Probiotic bacteria prevent hepatic damage and maintain colonic barrier function in a mouse model of sepsis (original) (raw)
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Anesthesiology, 2013
Background: Recent clinical trials indicate that probiotic administration in critical illness has potential to reduce nosocomial infections and improve clinical outcome. However, the mechanism(s) of probiotic-mediated protection against infection and sepsis remain elusive. The authors evaluated the effects of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium longum (BL) on mortality, bacterial translocation, intestinal epithelial homeostasis, and inflammatory response in experimental model of septic peritonitis. Methods: Cecal ligation and puncture (n = 14 per group) or sham laparotomy (n = 8 per group) were performed on 3-week-old FVB/N weanling mice treated concomitantly with LGG, BL, or vehicle (orally gavaged). At 24 h, blood and colonic tissue were collected. In survival studies, mice were given probiotics every 24 h for 7 days (LGG, n = 14; BL, n = 10; or vehicle, n = 13; shams, n = 3 per group). Results: Probiotics significantly improved mortality after sepsis (92 vs. 57% ...
Probiotic Bacteria Enhance Murine and Human Intestinal Epithelial Barrier Function
Gastroenterology, 2001
The probiotic compound, VSL#3, is efficacious as maintenance therapy in pouchitis and ulcerative colitis. The aim of this study was to determine the efficacy of VSL#3 as a primary therapy in the treatment of colitis in the interleukin (IL)-10 gene-deficient mouse. Mechanisms of action of VSL#3 were investigated in T84 monolayers. IL-10 gene-deficient and control mice received 2.8 × 108 colony-forming units per day of VSL#3 for 4 weeks. Colons were removed and analyzed for cytokine production, epithelial barrier function, and inflammation. VSL#3 or conditioned media was applied directly to T84 monolayers. Treatment of IL-10 gene-deficient mice with VSL#3 resulted in normalization of colonic physiologic function and barrier integrity in conjunction with a reduction in mucosal secretion of tumor necrosis factor α and interferon γ and an improvement in histologic disease. In vitro studies showed that epithelial barrier function and resistance to Salmonella invasion could be enhanced by exposure to a proteinaceous soluble factor secreted by the bacteria found in the VSL#3 compound. Oral administration of VSL#3 was effective as primary therapy in IL-10 gene-deficient mice, and had a direct effect on epithelial barrier function.
Applied and Environmental Microbiology, 2011
Prophylactic probiotic therapy has shown beneficial effects in an experimental rat model for acute pancreatitis on the health status of the animals. Mechanisms by which probiotic therapy interferes with severity of acute pancreatitis and associated sepsis, however, are poorly understood. The aims of this study were to identify the probiotic-induced changes in the gut microbiota and to correlate these changes to disease outcome. Duodenum and ileum samples were obtained from healthy and diseased rats subjected to pancreatitis for 7 days and prophylactically treated with either a multispecies probiotic mixture or a placebo. Intestinal microbiota was characterized by terminal-restriction fragment length polymorphism (T-RFLP) analyses of PCRamplified 16S rRNA gene fragments. These analyses showed that during acute pancreatitis the host-specific ileal microbiota was replaced by an "acute pancreatitis-associated microbiota." This replacement was not reversed by administration of the probiotic mixture. An increase, however, was observed in the relative abundance of a novel bacterial phylotype most closely related to Clostridium lituseburense and referred to as commensal rat ileum bacterium (CRIB). Specific primers targeting the CRIB 16S rRNA gene sequence were developed to detect this phylotype by quantitative PCR. An ileal abundance of CRIB 16S rRNA genes of more than 7.5% of the total bacterial 16S rRNA gene pool was correlated with reduced duodenal bacterial overgrowth, reduced bacterial translocation to remote organs, improved pancreas pathology, and reduced proinflammatory cytokine levels in plasma. Our current findings and future studies involving this uncharacterized bacterial phylotype will contribute to unraveling one of the potential mechanisms of probiotic therapy.
Strain-Specific Effects of Probiotics on Gut Barrier Integrity following Hemorrhagic Shock
Infection and Immunity, 2005
These properties may be of benefit in the preservation of gut barrier integrity after injury or stress. In this study, we examined the effect of two Lactobacillus strains selected for their pathogen exclusion properties on intestinal barrier integrity following hemorrhagic shock. Additionally, the responsiveness of the macrophage cell line RAW 264.7 to combined exposure to Lactobacillus DNA or oligodeoxynucleotides containing CpG motifs (CpG-ODN) and endotoxin was assessed by measuring tumor necrosis factor alpha (TNF-␣) release. Rats were administered lactobacilli (5 ؋ 10 9 CFU) or vehicle for 7 days and were subjected subsequently to hemorrhagic shock by withdrawal of 2.1 ml blood/100 g tissue. Levels of plasma endotoxin, bacterial translocation to distant organs, and filamentous actin (F-actin) in the ileum were determined 24 h later. Rats treated with Lactobacillus rhamnosus showed reduced levels of plasma endotoxin (8 ؎ 2 pg/ml versus 24 ؎ 4 pg/ml; P ؍ 0.01), bacterial translocation (2 CFU/gram versus 369 CFU/gram; P < 0.01), and disruption of F-actin distribution following hemorrhagic shock compared with nontreated control rats. In contrast, pretreatment with Lactobacillus fermentum had no substantial effect on gut barrier integrity. Interestingly, DNA preparations from both lactobacilli reduced endotoxin-induced TNF-␣ release dose dependently, whereas CpG-ODN increased TNF-␣ release. In conclusion, the pathogen exclusion properties of both Lactobacillus strains and the reduction of endotoxin-induced inflammation by their DNA in vitro are not prerequisites for a beneficial effect of probiotic therapy on gut barrier function following hemorrhagic shock. Although pretreatment with Lactobacillus spp. may be useful to preserve gut barrier integrity following severe hypotension, a thorough assessment of specific strains seems to be essential.
