout (Lcn2(-/-)) mice demonstrated comparable increases in susceptibility to infection with K. pneumoniae or E. coli. These mice also had increased enteric bacterial translocation from the gut to the mesenteric lymph nodes and exhibited reduced liver regeneration after PHx. Treatment with interleukin (IL)-6 stimulated hepatocytes to produce LCN2 in vitro and in vivo. Hepatocyte-specific ablation of the IL-6 receptor or Stat3, a major downstream effector of IL-6, markedly abrogated LCN2 elevation in vivo. Furthermore, chromatin immunoprecipitation (ChIP) assay revealed that STAT3 was recruited to the promoter region of the Lcn2 gene upon STAT3 activation by IL-6. Hepatocytes are the major cell type responsible for LCN2 production after bacterial infection or PHx, and this response is dependent on IL-6 activation of the STAT3 signaling pathway. Thus, hepatocyte-derived LCN2 plays an important role in inhibiting bacterial infection and promoting liver regeneration.

Lactobacillus Infection of Total Hip Arthroplasty After Probiotic Ingestion

We present the first reported case of a total hip arthroplasty infected with Lactobacillus casei as a result of enteric bacterial translocation. A 76-year-old woman was found to have an infected right total hip arthroplasty hip 4 and a half years after her primary procedure. The patient who was treated underwent a 2-stage revision total hip arthroplasty. This patient was a regular consumer of probiotic yoghurt drinks and had multiple risk factors for developing this rare infection. Because of the high mortality of infections caused by lactobacillus, if a patient develops a chronic lactobacillus prosthetic joint infection, we recommend aggressive 2-stage revision arthroplasty surgery with multidisciplinary management involving both orthopedic and infectious diseases specialists.

Probiotics Are Sensitive Microorganisms: Lactobacillus Can Be Affected by Stomach Acid, Antibiotic, and Bowel Cleansing

We read with great interest the article by Mangell et al. entitled ‘‘Lactobacillus plantarum 299v does not reduce enteric bacteria or bacterial translocation in patients undergoing colon resection’’ [1]. The authors show that Lactobacillus plantarum 299v did not reduce enteric bacteria or bacterial translocation in patients undergoing colon resection. Although the study was well presented, there are some limitations and a few points on the affects of probiotics in the study protocol that we would like to address. Bowel cleansing before surgery can change the concentration of gut microbiota. Also, the patients had consumed food with L. plantarum 299v for 8 days in the preoperative period; however in the postoperative period, the patients had consumed L. plantarum 299v without food for 5 days. Foods typically contain fermentable substrates that can help nourish probiotic organisms as they transit through the gastrointestinal tract. Gastric pH following food intake is usually in the range of 4–7. Many lactobacilli and bifidobacteria secrete hydrolytic enzymes that can aid in the digestion of foods. Gastric pH is below 2 in the fasting state, which rapidly kills probiotics [2]. The main factors affecting the viability of probiotics in the gastrointestinal tract are the acidic environment of the stomach and the presence of bile in the duodenum. Significant numbers of probiotic bacteria can be destroyed unless they have some acid protection. Low pH is one of the most important factors that restricts the growth and stability of probiotic bacteria [3, 4]. Recent evidence shows that the dual-coating technology of probiotic bacteria enhances the survival and the amount of bacteria reaching the distal gut [5]. If there is an encapsulation technique of acid protection against L. plantarum 299v, it should be mentioned in this article. Preoperative and postoperative food intake might influence the transit of L. plantarum 299v to the distal gastrointestinal tractus. On the other hand, preoperative antibiotic prophylaxis may alter gut microbiota as well. The detection of bacterial genome in the lymph node does not reliably indicate recent bacterial translocation. Some bacteria might have already translocated in the preprobiotic phase, and scant amounts of these translocated bacteria might not be clinically important. Supporting this hypothesis, the authors did not mention any correlation with bacterial translocation and postoperative septic complications. And finally, two of these patients had translocation of lactobacilli, which is not a pathogenic bacterium. The rate of postoperative complications, although not significant between groups, is markedly decreased in the probiotic group. The overall complication rate, 16 versus 31 % (nearly twice as much in the control group), needs further comment. As a conclusion, probiotics are sensitive microbial agents to various noxious stimuli. Viability of probiotics in gastrointestinal tractus depends on some factors such as gastric acidity, bile acids, enzymes in intestine, antibiotics and bowel cleansing.

