Dextran Sulfate Sodium-induced Colitis Research Articles

ARGINASE 2 AMELIORATES EXPERIMENTAL COLITIS THROUGH ANTIOXIDANT EFFECTS VIA SPERMIDINE PRODUCTION

Abstract BACKGROUND Spermidine which is a type of polyamine, shows elevated levels in patients with ulcerative colitis and is implicated in the pathogenesis of ulcerative colitis (UC). Arginase 2 (ARG2) plays a critical role in spermidine production. This study aimed to determine the role and mechanism of endogenous spermidine by using ARG2-deficient mice. METHODS The protective role of spermidine against oxidative stress was examined by intracellular reactive oxygen species levels and cell viability. The physiological role of spermidine was investigated using Arg2 knockdown cells with reduced spermidine. The importance of ARG2 in inflammation was examined in the dextran sulfate sodium-induced colitis model. Protein expression levels of ARG2 and accumulation of spermidine in patients with UC were evaluated by immunohistochemistry of the rectum. RESULTS ARG2 protein expression and the accumulation of spermidine were upregulated in the rectum of mice with dextran sulfate sodium colitis. Spermidine upregulated antioxidant genes in the cells. Arg2 knockdown cells showed reduced antioxidant activity. Dextran sulfate sodium colitis was more severe in Arg2-deficient mice, and organoids derived from Arg2-deficient mice showed diminished tolerance to oxidative stress. Furthermore, in the rectum of patients with UC, ARG2 and spermidine expression levels were higher in the active phase than in the remission phase. CONCLUSIONS Endogenous spermidine in the intestinal epithelium induced by ARG2 has a protective role in colitis. Spermidine may be a promising new therapeutic target for inflammatory bowel disease.

Dietary Iron Is Necessary to Support Proliferative Regeneration after Intestinal Injury

BackgroundTissue repair and regeneration in the gastrointestinal system are crucial for maintaining homeostasis, with the process relying on intricate cellular interactions and affected by micro- and macro-nutrients. Iron, essential for various biological functions, plays a dual role in tissue healing by potentially causing oxidative damage and participating in anti-inflammatory mechanisms, underscoring its complex relationship with inflammation and tissue repair. ObjectiveThe study aimed to elucidate the role of low dietary iron in gastrointestinal tissue repair. MethodsWe utilized quantitative iron measurements to assess iron levels in inflamed regions of patients with ulcerative colitis and Crohn’s disease. In addition, 3 mouse models of gastrointestinal injury/repair (dextran sulfate sodium-induced colitis, radiation injury, and wound biopsy) were used to assess the effects of low dietary iron on tissue repair. ResultsWe found that levels of iron in inflamed regions of both patients with ulcerative colitis and Crohn’s disease are elevated. Similarly, during gastrointestinal repair, iron levels were found to be heightened, specifically in intestinal epithelial cells across the 3 injury/repair models. Mice on a low-iron diet showed compromised tissue repair with reduced proliferation. In standard diet, epithelial cells and the stem cell compartment maintain adequate iron stores. However, during a period of iron deficiency, epithelial cells exhaust their iron reserves, whereas the stem cell compartments maintain their iron pools. During injury, when the stem compartment is disrupted, low iron levels impair proliferation and compromise repair mechanisms. ConclusionsLow dietary iron impairs intestinal repair through compromising the ability of epithelial cells to aid in intestinal proliferation.

Synbiotic Combination between Lactobacillus paracasei VL8 and Mannan-Oligosaccharide Repairs the Intestinal Barrier in the Dextran Sulfate Sodium-Induced Colitis Model by Regulating the Intestinal Stem Cell Niche.

