Increased Colon Length Research Articles

Protective effect of Pai-Nong-San against AOM/DSS-induced CAC in mice through inhibiting the Wnt signaling pathway.

Pai-Nong-San (PNS), a prescription of traditional Chinese medicine, has been used for years to treat abscessation-induced diseases including colitis and colorectal cancer. This study was aimed to investigate the preventive effects and possible protective mechanism of PNS on a colitis-associated colorectal cancer (CAC) mouse model induced by azoxymethane (AOM)/dextran sodium sulfate (DSS). The macroscopic and histopathologic examinations of colon injury and DAI score were observed. The inflammatory indicators of intestinal immunity were determined by immunohistochemistry and immunofluorescence. The high throughput 16S rRNA sequence of gut microbiota in the feces of mice was performed. Western blot was used to investigate the protein expression of the Wnt signaling pathway in colon tissues. PNS improved colon injury, as manifested by the alleviation of hematochezia, decreased DAI score, increased colon length, and reversal of pathological changes. PNS treatment protected against AOM/DSS-induced colon inflammation by regulating the expression of CD4+ and CD8+ T cells, inhibiting the production of HIF-α, IL-6, and TNF-α, and promoting the expression of IL-4 and IFN-γ in colon tissues. Meanwhile, PNS improved the components of gut microbiota, as measured by the adjusted levels of Firmicutes, Bacteroidetes, Proteobacteria, and Lactobacillus. PNS down-regulated the protein expression of p-GSK-3β, β-catenin, and c-Myc, while up-regulating the GSK-3β and p-β-catenin in colon tissues of CAC mice. In conclusion, our results suggested that PNS exhibits protective effect on AOM/DSS-induced colon injury and alleviates the development of CAC through suppressing inflammation, improving gut microbiota, and inhibiting the Wnt signaling pathway.

Isosteviol Sodium Exerts Anti-Colitic Effects on BALB/c Mice with Dextran Sodium Sulfate-Induced Colitis Through Metabolic Reprogramming and Immune Response Modulation.

PurposeInflammatory bowel diseases (IBDs) are global health problems that are associated with immune regulation, but clinical IBDs treatment is currently inadequate. Effective preventive or therapeutic methods for immune disorders rely on controlling the function of immune cells. Isosteviol sodium (STV-Na) has antioxidant activity, but the therapeutic effect of STV-Na against IBD remain undocumented. Herein, we investigated the therapeutic effect of STV-Na in mice models with IBDs.MethodsMice received 3.5% DSS for 7 days to establish IBD models. Intraperitoneal STV-Na was given 2 days before DSS and lasted for 9 days. Commercially available drugs used in treating IBDs (5-aminosalicylic acid, dexamethasone, and infliximab) were used as positive controls. Samples were collected 7 days after colitis induction. Histopathological score, biochemical parameters, molecular biology methods, and metabolomics were used for evaluating the therapeutic effect of STV-Na.ResultsOur data revealed that STV-Na could significantly alleviate colon inflammation in mice with colitis. Specifically, STV-Na treatment improved body weight loss, increased colon length, decreased histology scores, and restored the hematological parameters of mice with colitis. The untargeted metabolomics analysis revealed that metabolic profiles were restored by STV-Na treatment. Furthermore, STV-Na therapy suppressed the number of CD68 macrophages and F4/80 cell infiltration. And STV-Na suppressed M1 and M2 macrophage numbers along with the mRNA expressions of proinflammatory cytokines. Moreover, STV-Na administration increased the number of regulatory T (Treg) cells while decreasing Th1/Th2/Th17 cell counts in the spleen. Additionally, STV-Na treatment restored intestinal barrier disruption in DSS-triggered colitis tissues by ameliorating the TJ proteins, increasing goblet cell proportions, and mucin protein production, and decreasing the permeability to FITC-dextran, which was accompanied by decreased plasma LPS and DAO contents.ConclusionThese results indicate that STV-Na can ameliorate colitis by modulating immune responses along with metabolic reprogramming, and could therefore be a promising therapeutic strategy for IBDs.