Neutrophil priming by hypoxic preconditioning protects against epithelial barrier damage and enteric bacterial translocation in intestinal ischemia/reperfusion

Intestinal ischemia/reperfusion (I/R) induces mucosal barrier dysfunction and bacterial translocation (BT). Neutrophil-derived oxidative free radicals have been incriminated in the pathogenesis of ischemic injury in various organs, but their role in the bacteria-containing intestinal tract is debatable. Primed neutrophils are characterized by a faster and higher respiratory burst activity associated with more robust bactericidal effects on exposure to a second stimulus. Hypoxic preconditioning (HPC) attenuates ischemic injury in brain, heart, lung and kidney; no reports were found in the gut. Our aim is to investigate whether neutrophil priming by HPC protects against intestinal I/R-induced barrier damage and bacterial influx. Rats were raised in normoxia (NM) or kept in a hypobaric hypoxic chamber (380 Torr) 17 h/day for 3 weeks for HPC, followed by sham operation or intestinal I/R. Gut permeability was determined by using an ex vivo macromolecular flux assay and an in vivo magnetic resonance imaging-based method. Liver and spleen homogenates were plated for bacterial culturing. Rats raised in HPC showed diminished levels of BT, and partially improved mucosal histopathology and epithelial barrier function compared with the NM groups after intestinal I/R. Augmented cytokine-induced neutrophil chemoattractant (CINC)-1 and -3 levels and myeloperoxidase activity correlated with enhanced infiltration of neutrophils in intestines of HPC-I/R compared with NM-I/R rats. HPC alone caused blood neutrophil priming, as shown by elevated production of superoxide and hydrogen peroxide on stimulation, increased membrane translocation of cytosolic p47phox and p67phox, as well as augmented bacterial-killing and phagocytotic activities. Neutrophil depletion reversed the mucosal protection by HPC, and aggravated intestinal leakiness and BT following I/R. In conclusion, neutrophil priming by HPC protects against I/R-induced BT via direct antimicrobial activity by oxidative respiratory bursts and through promotion of epithelial barrier integrity for luminal confinement of enteric bacteria.

Lactobacillus plantarum 299v Does Not Reduce Enteric Bacteria or Bacterial Translocation in Patients Undergoing Colon Resection

Probiotics may exert beneficial effects in the gastrointestinal tract. This randomized trial investigated the effect of the probiotic Lactobacillus plantarum 299v on the intestinal load of potentially pathogenic bacteria, bacterial translocation, and cell proliferation in elective colon surgery. Seventy-five patients were randomized to pre- and postoperative oral intake of Lactobacillus plantarum 299v or placebo. Rectal swabs and mucosal biopsies were taken before the start of intake, after 1 week, at surgery, and after 6 days, weeks, and months. Viable counts were quantified for clostridia, Enterobacteriaceae, Gram-negative anaerobes, and lactobacilli. Bacterial translocation was determined by the analysis of bacterial DNA genes in mesenteric lymph nodes. Ki-67 was used as a marker of cell proliferation in normal mucosa and tumor. Lactobacillus plantarum 299v was given without adverse effects. Lactobacillus plantarum 299v as well as Enterobacteriaceae and Gram-negative anaerobes increased in the colon 1 week after the administration of Lactobacillus plantarum 299v. There were no significant differences between patients receiving Lactobacillus plantarum 299v and placebo in the incidence of bacterial translocation (27 vs. 13%) and postoperative complications (16 vs. 31%). Lactobacillus plantarum 299v was established in the intestine, but no inhibitory effect on enteric bacteria, bacterial translocation, or postoperative complications was found. The mechanism behind the protective effects of probiotics found in animal and some human studies remain elusive and require further explorations. No adverse effects were recorded after the administration of high doses of Lactobacillus plantarum 299v.

Pyogenic Ventriculitis following Enteral Bacterial Translocation in a Patient with Small Bowel Obstruction

The authors present a rare case of ventriculitis secondary to cerebro spinal fluid (CSF) colonization with Escherichia coli species in a 65-year-old woman. Passage of bacterial organisms from the lumen of the gastrointestinal tract to the bloodstream or lymphatic tissue is known as translocation. Once in the bloodstream, particular bacteria are able to cross the blood-brain barrier and migrate to CSF. Elective abdominal surgery, intestinal obstruction, colorectal cancer, ischaemic reperfusion injury and pancreatitis have all increased the risk of this phenomenon. This account highlights particular events in presentation and management of such a case, followed by a brief literature review.