Dextran Sulfate Sodium-induced Colitis Research Articles

The effect and mechanism of Huangqin-Baishao herb pair in the treatment of dextran sulfate sodium-induced ulcerative colitis

BackgroundThe haungqing (Scutellariae Radix) and baishao (Paeoniae Radix Alba) herb pair (HBHP) is a common prescribed herbal formula or is added to other traditional Chinese medicine (TCM) prescriptions to treat ulcerative colitis (UC). However, the underlying mechanism is unclear. PurposeElucidate the efficacy and potential mechanism of HBHP against UC. MethodsFirst, The UC model of mice induced by dextran sulfate sodium (DSS) was established. The mice were randomly divided into Control group, DSS group, SASP group (390 mg/kg), and HPHP group (1.95 g/kg), with 8 mice per group. Drugs were administrated via oral gavage for 7 days. Then, Disease activity index (DAI), length of the colon, histopathology, and changes in inflammatory cytokines in colonic tissues were analyzed to assess the effect of HBHP on UC. Besides, Network pharmacology was applied to identify the active compounds, core targets of HBHP in the treatment of UC, and the corresponding signaling pathways to explore the underlying mechanisms. Finally, Western blot (WB), immunohistochemistry (IHC) and molecular docking were performed to validate the results. ResultsHBHP significantly reduced DAI score and decreased colon length shortening in DSS-induced UC mice. The administration of HBHP was able to effectively alleviated mucosal ulceration and epithelial destruction. In addition, HBHP treatment obviously - reduced the expressions of TNF-α, IL-6, and IL-1β in colon tissues (p < 0.05 or p < 0.01). 35 bioactive compounds and 290 HBHP targets related to UC were obtained. Among them 3 key active compounds (baicalein, panicolin, and norwogonin) with higher degree values in the drug-compound-target network and 21 hub genes (STAT3, JAK2, SRC, AKT1, PIK3CA, and VEGFA, etc.) were identified. KEGG enrichment analysis suggested that HBHP's mechanisms mainly involve the JAK-STAT pathway. Abnormal activation of JAK/STAT signaling is believed to be involved in the pathogeneses of UC. Notably, WB and IHC showed that HBHP significantly down-regulated the protein expression levels of p-JAK2 (p < 0.05) and p-STAT3 (p < 0.05 or p < 0.01). JAK2 and STAT3 might be core targets for the action of HBHP; this possibility was also supported by molecular docking. ConclusionsHBHP could alleviate DSS-induced UC, reduce tissue inflammation, and its mechanism might primarily be achieved by inhibiting JAK2/STAT3 signaling pathway. Meanwhile, our work revealed that network pharmacology combined with experimental verification is a cogent means of studying the mechanism of TCM.

Egg Yolk Lipids Alleviated Dextran Sulfate Sodium-Induced Colitis by Inhibiting NLRP3 Inflammasome and Regulating Gut Microbiota.

The increasing incidence of inflammatory bowel disease (IBD) has become a global phenomenon. Egg yolk lipids are one of the essential dietary foods, but its effects on intestinal immunity remain unclear. Here, egg yolk lipids are obtained using ethanol extraction and a total of 601 kinds of lipids are detected via lipidomics, including 251 kinds of triglycerides, 133 kinds of phosphatidylcholines, 44 kinds of phosphatidylethanolamines. Then, the study finds that egg yolk lipids significantly alleviate dextran sulfate sodium-induced colitis and reduce the production of inflammatory factors. Meanwhile, egg yolk lipids also maintain intestinal barrier integrity and decrease lipopolysaccharide translocation by alleviating intestinal structure damage and increasing the numbers of goblet cells and mucin 2. Mechanistically, egg yolk lipids attenuate colitis by inhibiting the assembly and activation of NLRP3 inflammasome. Moreover, the study also finds that egg yolk lipids reverse gut microbiota dysbiosis referring to increased relative abundance of Bacteroides acidifaciens and decrease relative abundance of Akkermansia muciniphila, as well as increased short chain fatty acids concentration in the gut. Together, the study elucidates the anti-colitis effect of egg yolk lipids and provides positive evidences for egg yolk lipids involving in dietary strategy and IBD therapy.

