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2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Fang Dong ◽  
Fangfei Xiao ◽  
Xiaolu Li ◽  
Youran Li ◽  
Xufei Wang ◽  
...  

Abstract Background Compelling evidences demonstrated that gut microbiota dysbiosis plays a critical role in the pathogenesis of inflammatory bowel diseases (IBD). Therapies for targeting the microbiota may provide alternative options for the treatment of IBD, such as probiotics. Here, we aimed to investigate the protective effect of a probiotic strain, Pediococcus pentosaceus (P. pentosaceus) CECT 8330, on dextran sulfate sodium (DSS)-induced colitis in mice. Methods C57BL/6 mice were administered phosphate-buffered saline (PBS) or P. pentosaceus CECT 8330 (5 × 108 CFU/day) once daily by gavage for 5 days prior to or 2 days after colitis induction by DSS. Weight, fecal conditions, colon length and histopathological changes were examined. ELISA and flow cytometry were applied to determine the cytokines and regulatory T cells (Treg) ratio. Western blot was used to examine the tight junction proteins (TJP) in colonic tissues. Fecal short-chain fatty acids (SCFAs) levels and microbiota composition were analyzed by targeted metabolomics and 16S rRNA gene sequencing, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of orthologous groups of proteins (COG) pathway analysis were used to predict the microbial functional profiles. Results P. pentosaceus CECT 8330 treatment protected DSS-induced colitis in mice as evidenced by reducing the weight loss, disease activity index (DAI) score, histological damage, and colon length shortening. P. pentosaceus CECT 8330 decreased the serum levels of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), and increased level of IL-10 in DSS treated mice. P. pentosaceus CECT 8330 upregulated the expression of ZO-1, Occludin and the ratio of Treg cells in colon tissue. P. pentosaceus CECT 8330 increased the fecal SCFAs level and relative abundances of several protective bacteria genera, including norank_f_Muribaculaceae, Lactobacillus, Bifidobacterium, and Dubosiella. Furthermore, the increased abundances of bacteria genera were positively correlated with IL-10 and SCFAs levels, and negatively associated with IL-6, IL-1β, and TNF-α, respectively. The KEGG and COG pathway analysis revealed that P. pentosaceus CECT 8330 could partially recover the metabolic pathways altered by DSS. Conclusions P. pentosaceus CECT 8330 administration protects the DSS-induced colitis and modulates the gut microbial composition and function, immunological profiles, and the gut barrier function. Therefore, P. pentosaceus CECT 8330 may serve as a promising probiotic to ameliorate intestinal inflammation.


2021 ◽  
Vol 14 (4) ◽  
pp. 2227-2233
Author(s):  
Kevin Tjoa ◽  
Kusmardi Kusmardi ◽  
Yurnadi Hanafi Midoen

Colorectal cancer (CRC) is the world’s third most cancer and the second highest mortality rate. The searching for new anti-inflammation substances with less adverse effects than aspirin for chemoprevention and adjuvant chemotherapy of CRC is running. The most notable one is fish oil containing omega 3. Kusmardi, et al. studied that industrial waste fish oil omega-3 level comes close enough to conventional fish oil industry. Study aims to reducing the level IL-6 on mice colon tissue being induced CRC using AOM/DSS by fish oil administration. Thirty male Swiss Webster mice are grouped into six treatments: positive control (aspirin), negative control (physiological saline), normal, high dose (fish oil 6mg/kgBW), medium dose (fish oil 3mg/kgBW), dan solvent control (corn oil). Colon tissue was stained using anti IL-6 antibody. Ten photos per slide were taken by microscope (400x), analyzed for the IL-6 expression by ImageJ®, and quantified for H-score. Data was analyzed using SPSS 24.0 (CI 95%) and p-value <0.05 is consider significant. Data are not normally distributed with median of 161.64 (119.4-260.67). Kruskal-Wallis test is significant in addition with Mann-Whitney test shows only high dose group has significant difference to negative control (p=0.008), medium dose (p=0.016) dan and solvent control (p=0.008). No significant difference reported between high dose and positive control group (p=0.69). High dose industrial waste fish oil can lower IL-6 expression in mice colon tissue induced CRC using AOM/DSS.