Previously, Lactobacillus paracasei VL8, a lactobacillus strain isolated from the traditional Finnish fermented dairy product Viili, demonstrated immunomodulatory and antibacterial effects. The prebiotic mannan-oligosaccharide (MOS) further promoted its antibacterial activity and growth performance, holding promise for maintaining intestinal health. However, this has not been verified in vivo. In this study, we elucidated the process by which L. paracasei VL8 and its synbiotc combination (SYN) with MOS repair the intestinal barrier function in dextran sodium sulfate (DSS)-induced colitis mice. SYN surpasses VL8 or MOS alone in restoring goblet cells and improving the tight junction structure. Omics analysis on gut microbiota reveals SYN's ability to restore Lactobacillus spp. abundance and promote tryptophan metabolism. SYN intervention also inhibits the DSS-induced hyperactivation of the Wnt/β-catenin pathway. Tryptophan metabolites from Lactobacillus induce intestinal organoid differentiation. Co-housing experiments confirm microbiota transferability, replicating intestinal barrier repair. In conclusion, our study highlights the potential therapeutic efficacy of the synbiotic combination of Lactobacillus paracasei VL8 and MOS in restoring the damaged intestinal barrier and offers new insights into the complex crosstalk between the gut microbiota and intestinal stem cells.

Antagonizing interleukin-5 receptor ameliorates dextran sulfate sodium-induced experimental colitis in mice through reducing NLRP3 inflammasome activation

Inflammatory bowel disease (IBD) is a condition characterized by inflammation in the gastrointestinal tract. Reducing intestinal inflammation is a promising approach for treating IBD. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, a critical component of the innate immune system, is implicated in the pathogenesis of IBD. Therefore, inhibiting NLRP3 inflammasome activation is a potential therapeutic strategy for IBD. In this study, we investigated the effects of the interleukin-5 (IL-5) receptor antagonist YM-90709 on dextran sulfate sodium-induced experimental colitis in mice. We found that YM-90709 reduced the expressions of IL-1β and caspase-1 p20 in the colon and ameliorated colitis. Furthermore, we identified YM-90709 as an effective agent for inhibiting NLRP3 inflammasome activation. Knockdown of IL-5 receptor or using an inhibitor of STAT5, a key transcription factor downstream of the IL-5/IL-5 receptor signal pathway, also reduced NLRP3 inflammasome-dependent IL-1β release and ASC speck formation. Our study is the first to demonstrate that the NLRP3 inflammasome may be a downstream signal of IL-5/IL-5 receptor and that YM-90709 protects against IBD by inhibiting IL-5 receptor. These findings suggest a new strategy for regulating intestinal inflammation and managing IBD.

Circadian Rhythm Perturbation Aggravates Gut Microbiota Dysbiosis in Dextran Sulfate Sodium-Induced Colitis in Mice.

Circadian rhythm disruption is increasingly considered an environmental risk factor for the development and exacerbation of inflammatory bowel disease. We have reported in a previous study that nychthemeral dysregulation is associated with an increase in intestinal barrier permeability and inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. To investigate the effect of circadian rhythm disruption on the composition and diversity of the gut microbiota (GM), sixty male C57BL/6J mice were initially divided to two groups, with the shifted group (n = 30) exposed to circadian shifts for three months and the non-shifted group (n = 30) kept under a normal light-dark cycle. The mice of the shifted group were cyclically housed for five days under the normal 12:12 h light-dark cycle, followed by another five days under a reversed light-dark cycle. At the end of the three months, a colitis was induced by 2% DSS given in the drinking water of 30 mice. Animals were then divided into four groups (n = 15 per group): sham group non-shifted (Sham-NS), sham group shifted (Sham-S), DSS non-shifted (DSS-NS) and DSS shifted (DSS-S). Fecal samples were collected from rectal content to investigate changes in GM composition via DNA extraction, followed by high-throughput sequencing of the bacterial 16S rRNA gene. The mouse GM was dominated by three phyla: Firmicutes, Bacteroidetes and Actinobacteria. The Firmicutes/Bacteroidetes ratio decreased in mice with induced colitis. The richness and diversity of the GM were reduced in the colitis group, especially in the group with inverted circadian rhythm. Moreover, the GM composition was modified in the inverted circadian rhythm group, with an increase in Alloprevotella, Turicibacter, Bacteroides and Streptococcus genera. Circadian rhythm inversion exacerbates GM dysbiosis to a less rich and diversified extent in a DSS-induced colitis model. These findings show possible interplay between circadian rhythm disruption, GM dynamics and colitis pathogenesis.

Anthocyanin Extracted from Purple Sweet Potato Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice by Suppressing Pyroptosis and Altering Intestinal Flora Structure.