Chaenomeles sinensis polysaccharide and its carboxymethylated derivative alleviate dextran sulfate sodium-induced ulcerative colitis via suppression of inflammation and oxidative stress

Chaenomeles sinensis fruit polysaccharide (CSP) and carboxymethylated CSP (CSP-M) were prepared using ultrasound extraction and the sodium hydroxide-chloroacetic acid method. Structural analysis revealed that both CSP and CSP-M mainly consisted of glucose, arabinose, rhamnose, glucuronic acid, galactose, and xylose, and the introduction of carboxymethyl did not damage the polymer chain of CSP. In vivo studies verified that both CSP and CSP-M could remarkably alleviate the symptoms of ulcerative colitis (UC) mice and reduce intestinal epithelial cell depletion, along with the infiltration of inflammatory cells in colon tissue, by mediating the expression of myeloperoxidase (MPO), inflammatory factors [tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6], and oxidative stress factors [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and nitric oxide (NO)]. Most importantly, the introduction of carboxymethyl significantly enhanced the anti-UC activity of CSP, confirming the efficacy of carboxymethylation as a method to enhance the biological activities of CSP, thereby suggesting the potential of CSP-M as a therapeutic option for UC.

Portulaca oleracea L. polysaccharide alleviates dextran sulfate sodium-induced ulcerative colitis by regulating intestinal homeostasis

Portulaca oleracea L. (purslane) is a vegetable that contains a variety of active compounds with nutritional properties and has the potential to treat ulcerative colitis (UC). However, the mechanisms underlying the effects of Portulaca oleracea L. polysaccharide (POP) in alleviating UC remain unclear. In this study, we prepared an aqueous extract of purslane and separated a fraction with molecular weight >10 kDa using membrane separation. This fraction was used to isolate POP. The effect of POP on gut microbiota and colon transcriptome in dextran sulfate sodium-induced UC model mice was evaluated. POP treatment reduced inflammation and oxidative stress imbalance in UC mice. In addition, POP improved the intestinal barrier and regulated intestinal homeostasis. Importantly, POP was found to regulate gut microbiota, maintain the levels of retinol and short-chain fatty acids in the gut, promote the proliferation and differentiation of B cells in the colon, and increase the expression of immunoglobulin A. These results provide novel insights into the role of POP in regulating intestinal homeostasis, which should guide further development of POP as a functional food.

Cynarin ameliorates dextran sulfate sodium-induced acute colitis in mice through the STAT3/NF-κB pathway

Objective Cynarin is a derivative of hydroxycinnamic acid presented in various medicinal plants, such as Cynara scolymus L. and Onopordum illyricum L. To date, the antioxidant and antihypertensive activities of cynarin have been reported. However, whether cynarin has a therapeutic impact on ulcerative colitis (UC) is unclear. Therefore, the aim of this study was to explore the potential effect of cynarin on dextran sulfate sodium (DSS)-induced acute colitis in vivo and on lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced RAW264.7 and J774A.1 cellular inflammation model in vitro. Methods and Results In this study, we investigated that cynarin alleviated clinical symptoms in animal models, including disease activity index (DAI) and histological damage. Furthermore, cynarin can attenuate colon inflammation through decreasing the proportion of neutrophils in peripheral blood, reducing the infiltration of neutrophils, and macrophages in colon tissue, inhibiting the release of pro-inflammatory cytokines and suppressing the expression of STAT3 and p65. In cellular inflammation models, cynarin inhibited the expression of M1 macrophage markers, such as TNF-α, IL-1β, and iNOS. Besides, cynarin suppressed the expression of STAT3 and p65 as well as the phosphorylation of STAT3, p65. Cynarin inhibited the polarization of RAW264.7 and J774A.1 cells toward M1 and alleviated LPS/IFN-γ-induced cellular inflammation. Conclusion Considering these results, we conclude that cynarin mitigates experimental UC partially through inhibiting the STAT3/NF-кB signaling pathways and macrophage polarization toward M1. Accordingly, cynarin might be a potential and effective therapy for UC.

Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis-Related Th17 Response by Host-Microbe Retinoic Acid Biosynthesis.

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.

