Sulfate Sodium-induced Colitis In Mice Research Articles

Establishment of Food Allergy Model in Dextran Sulfate Sodium Induced Colitis Mice.

Food allergy (FA) has become a global food safety issue. Evidence suggests that inflammatory bowel disease (IBD) can increase the incidence of FA, but it is mostly based on epidemiological studies. An animal model is pivotal for unraveling the mechanisms involved. However, dextran sulfate sodium (DSS)-induced IBD models may cause substantial animal losses. To better investigate the effect of IBD on FA, this study aimed to establish a murine model to fit both IBD and FA symptoms. Firstly, we compared three DSS-induced colitis models by monitoring survival rate, disease activity index, colon length, and spleen index, and then eliminated the colitis model with a 7-day administration of 4% due to high mortality. Moreover, we evaluated the modeling effects on FA and intestinal histopathology of the two models selected and found the modeling effects were similar in both the colitis model with a 7-day administration of 3% DSS and the colitis model with long-term administration of DSS. However, for animal survival reasons, we recommend the colitis model with long-term administration of DSS.

Protective Effect of Lactiplantibacillus plantarum subsp. plantarum SC-5 on Dextran Sulfate Sodium-Induced Colitis in Mice.

Inflammatory bowel disease (IBD) is a specific immune-associated intestinal disease. At present, the conventional treatment for patients is not ideal. Probiotics are widely used in the treatment of IBD patients due to their ability to restore the function of the intestinal mucosal barrier effectively and safely. Lactiplantibacillus plantarum subsp. plantarum is a kind of probiotic that exists in the intestines of hosts and is considered to have good probiotic properties. In this study, we evaluated the therapeutic effect of Lactiplantibacillus plantarum subsp. plantarum SC-5 (SC-5) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. We estimated the effect of SC-5 on the clinical symptoms of mice through a body weight change, colon length, and DAI score. The inhibitory effects of SC-5 on the levels of cytokine IL-1β, IL-6, and TNF-α were determined by ELISA. The protein expression levels of NF-κB, MAPK signaling pathway, and the tight junction proteins occludin, claudin-3, and ZO-1 were verified using Western Blot and immunofluorescence. 16S rRNA was used to verify the modulatory effect of SC-5 on the structure of intestinal microbiota in DSS-induced colitis mice. The results showed that SC-5 could alleviate the clinical symptoms of DSS-induced colitis mice, and significantly reduce the expression of pro-inflammatory cytokines in the colon tissue. It also attenuated the inflammatory response by inhibiting the protein expression of NF-κB and MAPK signaling pathways. SC-5 improved the integrity of the intestinal mucosal barrier by strengthening tight junction proteins. In addition, 16S rRNA sequencing demonstrated that SC-5 was effective in restoring intestinal flora balance, as well as in increasing the relative abundance and diversity of beneficial microbiota. These results indicated that SC-5 has the potential to be developed as a new probiotic candidate that prevents or alleviates IBD.

Interleukin 11 confers resistance to dextran sulfate sodium-induced colitis in mice

Intestinal homeostasis is tightly regulated by epithelial cells, leukocytes, and stromal cells, and its dysregulation is associated with inflammatory bowel diseases. Interleukin (IL)-11, a member of the IL-6 family of cytokines, is produced by inflammatory fibroblasts during acute colitis. However, the role of IL-11 in the development of colitis is still unclear. Herein, we showed that IL-11 ameliorated DSS-induced acute colitis in mouse models. We found that deletion of Il11ra1 or Il11 rendered mice highly susceptible to DSS-induced colitis compared to the respective control mice. The number of apoptotic epithelial cells was increased in DSS-treated Il11ra1- or Il11-deficient mice. Moreover, we showed that IL-11 production was regulated by reactive oxygen species (ROS) produced by lysozyme M-positive myeloid cells. These findings indicate that fibroblast-produced IL-11 plays an important role in protecting the mucosal epithelium in acute colitis. Myeloid cell-derived ROS contribute to the attenuation of colitis through the production of IL-11.

Knockdown of TRIM8 alleviates dextran sulfate sodium-induced colitis in mice by inhibiting the NF-κB signaling pathway.