The objective of this study was to examine the impact and underlying mechanisms of pelargonidin-3-galactoside (Pg3gal) produced from purple sweet potatoes on colonic inflammation induced by dextran sulfate sodium (DSS) in a murine model of ulcerative colitis (UC). C57BL/6J mice were categorized into four groups (n = 6 per group): DSS+Pg3gal, control, control+Pg3gal, and DSS. Colitis was induced by providing free access to 3% DSS for 10 days. The DSS+Pg3gal model mice received DSS concurrently with intragastric Pg3gal (25 mg/kg). The health of the mice was carefully monitored on a regular basis, and scores for the Disease Activity Index (DAI) were documented. A histological assessment was conducted using hematoxylin and eosin staining to evaluate the extent of mucosal injury present. The expression levels of IL-6, NLRP3, ASC, cleaved-Caspase-1, TNF-α, N-GSDMS, and cleaved-IL-1β proteins were evaluated by Western blot analysis. The process of 16S rRNA sequencing was carried out to examine the composition and relative abundance of gut microbiotas within the intestines of the mice. The DAI results revealed that Pg3gal significantly attenuated the DSS-induced UC in mice. In addition, it successfully alleviated the decline in colon size, improved the condition of colonic tissue, and significantly inhibited the production of proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the colon tissues. Additionally, Pg3gal modulated the DSS-induced imbalanced gut microbiota, as evidenced by decreased Proteobacteria and Deferribacteres and simultaneous elevation in Firmicutes, Bacteroidetes, and Verrucomicrobia. In summary, Pg3gal alleviated DSS-induced UC by inhibiting pyroptosis in intestinal epithelial cells and enhancing the structural integrity of the gut microbiota.

Genistein Alleviates Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice by Regulating Th17/Treg Cell Balance: Implication for the G Protein-coupled Estrogen Receptor

Objectives This study aimed to evaluate the therapeutic effects and mechanism of genistein on dextran sulfate sodium-induced mouse model of ulcerative colitis (UC). Materials and Methods A DSS-induced mouse model for UC was used in this study. Mice were then treated with genistein or a combination of genistein and the G protein-coupled estrogen receptor (GPER) antagonist G15. Colon length, disease activity index (DAI), spleen index (SI), histopathological alterations, and integrity of the colonic barrier were evaluated. The expression of inflammatory cytokines and antioxidant capacity were detected. Populations of T helper 17 cells (Th17) and Regulatory T cells (Treg) in the mesenteric lymph nodes (MLN) were analyzed. The expression of a transcription factor for Th17 and Treg in the colonic tissues was detected. Results Genistein treatment significantly alleviated DSS-induced colitis, summarized as increased colonic length, decreased DAI, SI, improved histopathological alterations, and colonic barrier integrity. Genistein treatment restrained pro-inflammatory cytokines and oxidative enzyme release while promoting anti-inflammatory and anti-oxidative enzyme release. Flow cytometry indicated that genistein significantly reduced the Th17 population while boosting Treg populations. Furthermore, genistein inhibited the expression of transcription factors associated with Th17 and promoted the expression of transcription factors associated with Treg in the colonic tissue. Intriguingly, these observed effects of genistein were abolished when UC mice were treated with a combination of genistein and GPER antagonist G15. Conclusion This study suggests that genistein is potent in protecting against DSS-induced colonic injuries by rebalancing Th17/Treg and that GPER may be a vital target for genistein-mediated immunomodulatory effects in UC.

D-alanine Inhibits Murine Intestinal Inflammation by Suppressing IL-12 and IL-23 Production in Macrophages.