2021 ◽  
Vol 12 (2) ◽  
pp. 68-76
Author(s):  
Evelynne Silva ◽  
Ítalo Medeiros Azevedo ◽  
Irami Araújo Filho ◽  
Aldo Cunha Medeiros

Objective: This study aimed to investigate the effect of A. chica extract on the evolution of experimental rectocolitis in rats, and the expression of the pro-inflammatory cytokines TNF-a, IL-1β and IL-6 in colonic tissue. Methods: Wistar rats weighing 275±23g were distributed into 4 groups of 6 animals each. Rectocolitis was induced in rats by rectal administration of trinitrobenzene sulfonic acid (TNBS). Seventy-two hours after TNBS injection, animals were treated daily for 6 days. Groups: 1. Normal control group without induction of rectocolitis. Received 0.9% saline injection v.o. by gavage during treatment. 2. TNBS rectocolitis group, treated with normal saline (SN) by gavage (TNBS+SN); 3. TNBS rectocolitis group treated with A. chica extract (ACE), receiving a daily dose of 300 mg of A. chica extract by gavage (TNBS+ACE);4. TNBS rectocolitis group treated with mesalazine, receiving a daily dose of 100 mg/kg of mesalazine orally (TNBS+MEZ). Macroscopic examination of the colon and dosing of TNF-α, IL-1β and IL-6 in colon tissue were performed. Results: There was a reduction in weight in animals treated only with TNBS+NS. No difference in weight was observed comparing the animals treated with ACE and MEZ. In the control group no mucosal ulcers or edema of the colon wall were observed. Several mucosal ulcers, edema and hyperemia occurred in the colon of rats in the TNBS+SN group. In two of the animals in this group there was colon perforation, tamponated by omentum. A reduction of mucosal ulcers number in the TNBS+ACE (crajiru) group was seen, compared to the TNBS+SN and TNBS+MEZ group. There was a significant reduction of TNF-α, IL-1β and IL-6 in the colon tissue of animals treated with crajiru extract, TCBS+ACE group, when compared to the control group (p<0.001), TNBS+SN group, and TNBS+MEZ groups (p<0.001). Conclusion: This is the first study to show that A. chica extract positively influences the treatment of TNBS/induced rectocolitis through its antiinflamatory activity. More comprehensive studies are needed to understand the underlying mechanisms.


Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 123
Author(s):  
Qilyu Zhou ◽  
Ruyang Yu ◽  
Tianlong Liu ◽  
Yeye Li ◽  
Jia Zhong ◽  
...  

Coix seed is a functional food in the Chinese diet that possesses the ability to alleviate ulcerative colitis clinically. However, the underlying mechanisms remain ambiguous. In this study, we investigated the protective effect of the Coix seed diet on experimental colitis mice. The mice were randomly divided into four groups: control group, model group, Coix seed feed group, and positive control group. The maintenance feed of the mice was replaced with Coix seed feed 10 days before orally administering the mice 5% (w/v) dextran sulfate sodium drink. As a result, the Coix seed feed alleviated colitis symptoms, maintained the complete blood count at a normal level, reduced the pathological score, relieved inflammatory cytokine secretion, and alleviated oxidative stress. Network pharmacology analysis was used for further exploration of the targets of Coix seed feed. The results showed that T-cell regulation is one of the targets of Coix seed feed, and the analysis of the T-lymphocyte subset and innate immune cell distribution of the colon tissue supported the network pharmacology results. In conclusion, Coix seed, as a staple food, can alleviate experimental colitis, and the mechanism may be related to the immune regulation effect of Coix seeds.


Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 80
Author(s):  
Thunnicha Ondee ◽  
Krit Pongpirul ◽  
Kantima Janchot ◽  
Suthicha Kanacharoen ◽  
Thanapat Lertmongkolaksorn ◽  
...  

Fat reduction and anti-inflammation are commonly claimed properties of probiotics. Lactiplantibacillus plantarum and Enterococcus faecium were tested in high fat-induced obesity mice and in vitro experiments. After 16 weeks of probiotics, L. plantarum dfa1 outperforms E. faecium dfa1 on the anti-obesity property as indicated by body weight, regional fat accumulation, serum cholesterol, inflammatory cytokines (in blood and colon tissue), and gut barrier defect (FITC-dextran assay). With fecal microbiome analysis, L. plantarum dfa1 but not E. faecium dfa1 reduced fecal abundance of pathogenic Proteobacteria without an alteration in total Gram-negative bacteria when compared with non-probiotics obese mice. With palmitic acid induction, the condition media from both probiotics similarly attenuated supernatant IL-8, improved enterocyte integrity and down-regulated cholesterol absorption-associated genes in Caco-2 cell (an enterocyte cell line) and reduced supernatant cytokines (TNF-α and IL-6) with normalization of cell energy status (extracellular flux analysis) in bone-marrow-derived macrophages. Due to the anti-inflammatory effect of the condition media of both probiotics on palmitic acid-activated enterocytes was neutralized by amylase, the active anti-inflammatory molecules might, partly, be exopolysaccharides. As L. plantarum dfa1 out-performed E. faecium dfa1 in anti-obesity property, possibly through the reduced fecal Proteobacteria, with a similar anti-inflammatory exopolysaccharide; L. plantarum is a potentially better option for anti-obesity than E. faecium.