Probiotic potential of Lactobacillus isolated from horses and its therapeutic effect on DSS-induced colitis in mice

Inflammatory bowel disease (IBD) is a refractory disease that endangers both humans and animals. In recent times, Lactobacillus have been used to treat animal diseases. It may be a good choice to try to isolate Lactobacillus with probiotic potential to treat IBD. Equine, as a kind of hindgut fermentation animal has rich intestinal microflora, but data regarding this is scarce. The isolation of Lactobacillus with probiotic potential from equine may become a new method for the treatment of IBD.Four isolates of Lactobacillus were isolated from fresh feces of healthy male adult horses and analyzed their biological characteristics. According to the phylogenetic analysis, A2.5 and A7.1 were identified as Pediococcus pentosaceus, A3 as Lactobacillus plantarum, and B8.2 as Weissella cibaria. All four isolates showed tolerance to the environment of acid, bile salt concentration and simulated artificial gastrointestinal fluid. The hydrophobic rate and self-aggregation rate of A3 were close to 100%, and the adhesion rate was 28.85 ± 0.74%. Four isolates were negative in hemolysis test and sensitive to common antibiotics and different isolates had different sensitivity to antibiotics. The four isolates had antibacterial and antioxidant activities which can reflect their probiotic potential. Furthermore, they could regulate the LPS (Lipopolysaccharides) stimulated Caco-2 cells. We chose A3 as the treatment strain to intervene Dextran sulfate sodium salt (DSS)-induced mice. The results showed that compared with DSS group, DSS + A3 group exhibited reduced Disease activity index (DAI), increased colon length, reduced pathological score and regulated cytokine secretion at the level of gene expression. In this study, four isolates of Lactobacillus with probiotic potential were isolated, and Lactobacillus plantarum A3 with reduced ulcerative colitis in mice was screened. It might provide a potential treatment for IBD.

Leonurine protects against ulcerative colitis by alleviating inflammation and modulating intestinal microflora in mouse models.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the colon. The aim of the present study was to explore the effects of leonurine (YMJ) on inflammation and intestinal microflora in colonic tissues of a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model. Mice were randomly divided into control (n=5), DSS (n=5, treated with DSS) and DSS+YMJ (n=5, treated with DSS and YMJ) groups. Body weight was recorded, disease activity index (DAI) was calculated, and colon histopathology was evaluated using hematoxylin and eosin staining. Serum interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-1β levels were examined using ELISA. Expression levels of nuclear factor-κB (p65) and phosphorylated (p)-p65 were evaluated via western blotting. 16S ribosomal RNA was extracted from mouse feces. Composition or abundance changes of intestinal microflora were analyzed. The results indicated that YMJ treatment (DSS+YMJ group) significantly increased body weight, reduced DAI scores and increased colon length in UC mouse models compared with those in the DSS group (P<0.05). YMJ significantly reduced inflammatory infiltration, significantly decreased serum TNF-α, IL-6 and IL-1β levels (P<0.05) and significantly downregulated the p-p65/p65 ratio compared with the DSS group (P<0.05). YMJ increased the quantity of the intestinal flora and improved intestinal microflora diversity in the mice of the DSS group. Specifically, YMJ partly regulated intestinal microflora in feces, including a reduction of Bifidobacterium, and an increase in Parasutterella and Ackermania. In conclusion, YMJ improved disease outcomes of the UC mice, reduced the levels of serum inflammatory factors and increased the ratio of beneficial bacteria in the intestinal tract.

Dietary Tangeretin Alleviated Dextran Sulfate Sodium-Induced Colitis in Mice via Inhibiting Inflammatory Response, Restoring Intestinal Barrier Function, and Modulating Gut Microbiota.