Although TRIpartite Motif containing 8 (TRIM8) gene plays an important role in a number of biological processes, such as inflammation, its function and mechanism in ulcerative colitis (UC) remain unknown. The UC model was established by feeding mice with 3.5% dextran sulfate sodium (DSS). The animals were divided into the following four groups: control group, DSS group, DSS+short hairpin (sh)-NC group, and DSS+sh-TRIM8 group. Changes in body weight and disease activity index (DAI) score of mice in all the groups were recorded for 7 days. The animals were executed at the end of the experiment, and the expression of TRIM8 in colon tissue was detected by polymerase chain reaction and Western blot assays. The length of colon was measured, and the histopathological changes in mice colon were examined by hematoxylin and eosin staining. The expression of pro-inflammatory factors in mice serum and colonic tissue homogenate was detected by enzyme-linked-immunosorbent serologic assay. The expression of nuclear factor kappa B (NF-κB) pathway-related proteins in colonic tissues was detected by Western-blot analysis. TRIM8 was highly expressed in the colonic tissues of UC mice. Knockdown of TRIM8 improved DSS-induced weight loss, increased DAI score, shortened colon length, and alleviated colonic injury and inflammation in mice. Western-blot experiments showed that knockdown of TRIM8 inhibited DSS-induced phosphorylation of p65 and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) protein but increased IκBα expression. Knockdown of TRIM8 inhibits UC injury and inflammatory response caused by DSS. This could be related to the regulation of NF-κB signaling pathway by TRIM8 protein.

Salidroside alleviates dextran sulfate sodium-induced colitis in mice by modulating the gut microbiota.

Dysbiosis causes continuous progress of inflammatory bowel disease (IBD). Herein, we aim to explore whether Salidroside (Sal), which is a major glycoside extracted from Rhodiola rosea L., could ameliorate dextran sulfate sodium (DSS)-induced colitis by modulating the microbiota. Results showed that oral treatment with 15 mg kg-1 of Sal inhibited DSS-induced colitis in mice as evidenced by colon length, histological analysis, disease activity index (DAI) score, and the proportion and number of macrophages in the intestine. The gut microbiota of colitic mice was also partly restored by Sal. A fecal microbiota transplantation (FMT) study was designed to verify the causality. Compared with DSS-treated mice, FM from the Sal-treated donor mice significantly mitigated the symptoms of colitic mice, including reducing the DAI score, alleviating tissue damage, boosting the expression of mucin protein (mucin-2) and tight junction (TJ) proteins (occludin and zonula occludens-1 (ZO-1), and decreasing M1 macrophages in the gut. It was found that both Sal and FMT affected the structure and abundance of the gut microbiota as reflected by the decreased relative abundance of Turicibacter, Alistipes, Romboutsia and the increased relative abundance of Lactobacillus at the genus level. Moreover, the anti-inflammatory effect of Sal disappeared when the gut microbiota was depleted by antibiotics, demonstrating that Sal alleviated the intestinal inflammation in a gut microbiota-dependent manner. Thus, Sal could be a remarkable candidate as a functional food for colitis.

Dietary 5-demethylnobiletin attenuated dextran sulfate sodium-induced colitis in mice by inhibiting immune response and regulating gut microbiota.

This study investigated the preventive effect of 5-demethylnobiletin (5DN), a natural polymethoxyflavone found mainly in citrus fruits, on dextran sulfate sodium (DSS)-induced colitis in mice and explored its potential mechanisms. Our results indicated that dietary 5DN (0.05% w/w in diet) could alleviate colitis symptoms in DSS-treated mice by preventing body weight loss, reducing the disease activity index, decreasing the colon weight to colon length ratio, and lessening colon tissue damage. Additionally, 5DN inhibited the inflammatory response in colitis mice through decreasing the production of inflammatory cytokines. Immunohistochemical analysis revealed that 5DN could reverse the DSS-induced decrease in the expression of claudin-1 and ZO-1 to improve the intestinal barrier function. Furthermore, 5DN altered gut microbiota dysbiosis in DSS-treated mice via up-regulating the level of probiotics (Roseburia) and down-regulating the level of pathogenic bacteria (Clostridium, Parabacteroides, and Sutterella). Taken together, these data provided a solid scientific basis for utilizing 5DN as a therapeutic candidate in colitis and related diseases.

The beneficial effects of Fomitopsis pinicola chloroform extract on a dextran sulfate sodium-induced ulcerative colitis mice model.