Free D-amino acids, which have different functions from L-amino acids, have recently been discovered in various tissues. However, studies on the potential interactions between intestinal inflammation and D-amino acids are limited. We examined the inhibitory effects of D-alanine on the pathogenesis of intestinal inflammation. We investigated serum D-amino acid levels in 40 patients with ulcerative colitis and 34 healthy volunteers. For 7 days [d], acute colitis was induced using dextran sulphate sodium in C57BL/6J mice. Plasma D-amino acid levels were quantified in mice with dextran sulphate sodium-induced colitis, and these animals were administered D-alanine via intraperitoneal injection. IFN-γ, IL-12p35, IL-17A, and IL-23p19 mRNA expression in the colonic mucosa was measured using real-time polymerase chain reaction [PCR]. In vitro proliferation assays were performed to assess naïve CD4+ T cell activation under Th-skewing conditions. Bone marrow cells were stimulated with mouse macrophage-colony stimulating factor to generate mouse bone marrow-derived macrophages. Serum D-alanine levels were significantly lower in patients with ulcerative colitis than in healthy volunteers. Dextran sulphate sodium-treated mice had significantly lower plasma D-alanine levels than control mice. D-alanine-treated mice had significantly lower disease activity index than control mice. IFN-γ, IL-12p35, IL-17A, and IL-23p19 mRNA expression levels were significantly lower in D-alanine-administered mice than in control mice. D-alanine suppressed naïve T cell differentiation into Th1 cells in vitro, and inhibited the production of IL-12p35 and IL-23p19 in bone marrow-derived macrophages. Our results suggest that D-alanine prevents dextran sulphate sodium-induced colitis in mice and suppresses IL-12p35 and IL-23p19 production in macrophages.

Effect of by BIOVITA 3 (a Blend of Three Probiotics) on Dextran Sulfate Sodium-Induced Colitis in Mice

Effect of by BIOVITA 3 (a Blend of Three Probiotics) on Dextran Sulfate Sodium-Induced Colitis in Mice

5-Methoxytryptophan Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting the Intestinal Epithelial Damage and Inflammatory Response.

Colitis is a refractory intestinal inflammatory disease significantly affecting the quality of a patient's life and increasing the risk of exacerbation. The primary factors leading to colitis encompass infections, insufficient blood flow, and the buildup of collagen as well as white blood cells. Among various available therapeutics, 5-methoxytryptophan (5-MTP) has emerged as one of the protectants by inhibiting inflammatory damage. Nonetheless, there is no report on the role of 5-MTP in the treatment of colitis. To verify the anti-inflammatory effect of 5-MTP in vivo, we first constructed mouse model with dextran sulfate sodium-induced colitis. Furthermore, the macrophage infiltration and release of inflammatory factors through western blot (WB) and hematoxylin-eosin staining analyses were examined. Intestinal epithelial cell tight junction damage and apoptosis were investigated by WB analysis, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Finally, we examined the generation of cellular inflammation and analyzed the influence of 5-MTP on M1 polarization at the cellular level. This study initially confirmed that 5-MTP possessed an excellent therapeutic effect on colitis. 5-MTP inhibits macrophage infiltration and the generation of inflammatory factors. In addition to its effects on immune cells, 5-MTP significantly inhibits intestinal epithelial cell tight junction damage and apoptosis in vivo. Moreover, it inhibits inflammation and M1 polarization response in vitro. 5-MTP counteracts excessive inflammation, thereby preventing intestinal epithelial tight junction damage. In addition, inhibition of apoptosis suggests that 5-MTP may be a potential therapeutic agent for colitis.

Resistant starch and tannic acid synergistically ameliorated dextran sulfate sodium-induced ulcerative colitis, particularly in the distal colon.

We previously confirmed that tannic acid could delay the metabolism of resistant starch in vitro, which suggested that tannic acid might deliver resistant starch to the distal colon in vivo. Accordingly, co-supplementation of resistant starch and tannic acid might be beneficial for keeping the distal colon healthy. Thus, this study compared the effects of resistant starch, tannic acid and their mixtures on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. It was found that the mixtures had a more profound effect on ameliorating DSS-induced ulcerative colitis than resistant starch or tannic acid. In particular, the mixtures reversed the histology damage of the distal colon induced by DSS, while resistant starch or tannic acid alone did not. The mixtures also had a stronger ability to resist oxidative stress and inhibit inflammation in the distal colon. These results suggested that resistant starch and tannic acid synergistically alleviated DSS-induced ulcerative colitis, particularly in the distal colon. On the other hand, DSS decreased the production of short-chain fatty acids and induced significant microbial disorder, while the administration of resistant starch, tannic acid and their mixtures reversed the above shifts caused by DSS. In particular, the mixtures exhibited stronger prebiotic activity, as indicated by the microbial composition and production of short-chain fatty acids. Therefore, it was inferred that tannic acid delivered resistant starch to the distal colon of mice, and thus the mixtures had stronger prebiotic activity. As a result, the mixtures effectively alleviated ulcerative colitis in the whole colon.