Author(s):  
Hai-Yan Wang ◽  
Wei Ge ◽  
Su-Qing Liu ◽  
Jian Long ◽  
Qing-Qing Jiang ◽  
...  

Follicular helper T cells (Tfh) regulate the differentiation of germinal center B cells and maintain humoral immunity. Notably, imbalances in Tfh differentiation often lead to the development of autoimmune diseases, including inflammatory bowel disease (IBD). Curcumin, a natural product derived from Curcuma longa, is effective in relieving IBD in humans and animals, and its mechanisms of immune regulation need further elaboration. In this study, dextran sodium sulfate induced ulcerative colitis in BALB/c mice, and curcumin was administered simultaneously for 7 days. Curcumin effectively upregulated the change rate of mouse weight, colonic length, down-regulated colonic weight, index of colonic weight, colonic damage score and the levels of pro-inflammatory cytokines IL-6, IL-12, IL-23 and TGF-[Formula: see text]1 in colonic tissues of colitis mice. Importantly, curcumin regulated the differentiation balance of Tfh and their subpopulation in colitis mice; the percentages of Tfh (CD4[Formula: see text]CXCR5[Formula: see text]BCL-6[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]PD-1[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]PD-L1[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]ICOS[Formula: see text], Tfh17 and Tem-Tfh were downregulated significantly, while CD4[Formula: see text]CXCR5[Formula: see text]Blimp-1[Formula: see text], Tfh1, Tfh10, Tfh21, Tfr, Tcm-Tfh and Tem-GC Tfh were upregulated. In addition, curcumin inhibited the expression of Tfh-related transcription factors BCL-6, p-STAT3, Foxp1, Roquin-1, Roquin-2 and SAP, and significantly upregulated the protein levels of Blimp-1 and STAT3 in colon tissue. In conclusion, curcumin may be effective in alleviating dextran sulfate sodium-induced colitis by regulating Tfh differentiation.


2021 ◽  
Vol 11 ◽  
Author(s):  
Weijun Wang ◽  
Shuxin Tian ◽  
Xin Jiang ◽  
Suya Pang ◽  
Huiying Shi ◽  
...  

Background and Study AimsPrevious studies have identified that colorectal cancer has different fucosylation levels compared to the normal colon. Ulex europaeus agglutinin-I (UEA-I), which specifically combines with α1-2 fucose glycan, is usually used to detect fucosylation levels. Therefore, we used confocal laser endomicroscopy (CLE) to investigate fluorescently labeled UEA-Fluorescein isothiocyanate (FITC) for detecting colonic cancer.Patients and MethodsWe stained frozen mouse colon tissue sections of normal, adenoma, and adenocarcinoma species with UEA-FITC to detect fucosylation levels in different groups. White light endoscopy and endocytoscopy were first used to detect the lesions. The UEA-FITC was then stained in the mice and human colon tissues in vitro. The CLE was used to detect the UEA-FITC levels of the corresponding lesions, and videos were recorded for quantitation analysis. The diagnostic accuracy of UEA-FITC using CLE was evaluated in terms of sensitivity and specificity.ResultsThe UEA expression level in colorectal cancer was lower than that in normal intestinal epithelium. The fluorescence intensity ratio of UEA-FITC in colorectal cancer was significantly lower than that in normal tissue detected by CLE in both mice and humans. The combination of UEA-FITC and CLE presented a good diagnostic accuracy with a sensitivity of 95.6% and a specificity of 97.7% for detecting colorectal cancer. The positive and negative predictive values were 91.6% and 95.6%, respectively. Overall, 95.6% of the sites were correctly classified by CLE.ConclusionsWe developed a new imaging strategy to improve the diagnostic efficacy of CLE by using UEA-FITC.


2021 ◽  
Author(s):  
Lívia Mendonça Pascoal ◽  
Sarah Rodrigues Chagas ◽  
Francisco J. Pallarés ◽  
Juan J. Quereda ◽  
Juan Manuel Herrero Medrano ◽  
...  