As an intestinal non-specific inflammatory lesion, ulcerative colitis (UC) affects the health of many individuals. This study examined the possible beneficial effects of the chloroform extract of Fomitopsis pinicola (Swartz.: Fr) Karst (FPKc) on UC. The mice were given free access to drink with 4% dextran sulfate sodium (DSS) for 1 week to establish acute UC model. Next, 35 mg of FPKc or sulfasalazine (SASP) was given to the mice via gavage for 3 weeks. The disease activity index (DAI) and colonic mucosa damage index (CMDI) scores were calculated. The colon tissues of the mice were collected to measure the length and perform hematoxylin and eosin staining. The thymus and spleen indexes were determined. Interleukin (IL)-6, IL-8, tumor necrosis factor-α, aminotransferase (AST) and alanine aminotransferase (ALT) levels in the serum were determined. FPKc or SASP treatment alleviated hematochezia and weight loss, ameliorated DAI and CMDI scores, and improved the crypt structure and length of the colon tissues. Relative to the UC model group, the spleen index in the FPKc group was reduced, which was accompanied by decreases of the IL-6 and IL-8 levels in the serum. FPKc also lowered the AST and ALT levels in the serum of the UC mice. FPKc protected the mice from DSS-induced UC injury. It may be that FPKc activates immune regulation and downregulates the expression of pro-inflammatory cytokines.

Moxibustion improved the effect of fecal microbiota transplantation donor to dextran sulfate sodium-induced colitis in mice.

Fecal microbiota transplantation (FMT) is beneficial for several gastrointestinal diseases because it alters the intestinal microbiota of recipients. The efficacy of FMT is related to the microbial structure and composition of the donor. Mild moxibustion is a non-invasive and safe traditional Chinese therapy that can regulate the gut microbiota. In this study, we investigated whether moxibustion improved the efficacy of FMT in donors using a dextran sulfate sodium (DSS)-induced colitis mouse model. Normal mice were treated with mild moxibustion at acupoints ST25 and ST36 for 7 days. DSS (2%) was administered for 7 days to induce colitis. FMT was performed on Day 8 and lasted for 7 days. The effect of FMT on mice with DSS was observed on Day 21. Using hematoxylin and eosin staining and immunofluorescence, we analyzed the pathology and cell proliferation after FMT in DSS mice. In addition, using 16 S rDNA sequencing analysis, we investigated the gut microbiota of mice. The results indicated that moxibustion altered the colonic microbial community and increased the relative abundance of specific bacteria without changes in morphology and physiological function in normal mice. FMT using donors with moxibustion reduced body weight loss, inflammation, abnormal microbial community structure, and the relative abundance of some bacteria. These results provide potential strategies for the safe and targeted improvement of FMT donors.

Heat-Killed Bifidobacterium bifidum B1628 May Alleviate Dextran Sulfate Sodium-Induced Colitis in Mice, and the Anti-Inflammatory Effect Is Associated with Gut Microbiota Modulation.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with gut dysbiosis. This study aimed to investigate the effects of heat-killed Bifidobacterium bifidum B1628 (HB1628) in dextran sulfate sodium (DSS)-induced colitis in mice. The following three mouse groups were included (n = eight per group): NC (normal control), DSS (colitis), and HB1628 (colitis and postbiotic). The mice in the DSS group showed significant weight loss and histological damage, developed bloody diarrhea, scored high in the disease activity index (DAI), and exhibited increases in pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]-α) and decreases in an anti-inflammatory cytokine (IL-13) in the serum. These changes were accompanied by gut microbiota modulation in colitis mice (decreases in Rikenellaceae and Eubacterium; increases in Peptostreptococcaceae, Bacteroides vulgatus, and Parasutterella excrementihominis). The HB1628 group had lower DAIs, histology scores, and serum levels of pro-inflammatory cytokines (IL-1β and TNF-α), but higher levels of an anti-inflammatory cytokine (IL-13), compared with the DSS group, suggesting a less severe inflammatory state after the HB1628 intervention. Additionally, HB1628 improved DSS-induced gut dysbiosis, which is evidenced by increases in intestinal beneficial bacteria, such as Lactobacillus, and decreases in known unfavorable taxa in IBD, e.g., Porphyromonadaceae, Subdoligranulum, Lachnospiraceae bacterium 3_1_46FAA, and Alistipes indistinctus. Functional metagenomics revealed three significantly enriched metabolic pathways in the HB1628 group (namely, the aerobic respiration I [cytochrome c] pathway and the superpathways of L-phenylalanine biosynthesis and L-tryptophan biosynthesis, respectively). In conclusion, our results showed that HB1628 effectively improved the inflammation state and tissue damage in DSS-induced colitis mice, and the symptom relief effect was accompanied by obvious gut microbiota remodulation.

