Dextran Sulfate Sodium Group Research Articles

Protective effect and mechanism of Lactobacillus rhamnosus on immune checkpoint inhibitors related colitis in mice

Objective: Modeling the immune-related adverse events (irAE) colitis in mice, and explore the protective effect and related mechanism of Lactobacillus rhamnosus GG (LGG) on irAE colitis. Methods: C57BL/6 mice were divided into dextran sodium sulfate (DSS) group (n=3), DSS+anti-programmed death receptor 1 (PD-1) group (n=4), DSS+anti-PD-1+anti-cytotoxic T lymphocyte associated protein 4 (CTLA-4) Group (n=4), DSS+anti-PD-1+anti-CTLA-4+LGG group (n=4), all were given corresponding drugs and probiotics intervention. The severity of colitis were assessed by weight loss, disease activity index (DAI), colon length, colon histopathological score. The inflammatory cytokines and T cell immunity of CD4+, CD8+, FoxP3+regulatory T cells (Treg), were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical staining respectively. Results: Compared to DSS group, the Day 9 weight [(87.40±1.79)% vs (94.57±0.53)%, P<0.05], colon length [(5.33±0.27)cm vs (6.63±0.12)cm, P<0.05] were lower, and DAI score(2.66±0.24 vs 0.89±0.48), colon histopathological score (12.50±1.04 vs 5.67±0.33), tumor necrosis factor-α (TNF-α) (6.73±1.68 vs 0.91±0.40) (P<0.05), as well CD8+T cells (156.80±8.84 vs 89.00±6.66) and FoxP3+Treg cells (103.80±2.66 vs 48.33±3.18) (P<0.05) were higher in DSS+anti-PD-1+anti-CTLA-4 group. Compared to DSS+anti-PD-1+anti-CTLA-4 group, the DAI score(1.83±0.17 vs 2.66±0.24), colonic histopathology score (8.75±0.63 vs 12.50±1.04), TNF-α level (1.32±0.18 vs 6.73±1.68) (P<0.05) were lower; and CD8+T cells(97.75±3.75 vs 156.80±8.84, P<0.01) level was lower with higher FoxP3+Treg cells (126.00±8.33 vs 103.80±2.66, P=0.046) in DSS+anti-PD-1+anti-CTLA-4+LGG group. Conclusion: DSS combined with anti-PD-1 and anti-CTLA-4 can successfully modeling the irAE colitis in mice, LGG can reduce irAE colitis severity by regulating Treg cells.

Effects of Vitamin D3 on Intestinal Flora in a Mouse Model of Inflammatory Bowel Disease Treated with Rifaximin.

BackgroundRifaximin is an antimicrobial agent used to treat inflammatory bowel disease (IBD). Vitamin D3 can control IBD due to its effects on inflammatory cytokines. The purpose of this study was to assess the effect of vitamin D3 on the intestinal flora of a dextran sulfate sodium (DSS)-induced mouse model treated with rifaximin.Material/MethodsThe mouse model of IBD was developed using DSS (4%) administered via the drinking water. Twenty-four male C57BL6 mice were divided into the control group with a normal diet (N=6), the DSS group with a normal diet (N=6), the DSS group with a normal diet treated with rifaximin (N=6), and the DSS group with a normal diet treated with rifaximin and vitamin D3 (N=6). After 14 days, the colonic tissue was studied histologically. Serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and enzyme-linked immunosorbent assay (ELISA) were used to measure the level of IL-6 and P65, and phospho-p65 was measured by western blot. 16S rRNA gene sequencing was used to analyze fecal samples.ResultsIn the DSS mouse model of IBD, rifaximin reduced the inflammation severity of the colon and reduced the expression of phospho-p65, p65, TNF-α, and IL-6. In the DSS+rifaximin+vitamin D3 group, the therapeutic influences of rifaximin, in terms of weight loss and colonic disease activity, were significantly reduced, and the gut microbiota of the mice were completely changed in composition and diversity.ConclusionsIn a mouse model of IBD, treatment with vitamin D3 significantly increased the metabolism of rifaximin and reduced its therapeutic effects.

Lactobacillus pentosus Increases the Abundance of Akkermansia and Affects the Serum Metabolome to Alleviate DSS-Induced Colitis in a Murine Model.