In this study, the preventive effect of tangeretin (TAN), a natural flavonoid derivative from citrus fruits, on the dextran sulfate sodium (DSS)-induced colitis in mice was evaluated. Our results showed that dietary TAN (0.04% and 0.08% w/w in the diet) significantly reduced the severity of colitis caused by DSS treatment in mice, evidenced by the increased colon length, the reduced disease activity index, and the attenuated colonic tissue damages. Moreover, dietary TAN inhibited the inflammatory response via down-regulating the overexpression of colonic inflammatory cytokines. Immunohistochemical analysis revealed that the intestinal barrier function was restored by TAN through enhancing claudin-1 and ZO-1 expressions. Additionally, dietary TAN modulated gut microbiota in colitic mice via enhancing gut microbiota diversity, ascending the level of beneficial bacteria, e.g., Lachnospiraceae and Lactobacillaceae, and descending the level of harmful bacteria, e.g., Enterobacteriaceae and Alistipes. Besides, dietary TAN promoted short-chain fatty acids production in DSS-treated mice. Altogether, these findings provided scientific evidence for the rational utilization of TAN as a preventive agent against colonic inflammation and related diseases.

Shinan Sea Salt Intake Ameliorates Colorectal Cancer in AOM/DSS with High Fat Diet-Induced C57BL/6N Mice

The anticancer effects of Shinan (Shinan-South Korea) sea salts on azoxymethane (AOM)/dextran sodium sulfate (DSS) with high fat diet (HFD)-induced colon cancer and obesity in C57BL/6N mice were studied. We prepared three types of sea salt: generally manufactured sea salt (GS), generally manufactured after filtering seawater (FS), and manufactured with only new seawater (NS). Sea salt intake increased colon length and reduced colon length/weight ratio, tumor number, and progression of colon cancer in colon tissue. The differently prepared sea salts also ameliorated liver injury. In addition, the mineral composition of each salt was different. Moreover, the sea salts enhanced activation of natural killer cell (CD56) expression in colon and spleen tissues. However, the mineral compositions of sea salts were not simply associated with anticancer effects in AOM/DSS+HFD induced mice. Thus, the anticolorectal cancer effects of sea salts may be mediated by different factors, which remain to be identified.

Metformin alleviates inflammation in oxazolone induced ulcerative colitis in rats: plausible role of sphingosine kinase 1/sphingosine 1 phosphate signaling pathway

Objectives Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is associated with high sphingosine kinase 1(SPHK1) expression in the colon, however its role in pathogenesis of UC is not clearly understood so, the aim of the present study was to clarify the role of SPHK1 and investigate whether the anti-inflammatory effects of metformin in UC is mediated by Sphingosine kinase 1/sphingosine 1 phosphate (S1P) signaling pathway. Material and methods Colitis was induced in adult male wistar rats by intra rectal administration of oxazolone in the fifth and seventh days from initial presensitization. Oxazolone treated rats were divided into untreated oxazolone group, metformin and mesalazine treated groups both in a dose of 100 mg/kg/day orally for 21 days. Along with these groups normal control and saline groups were used .Colitis was assessed by colon length, disease activity index (DAI) and histological examination of colontissue. Plasma samples were used to measure S1P.SPHK1 activity, signal transducer and activator of transcription −3(STAT-3), interleukin-6 (IL-6), nitric oxide (NO), myeloperoxidase activity (MPO), reduced glutathione (GSH) and tissue expression of intracellular cell adhesion molecule −1(ICAM-1) and caspase-3 genes were measured in tissue. Results Metformin successfully attenuated oxazolone colitis by increasing colon length, decreasing DAI and improved colon histologic picture. Metformin also induced a significant decrease in Plasma SIP, SPHK1 activity, inflammatory, oxidative stress markers, ICAM-1 and Caspase-3 genes expression compared to oxazolone group. Conclusion It is revealed that metformin alleviated inflammation and underlying mechanism may result from inhibition of SPHK1/S1P signaling pathway.