Qu-Yu-Jie-Du Decoction Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulation of Neutrophils and Macrophage Infiltration.

Inflammatory bowel disease (IBD) is becoming a global disease. A percentage of IBD patients will not react to therapy or will lose their response. Qu-Yu-Jie-Du Decoction (QYJD) is a traditional Chinese medicine formula commonly used for intestinal diseases. It has been reported that QYJD has an anti-inflammatory effect, but the mechanism is not fully understood. In this study, we mainly evaluated the anti-inflammatory effect of QYJD and explored the possible mechanisms. Twenty-four BALB/c mice were randomly divided into 4 groups according to their body weight, namely, the control group, the dextran sulfate sodium (DSS) group, the DSS + QYJD group, and the QYJD group. Mice were given 3% DSS drinking water freely, and at the same time, mice were given normal saline or QYJD (4.44 mg/g/d), respectively. Mental state, faeces, and weight were recorded every day. On the 10th day, the mice were sacrificed and collected for investigation. The length of the mice colon was measured. Histological analysis was used to detect the morphological changes in the colon. Immunohistochemistry was used to measure the infiltration of macrophages (F4/80, CD163) and neutrophils (Ly6G). Colorimetry was used to detect the myeloperoxidase (MPO) activity of colon tissues. ELISA was utilized to detect associated inflammatory cytokines and chemokines in colon tissues. QYJD alleviated the weight loss and colitis symptoms of mice caused by DSS. QYJD fought against the shortening of the intestine caused by DSS; that is, it improved the decline of intestinal compliance in mice and had a protective effect on colon tissues. The mechanisms were related to downregulating macrophages and neutrophils in colon tissues of infiltration. Besides, QYJD simultaneously reduced the activity of myeloperoxidase activity (MPO) and the contents of IL-1β, IL-6, TNF-α, TGF-β, CCL2, and CXCL2 in colon tissues. QYJD can ameliorate DSS-induced colitis in mice and the mechanism is connected with a reduction in neutrophil and macrophage infiltration.

Epoxymicheliolide prevents dextran sulfate sodium-induced colitis in mice by inhibiting TAK1-NF-κB pathway and activating Keap1-NRF2 signaling in macrophages.

Ulcerative colitis (UC) is an unspecific colorectal inflammation associated with macrophages overactivation. Therefore, macrophage-targeted treatment has been considered a promising strategy for UC therapy. Epoxymicheliolide (EMCL) is a compound from Aucklandia lappa Decne, a TCM for treating gastrointestinal inflammatory diseases. The purpose of this study is to investigate the therapeutic effect of EMCL on DSS-induced mice colitis through the anti-inflammatory activity on macrophages and its underlying mechanisms. We found that EMCL inhibited the release of NO and PGE2 by down-regulating the expression of iNOS and COX2, while suppressed the expression of IL-1β, IL-6, and TNF-α in LPS-stimulated RAW264.7 macrophages. EMCL also inhibited NO production in LPS-activated peritoneal macrophages and TNFα-stimulated RAW264.7 cells. Moreover, EMCL blocked the phosphorylation of TAK1, IKKα/β, and IκBα, as well as IκBα degradation, thereby inhibiting the NF-κB pro-inflammatory signaling. Furthermore, EMCL decreased the intracellular ROS, by activating the NRF2 antioxidant pathway. CETSA and molecular docking showed that EMCL might form a covalent bond with Cys174 of TAK1 or Cya151 of Keap1, which may contribute to EMCL-mediated actions. Additionally, a thiol donor β-mercaptoethanol obviously abolished EMCL-mediated actions in vitro, suggesting the crucial role of the α, γ-unsaturated lactone of EMCL on its anti-inflammatory effects. Furthermore, EMCL not only ameliorated symptoms of colitis and colon barrier injury, but also decreased the levels of pro-inflammatory cytokines, MPO, NO, and MDA in DSS-challenged mice. Thus, our study demonstrated that EMCL ameliorated UC by targeting NF-κB and Nrf2 pathways, indicating it may server as a promising drug candidate for UC therapy.

