scholarly journals Preventive Effects of Escherichia coli Strain Nissle 1917 on Acute and Chronic Intestinal Inflammation in Two Different Murine Models of Colitis

2004 ◽  
Vol 11 (2) ◽  
pp. 372-378 ◽  
Author(s):  
Michael Schultz ◽  
Ulrike G. Strauch ◽  
Hans-Jörg Linde ◽  
Sonja Watzl ◽  
Florian Obermeier ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Proinflammatory Cytokines ◽  
Intestinal Inflammation ◽  
Experimental Colitis ◽  
Cytokine Secretion ◽  
Murine Models ◽  
Chronic Colitis ◽  
E Coli ◽  
Ifn Γ ◽  
Chronic Intestinal Inflammation

ABSTRACT Escherichia coli strain Nissle 1917 (EcN) is as effective in maintaining remission in ulcerative colitis as is treatment with mesalazine. This study aims to evaluate murine models of acute and chronic intestinal inflammation to study the antiinflammatory effect of EcN in vivo. Acute colitis was induced in mice with 2% dextran-sodium sulfate (DSS) in drinking water. EcN was administered from day −2 to day +7. Chronic colitis was induced by transfer of CD4+ CD62L+ T lymphocytes from BALB/c mice in SCID mice. EcN was administered three times/week from week 1 to week 8 after cell transfer. Mesenteric lymph node (MLN) cytokine secretion (of gamma interferon [IFN-γ], interleukin 5 [IL-5], IL-6, and IL-10) was measured by enzyme-linked immunosorbent assay. Histologic sections of the colon were analyzed by using a score system ranging from 0 to 4. Intestinal contents and homogenized MLN were cultured, and the number of E. coli-like colonies was determined. EcN was identified by repetitive extragenic palindromic (REP) PCR. EcN administration to DSS-treated mice reduced the secretion of proinflammatory cytokines (IFN-γ, 32,477 ± 6,377 versus 9,734 ± 1,717 [P = 0.004]; IL-6, 231 ± 35 versus 121 ± 17 [P = 0.02]) but had no effect on the mucosal inflammation. In the chronic experimental colitis of the transfer model, EcN ameliorated the intestinal inflammation (histology score, 2.7 ± 0.2 versus 1.9 ± 0.3 [P = 0.02]) and reduced the secretion of proinflammatory cytokines. Translocation of EcN and resident E. coli into MLN was observed in the chronic colitis model but not in healthy controls. Administration of EcN ameliorated acute and chronic experimental colitis by modifying proinflammatory cytokine secretion but had no influence on the acute DSS-induced colitis. In this model, preexisting colitis was necessary for translocation of EcN and resident E. coli into MLN.

scholarly journals Inflammation-Induced Acid Tolerance GenesgadABin Luminal Commensal Escherichia coli Attenuate Experimental Colitis

2013 ◽  
Vol 81 (10) ◽  
pp. 3662-3671 ◽  
Author(s):  
Sandrine Tchaptchet ◽  
Ting-Jia Fan ◽  
Laura Goeser ◽  
Alexi Schoenborn ◽  
Ajay S. Gulati ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Acid Tolerance ◽  
Experimental Colitis ◽  
Intestinal Epithelial ◽  
Content Type ◽  
E Coli ◽  
Chronic Intestinal Inflammation