Retraction: Dealcoholized muscadine wine was partially effective in preventing and treating dextran sulfate sodium-induced colitis and restoring gut dysbiosis in mice.

Retraction of 'Dealcoholized muscadine wine was partially effective in preventing and treating dextran sulfate sodium-induced colitis and restoring gut dysbiosis in mice' by Hao Li et al., Food Funct., 2023, 14, 5994-6011, https://doi.org/10.1039/D3FO00047H.

Co-administration of 1,25-dihydroxyvitamin D3 and infliximab improves colitis in mice by modulating Treg differentiation.

The combination of TNF-α inhibitors and vitamin D in colitis remains to be elucidated. In the present study, we revealed the benefit of infliximab (IFX) and vitamin D in a mouse model of Ulcerative colitis (UC). A dextran sulfate sodium-induced colitis model was used. The therapeutic effect of the combination was evaluated by symptom and histopathology analysis. The synergistic mechanism was explored by detecting the regulatory effect of the combined therapy on Regulatory T cell (Treg) differentiation. IFX and 1,25-dihydroxyvitamin D3 (VitD3) synergistically prevented the development of colitis by improving clinical signs, pathological and hematological manifestation, and inhibiting intestinal inflammation (decreasing TNF-α, IL-1β, and IL-6). Co-administration of IFX (2.5 mg/kg) with VitD3 or IFX (5.0 mg/kg) with VitD3 was more effective than administration of IFX (2.5 mg/kg, 5.0 mg/kg). There was no difference in therapeutic effect between IFX (5.0 mg/kg) and VitD3+ IFX (2.5 mg/kg) groups or between the VitD3+IFX (5.0 mg/kg) and VitD3+ Azathioprine (AZA) groups. VitD3 or combination therapy showed more powerful regulation of splenetic Treg differentiation and IL-10 production than IFX alone. Moreover, VitD3 alone or in combination induced higher levels of Foxp3 and IL-10 than IFX in colon tissue. In ulcerative colitis patients, serum VitD3 levels positively correlated with Treg levels. VitD3 and IFX synergistically inhibit colitis based on their powerful regulation of Treg differentiation. VitD3 combined with IFX is an alternative therapy for patients who are intolerant to standard doses of IFX or combination of IFX and AZA.

Li-Hong Tang alleviates dextran sodium sulfate-induced colitis by regulating NRF2/HO-1 signaling pathway and gut microbiota.

Ulcerative colitis (UC) is marked by recurring inflammation. Existing treatments are ineffective and may have toxic side effects. Thus, new therapeutic agents are urgently needed. We studied the botanical formula "Li-Hong Tang (LHT)", which contains two main ingredients, Salvia plebeia R. Br and Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba. In this study, we aimed to identify the effects of LHT on UC and explore its potential mechanism. LHT was analyzed using a mass spectrometer (MS). DSS at a dose of 2.5% was utilized to develop UC in mice. The administered groups received low, medium, and high dosages (0.32g/kg, 0.64g/kg, and 1.28g/kg) of LHT and the positive medication, sulfasalazine (0.2g/kg), respectively. Body weight, disease activity index (DAI) score, colon length, spleen index, serum myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD) and inflammatory factor concentrations were monitored. The expression of NRF2 and HO-1 in colonic tissues was evaluated by immunohistochemistry. 16S rDNA sequencing was employed to investigate alterations in the gut microbiota of the mice, aiming to elucidate the extent of LHT's impact. LHT may ameliorate DSS-induced colitis in mice by lowering inflammation, reducing oxidative stress, restoring the intestinal barrier, and influencing the NRF2/HO-1 pathway. Moreover, LHT treatment exhibited a regulatory effect on the gut microbiota, characterized by elevated levels of Patescibacteria, Verrucomicrobiota, Candidatus_Saccharimonas, Lactobacillus, and Ligilactobacillus levels while decreasing Oscillibacter and Colidextribacter levels. Further study indicated that MPO, NO, and inflammatory factors were positively correlated with Oscillibacter, Colidextribacter, Escherichia-Shigella, Anaerostines, and negatively with Lactobacillus, Clostridiales_unclassified, Candidatus_Saccharimonas, and Patescibacteria. Furthermore, colony network analysis revealed that Lactobacillus was negatively associated with Oscillibacter and Colidextribacter, whereas Oscillibacter was positively related to Colidextribacter. LHT protects against DSS-induced mice by inhibiting the inflammatory response, oxidative stress, and mucosal injury. The protective role may involve regulating the NRF2/HO-1 signaling pathway and gut microbiota.