Critical care (London, England), 2014
One proposed benefit of probiotic therapy is that probiotic bacterial cell-wall binding to intestinal cell pathogen-recognition receptors activates protective innate immunity. However, in critically ill patients, intestinal epithelium disruption by shock or other insults may compromise this compartmentalized response and cause systemic bacteria and cell-wall translocation. The effects of intravascular introduction of probiotic bacterial cell wall are unclear. We investigated 24-hour infusions of purified cell wall from Lactobacillus gasseri ATC33323 (L. gasseri), a probiotic bacterium, in Sprague-Dawley rats (n = 49). Increasing cell-wall doses (0 (control), 10, 20, 40, 80, or 160 mg/kg over 24 hours) produced dose-ordered decreases in survival measured after 168 hours (11 survivors/11 total (100%), seven of seven (100%), seven of seven (100%), six of eight (75%), five of eight (63%), and one of nine (11%), respectively, P < 0.0001). The L. gasseri cell wall was equally or more l...
Journal of Gastrointestinal Surgery, 2006
Chronic feeding with enteral immune-enhancing diets (IEDs) provides benefits based on composition of the diet, route of feeding, and timing of feeding in relation to timing of trauma or surgery. Our prior studies of acute feeding in naïve rats demonstrated that IED promotes blood flow and proinflammatory cytokines in the ileum. We hypothesized that chronic feeding with IED would shift gut immune status to an anti-inflammatory state during chronic sepsis, resulting in an altered state of cytokine expression in the gut. Five days prior to feeding, gauze was implanted subcutaneously in the backs of male Sprague-Dawley rats, which were fed for 3 days with either control diet (CD, Boost; Mead-Johnson, Evansville, IL) or IED (Impact; Novartis) and randomly assigned to one of four groups: saline control (NS) C control diet (CD), sepsis (EC) C CD, NS C IED, or EC C IED. EC rats were inoculated with 10 9 CFU Escherichia coli and 10 9 CFU Bacteroides fragilis in 2 ml normal saline into the back sponge while NS rats received 2 mL normal saline alone. After 3 days, animals were anesthetized and gut tissue samples were harvested and frozen at -80 C. Tissue protein was extracted and ELISA was performed for interleukin (IL-1b, IL-5, IL-6, IL-10, tumor necrosis factor (TNF)-a, and interferon (IFN)-g. In saline controls, IED feeding decreased IL-1b, IL-5, IL-6, TNF-a, and IFN-g and increased IL-10 compared with CD-fed animals. In septic animals, IED feeding increased IL-5 and IL-6, while decreasing IFN-g and IL-10 in the distal third of the small intestine compared with CD-fed septic rats, whereas IL-1b and TNF-a levels were unchanged. Chronic IED feeding produced a anti-inflammatory state via decreased IFN-g and increased IL-5 and IL-6, which both promote gut IgA class switching, suggesting that the gut is shifted toward humoral immunity during chronic IED feeding in septic rats. ( J GASTROINTEST SURG 2006;10:46-53) Ó
Impact of a probiotic Enterococcus faecalis in a gnotobiotic mouse model of experimental colitis
Molecular Nutrition & Food Research, 2011
Scope: IL-10-deficient (IL-10 À/À ) mice are susceptible to the development of chronic intestinal inflammation in response to the colonization with commensal Enterococcus faecalis isolates. The aim of this study was to characterize the impact of a probiotic E. faecalis strain in germfree, wild-type (WT), and disease-susceptible IL-10 À/À mice. Methods and results: The probiotic E. faecalis and the colitogenic control strain OG1RF induced IL-6 and IFN-g inducible protein-10 secretion in the murine intestinal epithelial cell line Mode K. Epithelial cell activation involved nuclear factor k B, p38 and extracellular signalregulated kinase 1/2-dependent pathways. Mouse embryonic fibroblasts from WT and tolllike receptor-2-deficient (TLR-2 À/À ) mice confirmed that both E. faecalis strains trigger pro-inflammatory responses via the pattern recognition receptor TLR-2. Monoassociation of germ-free IL-10 À/À mice with the probiotic E. faecalis strain revealed pro-inflammatory epithelial cell activation and colonic tissue pathology. The non-pathogenic nature of E. faecalis was confirmed in monoassociated WT mice. 2-DE and MALDI-TOF MS identified the ER stress chaperone Hspa5 (glucose-regulated protein 78) and 3-mercaptopyruvate sulfurtransferase as key targets in the epithelium from IL-10 À/À and TLR-2 À/À mice. Conclusion: This study shows the potential of probiotic bacteria to initiate pro-inflammatory responses in the disease-susceptible but not the normal host.
Clinical Nutrition Supplements, 2008
Hormones, mediators and immunity 2 69 of unstimulated cells). Furthermore, the MCT-induced increase in CD11b and CD66b expression (196% and 235% of unstimulated cells, respectively) was not inhibited by pre-incubation with 500 ng/mL PTX [222% (CD11b) and 251% (CD66b)] or 1000 ng/mL PTX [199% (CD11b) and 247% (CD66b)]. Conclusion: MCT-induced neutrophil activation appears not to involve the action of a PTX-sensitive GPCR, such as GPR84. References [1] Wang J et al. Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84.