Gentianine alleviates dextran sulfate sodium-induced ulcerative colitis via inhibition of TLR4/NLRP3-mediated pyroptosis

ObjectivesUlcerative colitis (UC) is a common inflammatory bowel disorder. Gentiana scabra Bunge is a traditional medicinal plant that is used to treat a variety of diseases. Studies have shown that gentianine (GTN) from Gentiana scabra inhibits the development of inflammatory diseases. The purpose of this study was to investigate the effect and possible mechanism of action of GTN on UC in mice. MethodsAn animal model of UC was established using dextran sulfate sodium (DSS). Mice were administered intraperitoneally with GTN (12.5, 25, or 50 mg/kg/day) for seven days. Body weight and disease activity index (DAI) were monitored daily during GTN administration. Colon length, pathological changes, and myeloperoxidase (MPO) activity were measured following GTN administration. The signalling pathways regulated by GTN were analysed using machine learning. HT-29 cells were used to verify the effect and mechanism of action of GTN on UC in vitro. ResultsGTN suppressed weight loss, shortened colon length, alleviated colon injury, and reduced the DAI score and MPO activity of mice with UC in a dose-dependent manner. Further analysis showed that GTN inhibited the NOD-like receptor (NLR) signalling pathway. GTN markedly decreased the levels of NLR signalling pathway-related proteins. Moreover, GTN decreased the levels of pyroptosis-related proteins, IL-1β and IL-18. The in vitro data were consistent with those of animal experiments. Furthermore, TLR4 and NLRP3 overexpression eliminated the protective effects of GTN in HT-29 cells. ConclusionGentianine alleviated DSS-induced UC by inhibiting TLR4/NLRP3-mediated pyroptosis.

Bacteroides vulgatus alleviates dextran sodium sulfate-induced colitis and depression-like behaviour by facilitating gut-brain axis balance.

Patients with inflammatory bowel disease (IBD) have a higher prevalence of depression. Gut microbiota dysbiosis plays an important role in IBD and depression. However, few studies have explored the characteristic microbiota of patients with IBD and depression (IBDD), or their role in IBDD. We performed deep metagenomic sequencing and 16S rDNA quantitative PCR to characterise the gut microbial communities of patients with IBDD and patients with IBD without depression (IBDND). We then assessed the effect of the microbiota on colitis and depression in mouse models of dextran sulfate sodium salt (DSS)-induced colitis and lipopolysaccharide (LPS)-induced depression. Furthermore, liquid chromatography-tandem mass spectrometry was used to analyse the microbiota-derived metabolites involved in gut-brain communication. Evans Blue tracer dye was used to assess blood-brain barrier (BBB) permeability. Our results showed that the faecal abundance of Bacteroides vulgatus (B. vulgatus) was lower in patients with IBDD than in those with IBDND. In the DSS-induced colitis mouse model, the B. vulgatus group showed a significantly lower disease activity index score, lesser weight loss, and longer colon length than the DSS group. Moreover, B. vulgatus relieved depression-like behaviour in the DSS-induced colitis mouse model and in the LPS-induced depression mouse model. Furthermore, the key metabolite of B. vulgatus was p-hydroxyphenylacetic acid (4-HPAA), which was found to relieve intestinal inflammation and alleviate depression-like behaviours in mouse models. By increasing the expression of the tight junction protein claudin-5 in the vascular endothelium of the BBB, B. vulgatus and 4-HPAA play critical roles in gut-brain communication. B. vulgatus and B. vulgatus-derived 4-HPAA ameliorated intestinal inflammation and relieved depressive symptoms through the gut-brain axis. Thus, administration of B. vulgatus or 4-HPAA supplementation is a promising therapeutic strategy for treating IBD, particularly IBDD.

Restrictive diets have a beneficial impact on dextran sodium sulfate-induced colitis in male mice

BackgroundPreviously, we assessed the impact of restrictive diets, including caloric restriction (CR), intermittent fasting (IF), or fasting-mimicking diet (FMD), on a healthy gastrointestinal tract. We revealed that each of the diets shows anti-inflammatory outcomes. ObjectiveThe current study aimed to verify the diets' applicability in treating colitis. MethodsWe exposed a mouse model with mild chronic dextran sodium sulfate (DSS)-induced colitis to ad libitum control feeding, CR, IF, or FMD. The collected samples were analyzed for markers of inflammation. ResultsThe diets reduced DSS-triggered increases in spleen weight and myeloperoxidase (MPO) activity. Diet intervention also influenced occludin levels, small intestine morphology, as well as cytokine and inflammatory gene expression, mainly in the mucosa of the proximal colon. The diets did not reverse DSS-enhanced gut permeability and thickening of the colon muscularis externa. Concerning inflammatory gene expression, the impact of DSS and the dietary intervention was limited to the colon as we did not measure major changes in the jejunum mucosa, Peyer's patches, and mesenteric lymph nodes. Further, rather modest changes in the concentration of intestinal bile acids were observed in response to the diets, whereas taurine and its conjugates levels were strongly affected. ConclusionsDespite the differences in the dietary protocol, the tested diets showed very similar impacts and, therefore, may be interchangeable when aiming to reduce inflammation in the colon. However, FMD showed the most consistent beneficial impact.