Administering Lactiplantibacillus fermentum F6 decreases intestinal Akkermansia muciniphila in a dextran sulfate sodium-induced rat colitis model.

Probiotics are increasingly used to manage gut dysbiosis-related conditions due to their robust ability to manipulate the gut microbial community. However, few studies have reported that probiotics can specifically modulate individual gut microbes. This study demonstrated that administering the probiotic, Lactiplantibacillus fermentum F6, could ameliorate dextran sulfate sodium-induced colitis in a rat model, evidenced by the decreases in the disease activity index score, histopathology grading, and serum pro-inflammatory cytokine levels, as well as the increase in the serum anti-inflammatory cytokine levels. Shotgun metagenomics revealed that the fecal metagenomic of colitis rats receiving the probiotic intervention contained substantially fewer Akkermansia muciniphila than the dextran sulfate sodium group. Thus, the probiotic mechanism might be exerted by reducing specific gut microbial species associated with disease pathogenesis. A new paradigm for designing probiotics that manage diseases through direct and precise manipulation of gut microbes has been provided through this study.

Exopolysaccharide production by Lactobacillus plantarum T10 is responsible for the probiotic activity in enhancing intestinal barrier function in vitro and in vivo.

Lactobacillus probiotics exert their effects in a strain-specific and metabolite-specific manner. This study aims to identify lactobacilli that can effectively enhance the intestinal barrier function both in vitro and in vivo and to investigate the underlying metabolite and molecular mechanisms involved. Nine Lactobacillus isolates were evaluated for their ability to enhance the IPEC-J2 cellular barrier function and for their anti-inflammatory and anti-apoptotic effects in IPEC-J2 cells after an enterotoxigenic Escherichia coli challenge. Of the nine isolates, L. plantarum T10 demonstrated significant advantages in enhancing the cellular barrier function and displayed anti-inflammatory and anti-apoptotic activities in vitro. The bioactivities of L. plantarum T10 were primarily attributed to the production of exopolysaccharides, which exerted their effects through the TLR-mediated p38 MAPK pathway in ETEC-challenged IPEC-J2 cells. Furthermore, the production of EPS by L. plantarum T10 led to the alleviation of dextran sulfate sodium-induced colitis by reducing intestinal damage and enhancing the intestinal barrier function in mice. The EPS is classified as a heteropolysaccharide with an average molecular weight of 23.0 kDa. It is primarily composed of mannose, glucose, and ribose. These findings have practical implications for the targeted screening of lactobacilli used in the production of probiotics and postbiotics with strain-specific features of exopolysaccharides.

Reciprocal regulation of protein arginine deiminase 2 and 4 expression in the colonic mucosa of ulcerative colitis.

Neutrophils express protein arginine deiminase 2 and PAD4, both of which mediate the citrullination of target proteins to induce production of neutrophil extracellular traps. Although PAD-dependent NETs trigger inflammatory bowel disease, the mechanisms governing the expression of PAD2 and PAD4 are poorly understood. In this study, we tried to clarify expression mechanisms of PAD2 and PAD4 in the colonic mucosa of patients with ulcerative colitis and Crohn's disease. Administration of Cl-amidine, a pan PAD-inhibitor, attenuated the development of dextran sodium sulfate-induced colitis, the effects of which were accompanied by reduced IL-6 and TNF-α production by colonic lamina propria mononuclear cells upon exposure to Toll-like receptor ligands. The mRNA expression of colonic PAD2 and PAD4 was negatively and positively correlated with disease activity and pro-inflammatory cytokine responses in patients with UC, respectively. Reciprocal regulation of PAD2 and PAD4 mRNA expression was observed in the colonic mucosa of UC patients, but not in those of CD patients. PAD4 mRNA expression was correlated with disease activity and pro-inflammatory cytokine responses in patients with CD. Collectively, these data suggest that reciprocal regulation of PAD2 and PAD4 expression is associated with disease activity in UC patients.