TDAG51 deficiency attenuates dextran sulfate sodium-induced colitis in mice

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a group of chronic inflammatory diseases of the gastrointestinal tract. Although the multifactorial etiology of IBD pathogenesis is relatively well documented, the regulatory factors that confer a risk of IBD pathogenesis remain less explored. In this study, we report that T-cell death-associated gene 51 (TDAG51/PHLDA1) is a novel regulator of the development of dextran sulfate sodium (DSS)-induced colitis in mice. TDAG51 expression was elevated in the colon tissues of DSS-induced experimental colitis mice. TDAG51 deficiency protected mice against acute DSS-induced lethality and body weight changes and disease severity. DSS-induced structural damage and mucus secretion in colon tissues were significantly reduced in TDAG51-deficient mice compared with wild-type mice. We observed similar results in a DSS-induced chronic colitis mouse model. Finally, we showed that the production of inflammatory mediators, including proinflammatory enzymes, molecules and cytokines, was decreased in DSS-treated TDAG51-deficient mice compared with DSS-treated wild-type mice. Thus, we demonstrated that TDAG51 deficiency plays a protective role against DSS-induced colitis by decreasing the production of inflammatory mediators in mice. These findings suggest that TDAG51 is a novel regulator of the development of DSS-induced colitis and is a potential therapeutic target for IBD.

Wogonin regulates colonocyte metabolism via PPARγ to inhibit Enterobacteriaceae against dextran sulfate sodium-induced colitis in mice.

To investigate the potential effects and mechanism of wogonin on dextran sulfate sodium (DSS)-induced colitis, 70 male mice were administered wogonin (12.5, 25, 50 mg·kg-1 ·d-1 , i.g.) for 10 days, meanwhile, in order to induce colitis, the mice were free to drink 3% DSS for 6 days. We found that wogonin could obviously ameliorate DSS-induced colitis, including preventing colon shortening and inhibiting pathological damage. In addition, wogonin could increase the expression of PPARγ, which not only restores intestinal epithelial hypoxia but also inhibits iNOS protein to reduce intestinal nitrite levels. All these effects facilitated a reduction in the abundance of Enterobacteriaceae in DSS-induced colitis mice. Therefore, compared with the DSS group, the number of Enterobacteriaceae in the intestinal flora was significantly reduced after administration of wogonin or rosiglitazone by 16s rDNA technology. We also verified that wogonin could promote the expression of PPARγ mRNA and protein in Caco-2 cells, and this effect disappeared when PPARγ signal was inhibited. In conclusion, our study suggested that wogonin can activate the PPARγ signal of the Intestinal epithelium to ameliorate the Intestinal inflammation caused by Enterobacteriaceae bacteria expansion.

Protective effects of 4-geranyloxy-2,6-dihydroxybenzophenonel on DSS-induced ulcerative colitis in mice via regulation of cAMP/PKA/CREB and NF-κB signaling pathways.

Hypericum sampsonii Hance has traditionally been used to treat enteritis and diarrhea. As one of the main benzophenones isolated from H. sampsonii, 4-geranyloxy-2,6-dihydroxybenzophenonel (4-GDB) has been shown to possess anti-inflammatory effects. However, the therapeutic effect and potential mechanisms of 4-GDB in ulcerative colitis (UC) remain unclear. This study aimed to evaluate the role of 4-GDB in UC using a dextran sulfate sodium-induced colitis mouse model. Intragastric administration of 4-GDB (20 mg/kg/day) for 8 days significantly attenuated colonic injury, reduced the expression of inflammatory mediators, and improved colonic barrier function in mice with colitis. Furthermore, in vivo and in vitro experiments indicated that 4-GDB could activate cAMP/PKA/CREB and inhibit the NF-κB pathway. Collectively, 4-GDB may be a potential agent for treating UC by regulating the cAMP/PKA/CREB and NF-κB pathways.

Fucoidan Ameliorated Dextran Sulfate Sodium-Induced Ulcerative Colitis by Modulating Gut Microbiota and Bile Acid Metabolism.