Basis with RNA-Seq and WGCNA to explore the effect of Frankincense essential oil on dextran sodium sulfate-induced ulcerative colitis through MAPK/NF-κB signaling

PurposeFrankincense has been shown in studies to have healing benefits for people with ulcerative colitis (UC). However, its underlying mechanisms have not been fully investigated. The objective of this study was to explore the potential molecular mechanisms of Frankincense essential oil (FREO) in improving dextran sodium sulfate (DSS)-induced UC from multiple perspectives. MethodsThe FREO components were analyzed by GC–MS, and the interactions between the key active components and the mechanism of FREO were determined based on RNA-seq, “quantity-effect” weighting coefficient network pharmacology, WGCNA and pharmacodynamic experiments. The protection of FREO against DSS-induced UC mice was assessed by behavioral and pathological changes through mice. The expression of pro-inflammatory cytokines was measured using enzyme-linked immunosorbent assay. The expression of MAPK and NF-κB-related proteins by the Western Blotting and immunohistochemistry method. ResultsTreatment with FREO significantly improved the symptoms of weight loss, diarrhea, stool blood, and colon shortening in UC mice. Reduced intestinal mucosal damage and the degree of inflammatory cell infiltration in the colon. Decreased TNF-α and IL-6 levels in mice's serum and inhibited phosphorylation of ERK, p65 in MAPK and NF-κB signaling. ConclusionFREO may decrease the inflammatory response to reduce the symptoms of UC by modulating the MAPK/ NF-κB pathway. This may be due to the synergistic interaction of the effective ingredient Hepten-2-yl tiglate, 6-methyl-5-, Isoneocembrene A and P-Cymene. This study provides a promising drug candidate and a new concept for the treatment of UC.

Curcumin-loaded high internal phase emulsions alleviated dextran sulfate sodium-induced ulcerative colitis in mice via inhibiting inflammatory response and modulating gut microbiota

Curcumin is a polyphenol compound that presents an anti-colitis effect. However, oral curcumin exhibits limited in vivo biological efficacy, which may be solved by the use of high internal phase emulsions (HIPEs) that show remarkable abilities: bioactive compounds delivery, high chemical stability and loading capacity, as well as controlled release, etc. The objective of this study was to investigate the preventive effect of curcumin-loaded HIPEs using a dextran sulfate sodium (DSS)-induced colitis C57BL/6J mice model. After 30 mg/ml DSS treatment, all mice exhibited weight loss and shortening of colon tissues to different extents. Compared to the DSS group, the disease activity index and weight loss were considerably suppressed in the curcumin-loaded corn oil and curcumin-loaded HIPEs groups. These groups also exhibited reduced colonic crypt damage, mucosal inflammation and cellular infiltration in the histopathological sections of the colon. Dietary curcumin-loaded HIPEs inhibited the inflammatory response via reducing the contents of inflammatory factors (IL-6, TNF-α and IL-1β) and increasing the content of anti-inflammatory factor (IL-10) significantly. And the relative abundances of Firmicutes and Bacteroidetes were highly reduced and increased, respectively. These findings provide insights into expanding the utilization of curcumin and HIPEs in food systems for the treatment of colon inflammation and related diseases.

An efficient co-delivery system based on multilayer structural nanoparticles for programmed sequential release of resveratrol and vitamin D3 to combat dextran sodium sulfate-induced colitis in mice