ABSTRACTDysregulated immune responses to commensal intestinal bacteria, includingEscherichia coli, contribute to the development of inflammatory bowel diseases (IBDs) and experimental colitis. Reciprocally,E. coliresponds to chronic intestinal inflammation by upregulating expression of stress response genes, includinggadAandgadB. GadAB encode glutamate decarboxylase and protectE. colifrom the toxic effects of low pH and fermentation acids, factors present in the intestinal lumen in patients with active IBDs. We hypothesized thatE. coliupregulatesgadABduring inflammation to enhance its survival and virulence. Using real-time PCR, we determinedgadABexpression in luminalE. colifrom ex-germfree wild-type (WT) and interleukin-10 (IL-10) knockout (KO) (IL-10−/−) mice selectively colonized with a commensalE. coliisolate (NC101) that causes colitis in KO mice in isolation or in combination with 7 other commensal intestinal bacterial strains.E. colisurvival and host inflammatory responses were measured in WT and KO mice colonized with NC101 or a mutant lacking thegadABgenes (NC101ΔgadAB). The susceptibility of NC101 and NC101ΔgadABto killing by host antimicrobial peptides and their translocation across intestinal epithelial cells were evaluated using bacterial killing assays and transwell experiments, respectively. We show that expression ofgadABin luminalE. coliincreases proportionately with intestinal inflammation in KO mice and enhances the susceptibility of NC101 to killing by the host antimicrobial peptide cryptdin-4 but decreases bacterial transmigration across intestinal epithelial cells, colonic inflammation, and mucosal immune responses. Chronic intestinal inflammation upregulates acid tolerance pathways in commensalE. coliisolates, which, contrary to our original hypothesis, limits their survival and colitogenic potential. Further investigation of microbial adaptation to immune-mediated inflammation may provide novel insights into the pathogenesis and treatment of IBDs.

scholarly journals Escherichia coli Strain Nissle 1917 Ameliorates Experimental Colitis via Toll-Like Receptor 2- and Toll-Like Receptor 4-Dependent Pathways

2006 ◽  
Vol 74 (7) ◽  
pp. 4075-4082 ◽  
Author(s):  
A. Grabig ◽  
D. Paclik ◽  
C. Guzy ◽  
A. Dankof ◽  
D. C. Baumgart ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
T Cells ◽  
Knockout Mice ◽  
Selective Reduction ◽  
Experimental Colitis ◽  
Defense Responses ◽  
Coli Strain ◽  
Cytokine Secretion ◽  
Toll Like Receptor ◽  
E Coli

ABSTRACT Toll-like receptors (TLRs) are key components of the innate immune system that trigger antimicrobial host defense responses. The aim of the present study was to analyze the effects of probiotic Escherichia coli Nissle strain 1917 in experimental colitis induced in TLR-2 and TLR-4 knockout mice. Colitis was induced in wild-type (wt), TLR-2 knockout, and TLR-4 knockout mice via administration of 5% dextran sodium sulfate (DSS). Mice were treated with either 0.9% NaCl or 107 E. coli Nissle 1917 twice daily, followed by the determination of disease activity, mucosal damage, and cytokine secretion. wt and TLR-2 knockout mice exposed to DSS developed acute colitis, whereas TLR-4 knockout mice developed significantly less inflammation. In wt mice, but not TLR-2 or TLR-4 knockout mice, E. coli Nissle 1917 ameliorated colitis and decreased proinflammatory cytokine secretion. In TLR-2 knockout mice a selective reduction of gamma interferon secretion was observed after E. coli Nissle 1917 treatment. In TLR-4 knockout mice, cytokine secretion was almost undetectable and not modulated by E. coli Nissle 1917, indicating that TLR-4 knockout mice do not develop colitis similar to the wt mice. Coculture of E. coli Nissle 1917 and human T cells increased TLR-2 and TLR-4 protein expression in T cells and increased NF-κB activity via TLR-2 and TLR-4. In conclusion, our data provide evidence that E. coli Nissle 1917 ameliorates experimental induced colitis in mice via TLR-2- and TLR-4-dependent pathways.

scholarly journals Streptomycin-Induced Inflammation Enhances Escherichia coli Gut Colonization Through Nitrate Respiration

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Alanna M. Spees ◽  
Tamding Wangdi ◽  
Christopher A. Lopez ◽  
Dawn D. Kingsbury ◽  
Mariana N. Xavier ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Microbial Community ◽  
Intestinal Inflammation ◽  
Anaerobic Bacteria ◽  
Nitrate Respiration ◽  
Colonization Resistance ◽  
Content Type ◽  
E Coli ◽  
Gut Colonization ◽  
Facultative Anaerobic Bacteria