Lactobacillus pentosus has the beneficial function of regulating the host’s immune system and plays an indispensable role in intestinal health. The purpose of this study was to investigate the specific mechanism by which L. pentosus relieves dextran sulfate sodium (DSS) induced ulcerative colon inflammation. We randomly divided 24 mice into three groups, which were administered either a basic diet, drinking water with 2.5% DSS (DSS), or drinking water with 2.5% DSS and intragastric administration of L. pentosus (DSS + L. pentosus). DSS was added to the drinking water on days 8 to 12, and L. pentosus was administered on days 12 to 19. Serum was collected for metabolomic analysis, colon length and weight were measured, and colon contents were collected to detect microbial structural composition. Compared with the DSS group, the DSS + L. pentosus group had significantly higher levels of indolepyruvate and pantothenic acid in the serum and significantly lower levels of 3,4-dimethyl-5-pentyl-2-furannonanoic acid and 5-oxo-6-trans-leukotriene B4. Moreover, compared with the other two groups, the DSS + L. pentosus group had a significantly greater abundance of Akkermansia. The abundance of Akkermansia was positively correlated with indolepyruvate and pantothenic acid levels. Therefore, L. pentosus can interact with Akkermansia to increase its abundance in the intestinal tract. This results in the production of metabolites that are beneficial for the regulation of intestinal immunity, thereby alleviating DSS-induced ulcerative colon inflammation.

Anti-inflammatory Activity of Mollugin on DSS-induced Colitis in Mice.

We aimed to explore the anti-inflammatory activity of mollugin extracted from Rubia cordifolia L, a traditional Chinese medicine, on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. Thirty C57BL/6 mice were divided into a control group (n=6), a model group (n=6), and three experimental groups (40, 20, 10 mg/kg of mollugin, n=6 each). DSS solution (3%) was given to mice in the model group and experimental groups from day 4 to day 10 to induce the mouse UC model. Mice in the experimental groups were intragastrically administrated mollugin from day 1 to day 10. Animals were orally given distilled water in the control group for the whole experiment time and in the model group from day 1 to day 3. The changes in colon pathology were detected by hematoxylin and eosin (HE) staining. Interleukin-1β (IL-1β) in the serum, and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN) in the tissues were measured by enzyme linked immunosorbent assay. Expression levels of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 in the colon tissues were detected by immunohistochemistry. Results showed that mollugin could significantly reduce weight loss and the disease activity index in the DSS-induced UC mouse model. HE examinations demonstrated that mollugin treatment effectively improved the histological damage (P<0.05). The overproduction of IL-1β and TNF-α was remarkably inhibited by mollugin treatment at doses of 20 and 40 mg/kg (P<0.05). Additionally, the levels of TLR4 in colon tissues were significantly reduced in mollugin-treated groups compared with the DSS group. Our findings demonstrated that mollugin ameliorates DSS-induced UC by inhibiting the production of pro-inflammatory chemocytokines.

Overexpression of miR-31 regulates TLR4/NF-κB signaling pathway and apoptotic protein in colitis model mice

Objective: To investigate the effects of miR-31 on TLR4/NF-κB signaling pathway and apoptosis-related proteins in dextran sulfate sodium (DSS) induced mouse colon colitis. Methods: ① Mouse model of colon colitis: 1% DSS was used to induce mouse ulcerative colitis (UC). Fourteen FVB non-transgenic mice were randomly divided into control group (n= 6), DSS group (n= 8), and 16 FVB miR-31 transgenic mice were randomly divided into miR-31 overexpression group (n= 8), miR-31 overexpression +DSS group (n= 8). DSS was dissolved in water and administered to mice by drinking water. The DSS group and miR-31+DSS group drank 1% DSS water in the first week, normal sterilized water in the second week, and 1% DSS water in the third week, after 5 weeks, the modeling was completed, then the colon tissues of the mice were collected. Western blot and IHC were used to detect the expressions of NF-κB p65, TLR4, Bax and Bcl-2 proteins in mouse colon tissue, TUNEL was used to detect apoptosis of mouse colon tissues. ② Cell culture experiments: Transfection of miR-31mimic and inhibitor by lipofectamine resulted in overexpression or knockdown of miR-31 in human colon epithelial cell line HCT 116 cells, each group was repeated three times and cells were collected 48 h later, Western blot was used to detect the expressions of NF-κB p65 and TLR4 protein. Results: ① In animal experiments, compared with the control group, the expression levels of NF-κB p65, TLR4 protein and apoptotic cell index in the DSS group and miR-31 overexpression group in mouse colon tissue were significantly increased (P＜0.05 or P＜0.01), and the Bcl-2 / Bax ratio was significantly reduced (P＜0.05 or P＜0.01); and compared with the DSS group, the expression levels of NF-κB p65, TLR4 protein and apoptotic cell index in the miR-31+DSS group were significantly increased (P＜0.01), while the Bcl-2/Bax ratio was significantly decreased (P＜0.01). ② In cell experiments, compared with the control group, the expression levels of NF-κB p65 and TLR4 protein in the over-expressed miR-31 group of HCT 116 cells were significantly increased (P＜0.05 or P＜0.01), the expressions of NF-κB p65 and TLR4 protein in miR-31 knockdown group were decreased (P＜0.05). Conclusion: miR-31 promotes the development of colitis by promoting TLR4/NF-κB signaling pathway and mediating apoptosis of intestinal epithelial cells.