Abstract Background: The present study aims to evaluate the efficacy of an intramuscular multivalent Escherichia coli vaccine for suckling piglets against infection not only by pathogenic E. coli but also by pathogens involved in Porcine Enteric Disease Complex (PEDC). Vaccinated Group had piglets vaccinated at days 10 and 20 of life with Colidex-C® (Vetia Animal Health, Spain), and Control Group had piglets that received sterile saline solution injection at the same days of life. We collected fecal samples in the farm from animals presenting diarrhea and intestinal mucosa swabs and ileum and colon tissue at slaughter and then performed PCR to identify E. coli virulence factors genes. Furthermore, we performed PCR to identify Lawsonia intracellularis, Brachyspira hyodisenteriae, and Salmonella spp.Results: Regarding fecal samples, 0% from Vaccinated Group was positive for E. coli, while Control Group had 94.1% of positive samples (p<0.0001). With respect to intestinal mucosa swab, 0% of the samples from Vaccinated Group were positive for E. coli, while 100% from Control Group were positive (p=0.001). Regarding ileum and colon tissue samples, 35% were positive for E. coli in Vaccinated Group and 85% in Control Group (p=0.001); Gcnt had a higher frequency of F41 (p=0.018), LT (p=0.018) and Sta (p=0.028) virulence factors genes. No sample was positive for Salmonella spp. nor for B. hyodisenteriae, but there were positive samples L. intracellularis; real-time PCR was performed and the frequencies found were 40% and 20% of ileum and colon positive samples in Vaccinated Group and 100% for ileum and 70% for colon in Control Group (p<0.001 for ileum and p=0.001 for colon).Conclusion: The results indicate that the E. coli vaccine for piglets may be a strategy to control E. coli infection. E. coli vaccines emerge as a probable strategy to help control L. intracellularis and, maybe, other enteric pathogens of pigs not evaluated in this study.


Author(s):  
Zi-Yi Wu ◽  
Yong-Qiao He ◽  
Tong-Min Wang ◽  
Da-Wei Yang ◽  
Dan-Hua Li ◽  
...  

Oncofetal chondroitin sulfate expression plays an important role in the development of tumors and the pathogenesis of malaria in pregnancy. However, the biosynthesis and functions of these chondroitin sulfates, particularly the tissue-specific regulation either in tumors or placenta, have not been fully elucidated. Here, by examining the glycogenes availability in chondroitin sulfate biosynthesis such as xylosytransferase, chondroitin synthase, sulfotransferase, and epimerase, the conserved or differential CS glycosylation in normal, colorectal cancer (CRC), and placenta tissue were predicted. We found that the expression of seven chondroitin sulfate biosynthetic enzymes, namely B4GALT7, B3GALT6, B3GAT3, CHSY3, CHSY1, CHPF, and CHPF2, were significantly increased, while four other enzymes (XYLT1, CHST7, CHST15, and UST) were decreased in the colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) patients. In the human placenta, where the distinct chondroitin sulfate is specifically bound with VAR2CSA on Plasmodium parasite-infected RBC, eight chondroitin sulfate biosynthesis enzymes (CSGALNACT1, CSGALNACT2, CHSY3, CHSY1, CHPF, DSE, CHST11, and CHST3) were significantly higher than the normal colon tissue. The similarly up-regulated chondroitin synthases (CHSY1, CHSY3, and CHPF) in both cancer tissue and human placenta indicate an important role of the proteoglycan CS chains length for Plasmodium falciparum VAR2CSA protein binding. Interestingly, twelve highly expressed chondroitin sulfate enzymes were significantly correlated to worse outcomes (prognosis) in both COAD and READ. Furthermore, we showed that the levels of chondroitin sulfate enzymes are significantly correlated with the expression of immuno-regulators and immune infiltration levels in CRCs and placenta, and involved in multiple essential pathways, such as extracellular matrix organization, epithelial-mesenchymal transition, and cell adhesion. Our study provides novel insights into the oncofetal chondroitin sulfate biosynthesis regulation and identifies promising targets and biomarkers of immunotherapy for CRC and malaria in pregnancy.


2021 ◽  
Author(s):  
Cameron B. Haas ◽  
Yu-Ru Su ◽  
Paneen Petersen ◽  
Xiaoliang Wang ◽  
Stephanie A Bien ◽  
...  

Abstract Background Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene-environment (GxE) interactions and may provide information on the underlying biological pathway. Objective We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. Methods We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based GxE approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case-control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4,839 genes with available genetically predicted expression. We meta-analyzed results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. Results We found suggestive evidence of interaction with folate intake for genes including glutathione S-Transferase Alpha 1 (GSTA1; p=4.3E-4), Tonsuko Like, DNA Repair Protein (TONSL; p=4.3E-4), and Aspartylglucosaminidase (AGA: p=4.5E-4). Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein. Conclusion We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk.


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