Multilayer structural nanoparticles (MSNPs) fabricated by layer-by-layer self-assembly were used for the co-encapsulation of resveratrol (Res) and vitamin D3 (Vd). Res and Vd co-encapsulated MSNPs (Res-Vd-MSNPs) were evaluated by appearance, morphology, particle size, ζ potential and encapsulation efficiency (EE). The results showed that Res-Vd-MSNPs were spherical in shape with a particle size of 625.4 nm and a surface charge of +26.1 mV. The EE of Res and Vd was as high as 93.6 % and 90.8 %, respectively. Res-Vd-MSNPs exhibited better stability and lower degradation rate in simulated gastric fluid, allowing the programmed sequential release of Vd and Res in simulated intestinal fluid and simulated colonic fluid, which was also confirmed by in vivo fluorescence imaging of mice. In addition, Res-Vd-MSNPs effectively alleviated the clinical symptoms of dextran sulfate sodium salt (DSS)-induced colitis in mice, including weight loss, diarrhea and fecal bleeding, and it especially exerted a preventive effect on DSS-induced colon tissue damage and colon shortening. Furthermore, Res-Vd-MSNPs suppressed the expression of anti-inflammatory cytokines such as TNF-α, IL-1β and IL-6 and ameliorated DSS-induced oxidative damage, decreased colonic myeloperoxidase (MPO) and nitric oxide (NO) activities and elevated glutathione (GSH) level in DSS-treated mice. This study illustrated that MSNPs were potential carriers for developing the co-delivery system for the synergistic prevention and treatment of ulcerative colitis.

Microalgae polysaccharides exert antioxidant and anti-inflammatory protective effects on human intestinal epithelial cells in vitro and dextran sodium sulfate-induced mouse colitis in vivo

Microalgae polysaccharides (MAPS) have emerged as novel prebiotics, but their direct effects on intestinal epithelial barrier are largely unknown. Here, MAPS isolated from Chlorella pyrenoidosa, Spirulina platensis, and Synechococcus sp. PCC 7002 were characterized as mainly branched heteropolysaccharides, and were bioavailable to Caco-2 cells based on fluorescein isothiocyanate labeling and flow cytometry analysis. These MAPS were equally effective to scavenge hydroxyl and superoxide radicals in vitro and to attenuate the H2O2-, dextran sodium sulfate-, tumor necrosis factor α-, and interleukin 1β-induced burst of intracellular reactive oxygen species and mitochondrial superoxide radicals, interleukin-8 production, cyclooxygenase-2 and inducible nitric oxide synthase expression, and/or tight junction disruption in polarized Caco-2 cells. MAPS and a positive drug Mesalazine were intragastrically administered to C57BL/6 mice daily for 7 d during and after 4-d dextran sodium sulfate exposure. Clinical signs and colon histopathology revealed equivalent anti-colitis efficacies of MAPS and Mesalazine, and based on biochemical analysis of colonic tight junction proteins, goblet cells, mucin 2 and trefoil factor 3 transcription, and colonic and peripheral pro-inflammatory cytokines, MAPS alleviated dextran sodium sulfate-induced intestinal epithelial barrier dysfunction, and their activities were even superior than Mesalazine. Overall, MAPS confer direct antioxidant and anti-inflammatory protection to intestinal epithelial barrier function.

Amelioration of dextran sodium sulphate-induced colitis in mice by treatment with Lactobacillus rhamnosus and Lactobacillus reuteri: Intraspecific and interspecific patterns

Amelioration of dextran sodium sulphate-induced colitis in mice by treatment with <em>Lactobacillus rhamnosus</em> and <em>Lactobacillus reuteri</em>: Intraspecific and interspecific patterns

β-sitosterol alleviates dextran sulfate sodium-induced experimental colitis via inhibition of NLRP3/Caspase-1/GSDMD-mediated pyroptosis.

Background: Inflammation-related NLRP3/Caspase-1/GSDMD-mediated pyroptosis is involved in the progression of ulcerative colitis (UC). β-sitosterol (SIT) was reported to have anti-inflammatory effects on experimental colitis, while the regulation of SIT on pyroptosis is unclear. Therefore, the present study aimed to define the protective and healing effects of SIT on dextran sulfate sodium (DSS)-induced experimental UC rats and human epithelial colorectal adenocarcinoma cells (Caco-2) and explore the underlying mechanisms that are responsible for its effects on NLRP3/Caspase-1/GSDMD-mediated pyroptosis in UC. Methods: UC model rats were established by oral 4% DSS. Following colitis injury, the animals received SIT (doses of 50, 100, and 200mg/kg) treatment for 2 weeks. For in vitro study, we exposed Caco-2-50mg/mL DSS with or without SIT (concentrations of 8 and 16μg/mL). Disease activity index (DAI) and histopathological injury were assessed in vivo. Activation proteins of nuclear factor kappa B (NF-κB) signaling axis, and tight junction-related proteins of zonula occludens-1 (ZO-1) and occludin were detected in colon tissues. TNF-α, IL-1β, and IL-18 in serum and cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Changes in NLRP3/Caspase-1/GSDMD-mediated pyroptosis signaling pathway activation were analyzed both in tissues and cells. Results: Our findings suggested that SIT treatment attenuated the severity of 4% DSS-induced UC by protecting rats from weight and colon length loss, and macroscopic damage. SIT also reduced proinflammatory factors production (TNF-α, IL-1β, and IL-18) in serum and cell supernatant. Mechanistically, SIT downregulated the expression levels of pyroptosis-related proteins including Caspase-1, cleaved-Caspase-1, NLRP3, GSDMD, and GSDMD-N in colon tissues and Caco-2 cells. Further analysis indicated that SIT maintained the colonic barrier integrity by enhancing the protein expression of ZO-1 and occludin. Conclusion: We confirmed that SIT exerts protective and therapeutic effects on DSS-induced colitis injury by suppressing NLRP3/Caspase-1/GSDMD-mediated pyroptosis and inflammation response. These findings demonstrated that SIT could be a potential medication for UC treatment.

