Ulcerative colitis is caused by various external factors and is an inflammatory disease that causes decreased intestinal function. Tenebrio molitor larvae contain more than 30 % fat, and the fat component consists of 45 % oleic acid, 20 % linoleic acid and 20 % polyunsaturated fatty acids. In this study, after administering Tenebrio molitor larva oil (TMLO) in a dextran sodium sulphate (DSS)-induced ulcerative colitis mouse model, the pathological findings and inflammatory markers of colitis were analysed to assess whether a colitis mitigation effect was achieved. In the TMLO-administered group, the colon length increased, the spleen weight decreased, and the body weight increased compared with that in the DSS group. In addition, the disease activity index level decreased, the mRNA expression level of inflammatory cytokines in the colon decreased, and the myeloperoxidase activity level significantly decreased. Also, the activity of the NF-κB pathway involved in the regulation of the inflammatory response was lower in the TMLO group than in the DSS group. Taken together, these results suggest that TMLO suppresses occurrence of acute ulcerative colitis in the DSS mouse model. Therefore, TMLO has the potential to be developed as a health food for the prevention and treatment of ulcerative colitis.
- MeSH
- antiflogistika farmakologie terapeutické užití MeSH
- kolitida * chemicky indukované farmakoterapie patologie MeSH
- larva MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- síran dextranu toxicita MeSH
- Tenebrio * MeSH
- ulcerózní kolitida * chemicky indukované farmakoterapie patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Intestinal inflammation induced with dextran sodium sulfate (DSS) is used to study acute or chronic ulcerative colitis in animal models. Decreased gut tissue anti-inflammatory cytokine IL-10 concentration and mRNA abundance are associated with the development of chronic bowel inflammation. Twelve piglets of 3 days old were fitted with an intragastric catheter and randomly allocated into control and DSS groups by administrating either sterile saline or 1.25 g of DSS/kg body weight (BW) in saline per day, respectively, for 10 days. Growth rate and food conversion efficiency were reduced (p<0.05) in the DSS piglets compared with the control group. Quantitative histopathological grading of inflammation in the jejunum and colon collectively showed that the DSS treatment resulted in 12 fold greater (p<0.05) inflammation severity scoring in the colon than in the jejunum, indicative of chronic ulcerative colitis in the colon. Upper gut permeability endpoint was 27.4 fold higher (p<0.05) in the DSS group compared with the control group. The DSS group had higher concentrations and mRNA abundances (p<0.05) of TNF-alpha and IL-6 in the jejunal and colonic tissues compared with the control group. Colonic concentration and mRNA abundance of IL-10 were reduced (p<0.05), however, jejunal IL-10 mRNA abundance was increased (p<0.05) in the DSS group compared with the control group. In conclusion, administration of DSS at 1.25 g/kg BW for 10 days respectively induced acute inflammation in the jejunum and chronic inflammation and ulcerative colitis in the colon with substantially decreased colonic concentration and mRNA abundance of IL-10 in the young pigs, mimicking the IL-10 expression pattern in humans Associated with chronic bowel inflammation.
- MeSH
- exprese genu MeSH
- interleukin-10 biosyntéza genetika MeSH
- kolon účinky léků metabolismus patologie MeSH
- novorozená zvířata MeSH
- prasata MeSH
- síran dextranu toxicita MeSH
- tenké střevo účinky léků metabolismus patologie MeSH
- ulcerózní kolitida chemicky indukované metabolismus patologie MeSH
- zánět chemicky indukované metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Isoquercitrin (quercetin-3-O-β-d-glucopyranoside) is a flavonoid that exhibited antioxidant and anti-inflammatory activities in a number of in vitro and in vivo studies. Experimental evidence from rodent models of inflammatory bowel disease is, however, lacking. This study was designed to examine whether isoquercitrin effectively and dose-dependently attenuates acute dextran sulfate sodium (DSS)-induced rat colitis. METHODS: Wistar rats were divided into negative control group (exposed to vehicle only), positive control group (DSS-induced colitis plus vehicle), low isoquercitrin group (DSS pretreated with isoquercitrin 1mg/kg/day) and high isoquercitrin group (DSS with isoquercitrin 10mg/kg/day). Isoquercitrin was administered daily for 14days, and during the last 7days rats drank DSS solution. The effect of isoquercitrin on DSS-induced colitis was assessed clinically (e.g. disease activity index), biochemically (tissue myeloperoxidase activity, local cyclooxygenase-2 expression), using histology (standard hematoxylin-eosin-based histomorphometry, immunohistochemical detection of inducible nitric oxide synthase) and hematology (blood count). RESULTS: Isoquercitrin dose-dependently ameliorated whole colon shortening and mitigated DSS-induced expression of cyclooxygenase-2 and inducible nitric oxide synthase in the descending segment of the organ. However, when different parts of colon were assessed histomorphometrically, the results did not globally support the protective role of this flavonoid. Tissue healing trends observable in the descending colon were not apparent in the rectum, where histological damage was most severe. CONCLUSIONS: We surmise that isoquercitrin may be effective in the prevention of acute colitis. Besides being dose-dependent, the potency of orally administered isoquercitrin may depend on the severity of tissue damage and/or on the site of its action.