Exercise Preconditioning Attenuates the Response to Experimental Colitis and Modifies Composition of Gut Microbiota in Wild-Type Mice.

This study investigated the suppressive effect of exercise preconditioning against colitis induced by high-fat diet (HF) plus dextran sulfate sodium (DSS) in wild-type mice. Male mice (C57BL/6) aged 6 weeks were assigned to standard chow (SC, n = 10) or HF (n = 10) or HF followed by DSS (HF+DSS, n = 10) or exercise preconditioning (EX) followed by HF+DSS (EX+HF+DSS, n = 10) for a total of 15 weeks. After 12 weeks of dietary treatments and/or exercise preconditioning, mice in the DSS groups were subjected to administration of 2 cycles of 5-day DSS (2% w/v) with a 7-day interval between cycles. HF resulted in colitis symptoms and histological changes, infiltration of immunity cells, decreased gut barrier proteins, increased pro-inflammatory and chemotactic cytokines and decreased anti-inflammatory cytokine such as adiponectin, which deteriorated after administration of DSS. Exercise preconditioning alleviated HF+DSS-induced colitis and caused significant modifications in gut microbiota: decreased Bacteroides vulgatus (p = 0.050) and increased Akkermansia muciniphila (p = 0.050). The current findings suggest that exercise preconditioning attenuates the severity of HF+DSS-induced colitis in C57BL/6 mice.

Baitouweng decoction alleviates dextran sulfate sodium-induced ulcerative colitis by regulating intestinal microbiota and the IL-6/STAT3 signaling pathway

Baitouweng (BTW) decoction, a Chinese traditional medicine prescription, has been used to treat ulcerative colitis (UC) over hundreds of years. In this study, we investigated the anti-inflammatory effects of BTW and intestinal flora of dextran sulfate sodium (DSS)-induced UC mice, and we investigated the mechanism of BTW in the preliminary treatment of UC. The aim of this study was to elucidate the mechanism of BTW in treating UC through molecular biology and high-throughput sequencing. DSS-induced UC mice were established and randomly divided into the following four groups: control group, DSS group, BTW group and sulfasalazine (SASP) group. Except for the control group, 3% DSS drinking water was given to each group for 7 days, and the other two groups were intragastrically administered with BTW and SASP. Mice were sacrificed after gavage for 10 days. Body weight loss, disease activity index (DAI), colon length, colon histopathology and the expression of inflammatory cytokines were measured. Intestinal content samples were collected, and intestinal flora differences were analyzed by 16S rDNA sequencing. BTW effectively reduced the symptoms and histopathological score of UC mice, and it reduced the production of IL-6, IL-1β and TNF-α. Activation of the IL-6/STAT3 pathway was also suppressed by BTW treatment. Moreover, 16S rDNA sequencing showed that the intestinal flora of mice in the DSS group was disordered compared to the control group. After treatment with BTW, the diversity of intestinal flora was significantly improved. At the phylum level, the proportion of Firmicutes to Bacteroidetes was decreased, and the ratio of Proteobacteria was decreased. At the genus level, the relative abundance of Escherichia-Shigella was decreased, but that of Lactobacillus and Akkermansia were increased. BTW significantly improved the inflammatory symptoms of mice with acute colitis, and the latent mechanism of BTW may be related to various signaling pathways, including the modulation of intestinal microflora and inflammatory signaling pathways, such as IL-6/STAT3.