Gut dysbiosis and bile acid (BA) metabolism disturbance are involved in the pathogenesis of ulcerative colitis. This study aimed to investigate the effect of fucoidan on BA metabolism and gut microbiota in dextran sulfate sodium-induced colitis mice. Our results showed that fucoidan effectively suppressed colonic inflammation and repaired the gut barrier. In addition, fucoidan increased the relative abundance of the Lachnospiraceae family, such as Turicibacter, Muribaculum, Parasutterella, and Colidextribacter, followed by an increase in short-chain fatty acids, especially in butyrate. Moreover, fucoidan modulated bile acid metabolism by elevating cholic acid, ursodeoxycholic acid, deoxycholic acid, and lithocholic acid and decreasing β-muricholic acid, which led to activation of FXR and TGR5 and further enhanced the gut barrier and suppressed colonic inflammation. Our results revealed that the effect of fucoidan alleviating colitis was largely mediated by gut microbiota, which was confirmed by the fecal transplantation experiment. Collectively, these findings provided the basis for fucoidan as a potential functional food for colitis.

Regulation of the Gut Microbiota and Inflammation by β-Caryophyllene Extracted from Cloves in a Dextran Sulfate Sodium-Induced Colitis Mouse Model.

Ulcerative colitis is an inflammatory bowel disease characterized by symptoms such as abdominal pain, diarrhea, bleeding, and weight loss. Ulcerative colitis is typically treated with anti-inflammatory drugs; however, these drugs are associated with various side effects, limiting their use. β-Caryophyllene (BCP), a natural compound derived from cloves, has antioxidant, antibacterial, and anti-inflammatory activities. In this study, we aimed to investigate the effects of BCP on colitis in a dextran sulfate sodium (DSS)-induced colitis mouse model. BCP was administered for seven days, followed by 2.5% DSS for additional seven days to induce colitis. Changes in stool weight, recovery of gut motility, colon length, colon histology, myeloperoxidase activity, inflammatory cytokines (TNF-α, IL-1β, IL-6, IgA, and IgG), and the gut microbiota were observed. Administration of BCP increased stool weight, restored gut motility, and considerably increased colon length compared to those in the untreated colitis mouse model. In addition, the amount of mucin and myeloperoxidase activity in the colon increased, whereas the concentrations of IL-1β, IL-6, and TNF-α decreased following the administration of BCP. Furthermore, BCP reduced the abundance of Proteobacteria which can cause intestinal immune imbalance. These results suggest that BCP has a potential to be developed as a preventive agent for colitis.

Nattokinase enhances the preventive effects of Escherichia coliNissle 1917 on dextran sulfate sodium-induced colitis in mice.

Nattokinase with excellent anti-thrombotic, anti-inflammatory, anti-tumor, and anti-hypertension properties has been used in the development of several healthcare products in many countries. The probiotic Escherichia coli Nissle 1917 (EcN) with anti-inflammatory effect is commonly used to treat inflammatory bowel disease. To determine whether nattokinase could enhance the therapeutic efficacy of EcN in colitis, a recombinant E. coli Nissle 1917 strain (EcNnatto) with nattokinase-expressing ability was successfully constructed, and the protective effect of the engineered strain on mice with experimental chronic colitis was investigated. Although both EcN and EcNnatto strains substantially alleviated the clinical symptoms and pathological abnormalities in colitis mice by regulating gut flora and maintaining intestinal barrier function, the EcNnatto strain was found to perform better than the control strain, based on a further increase in colon length and a downregulation in pro-inflammatory cytokines (IL-6 and TNF-α). Nattokinase expressed in EcN attenuated DSS-induced epithelial damage and restored the mucosal integrity by upregulating the levels of tight junction proteins, including ZO-1 and occludin. The expression level of Lgr5, a marker of intestinal stem cells, was also increased. Moreover, constitutively expressed nattokinase in EcN reversed the gut microbial richness and diversity in colitis mice. Based on our findings, nattokinase could strengthen the capacity of EcN to treat intestinal inflammation.

Novel Phocaeicola Strain Ameliorates Dextran Sulfate Sodium-induced Colitis in Mice.