ABSTRACTTreatment with streptomycin enhances the growth of human commensalEscherichia coliisolates in the mouse intestine, suggesting that the resident microbial community (microbiota) can inhibit the growth of invading microbes, a phenomenon known as “colonization resistance.” However, the precise mechanisms by which streptomycin treatment lowers colonization resistance remain obscure. Here we show that streptomycin treatment rendered mice more susceptible to the development of chemically induced colitis, raising the possibility that the antibiotic might lower colonization resistance by changing mucosal immune responses rather than by preventing microbe-microbe interactions. Investigation of the underlying mechanism revealed a mild inflammatory infiltrate in the cecal mucosa of streptomycin-treated mice, which was accompanied by elevated expression ofNos2, the gene that encodes inducible nitric oxide synthase. In turn, this inflammatory response enhanced the luminal growth ofE. coliby nitrate respiration in aNos2-dependent fashion. These data identify low-level intestinal inflammation as one of the factors responsible for the loss of resistance toE. colicolonization after streptomycin treatment.IMPORTANCEOur intestine is host to a complex microbial community that confers benefits by educating the immune system and providing niche protection. Perturbation of intestinal communities by streptomycin treatment lowers “colonization resistance” through unknown mechanisms. Here we show that streptomycin increases the inflammatory tone of the intestinal mucosa, thereby making the bowel more susceptible to dextran sulfate sodium treatment and boosting theNos2-dependent growth of commensalEscherichia coliby nitrate respiration. These data point to the generation of alternative electron acceptors as a by-product of the inflammatory host response as an important factor responsible for lowering resistance to colonization by facultative anaerobic bacteria such asE. coli.

scholarly journals Hapten-induced Colitis Is Associated with Colonic Patch Hypertrophy and T Helper Cell 2–Type Responses

1999 ◽  
Vol 189 (8) ◽  
pp. 1169-1180 ◽  
Author(s):  
Taeko Dohi ◽  
Kohtaro Fujihashi ◽  
Paul D. Rennert ◽  
Koichi Iwatani ◽  
Hiroshi Kiyono ◽  
...  
Keyword(s):  
Sulfonic Acid ◽  
Intestinal Inflammation ◽  
T Helper Cell ◽  
Trinitrobenzene Sulfonic Acid ◽  
Murine Models ◽  
T Helper ◽  
Mucosal Layer ◽  
Inflammatory Bowel ◽  
Ifn Γ ◽  
Tnbs Colitis

To investigate the potential involvement of T helper (Th)2-type responses in murine models of intestinal inflammation, we used trinitrobenzene sulfonic acid (TNBS)–hapten to induce inflammatory bowel disease in situations where Th1-type responses with interferon (IFN)-γ synthesis are either diminished or do not occur. Intracolonic administration of TNBS to either normal (IFN-γ+/+) or Th1-deficient IFN-γ knockout (IFN-γ−/−) BALB/c mice resulted in significant colitis. In IFN-γ−/− mice, crypt inflammation was more severe than in IFN-γ+/+ mice and was accompanied by hypertrophy of colonic patches with a lymphoepithelium containing M cells and distinct B and T cell zones resembling Peyer's patches. Hapten-specific, colonic patch T cells from both mouse groups exhibited a Th2 phenotype with interleukin (IL)-4 and IL-5 production. TNBS colitis in normal mice treated with anti–IL-4 antibodies or in IL-4−/− mice was less severe than in either IFN-γ+/+ or IFN-γ−/− mice. Our findings now show that the Th2-type responses in TNBS colitis are associated with colonic patch enlargement and inflammation of the mucosal layer and may represent a model for ulcerative colitis.

scholarly journals Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 517 ◽  
Author(s):  
Claudia Burrello ◽  
Maria Rita Giuffrè ◽  
Angeli Dominique Macandog ◽  
Angelica Diaz-Basabe ◽  
Fulvia Milena Cribiù ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Immune Cells ◽  
Intestinal Inflammation ◽  
Fecal Microbiota Transplantation ◽  
Experimental Colitis ◽  
Fecal Microbiota ◽  
Microbiota Composition ◽  
Chronic Intestinal Inflammation ◽  
Gut Microbiota Composition