Dihydroartemisinin prevents dextran sodium sulphate-induced colitis through inhibition of the activation of NLRP3 inflammasome and p38 MAPK signaling

Dihydroartemisinin (DHA), a sesquiterpene lactone derived from artemisinin, has been reported to possess anti-inflammation and anti-cancer activities. But its underlying protective mechanisms on dextran sodium sulphate (DSS)-induced colitis remain rarely reported. We applied a network pharmacology approach to predict the collective targets of DHA and acute colitis. GO and KEGG analyses were performed to investigate the enriched biological functions and signaling pathways of the collective targets. Furthermore, a DSS-induced colitis model was established to observe the protective effects of DHA. 83 common targets of DHA and acute colitis were identified and predominantly involved in several inflammation-related signaling pathways in colitis such as NOD-like receptor and MAPK signaling pathways. Additionally, DHA in vivo improved the clinical symptoms, reduced the production of pro-inflammatory factors IL-1β, IL-6 and TNF-α, and suppressed the formation of NLRP3 inflammasome. Moreover, DHA inhibited the phosphorylation of NF-κB p65 and p38 MAPK, but upregulated PPARγ and Ki-67 levels compared to the DSS group. Additionally, we found that DHA suppressed p38 activator-induced pro-inflammatory response, and p38 inhibitor attenuated the clinical symptoms and reduced the expression levels of pro-inflammatory mediators and NLRP3 while up-regulated the expression levels of PPARγ and Ki-67. Molecular docking analysis further verified the binding mode towards the DHA and p38 MAPK. In conclusion, DHA could protect DSS-induced colitis via suppressing the activation of NLRP3 inflammasome and p38 MAPK signaling.

Protective effects of L-theanine on rats with dextran sulfate sodium-induced inflammatory bowel disease.

The aim of this study is to evaluate the anti-inflammatory and protective effects of L-theanine in inflammatory bowel disease (IBD) and to identify the underlying molecular mechanisms. Rats were pre-treated with L-theanine at 0, 50, 200, or 800mg/kg/day. IBD was induced in rats using dextran sulfate sodium (DSS). Histopathological analysis suggests that L-theanine can suppress DSS-induced IBD with significant inhibition of inflammation in large and small intestinal tissues. Moreover, the 200mg/kg/day L-theanine-treated DSS group had higher body and small intestine weights, a lower disease activity index and expression of inflammatory factors than the DSS group without pre-treatment. In RNA sequencing and tandem mass tag labeling analyses, large number of mRNAs and proteins expression level differed when compared with the DSS-induced rats with and without 200mg/kg/day L-theanine pre-treatment. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway analysis indicates the anti-inflammatory activities of L-theanine in DSS-induced IBD, with a high representation of genes in "Cholesterol metabolism" and "Retinol metabolism" pathways. Analysis of protein-protein interaction networks further indicates the involvement of these two pathways. These studies suggest that medium-dose L-theanine pre-treatment could ameliorate DSS-induced IBD through molecular mechanisms involving cholesterol and retinol metabolism.

Antiplatelet agents'-ticagrelol and eptifibatide-safety in experimental colitis in mice.

To evaluate the side effects of two antiplatelet agents - ticagrelor and eptifibatide - in mice with experimentally-induced inflammatory bowel disease. This study was designed as a controlled, animal, drug safety investigation. C57Bl/6 mice were used to establish the ulcerative colitis model by exposure to dextran sulfate sodium (DSS), and divided into three experimental groups: eptifibatide-treated (150 µg/day intraperitoneally; n = 10), ticagrelol-treated (1 mg/day via gastric tube; n = 10), and DSS-control (plain drinking water; n = 10). An unmodeled non-DSS group served as the experimental control. Complete blood count was taken for all mice at baseline (day 0, treatment initiation) and after four days of treatment. On day 4, all animals were sacrificed for autopsy. The primary outcome measure was bleeding, and the secondary outcomes were change in platelet count, hemoglobin level, and hematocrit level. Neither ticagrelor nor eptifibatide treatment produced a significant effect on DSS colitis mice for the safety parameters measured. Platelet count and hemoglobin and hematocrit levels were statistically similar between the three DSS groups and the non-DSS control group (P > 0.05). Autopsy found no evidence of recent bleeding in liver, spleen, central nervous system or serous cavities. The antiplatelet agents ticagrelor and eptifibatide were safe in DSS colitis mice, suggesting their potential in humans suffering from ulcerative colitis, and supporting future safety studies.