B. adolescentis ameliorates chronic colitis by regulating Treg/Th2 response and gut microbiota remodeling

ABSTRACT Inflammatory bowel disease (IBD) is defined as an immune dysregulation disease with poor prognosis. Various therapies based on gut microbe modulation have been proposed. In this study, we aim to explore the therapeutic effect of B. adolescentis on IBD, as well as the immune and microecology mechanism of B. adolescentis in IBD. The fecal level of B. adolescentis was decreased in the IBD patients compared with the normal people in our cohort and the GMrepo database. To further clarify the role of B. adolescentis in IBD, we induced chronic colitis with three cycles of dextran sulfate sodium (DSS). We found B. adolescentis gavage exhibited protective effects as evidenced by the significantly decreased diarrhea score, spleen weight, and increased colon length. Accordingly, the cumulative histological grading was decreased in the B. adolescentis administration group. In addition, tight junction protein and mucin family were enhanced after B. adolescentis treatment. Furthermore, distinct effects were found with decreased pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β, IL-18, IL-22, IL-9 and increased anti-inflammatory cytokines IL-10, IL-4, IL-5. Importantly, the colon lamina propria in the B. adolescentis group consisted of more Treg and Th2 cells, which inhibited extreme gut inflammation. Additionally, 16srRNA sequencing showed an evident increase in the B:F ratio in the B. adolescentis group. In particular, B. adolescentis application inhibited the excessive growth of Akkermansia and Escherichia-Shigella in genus level. In conclusion, B. adolescentis refined the DSS-induced chronic colitis by stimulating protective Treg/Th2 response and gut microbiota remodeling. B. adolescentis regularly treatment might improve the therapeutic effects for inflammatory bowel disease.

Cohousing-mediated microbiota transfer from milk bioactive components-dosed mice ameliorate colitis by remodeling colonic mucus barrier and lamina propria macrophages

ABSTRACT Human milk oligosaccharides (HMOs) and milk fat globule membrane (MFGM) are highly abundant in breast milk, and have been shown to exhibit potent immunomodulatory effects. Yet, their role in the gut microbiota modulation in relation to colitis remains understudied. Since the mixtures of fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) perfectly mimic the properties and functions of HMOs, the combination of MFGM, FOS, and GOS (CMFG) has therefore been developed and used in this study. Here, CMFG were pre-fed to mice for three weeks to investigate its preventive effect on dextran sodium sulfate (DSS) induced colitis. Moreover, CMFG-treated and vehicle-treated mice were cohoused to further elucidate the preventive role of the gut microbiota transfer in colitis. At the end of the study, 16S rDNA gene amplicon sequencing, short-chain fatty acids (SCFAs) profiling, transcriptome sequencing, histological analysis, immunofluorescence staining and flow cytometry analysis were conducted. Our results showed that CMFG pre-supplementation alleviated DSS-induced colitis as evidenced by decreased disease activity index (DAI) score, reduced body weight loss, increased colon length and mucin secretion, and ameliorated intestinal damage. Moreover, CMFG reduced macrophages in the colon, resulting in decreased levels of IL-1β, IL-6, IL-8, TNF-α, and MPO in the colon and circulation. Furthermore, CMFG altered the gut microbiota composition and promoted SCFAs production in DSS-induced colitis. Markedly, the cohousing study revealed that transfer of gut microbiota from CMFG-treated mice largely improved the DSS-induced colitis as evidenced by reduced intestinal damage and decreased macrophages infiltration in the colon. Moreover, transfer of the gut microbiota from CMFG-treated mice protected against DSS-induced gut microbiota dysbiosis and promotes SCFAs production, which showed to be associated with colitis amelioration. Collectively, these findings demonstrate the beneficial role of CMFG in the gastrointestinal diseases, and further provide evidence for the rational design of effective prophylactic functional diets in both animals and humans.

Jellyfish skin polysaccharides enhance intestinal barrier function and modulate the gut microbiota in mice with DSS-induced colitis.

Jellyfish skin polysaccharides (JSP) were isolated from Rhopilema esculentum Kishinouye and contained 55.11% polysaccharides and 2.26% uronic acid. To examine the anti-inflammatory, antioxidant and immunomodulatory activities of JSP in vivo, C57BL/6 mice were induced to develop ulcerative colitis by dextran sulfate sodium (DSS) and the roles of dietary JSP supplementation in modulating colitis were explored. JSP supplementation reduced the symptoms of colitis in mice, increased colon length, protected goblet cells, and improved intestinal epithelial integrity and permeability. JSP modulated oxidative stress and inflammatory responses, which was demonstrated by reduced MPO activity, NO level, and levels of pro-inflammatory cytokines including TNF-α, IL-1β and IL-6 in mice. JSP suppressed NF-κB signaling pathways as evidenced by lower levels of phosphorylated p65 and IKB. Moreover, JSP supplementation enhanced the expression of tight junction proteins and mucins, and modulated the composition of the gut microbiota and the production of short-chain fatty acids. Taken together, these results reveal the anti-inflammatory effect of dietary JSP in vivo, suggesting the potential of JSP as a nutritional supplement or adjunct strategy in preventing or ameliorating colitis.