Previously, we isolated a novel Phocaeicola strain, Phocaeicola faecalis FXJYN30E22, from the feces of a healthy human from China. Metagenomic analysis revealed that the distribution of FXJYN30E22 differed in the intestinal tract of different hosts. We aimed to determine whether FXJYN30E22 protects against ulcerative colitis by employing a mouse model. In this study, dextran sulfate sodium was used to construct the UC model. The disease activity index, colon length, body weight changes, and histological scores were used as the pathological indicators to assess the anti-inflammatory effect of P. faecalis FXJYN30E22. Further, cytokine levels, tight junction mRNA expression levels, and short-chain fatty acid (SCFA) concentrations were also analyzed. Phocaeicola faecalis FXJYN30E22 could reduce the DSS-induced increase in DAI score, and enhance the colon length and body weight. Phocaeicola faecalis FXJYN30E22 could enhance TJ protein concentration and modulate the level of cytokines to reach levels close to those of the control group. FXJYN30E22 could also upregulate the concentrations of SCFA, which include acetate and butyrate. Based on the correlation analysis, four factors, including interleukin (IL)-6, IL-10, IL-1β levels, and propionate concentration, were related to the protective roles of FXJYN30E22 in UC mice to different degrees. According to an analysis of the genomic information, the potential protective effects of strain FXJYN30E22 may be associated with the secretion of SCFA by specific genes. These findings suggest that oral P. faecalis FXJYN30E22 could help maintain the epithelial barrier by regulating cytokine levels and secreting SCFA.

Protective Effect of Perilla Oil Against Dextran Sodium Sulfate-Induced Colitis in Mice Challenged with a High-Fat Diet.

This study investigated the effect of perilla oil (PO) on an ulcerative colitis mouse model. Five-week-old male C57BL/6J mice were divided into HD (high-fat diet control), HDD (high-fat diet along with dextran sodium sulfate [DSS] administration), HDD + FO, HDD + PO, and HDD + OO where HDD + FO, HDD + PO, and HDD + OO groups were treated with fish oil (FO), PO, and olive oil (OO), respectively. Biochemical analysis of serum, quantitative polymerase chain reaction, and western blotting of colon tissue were conducted to measure inflammatory marker levels. Administration of DSS resulted in colon shortening and a higher disease activity score than HD group. These symptoms were significantly reversed in the oil-treated groups. The body weight loss after DSS administration was significantly lower in the HDD + PO and HDD + OO groups than in the HDD and HDD + FO groups. PO significantly attenuated the levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-1β in the serum and colon. The mRNA expression levels of proinflammatory markers in the colon were reduced, whereas those of tight junction proteins and epithelial defense barrier-associated markers were increased by PO treatment. The protein expression of p-p65 was significantly lower in the PO-treated group than the HDD group. In summary, this study revealed that PO improved colitis in the DSS-induced mouse model, indicating its potential role in managing conditions such as ulcerative colitis.

Ameliorative Effect of Saccharomyces cerevisiae JKSP39 on Fusobacterium nucleatum and Dextran Sulfate Sodium-Induced Colitis Mouse Model

The aim of this study was to evaluate the ability of the Saccharomyces cerevisiae strain with probiotic properties isolated from Tibetan kefir grains to ameliorate Fusobacterium nucleatum (Fn) infection and dextran sulfate sodium (DSS) treatment-induced murine model of colitis. The tolerance to simulated gastrointestinal conditions, hydrophobicity test, autoaggregation assay, and the antioxidant effect of strains was used to screen one strain with colonization and probiotic potential. The murine model of colitis was established by giving 109 cfu Fn 3 weeks by intragastric administration and 3% DSS in water 1 week before sacrifice. The results indicated that S. cerevisiae JKSP39 (SC) possessed optimal probiotic characteristics in vitro. Supplementation with SC increased the body weight and the expression of anti-inflammatory cytokines (IL-4 and IL-10), while decreasing the disease activity index score and expression of proinflammatory cytokines (TNF-α, IL-6, and IL-17F) in mice undergoing experimental colitis as compared with the colitis model group. Additionally, tight junction proteins and the number of goblet cells per crypt were significantly increased in the SC group, which indicated that the gut barrier was well repaired. The mechanism of SC ameliorating Fn-DSS-induced colitis could be related to the decreased levels of reactive oxygen species (myeloperoxidase, total superoxide dismutase, catalase, H2O2, and malondialdehyde) in the colon, the inhibition of endoplasmic reticulum stress, and the regulation of gut microbiota.