Therapeutic effect of cinnamaldehyde on ulcerative colitis in mice induced by dextran sulfate sodium with Candida albicans colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway

To observe the efficacy of cinnamaldehyde on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) with Can-dida albicans(Ca) colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway in mice. C57 BL/6 mice were randomly divided into normal group, DSS group, DSS+Ca group, cinnamaldehyde group and mesalazine group. Mice in DSS+Ca group were given Ca(1×10~8 CFU per mouse) through intragastrical administration for 4 consecutive days and then distilled water with 3.0% DSS for 7 consecutive days. In cinnamaldehyde group and mesalazine group, in addition to the induction method of the DSS+Ca group, mice were given 75 mg·kg~(-1) cinnamaldehyde and 200 mg·kg~(-1) mesalazine accompanied with 3.0% DSS for 7 consecutive days, respectively. Mice in normal group and DSS group were correspondingly administered with distilled water. The general conditions of the mice were observed daily, the diseased activity index(DAI) score was calculated, and fungal loads of feces were detected by plate method. The mice were sacrificed on day 12, colon length was measured, colon mucosa damage index(CMDI) score was calculated, and histopathological analysis was carried out by HE staining. Anti-saccharomces cerevisiae antibody(ASCA) and β-1,3-glucan in serum, and TNF-α, IL-1β, IL-6, IL-8, IL-10 in serum and colon tissue were detected by ELISA. The contents of β-1,3-glucan and macrophage infiltration in colon tissues were examined by immunofluorescence staining. The protein expressions of dectin-1, TLR2, TLR4 and NF-κB were detected by Western blot and immunohistochemistry staining. The results showed that cinnamaldehyde could significantly improve the general conditions of UC mice with Ca colonization, decrease DAI and histopathological scores, reduce intestinal mucosal congestion, erosion and colon shortening, decrease Ca load in mouse feces and tissues, down-regulate the contents of ASCA and β-1,3-glucan in serum, reduce the contents of TNF-α, IL-1β, IL-6, IL-8 and increase IL-10 in serum and colon tissues, inhibit macrophages infiltration and down-regulate the protein expression of dectin-1, TLR2, TLR4 and NF-κB in colon tissue. These results suggested that cinnamaldehyde had a therapeutic effect on UC mice with Ca colonization, which might be related to the inhibition of Ca proliferation, the regulation of dectin-1/TLRs/NF-κB signaling pathways and the coordination of the balance between pro-inflammatory and anti-inflammatory factors.

The anti-inflammatory and immune-modulatory effects of OEA limit DSS-induced colitis in mice

Fatty acid ethanolamides acting on proliferator-activated receptor (PPAR)-α are among the endogenous lipid molecules that attenuate inflammatory processes and pain sensitivity. Whereas these properties are well-known for palmitoylethanolamide (PEA), the efficacy of oleoylethanolamide (OEA, first described as a satiety hormone synthesized in the jejunum) has been overlooked. In this study, we aimed to evaluate the effect of OEA administration in a mouse model of colitis. C57BL/6J mice were exposed to 2.5% dextran sodium sulphate (DSS) in drinking water for 5 days. Daily i.p. administration of 10 mg/kg OEA started 3 days before DSS and lasted for 12 days. The DSS-untreated control group received only ultrapure water. DSS mice treated with OEA had a significant improvement of disease score. OEA restored mRNA transcription of PPAR-α, of tight junctions and protective factors of colon integrity disrupted by DSS. The improvement correlated with significant decrease of colonic and systemic levels of pro-inflammatory cytokines compared to the DSS group. OEA antiinflammatory effects were mediated by the selective targeting of the TLR4 axis causing a downstream inhibition of nuclear factor kappa B (NF-κB)- MyD88-dependent and NLRP3 inflammation pathways. OEA treatment also inhibited DSS-induced increase of inflammatory cytokines levels in the mesenteric lymph nodes. Conclusions and implicationsThese results underscore the validity of OEA as a potent protective and anti-inflammatory agent in ulcerative colitis that may be exploited to broaden the pharmacological strategies against inflammatory bowel disease.