Selenium-Containing Amino Acids Protect Dextran Sulfate Sodium-Induced Colitis via Ameliorating Oxidative Stress and Intestinal Inflammation

BackgroundInflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation of the gastrointestinal tract. Oxidative stress plays a pivotal role in the pathogenesis of IBD. Selenium-containing amino acids reportedly have anti-oxidative and anti-inflammatory properties, but it remains unknown if selenium-containing amino acids can be used to treat IBD. This study aimed to investigate the effects of two selenium-containing amino acids – selenocysteine and selenocystine – on oxidative stress and chronic inflammation in a mouse model of dextran sulfate sodium (DSS)-induced IBD.MethodologyC57BL/6 mice were randomly assigned to the following six groups: control, DSS, DSS+selenocysteine, DSS+selenocystine, DSS+sodium selenite, and DSS+N-acetylcysteine (NAC). IBD was induced by 3% DSS. Pro-inflammatory cytokines [interleukin-1β (IL-1β), monocyte chemotactic protein 1 (MCP-1), IL-6, and tumor necrosis factor-α (TNF-α)] and markers for oxidative and anti-oxidative stress [malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (GPx)] were measured using immunohistochemical analysis.ResultsSelenocysteine and selenocystine significantly attenuated IBD-related symptoms, including preventing weight loss, decreasing disease activity index (DAI) scores, and increasing colon length. Selenocysteine and selenocystine significantly ameliorated the DSS-induced oxidative stress, as demonstrated by a reduction in ROS and MDA activity and an increase in SOD and GPx activity. IL-1, MCP-1, IL-6, and TNF-α levels were significantly increased in the IBD mice, while treatment with the selenium-containing amino acids significantly reduced the levels of these pro-inflammatory cytokines. In vivo safety analysis showed minimal side effects of the selenium-containing amino acids.ConclusionWe found that selenocysteine and selenocystine ameliorated DSS-induced IBD via reducing oxidative stress and intestinal inflammation, indicating that selenium-containing amino acids could be a novel therapeutic option for patients with IBD.

The dietary supplement Rhodiola crenulata extract alleviates dextran sulfate sodium-induced colitis in mice through anti-inflammation, mediating gut barrier integrity and reshaping the gut microbiome.

Rhodiola species are edible medicinal plants, which have been traditionally used in both Asia and Europe as an adaptogen, a tonic, an anti-depressant and anti-inflammatory supplement. However, whether it presents a therapeutic effect on colitis or not remains unknown. The aim of this study is to investigate the protective effect of a Rhodiola crenulata extract (RCE) on mice with DSS-induced colitis. RCE significantly alleviated the pathological abnormalities in colitic mice, including the correspondingly increased colon length, ameliorated colonic injury and reduced pro-inflammatory factors. The protective effect was similar to that of the positive control, 5-aminosalicylic acid. The DSS-induced epithelial apoptosis and maintained intestinal barrier function were attenuated by RCE through the upregulation of the level of tight junction proteins such as ZO-1 and occludin. Notably, RCE prevented gut dysbiosis in colitic mice by restoring the microbial richness and diversity, and decreasing the abundance of Proteobacteria phylum and opportunistic pathogenic Parasutterella and Staphylococcus, as well as increasing the abundance of beneficial microbes in Lactobacillus and Bifidobacterium, which were closely correlated with its protective effect against colitis. Meanwhile, chemical characterization of RCE was performed by UPLC-HR-MS to explain its material basis. A total of 63 compounds were identified, while the content of two bioactive ingredients (salidroside, 1.81%; rosavin, 0.034%) was determined.

CT colonography evaluation of the relationship between colon anatomy and diverticula.