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.

scholarly journals Dietary Emulsifiers Directly Impact Adherent-Invasive E. coli Gene Expression to Drive Chronic Intestinal Inflammation

Cell Reports ◽  
2020 ◽  
Vol 33 (1) ◽  
pp. 108229
Author(s):  
Emilie Viennois ◽  
Alexis Bretin ◽  
Philip E. Dubé ◽  
Alexander C. Maue ◽  
Charlène J.G. Dauriat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intestinal Inflammation ◽  
E Coli ◽  
Chronic Intestinal Inflammation

scholarly journals Escherichia coli Nissle 1917 Distinctively Modulates T-Cell Cycling and Expansion via Toll-Like Receptor 2 Signaling

2005 ◽  
Vol 73 (3) ◽  
pp. 1452-1465 ◽  
Author(s):  
Andreas Sturm ◽  
Klaus Rilling ◽  
Daniel C. Baumgart ◽  
Konstantinos Gargas ◽  
Tay Abou-Ghazalé ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Cycle ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Intestinal Inflammation ◽  
Toll Like Receptor ◽  
E Coli ◽  
Toll Like Receptor 2 ◽  
Cell Cycling

ABSTRACT Although the probiotic Escherichia coli strain Nissle 1917 has been proven to be efficacious for the treatment of inflammatory bowel diseases, the underlying mechanisms of action still remain elusive. The aim of the present study was to analyze the effects of E. coli Nissle 1917 on cell cycling and apoptosis of peripheral blood and lamina propria T cells (PBT and LPT, respectively). Anti-CD3-stimulated PBT and LPT were treated with E. coli Nissle 1917-conditioned medium (E. coli Nissle 1917-CM) or heat-inactivated E. coli Nissle 1917. Cyclin B1, DNA content, and caspase 3 expression were measured by flow cytometry to assess cell cycle kinetics and apoptosis. Protein levels of several cell cycle and apoptosis modulators were determined by immunoblotting, and cytokine profiles were determined by cytometric bead array. E. coli Nissle 1917-CM inhibits cell cycling and expansion of peripheral blood but not mucosal T cells. Bacterial lipoproteins mimicked the effect of E. coli Nissle 1917-CM; in contrast, heat-inactivated E. coli Nissle 1917, lipopolysaccharide, or CpG DNA did not alter PBT cell cycling. E. coli Nissle 1917-CM decreased cyclin D2, B1, and retinoblastoma protein expression, contributing to the reduction of T-cell proliferation. E. coli Nissle 1917 significantly inhibited the expression of interleukin-2 (IL-2), tumor necrosis factor α, and gamma interferon but increased IL-10 production in PBT. Using Toll-like receptor 2 (TLR-2) knockout mice, we further demonstrate that the inhibition of PBT proliferation by E. coli Nissle 1917-CM is TLR-2 dependent. The differential reaction of circulating and tissue-bound T cells towards E. coli Nissle 1917 may explain the beneficial effect of E. coli Nissle 1917 in intestinal inflammation. E. coli Nissle 1917 may downregulate the expansion of newly recruited T cells into the mucosa and limit intestinal inflammation, while already activated tissue-bound T cells may eliminate deleterious antigens in order to maintain immunological homeostasis.

scholarly journals Fucose Ameliorates Tryptophan Metabolism and Behavioral Abnormalities in a Mouse Model of Chronic Colitis

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 445 ◽  
Author(s):  
Mariya A. Borisova ◽  
Olga A. Snytnikova ◽  
Ekaterina A. Litvinova ◽  
Kseniya M. Achasova ◽  
Tatiana I. Babochkina ◽  
...  
Keyword(s):  
Social Behavior ◽  
Mouse Model ◽  
Intestinal Microbiota ◽  
Intestinal Inflammation ◽  
Preference Test ◽  
Chronic Colitis ◽  
Odor Preference ◽  
E Coli ◽  
Behavioral Abnormalities ◽  
Tryptophan Level