Ferroptosis mediated DSS-induced ulcerative colitis associated with Nrf2/HO-1 signaling pathway

Ulcerative colitis (UC) is an inflammatory disease characterized by an uncontrolled inflammatory response. Previous study showed that the immunological impairment elicted the alteration of inflammatory mediators, and ferroptosis was implicated with the lethal accumulation of reactive oxygen species (ROS). Therefore, this study aimed to investigate the role of ferroptosis in dextran sulfate sodium (DSS)-induced UC. The animal model was established and the molecular markers of ferroptosis were detected by using western blot. The results suggested that the expression of COX2 and ACSL4 was increased dramatically, while the level of GPX4 and FTH1 was deceased in 3% DSS group compared with Control group (P < 0.05). Meanwhile, the body weight and colon length were significantly increased, and the inflammation indexes and MDA levels were reduced in 3% DSS+ ferrostatin-1 group, 3% DSS+ liproxstatin-1 group and 3% DSS+ deferprone group compared to 3% DSS group (P < 0.05). Additionally, the mRNA and protein level of COX2 and ACSL4 were obviously upregulated, but the GPX4 and FTH1 expression were downregulated in 3% DSS group (P < 0.05); however, the expression level of COX2, ACSL4, GPX4 and FTH1 was revered after ferrostatin-1, liproxstatin-1 (Lip-1) or deferprone (DFP) administration. The immunohistochemical assay showed that the staining intensity of COX2 was decreased and the staining intensity of GPX4 was increased in 3% DSS+ Ferr-1 group compared with 3% DSS group (P < 0.05). Moreover, the nuclear factor erythoid 2-related 2 (Nrf2) and HO-1 expression were lower in 3% DSS+ Ferr-1 group than 3% DSS group (P < 0.05). These data revealed that suppressing ferroptosis could effectively ameliorate DSS-induced UC involved in blocking Nrf2/HO-1 signaling pathway.

Ameliorative effects of L-theanine on dextran sulfate sodium induced colitis in C57BL/6J mice are associated with the inhibition of inflammatory responses and attenuation of intestinal barrier disruption

This study investigated the effects of L-theanine supplementation on the colonic mucosa injury in C57BL/6J male mice treated with dextran sulfate sodium (DSS)-induced colitis. Treatment with L-theanine significantly decreased the disease activity index and ameliorated the inflammation-associated pathological damage in colon length, as well as the histopathological features of DSS-induced colitis. L-Theanine administration also inhibited DSS-induced changes in the colonic tissue that included myeloperoxidase by 4.5-fold and malondialdehyde by 2.3-fold in comparison to the DSS group. In addition, GSH was increased by 85% and lipopolysaccharides level was decreased by 55% in comparison to the DSS group. Proinflammatory cytokines expression, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, at the both protein and mRNA levels were also decreased significantly. Notably, the increase in serum content of lipopolysaccharides and colonic expressions of inducible nitric oxide synthase, cyclooxygenase-2, toll like receptor (TLR)-2, TLR-4, TLR-6, and TLR-9 induced by DSS were also significantly inhibited by L-theanine administration. In addition, L-theanine also attenuated the reduction of serum contents of diamine oxidase and the production of short-chain fatty acids in the colonic tissue, and gene expression of mucosal barrier zonula occludens-1 and claudin-1 in DSS-induced colitis. Furthermore, 16S rRNA phylogenetic sequencing revealed a shift in microbial community composition induced by DSS, but no significant difference was observed following L-theanine supplementation. Overall, our findings demonstrated that L-theanine inhibits intestinal inflammation and protects against intestinal barrier disruption in mice with DSS-induced colitis. Further clinical trials should be considered to assess the effects of L-theanine supplementation on oxidative and inflammatory responses in humans.

Anti-Inflammatory and Gut Microbiota Modulatory Effect of Lactobacillus rhamnosus Strain LDTM 7511 in a Dextran Sulfate Sodium-Induced Colitis Murine Model.