- MeSH
- kolitida chemicky indukované patologie prevence a kontrola MeSH
- krysa rodu rattus MeSH
- náhodné rozdělení MeSH
- ochranné látky terapeutické užití MeSH
- potkani Wistar MeSH
- quercetin analogy a deriváty terapeutické užití MeSH
- síran dextranu toxicita MeSH
- stupeň závažnosti nemoci * MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Reduced microbial diversity has been associated with inflammatory bowel disease (IBD) and probiotic bacteria have been proposed for its prevention and/or treatment. Nevertheless, comparative studies of strains of the same subspecies for specific health benefits are scarce. Here we compared two Bifidobacterium longum ssp. longum strains for their capacity to prevent experimental colitis. METHODS: Immunomodulatory properties of nine probiotic bifidobacteria were assessed by stimulation of murine splenocytes. The immune responses to B. longum ssp. longum CCM 7952 (Bl 7952) and CCDM 372 (Bl 372) were further characterized by stimulation of bone marrow-derived dendritic cell, HEK293/TLR2 or HEK293/NOD2 cells. A mouse model of dextran sulphate sodium (DSS)-induced colitis was used to compare their beneficial effects in vivo. RESULTS: The nine bifidobacteria exhibited strain-specific abilities to induce cytokine production. Bl 372 induced higher levels of both pro- and anti-inflammatory cytokines in spleen and dendritic cell cultures compared to Bl 7952. Both strains engaged TLR2 and contain ligands for NOD2. In a mouse model of DSS-induced colitis, Bl 7952, but not Bl 372, reduced clinical symptoms and preserved expression of tight junction proteins. Importantly, Bl 7952 improved intestinal barrier function as demonstrated by reduced FITC-dextran levels in serum. CONCLUSIONS: We have shown that Bl 7952, but not Bl 372, protected mice from the development of experimental colitis. Our data suggest that although some immunomodulatory properties might be widespread among the genus Bifidobacterium, others may be rare and characteristic only for a specific strain. Therefore, careful selection might be crucial in providing beneficial outcome in clinical trials with probiotics in IBD.
- MeSH
- Bifidobacterium klasifikace fyziologie MeSH
- dendritické buňky mikrobiologie patologie MeSH
- HEK293 buňky MeSH
- imunoenzymatické techniky MeSH
- kolitida chemicky indukované prevence a kontrola MeSH
- lidé MeSH
- modely nemocí na zvířatech * MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- probiotika farmakologie MeSH
- signální adaptorový protein Nod2 genetika metabolismus MeSH
- síran dextranu toxicita MeSH
- střeva mikrobiologie patofyziologie MeSH
- toll-like receptor 2 genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Microbial sensing by Toll-like receptors (TLR) and its negative regulation have an important role in the pathogenesis of inflammation-related cancer. In this study, we investigated the role of negative regulation of Toll-like receptors signaling and gut microbiota in the development of colitis-associated cancer in mouse model. METHODS: Colitis-associated cancer was induced by azoxymethane and dextran sodium sulfate in wild-type and in interleukin-1 receptor-associated kinase M (IRAK-M)-deficient mice with or without antibiotic (ATB) treatment. Local cytokine production was analyzed by multiplex cytokine assay or enzyme-linked immunosorbent assay, and regulatory T cells were analyzed by flow cytometry. Changes in microbiota composition during tumorigenesis were analyzed by pyrosequencing, and β-glucuronidase activity was measured in intestinal content by fluorescence assay. RESULTS: ATB treatment of wild-type mice reduced the incidence and severity of tumors. Compared with nontreated mice, ATB-treated mice had significantly lower numbers of regulatory T cells in colon, altered gut microbiota composition, and decreased β-glucuronidase activity. However, the β-glucuronidase activity was not as low as in germ-free mice. IRAK-M-deficient mice not only developed invasive tumors, but ATB-induced decrease in β-glucuronidase activity did not rescue them from severe carcinogenesis phenotype. Furthermore, IRAK-M-deficient mice had significantly increased levels of proinflammatory cytokines in the tumor tissue. CONCLUSIONS: We conclude that gut microbiota promotes tumorigenesis by increasing the exposure of gut epithelium to carcinogens and that IRAK-M-negative regulation is essential for colon cancer resistance even in conditions of altered microbiota. Therefore, gut microbiota and its metabolic activity could be potential targets for colitis-associated cancer therapy.
- MeSH
- azoxymethan toxicita MeSH
- cytokiny genetika metabolismus MeSH
- gastrointestinální trakt mikrobiologie MeSH
- karcinogeny toxicita MeSH
- kinázy asociované s receptory interleukinu-1 fyziologie MeSH
- kolitida chemicky indukované komplikace MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- messenger RNA genetika MeSH
- metagenom * MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- nádory tračníku etiologie metabolismus patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- průtoková cytometrie MeSH
- receptory interleukinu-1 metabolismus MeSH
- regulační T-lymfocyty imunologie metabolismus patologie MeSH
- signální transdukce MeSH
- síran dextranu toxicita MeSH
- toll-like receptory genetika metabolismus MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms - bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression.
- MeSH
- akutní nemoc MeSH
- antigeny CD11b biosyntéza genetika MeSH
- aplikace rektální MeSH
- bakteriální translokace MeSH
- butyráty metabolismus MeSH
- Clostridium tyrobutyricum fyziologie MeSH
- fosfoproteiny biosyntéza genetika MeSH
- imunokompetence MeSH
- interleukin-18 biosyntéza genetika MeSH
- kolon metabolismus mikrobiologie patologie MeSH
- mastné kyseliny metabolismus MeSH
- membránové proteiny biosyntéza genetika MeSH
- mucin 2 biosyntéza genetika MeSH
- muciny biosyntéza MeSH
- myši inbrední BALB C MeSH
- myši SCID MeSH
- myši MeSH
- organismy bez specifických patogenů MeSH
- probiotika terapeutické užití MeSH
- síran dextranu toxicita MeSH
- těžká kombinovaná imunodeficience genetika imunologie MeSH
- TNF-alfa biosyntéza genetika MeSH
- ulcerózní kolitida chemicky indukované genetika imunologie mikrobiologie patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
