scholarly journals Dietary Supplementation of Foxtail Millet Ameliorates Colitis-Associated Colorectal Cancer in Mice via Activation of Gut Receptors and Suppression of the STAT3 Pathway

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2367
Author(s):  
Bowei Zhang ◽  
Yingchuan Xu ◽  
Shuang Liu ◽  
Huan Lv ◽  
Yaozhong Hu ◽  
...  

Coarse cereal intake has been reported to be associated with reduced risk of colorectal cancer. However, evidence from intervention studies is absent and the molecular basis of this phenomenon remains largely unexplored. This study sought to investigate the effects of foxtail millet and rice, two common staple grains in Asia, on the progression of colitis-associated colorectal cancer (CAC) and define the mechanism involved. In total, 40 BALB/c mice were randomized into four groups. The Normal and azoxymethane/dextran sodium sulfate (AOM/DSS) groups were supplied with an AIN-93G diet, while the millet- and rice-treated groups were supplied with a modified AIN-93G diet. Compared to the AOM/DSS-induced CAC mice supplemented with rice, an increased survival rate, suppressed tumor burden, and reduced disease activity index were observed in the millet-treated group. The levels of IL-6 and IL-17 were decreased in the millet-treated group compared to both the AOM/DSS and AOM/DSS + rice groups. Millet treatment inhibited the phosphorylation of STAT3 and the related signaling proteins involved in cell proliferation, survival and angiogenesis. These beneficial effects were mediated by the activation of gut receptors AHR and GPCRs via the microbial metabolites (indole derivates and short-chain fatty acids) of foxtail millet. Moreover, millet-treatment increased the abundance of Bifidobacterium and Bacteroidales_S24-7 compared to the rice-treated mice. This study could help researchers to develop better dietary patterns that work against inflammatory bowel disease (IBD) and for CAC patients.

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Sijia Li ◽  
Chen Wang ◽  
Chengcheng Zhang ◽  
Yanhong Luo ◽  
Qianqian Cheng ◽  
...  

Although the strain-dependent effects of Bacteroides vulgatus on alleviating intestinal inflammatory diseases have been demonstrated, the literature has rarely focused on the underlying causes of this effect. In this study, we selected four B. vulgatus strains (FTJS5K1, FTJS7K1, FSDTA11B14, and FSDLZ51K1) with different genomic characteristics and evaluated their protective roles against dextran sulfate sodium- (DSS-) induced colitis. Compared to the other three tested strains, B. vulgatus 7K1 more strongly ameliorated the DSS-induced weight loss, shortening of the colon length, increased disease activity index scores, colonic tissue injury, and immunomodulatory disorder. In contrast, B. vulgatus 51K1 significantly worsened the DSS-induced alterations in the tumor necrosis factor-alpha (TNF-α) concentration and colonic histopathology. A comparative genomic analysis of B. vulgatus 7K1 and 51K1 showed that the beneficial effects of B. vulgatus 7K1 may be associated with some of its specific genes involved in the production of short-chain fatty acids or capsular polysaccharides and enhancement of its survivability in the gut. In conclusion, these findings indicate that the supplementation of B. vulgatus 7K1 is a potentially efficacious intervention for alleviating colitis and provides scientific support for the screening of probiotics with anticolitis effect.


2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Yu-Lin Xu ◽  
Cui-Ling Ding ◽  
Chun-Lin Qian ◽  
Zhong-Tian Qi ◽  
Wen Wang

AbstractInflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC) is a serious health issue, but etiopathological factors remain unclear. Although some studies reported the roles of Retinoid acid induced 16 (RAI16) in the tumorigenesis of hepatocellular carcinoma and PKA signaling, the roles of RAI16 in IBD and CRC are undressed. RAI16−/− mice were generated and the roles of RAI16 were addressed in dextran sodium sulfate (DSS) or azoxymethane (AOM)-DSS induced IBD or CAC mouse models, respectively. At first, RAI16−/− mice were viable, fertile with no apparent defects. Then, it was found that RAI16−/− mice were more susceptibility to colitis induced by DSS than wild type (WT) littermates, which was evaluated by disease activity index and histological score. Furthermore, the expressions of tissues repair associated molecules Cox2, Ereg and MMP-10 were significantly decreased in RAI16−/− colon under DSS treatment. Gut barrier related genes including antimicrobial peptides Reg3b and Reg3g and intestinal mucus genes Muc4, Muc6 and Muc20 were reduced in RAI16−/− colon. These findings indicated that RAI16 may function to affect genes involved in intestinal barrier function and immunoprotective inflammation. Accordingly, RAI16−/− mice displayed significantly increased tumor burden compared with WT mice assessed in CAC model induced by AOM/DSS. Much more Ki67 + nuclei were observed in RAI16−/− tumors suggesting RAI16 to be critical in colonic cell proliferation during tumorigenesis. Conclusively, we demonstrate the roles of RAI16 in colonic inflammation and inflammation-associated tumorigenesis by using a novel RAI16−/− mouse model for the first time.


Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1658
Author(s):  
Lucila A. Godínez-Méndez ◽  
Carmen M. Gurrola-Díaz ◽  
José Sergio Zepeda-Nuño ◽  
Natali Vega-Magaña ◽  
Rocio Ivette Lopez-Roa ◽  
...  

Animal digestive systems host microorganism ecosystems, including integrated bacteria, viruses, fungi, and others, that produce a variety of compounds from different substrates with healthy properties. Among these substrates, α-galacto-oligosaccharides (GOS) are considered prebiotics that promote the grow of gut microbiota with a metabolic output of Short Chain Fatty Acids (SCFAs). In this regard, we evaluated Lupinus albus GOS (LA-GOS) as a natural prebiotic using different animal models. Therefore, the aim of this work was to evaluate the effect of LA-GOS on the gut microbiota, SCFA production, and intestinal health in healthy and induced dysbiosis conditions (an ulcerative colitis (UC) model). Twenty C57BL/6 mice were randomly allocated in four groups (n = 5/group): untreated and treated non-induced animals, and two groups induced with 2% dextran sulfate sodium to UC with and without LA-GOS administration (2.5 g/kg bw). We found that the UC treated group showed a higher goblet cell number, lower disease activity index, and reduced histopathological damage in comparison to the UC untreated group. In addition, the abundance of positive bacteria to butyryl-CoA transferase in gut microbiota was significantly increased by LA-GOS treatment, in healthy conditions. We measured the SCFA production with significant differences in the butyrate concentration between treated and untreated healthy groups. Finally, the pH level in cecum feces was reduced after LA-GOS treatment. Overall, we point out the in vivo health benefits of LA-GOS administration on the preservation of the intestinal ecosystem and the promotion of SCFA production.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Dong Ki Park ◽  
Hye-Jin Park

The effect ofCordyceps militaris(CM) grown on germinated soybeans (GSC) in the inflammatory bowel disease (IBD) model was studied. To demonstrate the preventive effect of GSC extract in a dextran-sodium-sulfate- (DSS-) induced acute colitis mouse model, GSC was administered 2 days before DSS coadministration. GSC significantly suppressed DSS-induced disease activity index (DAI) as well as histopathological scores, compared to control or CM-treated group. To elucidate the anti-IBD activity of GSC, we checked the level of matrix metalloproteinases (MMPs) and inflammatory mediators. GSC extract decreased the level of MMP-3 and -9 mRNAs and p53 proteins. The level and activity of LPS-induced MMP-9 were reduced in GSC-treated RAW264.7 cells. It also attenuated the level of inducible nitric oxide synthase (iNOS) and tumor necrosis factor- (TNF-)αmRNAs both in colon tissue and in macrophage cells. These results suggest that GSC can be applied as a protective agent against IBDs.


Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1684 ◽  
Author(s):  
Larissa Celiberto ◽  
Roseli Pinto ◽  
Elizeu Rossi ◽  
Bruce Vallance ◽  
Daniela Cavallini

Modulation of the gut microbiota through the use of probiotics has been widely used to treat or prevent several intestinal diseases. However, inconsistent results have compromised the efficacy of this approach, especially in severe conditions such as inflammatory bowel disease (IBD). The purpose of our study was to develop a personalized probiotic strategy and assess its efficacy in a murine model of intestinal inflammation. Commensal bacterial strains were isolated from the feces of healthy mice and then administered back to the host as a personalized treatment in dextran sodium sulfate (DSS)-induced colitis. Colonic tissues were collected for histological analysis and to investigate inflammatory markers such as Il-1β, Il-6, TGF-β, and Il-10, and the enzyme myeloperoxidase as a neutrophil marker. The group that received the personalized probiotic showed reduced susceptibility to DSS-colitis as compared to a commercial probiotic. This protection was characterized by a lower disease activity index and reduced histopathological damage in the colon. Moreover, the personalized probiotic was more effective in modulating the host immune response, leading to decreased Il-1β and Il-6 and increased TGF-β and Il-10 expression. In conclusion, our study suggests that personalized probiotics may possess an advantage over commercial probiotics in treating dysbiotic-related conditions, possibly because they are derived directly from the host’s own microbiota.


2021 ◽  
Author(s):  
Jing Guo ◽  
Yan-yan Zhang ◽  
Mei Sun ◽  
Ling-fen Xu

Abstract Aim This study aimed to explore effect of curcumin on inflammatory bowel disease (IBD) in rats and its mechanism.Methods: A dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) rat model was established. The disease activity index (DAI) scores were calculated. The histopathological damage scores were determined by haematoxylin-eosin (H&E) staining. Regulatory T (Treg) cells and T helper 17 (Th17) cells in the spleen were analysed by flow cytometry. The levels of interleukin (IL)-10 and IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Results: Compared with the DSS model group, the curcumin group exhibited significantly reduced DAI scores and improvements in histopathological damage. The expression of CD4+IL-17+ Th17 cells was significantly lower and the expression of CD4+CD25+Foxp3+ Treg cells was significantly higher in the curcumin group than in the DSS group.Conclusion: Curcumin may be a new and effective treatment for IBD by regulating the balance of Treg/Th17 cells and the expression of IL-10 and IL-17A.


2018 ◽  
Vol 56 (10) ◽  
pp. 1267-1275 ◽  
Author(s):  
Angelika Hüppe ◽  
Jana Langbrandtner ◽  
Winfried Häuser ◽  
Heiner Raspe ◽  
Bernd Bokemeyer

Abstract Introduction Assessment of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC) is usually based on the physician’s evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDICD) and UC (GIBDIUC) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians’ documented activity indices. Methods Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements. Results Rank correlations were 0.56 (pMS, GIBDIUC) and 0.57 (HBI, GIBDICD), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories). Discussion There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiao-Fu Chen ◽  
Yuan Zhao ◽  
Yu Guo ◽  
Zhi-Ming Huang ◽  
Xie-Lin Huang

Abstract Background We aimed to externally validate for the first time the diagnostic ability of fibrinogen to identify active inflammatory bowel disease (IBD). Methods The research totally involved 788 patients with IBD, consisted of 245 ulcerative colitis (UC) and 543 Crohn’ s disease (CD). The Mayo score and Crohn disease activity index (CDAI) assessed disease activity of UC and CD respectively. The independent association between fibrinogen and disease activity of patients with UC or CD was investigated by multivariate logistic regression analyses. Area under the receiver operating characteristic curve (AUROC) assessed the performance of various biomarkers in discriminating disease states. Results The fibrinogen levels in active patients with IBD significantly increased compared with those in remission stage (P < 0.001). Fibrinogen was an independent predictor to distinguish disease activity of UC (odds ratio: 2.247, 95% confidence interval: 1.428–3.537, P < 0.001) and CD (odds ratio: 2.124, 95% confidence interval: 1.433–3.148, P < 0.001). Fibrinogen was positively correlated with the Mayo score (r = 0.529, P < 0.001) and CDAI (r = 0.625, P < 0.001). Fibrinogen had a high discriminative capacity for both active UC (AUROC: 0.806, 95% confidence interval: 0.751–0.861) and CD (AUROC: 0.869, 95% confidence interval: 0.839–0.899). The optimum cut-off values of fibrinogen 3.22 was 70% sensitive and 77% specific for active UC, and 3.87 was 77% sensitive and 81% specific for active CD respectively. Conclusions Fibrinogen is a convenient and practical biomarker to identify active IBD.