Gut Microbiota-mediated Alleviation of Dextran Sulfate Sodium-induced Colitis in Mice

Background and AimsGut dysbiosis characterized by an imbalanced microbiota is closely involved in the pathogenesis of a widespread gastrointestinal inflammatory disorder, inflammatory bowel disease (IBD). However, it is unclear how the complex intestinal microbiota affects development or resistant of mucosal inflammation. Our aim was to investigate the impact of the gut microbiota on susceptibility in a mouse model of ulcerative colitis. MethodsWe compared the susceptibility to dextran sulfate sodium (DSS)-induced colitis of inbred BALB/c mice obtained from the three main distributors of laboratory animals in Japan. Clinical symptoms of the colitis and the faecal microbiota were assessed. Cohousing approach was used to identify whether the gut microbiota is a primary factor determining disease susceptibility. ResultsHere, we showed differences in the susceptibility of BALB/c mice from the vendors to DSS colitis. Analysis of the gut microbiota using 16S rRNA sequencing revealed clear separation of the gut microbial composition among mice from the vendors. Notably, the abundance of the phylum Actinobacteriota was strongly associated with disease activity. We also observed the expansion of butyrate-producing Roseburia species in mice with decreased susceptibility of the disease. Further cohousing experiments showed that variation in clinical outcomes was more correlated with the gut microbiota than genetic variants among substrains from different suppliers. ConclusionsA BALB/c substrain that was resistant to DSS-induced colitis was observed, and the severity of DSS-induced colitis was mainly influenced by the gut microbiota. Targeting butyrate-producing bacteria could have therapeutic potential for ulcerative colitis.

Aged oolong tea alleviates dextran sulfate sodium-induced colitis in mice by modulating the gut microbiota and its metabolites

In this study, the mechanism of aged oolong tea (AOT) to alleviate colitis was investigated in terms of microbiome, metabolome, and fecal microbiota transplantation (FMT). AOT storage period could alleviate colitis in mice and there were some differences in AOT between storage periods, especially AOT-10. AOT improves UC by modulating oxidative stress and inflammatory factors and upregulating intestinal tight junction protein expression (Occludin, Claudin-1, ZO-1 and MUC2), which is associated with the recovery of gut microbiota. FMT and targeted metabolomics further demonstrate that the anti-inflammatory effects of AOT can reshape the gut microbiota through faecal bacterial transfer. Anti-inflammatory effects are exerted through the stimulation of metabolic pathways associated with amino acid, fatty acid and bile acid metabolites. Importantly, the study identified key bacteria (e.g., Sutterella, Clostridiaceae_Clostridium, Mucispirillum, Oscillospira and Ruminococcus) for the development and remission of inflammation. Conclusively, AOT may have great potential in the future adjuvant treatment of colitis.

Edible pueraria lobata-derived exosome-like nanovesicles ameliorate dextran sulfate sodium-induced colitis associated lung inflammation through modulating macrophage polarization

BackgroundInflammatory bowel diseases (IBD), such as severe colitis, are associated with the development of lung inflammation and tissue damage. Pueraria lobata (P. lobata) plays an essential role in controlling cytokines. However, the exact mechanism of the inflammation response is still unknown. Purpose: To investigate the effects of the P. lobata-derived exosomes-like nanovesicles (PLDENs) on colitis and their role in the lung inflammatory response. MethodsIn this study, we investigated the effects of PLDENs on the dextran sulfate sodium (DSS)-induced colitis and explored the mechanisms by forming the gut-lung axis. PLDENs were characterized by mass spectrometry-based proteomic analysis. ResultsThe results showed that PLDENs had significant preventive effects in DSS-induced colitis and pathological changes in colons in a dose-dependent manner. Simultaneously, the treatment of PLDENs could effectively reduce inflammatory changes in the lung. PLDENs could selectively regulate the composition of gut microbiota. ConclusionThese data suggested that the treatment of PLDENs could ‘attenuate DSS-induced colitis and lung inflammation, providing an efficacious supplement for reducing co-morbidities in IBD patients.