In this study, we aimed at investigating the relationship between diverticula and in vivo colonic features such as total colon length (TCL), using CTC. We also evaluated polyps, neoplastic lesions and the correlation among them. This retrospective study considered a series of patients who underwent CTC in our Hospital from 2010 to 2018. We evaluated TCL, the length of each colon segments and sigmoid colon diameter using dedicated software. We verified the presence of diverticula, polyps and neoplasm and measured the number of diverticula using a five-point class scale, evaluating the colonic segments involved by the disease and the number of diverticula for each segment. A logistic regression model was used to analyse the relationship between diverticula and the patients' age, sigmoid colonic diameter and the length of each colonic segments. The population finally included 467 patients, 177 males and 290 females (average age of 67 ± 12; range 45-96). The mean TCL was 169 ± 25 cm (range 115-241 cm). Out of the 467, 323 patients (69%) had at least one analyse. The patients with diverticula had a mean TCL significantly shorter than patients without diverticula (164 ± 22 vs 181 ± 27 cm; p = 0.001). Among the different variables, sigmoid colon length, sigmoid colon diameter and patient's age were correlated with diverticula (p < 0.01). Otherwise there is no association among diverticula, polyps and neoplasm. The presence of colonic diverticula was significantly inversely correlated with TCL.The TCL was not significantly correlated with polyps and cancers. The presence of colonic diverticula was significantly inversely correlated with total colon length, and in particular they significantly decreased with increasing colon length; our observation could contribute to the comprehension of diverticula pathogenesis.

Perilla Oil Alleviates High-Fat Diet-Induced Inflammation in the Colon of Mice by Suppressing Nuclear Factor-Kappa B Activation.

This study aimed to evaluate the effect of perilla oil (PO) on high-fat diet (HD)-induced colonic inflammation. Male C57BL/6J mice (5 weeks old) were divided into four groups: normal diet, HD, HD supplemented with fish oil (FO), and HD supplemented with PO, and were fed experimental diets for 16 weeks. PO significantly ameliorated (P < .05) the HD-induced colon inflammation as indicated by the increased colon length and low macroscopic score. PO increased the number of Bifidobacteria and reduced the number of Enterobacteriaceae, which in turn resulted in the lowering of endotoxin levels. Proinflammatory cytokines in serum and colon such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α were also decreased by PO treatment. In addition, PO suppressed the expression of cyclooxygenase 2 and inducible nitric oxide, and inhibited the activation of nuclear factor-κB in the colon while increasing the expression of the tight junction protein, Zonula occludens-1. The gene expression of GPR120, a membrane receptor activated by omega-3 fatty acids, was increased in the oil-treated groups. Altogether, PO improved HD-induced colon inflammatory conditions, and the effects were similar to those of FO, confirming that PO is a potential omega-3 fatty acid source for dietary supplements.

Upregulation of microRNA-219-5p relieves ulcerative colitis through balancing the differentiation of Treg/Th17 cells

Objective:This study aimed to investigate the specific regulatory roles of microRNA-219-5p (miR-219-5p) on ulcerative colitis (UC), and reveal the potential mechanisms relating with the differentiation of Treg/Th17 cells.Methods:The mouse model of chronic UC was established by oral administration of 3% dextran sodium sulfate for three cycles. After intravenous injected with lentivirus (LV)-miR-219-5p for 24 h, the disease activity index (DAI), colon length, as well as the serum levels of Interleukin (IL)-6, -17A, -21, and -23 were measured. In addition, the histopathological changes in colon tissues were observed by Hematoxylin-eosin staining. The differentiation of Treg/Th17 cells was detected by Flow cytometry, and the expression of retinoic acid-related orphan receptor (RORrt), signal transducer and activator of transcription 3 (STAT3), and forkhead box p3 (Foxp3) were detected by quantitative real-time PCR and Western blot.Results:MiR-219-5p was downregulated in colonic mucosal tissues of UC mice (P < 0.05). UC mice injected with LV-miR-219-5p exhibited significantly relieved histopathological changes of colon tissues, increased colon length, decreased DAI, as well as decreased serum levels of IL-6, -17A, -21, and -23 (P < 0.05). In addition, the injection of LV-miR-219-5p significantly increased the percentage of Treg cells via upregulating Foxp3, and decreased the percentage of Th17 cells via downregulating RORrt and STAT3 in UC mice (P < 0.05).Conclusion:The upregulation of miR-219-5p relieved the colonic damage and inflammation of UC through balancing the differentiation of Treg/Th17 cells.