Author(s):  
M. Sandhya Bhavani ◽  
S. Kavitha ◽  
B. Gowri ◽  
Abid Ali Bhat

Background: Inflammatory bowel disease (IBD) is the common cause of chronic gastrointestinal signs in dogs. The treatment possesses numerous difficulties due to the idiopathic nature of the disease. Conventional steroid therapy usually produces side effects on long term usage. Thus, there is a need for alternative therapies. When compared to human medicine, there is no published data on the use of budesonide and probiotic in the treatment of canine IBD in India. The present study was proposed to compare oral prednisolone, budesonide and probiotics in the management of canine inflammatory bowel disease. Methods: Thirty dogs with idiopathic IBD were selected and randomly grouped. They were subjected to therapy involving prednisolone, budesonide or probiotics. Clinical assessment was performed by calculation of the post treatment Clinical Inflammatory Bowel Disease Activity Index (CIBDAI) score, faecal score and endoscopy. Biochemical analysis of alkaline phosphatase and alanine transaminase were done to record side effects of steroid administration. Result: It was observed from the present study that both prednisolone and budesonide are equally effective in the management of IBD in dogs. Probiotics were found to be less effective when compared to prednisolone and budesonide in the treatment of IBD.


mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Marc A. Sze ◽  
Begüm D. Topçuoğlu ◽  
Nicholas A. Lesniak ◽  
Mack T. Ruffin ◽  
Patrick D. Schloss

ABSTRACT Colonic bacterial populations are thought to have a role in the development of colorectal cancer with some protecting against inflammation and others exacerbating inflammation. Short-chain fatty acids (SCFAs) have been shown to have anti-inflammatory properties and are produced in large quantities by colonic bacteria that produce SCFAs by fermenting fiber. We assessed whether there was an association between fecal SCFA concentrations and the presence of colonic adenomas or carcinomas in a cohort of individuals using 16S rRNA gene and metagenomic shotgun sequence data. We measured the fecal concentrations of acetate, propionate, and butyrate within the cohort and found that there were no significant associations between SCFA concentration and tumor status. When we incorporated these concentrations into random forest classification models trained to differentiate between people with healthy colons and those with adenomas or carcinomas, we found that they did not significantly improve the ability of 16S rRNA gene or metagenomic gene sequence-based models to classify individuals. Finally, we generated random forest regression models trained to predict the concentration of each SCFA based on 16S rRNA gene or metagenomic gene sequence data from the same samples. These models performed poorly and were able to explain at most 14% of the observed variation in the SCFA concentrations. These results support the broader epidemiological data that questions the value of fiber consumption for reducing the risks of colorectal cancer. Although other bacterial metabolites may serve as biomarkers to detect adenomas or carcinomas, fecal SCFA concentrations have limited predictive power. IMPORTANCE Considering that colorectal cancer is the third leading cancer-related cause of death within the United States, it is important to detect colorectal tumors early and to prevent the formation of tumors. Short-chain fatty acids (SCFAs) are often used as a surrogate for measuring gut health and for being anticarcinogenic because of their anti-inflammatory properties. We evaluated the fecal SCFA concentrations of a cohort of individuals with different colonic tumor burdens who were previously analyzed to identify microbiome-based biomarkers of tumors. We were unable to find an association between SCFA concentration and tumor burden or use SCFAs to improve our microbiome-based models of classifying people based on their tumor status. Furthermore, we were unable to find an association between the fecal community structure and SCFA concentrations. Our results indicate that the association between fecal SCFAs, the gut microbiome, and tumor burden is weak.


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