Growing evidence suggests that intestinal mucosa homeostasis impacts immunity, metabolism, the Central Nervous System (CNS), and behavior. Here, we investigated the effect of the monosaccharide fucose on inflammation, metabolism, intestinal microbiota, and social behavior in the Dextran Sulfate Sodium (DSS)-induced chronic colitis mouse model. Our data show that chronic colitis is accompanied by the decrease of the serum tryptophan level and the depletion of the intestinal microbiota, specifically tryptophan-producing E. coli and Bifidobacterium. These changes are associated with defects in the male mouse social behavior such as a lack of preference towards female bedding in an odor preference test. The addition of fucose to the test animals’ diet altered the bacterial community, increased the abundance of tryptophan-producing E. coli, normalized blood tryptophan levels, and ameliorated social behavior deficits. At the same time, we observed no ameliorating effect of fucose on colon morphology and colitis. Our results suggest a possible mechanism by which intestinal inflammation affects social behavior in male mice. We propose fucose as a promising prebiotic, since it creates a favorable environment for the beneficial bacteria that promote normalization of serum tryptophan level and amelioration of the behavioral abnormalities in the odor preference test.

Characterization of Skeletal Phenotype and Associated Mechanisms With Chronic Intestinal Inflammation in the Winnie Mouse Model of Spontaneous Chronic Colitis

2021 ◽  
Author(s):  
Ahmed Al Saedi ◽  
Shilpa Sharma ◽  
Ebrahim Bani Hassan ◽  
Lulu Chen ◽  
Ali Ghasem-Zadeh ◽  
...  
Keyword(s):  
Bone Loss ◽  
Mouse Model ◽  
Bone Formation ◽  
Intestinal Inflammation ◽  
Bone Microarchitecture ◽  
Mineral Apposition Rate ◽  
Serotonin Level ◽  
Chronic Colitis ◽  
Skeletal Phenotype ◽  
Chronic Intestinal Inflammation

Abstract Background Osteoporosis is a common extraintestinal manifestation of inflammatory bowel disease (IBD). However, studies have been scarce, mainly because of the lack of an appropriate animal model of colitis-associated bone loss. In this study, we aimed to decipher skeletal manifestations in the Winnie mouse model of spontaneous chronic colitis, which carries a MUC2 gene mutation and closely replicates ulcerative colitis. In our study, Winnie mice, prior to the colitis onset at 6 weeks old and progression at 14 and 24 weeks old, were compared with age-matched C57BL/6 controls. We studied several possible mechanisms involved in colitis-associated bone loss. Methods We assessed for bone quality (eg, microcomputed tomography [micro-CT], static and dynamic histomorphometry, 3-point bending, and ex vivo bone marrow analysis) and associated mechanisms (eg, electrochemical recordings for gut-derived serotonin levels, real-time polymerase chain reaction [qRT-PCR], double immunofluorescence microscopy, intestinal inflammation levels by lipocalin-2 assay, serum levels of calcium, phosphorus, and vitamin D) from Winnie (6–24 weeks) and age-matched C57BL6 mice. Results Deterioration in trabecular and cortical bone microarchitecture, reductions in bone formation, mineral apposition rate, bone volume/total volume, osteoid volume/bone surface, and bone strength were observed in Winnie mice compared with controls. Decreased osteoblast and increased osteoclast numbers were prominent in Winnie mice compared with controls. Upregulation of 5-HTR1B gene and increased association of FOXO1 with ATF4 complex were identified as associated mechanisms concomitant to overt inflammation and high levels of gut-derived serotonin in 14-week and 24-week Winnie mice. Conclusions Skeletal phenotype of the Winnie mouse model of spontaneous chronic colitis closely represents manifestations of IBD-associated osteoporosis/osteopenia. The onset and progression of intestinal inflammation are associated with increased gut-derived serotonin level, increased bone resorption, and decreased bone formation.

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