Incrimination of anaerobic bacteria in the induction of experimental colitis

1997 ◽  
Vol 272 (1) ◽  
pp. G10-G15 ◽  
Author(s):  
A. Garcia-Lafuente ◽  
M. Antolin ◽  
F. Guarner ◽  
E. Crespo ◽  
A. Salas ◽  
...  
Keyword(s):  
Anaerobic Bacteria ◽  
Experimental Colitis ◽  
Mucosal Damage ◽  
Trinitrobenzenesulfonic Acid ◽  
Sterile Culture ◽  
Colonic Flora ◽  
Submucosal Lesions ◽  
Eicosanoid Release ◽  
Transmural Inflammation

Commensal bacteria may participate in the pathogenesis of bowel inflammation. We studied the role of bacteria from the rat colonic flora on transmural inflammation induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). First, bacterial translocation to the colonic wall after induction of colitis was assessed by microbiological and histological methods. Second, rats with a colonic segment excluded from fecal transit were prepared for recolonization with preselected bacteria and used to test the effects of different species on inflammation (eicosanoid release, tissue myeloperoxidase) and damage (histology). Six strains (three aerobes and three anaerobes) were identified in colonic tissue 24 h after induction of colitis. Acridine staining showed bacteria in necrotic areas of the mucosa and invading the submucosa. Rats with excluded colon and sterile culture of luminal washings showed mild inflammation and low mucosal damage in response to TNBS. Rats colonized with anaerobes showed significantly higher eicosanoid release than rats colonized with aerobes only. Moreover, submucosal-lesions were mostly observed in rats with anaerobes. Our findings suggest that colonic anaerobes play a key role in transmural inflammation.

Central interleukin-1 receptors contribute to suppression of feeding after acute colitis in the rat

1994 ◽  
Vol 266 (5) ◽  
pp. R1659-R1663 ◽  
Author(s):  
K. J. McHugh ◽  
S. M. Collins ◽  
H. P. Weingarten
Keyword(s):  
Receptor Antagonist ◽  
Interleukin 1 ◽  
Chronic Administration ◽  
Experimental Colitis ◽  
Trinitrobenzenesulfonic Acid ◽  
Acute Colitis ◽  
Osmotic Minipump ◽  
Intrarectal Administration

Experimental colitis, induced in rats by intrarectal administration of trinitrobenzenesulfonic acid (TNB), results in a suppression of eating for 3 days. Because interleukin-1 (IL-1) is elevated within 24 h after TNB treatment, and because chronic administration of IL-1 leads to a pattern of anorexia similar to that seen after TNB, we evaluated the role of endogenous IL-1 in the anorexia observed in the TNB model. Human recombinant IL-1 receptor antagonist (rhIL-1ra) was administered chronically via osmotic minipump either peripherally or centrally after TNB treatment. Peripheral delivery of 40 micrograms/h rhIL-1ra significantly attenuated TNB-induced anorexia. However, 24 micrograms/h rhIL-1ra attenuated TNB-induced anorexia only when delivered centrally, not peripherally. These findings implicate central IL-1 receptors in the suppression of eating during acute experimental colitis but leave open a possible involvement of peripheral IL-1 receptors.

scholarly journals Bactericidal Permeability Increasing Protein Deficiency Aggravates Acute Colitis in Mice by Increasing the Serum Levels of Lipopolysaccharide

2021 ◽  
Vol 11 ◽  
Author(s):  
Qingli Kong ◽  
Zhe Lv ◽  
Yun Kang ◽  
Yunqing An ◽  
Zhenlong Liu ◽  
...  
Keyword(s):  
Abdominal Cavity ◽  
Experimental Colitis ◽  
Serum Levels ◽  
Mucosal Damage ◽  
Rt Pcr ◽  
Acute Colitis ◽  
Fecal Microbiome ◽  
Murine Colitis ◽  
Number Of Bacteria

ObjectiveThe objective of this study was to understand the role of bactericidal permeability increasing protein (BPI) in the pathogenesis of experimental murine colitis.MethodsWe used the Cre-LoxP system to generate BPI knockout (BPI KO) mice. Acute colitis was induced in BPI KO mice and wild-type (WT) mice by subjecting the mice to 5% dextran sulfate sodium (DSS). Mice were observed for symptoms of experimental colitis. The survival of BPI KO mice to infection with Acinetobacter baumannii, a gram-negative bacterium, was also assessed.ResultsSouthern blot, RT-PCR, and western blot results showed that the 2nd and 3rd exons of the murine Bpi gene were knocked out systemically, confirming successful construction of the BPI KO mouse. BPI KO mice subjected to DSS showed increased symptoms of experimental colitis, increased colonic mucosal damage, increased epithelial permeability, elevated levels of serum LPS, and a disrupted fecal microbiome as compared with WT mice. Furthermore, BPI KO mice challenged intraperitoneally with A. baumannii died sooner than WT mice, and the total number of bacteria in the abdominal cavity, spleen, and liver was increased in BPI KO mice as compared to WT mice.ConclusionsWe successfully generated BPI KO mice. The BPI KO mice developed worse colitis than WT mice by increased colitis symptoms and colonic mucosal damage, elevated levels of serum LPS, and a disrupted microbiome. BPI could be a potential target for treatment of ulcerative colitis in humans.