Anti-inflammatory properties and gut microbiota modulation of an alkali-soluble polysaccharide from purple sweet potato in DSS-induced colitis mice

In this study, the potential effects of a novel alkali-soluble polysaccharide (ASPP) from purple sweet potato on colonic histopathology, inflammation and microbiota composition in dextran sulfate sodium (DSS)-induced colitis mice were evaluated. The results indicated that ASPP restored the immune organ indices, increased colon length, improved colonic histopathology in colitis mice as well as inhibited the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in colonic tissue and serum. Moreover, 16S rRNA phylogenetic sequencing revealed that ASPP ameliorated the compositions and functions of gut microbiota in DSS-induced colitis mice. It was found that Parasutterella, Desulfovibrio, Lachnospiraceae, Lactobacillus, Erysipelotrichaceae, Bacteroidetes were the key bacteria associated with ulcerative colitis (UC). Taken together, ASPP alleviated colonic inflammation via blocking pro-inflammatory cytokines; meanwhile ASPP could modulate the structure of gut microbiota in DSS-induced colitis mice.

Saikosaponin-d ameliorates dextran sulfate sodium-induced colitis by suppressing NF-κB activation and modulating the gut microbiota in mice

Saikosaponin-d (SSd), extracts from Bupleurum falcatum L, exhibits anti-inflammatory and anti-infectious activities. However, the effect of SSd on intestinal inflammation has not been investigated. The aim of this study was to evaluate the effect of SSd on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice, and to elucidate the underlying mechanisms. UC was induced in mice by administrating 3% DSS in drinking water for 7 days. SSd (4 mg/kg and 8 mg/kg) was administered by gavage every day during the experimental process. The results showed that SSd treatment (8 mg/kg) significantly ameliorated UC mice by decreasing disease activity index (DAI), increasing colon length and improving pathological characteristics. SSd treatment (8 mg/kg) significantly suppressed the mRNA levels of pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β, increased that of anti-inflammatory cytokine IL-10. Furthermore, SSd (8 mg/kg) suppressed the activation of NF-κB by decreasing the degradation and phosphorylation of IκB. SSd (8 mg/kg) also protected the intestinal barrier by increasing the mRNA levels of mucin (Muc1 and Muc2) and the protein levels of zonula occludens-1 (ZO-1) and Claudin-1. The 16S rDNA gene high-throughput sequencing revealed that SSd treatment (8 mg/kg) increased the alpha diversity and regulated the structure of gut microbiota in UC mice. Taken together, our findings demonstrated that SSd (8 mg/kg) improved DSS-induced intestinal inflammation by inhibiting NF-κB activation and regulated the gut microbiota.

Effect of vegetable oils with different fatty acid composition on high-fat diet-induced obesity and colon inflammation.

BACKGROUND/OBJECTIVESDifferent fatty acids exert different health benefits. This study investigated the potential protective effects of perilla, olive, and safflower oils on high-fat diet-induced obesity and colon inflammation.MATERIALS/METHODSFive-week old, C57BL/6J mice were assigned to 5 groups: low-fat diet (LFD), high-fat diet (HFD) and high-fat diet supplemented with-perilla oil (HPO), olive oil (HOO), and safflower oil (HSO). After 16 weeks of the experimental period, the mice were sacrificed, and blood and tissues were collected. The serum was analyzed for obesity- and inflammation-related biomarkers. Gene expression of the biomarkers in the liver, adipose tissue, and colon tissue was analyzed. Micro-computed tomography (CT) analysis was performed one week before sacrifice.RESULTSTreatment with all the three oils significantly improved obesity-induced increases in body weight, liver weight, and epididymal fat weight as well as serum triglyceride and leptin levels. Treatment with perilla oil (PO) and safflower oil (SO) increased adiponectin levels. The micro-CT analysis revealed that PO and SO reduced abdominal fat volume considerably. The mRNA expression of lipogenic genes was reduced in all the three oil-supplemented groups and PO upregulated lipid oxidation in the liver. Supplementation of oils improved macroscopic score, increased colon length, and decreased serum endotoxin and proinflammatory cytokine levels in the colon. The abundance of Bifidobacteria was increased and that of Enterobacteriaceae was reduced in the PO-supplemented group. All three oils reduced proinflammatory cytokine levels, as indicated by the mRNA expression. In addition, PO increased the expression of tight junction proteins.CONCLUSIONSTaken together, our data indicate that the three oils exert similar anti-obesity effects. Interestingly, compared with olive oil and SO, PO provides better protection against high-fat diet-induced colon inflammation, suggesting that PO consumption helps manage inflammation-related diseases and provides omega-3 fatty acids needed by the body.