Inflammatory bowel disease (IBD) is a group of conditions involving chronic relapsing-remitting inflammation of the gastrointestinal tract with an unknown etiology. Although the cause–effect relationship between gut microbiota and IBD has not been clearly established, emerging evidence from experimental models supports the idea that gut microbes play a fundamental role in the pathogenesis of IBD. As microbiome-based therapeutics for IBD, the beneficial effects of probiotics have been found in animal colitis models and IBD patients. In this study, based on the dextran sulfate sodium (DSS)-induced colitis mouse model, we investigated Lactobacillus rhamnosus strain LDTM 7511 originating from Korean infant feces as a putative probiotic strain for IBD. The strain LDTM 7511 not only alleviated the release of inflammatory mediators, but also induced the transition of gut microbiota from dysbiotic conditions, exhibiting the opposite pattern in the abundance of DSS colitis-associated bacterial taxa to the DSS group. Our findings suggest that the strain LDTM 7511 has the potential to be used as a probiotic treatment for IBD patients in comparison to L. rhamnosus GG (ATCC 53103), which has been frequently used for IBD studies.

The effect of selected Lactobacillus strains on dextran sulfate sodium-induced mouse colitis model.

Inflammatory bowel disease (IBD) comprises two major illnesses: Crohn's disease (CD) and ulcerative colitis (UC). Dextran sulfate sodium (DSS) mouse colitis model has been used in understanding the mechanism of IBD. This study was conducted to examine selected Lactobacillus spp. as potential IBD treatment in the DSS-induced animal model. Balb/c mice were used and colitis was induced by adding 5% dextran sodium sulfate into the drinking water for 8 days. Colon length, disease activity index (DAI) and histological analysis were measured as markers of inflammation in DSS colitis mice. The majority of the Lactobacillus species significantly prevented the shortening of the colon length compared with the DSS group. The DAI scores of mice were significantly reduced following usage of four Lactobacillus strains included: Lactobacillus plantarum 03 and 06, Lactobacillus brevis 02 and Lactobacillus rhamnosus 01. The histological analysis exhibited that oral administration of Lactobacillus strains had therapeutic effects on mice colitis. L. plantarum and L. brevis showed better therapeutic effect against DSS-induced acute colitis mice. The probiotic activities of these three isolates indicated that the probiotic effects were strain specific and none of these useful bacteria could exhibit all of the valued probiotic properties simultaneously.

Tumor necrosis factor ligand-related molecule 1A affects the intestinal mucosal barrier function by promoting Th9/interleukin-9 expression.

ObjectivesTo investigate the effect of tumor necrosis factor ligand-related molecule 1A (TL1A) on the intestinal mucosal barrier in mice with chronic colitis.MethodsMale TL1A-overexpressing transgenic mice and male C57BL/6 wild-type mice were used to establish a dextran sodium sulfate (DSS)-induced colitis model. The expression of occludin and claudin-1 was observed. Bacterial distribution in the intestinal mucosa and Th9/interleukin (IL)-9 expression were detected. In vitro co-culture systems of naive CD4+ T cells and Caco-2 cells were established and TL1A was added. Changes in transepithelial electrical resistance and IL-9 expression were measured. CD4+IL-9 cells were detected by flow cytometry.ResultsDSS mice showed a significant down-regulation of occludin and claudin-1 compared with controls. Expression levels of occludin, zonulin-1, and claudin-1 in the Caco-2+TGF-β+IL-4+TL1A group were significantly lower than in the Caco-2+TGF-β+IL-4 group. Bacterial distribution was clearly disordered in the DSS group. Transmembrane resistance of the Caco-2+TGF-β+IL-4+TL1A group was significantly lower and IL-9 expression significantly higher than in the Caco-2+TGF-β+IL-4 group.ConclusionsTL1A overexpression promotes destruction of the intestinal mucosal barrier in mice with chronic colitis. The underlying mechanism may be associated with the promoting role of TL1A in Th9/IL-9 expression, which further destroys the mucosal barrier.

Effect of Omega-3 Fatty Acid Rich Oils; Fish Oil and Perilla Oil on High-Fat Diet Fed DSS-Induced Colitis Mice