scholarly journals Protein kinase C mediates experimental colitis in the rat

1999 ◽  
Vol 276 (3) ◽  
pp. G583-G590 ◽  
Author(s):  
James F. Brown ◽  
Qing Chang ◽  
Brian D. Soper ◽  
Barry L. Tepperman
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Content ◽  
Experimental Colitis ◽  
Neutrophil Infiltration ◽  
Mucosal Damage ◽  
Myeloperoxidase Activity ◽  
Causative Role ◽  
Trinitrobenzenesulfonic Acid ◽  
Kinase C

Protein kinase C (PKC) plays an important role in the cell signal transduction of many physiological processes. In contrast to these physiological responses, increases in PKC activity have also been associated with inflammatory disease states, including ulcerative colitis. The objective of this study was to examine the role of PKC as a causative mediator in initiation of experimentally induced colitis in the rat. Colitis was induced in rats by intrarectal (0.6 ml) instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS; 75 mg/kg in 50% ethanol) or the PKC activator phorbol 12-myristate 13-acetate (PMA; 1.5–3.0 mg/kg in 20% ethanol). Gross and histological mucosal damage, mucosal neutrophil infiltration, mucosal PKC activity, and PKC protein content for PKC isoforms α, β, δ, and ε were assessed 2 h to 14 days after an inflammatory challenge. Both PKC activity and mucosal injury increased significantly within 4 h of TNBS treatment. PKC activity was maximal at 7 days and declined at 14 days, whereas mucosal damage became maximal at 1 day and declined after 7 days. In contrast, neutrophil infiltration as assessed by myeloperoxidase activity only increased 12 h after TNBS treatment, became maximal 1 day after TNBS administration, and declined thereafter. PKCβ, -δ, and -ε were increased in response to TNBS, whereas PKCα protein content was decreased. The PKC antagonists staurosporine and GF-109203X (25 ng/kg iv) reduced TNBS-induced changes in mucosal PKC activity and the degree of mucosal damage. In contrast, neutropenia induced by antineutrophil serum treatment did not significantly affect the degree of injury or mucosal PKC activity. Furthermore, activation of mucosal PKC activity with PMA also induced mucosal damage, which was also inhibited by pretreatment with a PKC antagonist. In conclusion, these results suggest that increases in PKC activity play a causative role in TNBS-induced colitis. The PKC-mediated response to TNBS does not appear to involve neutrophil infiltration.

Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis: protective role of brain CRF

1999 ◽  
Vol 276 (4) ◽  
pp. G1027-G1036 ◽  
Author(s):  
Mulugeta Million ◽  
Yvette Taché ◽  
Peter Anton
Keyword(s):  
Experimental Colitis ◽  
Plasma Corticosterone ◽  
Protective Role ◽  
Histological Evaluation ◽  
Trinitrobenzenesulfonic Acid ◽  
Response To Stress ◽  
Intracerebroventricular Injections ◽  
Fischer Rats ◽  
Inbred Rat

We assessed the role of central corticotropin-releasing factor (CRF) in stress-induced worsening of colitis in inbred rat strains with hypo (Lewis/N) and hyper (Fischer344/N) CRF responses to stress. Intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNB) induced colitis of similar severity in both strains as assessed on day 7 by macroscopic scoring, histological evaluation, tissue myeloperoxidase (MPO) activity, and decrease in food intake and body weight. Colitis was inhibited by daily intracerebroventricular injections of CRF in both strains. Chronic stress (3 h/day, water avoidance or wrap restraint on alternate days for 6 days) aggravated colitis more in Lewis than Fischer rats (71 and 22% further increase in MPO activity, respectively). The CRF antagonist astressin injected intracerebroventricularly enhanced the colitis response to stress and caused mortality in both strains. Fischer rats had higher plasma corticosterone levels 20 min after stress alone on day 1 and after TNB plus stress on days 1 and 3 compared with Lewis. These data show that central CRF restrains the proinflammatory action of stress in experimental colitis.