2-O-β-d-Glucopyranosyl-l-ascorbic Acid, an Ascorbic Acid Derivative Isolated from the Fruits of Lycium Barbarum L., Modulates Gut Microbiota and Palliates Colitis in Dextran Sodium Sulfate-Induced Colitis in Mice.

In this study, the effects of 2-O-β-d-glucopyranosyl-l-ascorbic acid (AA-2βG), a natural ascorbic acid derivative from the fruits of Lycium barbarum, on treating the dextran sulfate sodium (DSS)-induced colitis in mice were investigated. The results revealed that AA-2βG had palliating effects on DSS-induced inflammatory bowel disease (IBD) in terms of slowing down the trends of body weight and solid fecal mass loss, reducing colitis disease activity index, improving serum physiological and biochemical indicators, increasing colon length, blocking proinflammatory cytokines, and increasing tight junction proteins. Additionally, AA-2βG treatment could promote the production of short-chain fatty acids and modulate the composition of the gut microbiota. The key bacteria related to IBD were found to be Porphyromonadaceae, Prevotellaceae, Rikenellaceae, Parasutterella, Parabacteroides, and Clostridium. The results indicated that AA-2βG might treat IBD through the regulation of gut microbiota, suggesting that AA-2βG has the potential to be used as a dietary supplement in the treatment of IBD.

Protective effect of Lactobacillus fermentum CQPC04 on dextran sulfate sodium–induced colitis in mice is associated with modulation of the nuclear factor-κB signaling pathway

Colitis severely affects the quality of life of patients, and lactic acid bacteria have been reported to be able to improve or treat colitis. In this study, we selected a strain of Lactobacillus fermentum (CQPC04) with good resistance in vitro to evaluate its effect on improvement in mice with dextran sulfate sodium (DSS)-induced colitis. We analyzed the effects of L. fermentum CQPC04 on mice with colitis macroscopically via colon length and histopathology. We also used conventional biochemical and ELISA kits, real-time quantitative PCR (RT-qPCR), and Western blotting to analyze microscopically the effects of L. fermentum CQPC04 on related oxidant indices and pro- and anti-inflammatory cytokines in serum and colon tissue of mice. The results indicated that L. fermentum CQPC04 notably increased colon length and ameliorated pathological damage of colon tissue in colitic mice. Serum indices showed that L. fermentum CQPC04 increased the enzyme activity of total superoxide dismutase (T-SOD) and catalase (CAT) and decreased the content of malondialdehyde (MDA) and the activity of myeloperoxidase (MPO). In addition, it inhibited the release of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), IFN-γ, IL-1β, IL-6, and IL-12, and increased the release of the anti-inflammatory cytokine IL-10 in serum. The RT-qPCR experiments confirmed that L. fermentum CQPC04 downregulated the expression of pro-inflammatory cytokine nuclear factor-κB-p65 (NF-κBp65), NF-κB inhibitor-α (IκB-α), TNF-α, IFN-γ, IL-1β, IL-6, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS), and upregulated the expression of IL-10 in colon tissue. Western blot analysis indicated that L. fermentum CQPC04 significantly reduced expression of NF-κBp65, TNF-α, IL-1β, COX-2, and iNOS in mouse colon tissues, and increased expression of IκB-α and superoxide dismutase 2 (SOD2). Thus, L. fermentum CQPC04 could effectively alleviate the symptoms of DSS-induced colitis mice and is a potential probiotic for human experiments.