Abstract Objectives The incidence of inflammatory bowel disease is increasing in newly developing countries, mainly awing to the westernization of the society. Consumption of high-fat diet has known to aggravate colitis. Omega-3 fatty acids are known to have several health benefits including anti-inflammatory effects and some studies have reported the effect of fish oil in experimental colitis. Perilla oil is obtained from the seeds of Perilla frutescens and is known to exert protective effects against obesity, inflammation and hepatic steatosis. We have previously shown that perilla oil has a similar effect like fish oil in high-fat diet induced colon inflammation. In this study, we wanted to investigate the effect fish oil and perilla oil on high-fat-fed, dextran sodium sulfate (DSS)-induced colitis in mice. Methods Six weeks old mice were divided into 4 groups; normal diet without DSS administration (ND), and three high-fat diet with DSS groups; control (HD + DSS), with fish oil supplementation (HDFO+DSS), with perilla oil supplementation (HDPO+DSS). The mice were fed with high-fat diet for 5 weeks prior to DSS administration by water for one week. The mice were sacrificed on the 7th day of DSS administration. Colon length and macroscopic score were measured. The levels of pro-inflammatory cytokines in serum were measured. The stools of the mice were collected for microbial analysis. Results The levels of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β were significantly reduced in FO and PO supplemented groups compared to HD + DSS. The colon length was reduced due to DSS administration compared to ND, and supplementation with FO and PO improved colon length and macroscopic score. Number of Enterobacteriaceae was higher in all DSS administered groups. However, FO and PO treated groups had significantly reduced Enterobacteriaceae. Conclusions The results of this study showed that fish oil and perilla oil exert protective effect against high-fat diet fed DSS-induced colitis. Both fish oil and perilla oil action on colon protection is similar. The experiments to confirm the mechanism of action which includes mRNA and protein analysis are ongoing. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Education).

The Effects of the Marine-Derived Polysaccharides Laminarin and Chitosan on Aspects of Colonic Health in Pigs Challenged with Dextran Sodium Sulphate.

This study examined the effects of dietary supplementation with laminarin or chitosan on colonic health in pigs challenged with dextran sodium sulphate (DSS). Weaned pigs were assigned to: (1) a basal diet (n = 22); (2) a basal diet + laminarin (n = 10); and (3) a basal diet + chitosan (n = 10). On d35, the basal group was split, creating four groups: (1) the basal diet (control); (2) the basal diet + DSS; (3) the basal diet + laminarin + DSS; and (4) the basal diet + chitosan + DSS. From d39–42, the pigs were orally challenged with DSS. On d44, colonic tissue/digesta samples were collected. The basal DSS group had reduced growth, higher pathology score and an increased expression of MMP1, IL13 and IL23 compared with the controls (p < 0.05); these parameters were similar between the DSS-challenged groups (p > 0.05). In the basal DSS group, the relative abundance of beneficial taxa including Prevotella and Roseburia were reduced while Escherichia/Shigella were increased, compared with the controls (p < 0.05). The relative abundance of Escherichia/Shigella was reduced and the molar proportions of acetate were increased in the laminarin DSS group compared with the basal DSS group (p < 0.01), suggesting that laminarin has potential to prevent pathogen proliferation and enhance the volatile fatty acid profile in the colon in a porcine model of colitis.

Dihydroartemisinin ameliorates dextran sulfate sodium induced inflammatory bowel diseases in mice.

In the present study, the effects of dihydroartemisinin (DHA) on inflammatory bowel diseases (IBD) mice model induced by dextran sulfate sodium (DSS) were determined. Hematoxylin and eosin staining was used to assess the intestines of mice treated with DSS and DHA. The expression of inflammatory factors and cell junction-associated genes was measured using reverse transcription-quantitative PCR (RT-qPCR) and Western blot. The effects of DSS and DHA on the gut microbiome were measured using 16S recombinant (r) DNA gene analysis. DHA could improve the diarrhea and bloody stool induced by DSS, and decrease the serum levels of TNF-α, IL-1β and IL-23 of the DSS group. DHA could notably reduce the infiltration of the inflammatory cells and significantly decrease the expression of TNF-α and IL-1β in the intestines of the DSS treated mice. The expression of cell junction-associated genes such as EpCAM and Claudins, were down-regulated in the DSS group, and DHA could recover the expression of these cell junction-associated genes. The 16S rDNA gene analysis demonstrated that Bacteroidetes and Verrucomicrobia decreased, while Firmicutes and Proteobacteria increased in the DSS group, and DHA could recover the abundance of these gut bacteria altered by DSS. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that DHA could partly recover the pathways altered by DSS. DHA could obviously ameliorate the symptoms of IBD induced by DSS by regulation of the expression of inflammation and cell junction-associated genes and gut microbiota, suggesting its potential for the treatment of IBD.