Role of filter media in an anaerobic fixed-bed reactor

1995 ◽  
Vol 31 (9) ◽  
pp. 137-144 ◽  
Author(s):  
T. Miyahara ◽  
M. Takano ◽  
T. Noike
Keyword(s):  
Anaerobic Bacteria ◽  
Fixed Bed ◽  
Methanogenic Bacteria ◽  
The Other ◽  
Fixed Bed Reactor ◽  
Filter Media ◽  
Fixed Bed Reactors ◽  
Attached Bacteria ◽  
The Relationship

The relationship between the filter media and the behaviour of anaerobic bacteria was studied using anaerobic fixed-bed reactors. At an HRT of 48 hours, the number of suspended acidogenic bacteria was higher than those attached to the filter media. On the other hand, the number of attached methanogenic bacteria was more than ten times as higher than that of suspended ones. The numbers of suspended and deposited acidogenic and methanogenic bacteria in the reactor operated at an HRT of 3 hours were almost the same as those in the reactor operated at an HRT of 48 hours. Accumulation of attached bacteria was promoted by decreasing the HRT of the reactor. The number of acidogenic bacteria in the reactor packed sparsely with the filter media was higher than that in the closely packed reactor. The number of methanogenic bacteria in the sparsely packed reactor was lower than that in the closely packed reactor.

scholarly journals Role of Dietary Nutritional Treatment on Hepatic and Intestinal Damage in Transplantation with Steatotic and Non-Steatotic Liver Grafts from Brain Dead Donors

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2554
Author(s):  
Marc Micó-Carnero ◽  
Araní Casillas-Ramírez ◽  
Albert Caballeria-Casals ◽  
Carlos Rojano-Alfonso ◽  
Alfredo Sánchez-González ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Mucosal Damage ◽  
Hepatic Damage ◽  
Intestinal Damage ◽  
Edema Formation ◽  
Steatotic Liver ◽  
Damage And Failure

Herein, we investigate whether: (1) the administration of glucose or a lipid emulsion is useful in liver transplantation (LT) using steatotic (induced genetically or nutritionally) or non-steatotic livers from donors after brain death (DBDs); and (2) any such benefits are due to reductions in intestinal damage and consequently to gut microbiota preservation. In recipients from DBDs, we show increased hepatic damage and failure in the maintenance of ATP, glycogen, phospholipid and growth factor (HGF, IGF1 and VEGFA) levels, compared to recipients from non-DBDs. In recipients of non-steatotic grafts from DBDs, the administration of glucose or lipids did not protect against hepatic damage. This was associated with unchanged ATP, glycogen, phospholipid and growth factor levels. However, the administration of lipids in steatotic grafts from DBDs protected against damage and ATP and glycogen drop and increased phospholipid levels. This was associated with increases in growth factors. In all recipients from DBDs, intestinal inflammation and damage (evaluated by LPS, vascular permeability, mucosal damage, TLR4, TNF, IL1, IL-10, MPO, MDA and edema formation) was not shown. In such cases, potential changes in gut microbiota would not be relevant since neither inflammation nor damage was evidenced in the intestine following LT in any of the groups evaluated. In conclusion, lipid treatment is the preferable nutritional support to protect against hepatic damage in steatotic LT from DBDs; the benefits were independent of alterations in the recipient intestine.

scholarly journals PRKAR2A deficiency protects mice from experimental colitis by increasing IFN-stimulated gene expression and modulating the intestinal microbiota

2021 ◽  
Author(s):  
Lumin Wei ◽  
Rongjing Zhang ◽  
Jinzhao Zhang ◽  
Juanjuan Li ◽  
Deping Kong ◽  
...  
Keyword(s):  
Experimental Colitis ◽  
Regulatory Subunit ◽  
Protective Effects ◽  
Intestinal Epithelial ◽  
Catalytic Subunits ◽  
Regulatory Subunits ◽  
Pka Regulatory Subunit ◽  
Cross Fostering ◽  
Specific Deletion

AbstractProtein kinase A (PKA) plays an important role in regulating inflammation via its catalytic subunits. Recently, PKA regulatory subunits have been reported to directly modulate some signaling pathways and alleviate inflammation. However, the role of PKA regulatory subunits in colonic inflammation remains unclear. Therefore, we conducted this study to investigate the role of the PKA regulatory subunit PRKAR2A in colitis. We observed that PRKAR2A deficiency protected mice from dextran sulfate sodium (DSS)-induced experimental colitis. Our experiments revealed that the intestinal epithelial cell-specific deletion of Prkar2a contributed to this protection. Mechanistically, the loss of PRKAR2A in Prkar2a−/− mice resulted in an increased IFN-stimulated gene (ISG) expression and altered gut microbiota. Inhibition of ISGs partially reversed the protective effects against DSS-induced colitis in Prkar2a−/− mice. Antibiotic treatment and cross-fostering experiments demonstrated that the protection against DSS-induced colitis in Prkar2a−/− mice was largely dependent on the gut microflora. Altogether, our work demonstrates a previously unidentified function of PRKAR2A in promoting DSS-induced colitis.

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