Phenolics from Dendrobium officinale Leaf Ameliorate Dextran Sulfate Sodium-Induced Chronic Colitis by Regulating Gut Microbiota and Intestinal Barrier.

The increasing incidence of colitis and the side effects of its therapeutic drugs have led to the search for compounds of natural origin, including phenolics, as new treatments for colitis. In this study, the potential mechanism of Dendrobium officinale leaf phenolics (DOP) on the relief of dextran sulfate sodium (DSS)-induced colitis was explored. The results showed that DOP treatment for 36 days reduced the symptoms of colitis caused by DSS, including reduction of the disease activity index and alleviation of colonic tissue damage. In addition, DOP downregulated the expression of key proteins of the TLR4/NF-κB signaling pathway and reduced the production of inflammatory cytokines. Furthermore, DOP could enhance the expression of tight junction proteins including ZO-1, Occludin, and Claudin-1 to restore intestinal mucosal barrier function. DOP also effectively regulates disordered intestinal flora and enhances the production of short-chain fatty acids, which is also beneficial in modulating gut internal environmental homeostasis, inhibiting inflammation, and restoring the intestinal barrier. These findings indicated that DOP can ameliorate DSS-induced chronic colitis by regulating gut microbiota, intestinal barrier, and inflammation, and it is a promising ingredient from D. officinale.

Cyberlindnera jadinii and Kluyveromyces lactis, two fungi used in food processes, have potential probiotic effects on gut inflammation.

The food industry has always used many strains of microorganisms including fungi in their production processes. These strains have been widely characterized for their biotechnological value, but we still know very little about their interaction capacities with the host at a time when the intestinal microbiota is at the center of many pathologies. In this study, we characterized five yeast strains from food production which allowed us to identify two new strains with high probiotic potential and beneficial effects in a model of intestinal inflammation.

Blautia producta displays potential probiotic properties against dextran sulfate sodium-induced colitis in mice

Blautia has attracted attention because of its potential efficacy in ameliorating host energy metabolism and inflammation. This study aims to investigate the influences of Blautia producta D4 on colitis induced by dextran sulfate sodium (DSS) and to reveal the underlying mechanisms. Results showed that B. producta D4 intervention significantly relieved body weight loss, and suppressed the elevation of pro-inflammatory cytokines (including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)) and excessive oxidative stress (myeloperoxidease (MPO) activity, superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, and malondialdehyde (MDA) level) in colitis mice. Moreover, the concentrations of tight junction proteins (occludin, claudin-1, and ZO-1) related to the intestinal barrier were obviously elevated, and colitis-related TLR4/NF-κB pathway activation was remarkably inhibited after B. producta D4 intervention. The intestinal microbial disorder was evidently ameliorated by increasing the relative abundance of Clostridium sensu stricto 1, Bifidobacterium, GCA-900066225, Enterorhabdus, and reducing the relative abundance of Lachnospiraceae NK4A136 group. In conclusion, oral administration of B. producta D4 could ameliorate DSS-induced colitis by suppressing inflammatory responses, maintaining the intestinal barrier, inhibiting TLR4/ NF-κB pathway, and regulating intestinal microbiota balance. These results are conducive to accelerate the development of B. producta D4 as a functional probiotic for colitis.

Fermented rice bran supplementation attenuates colonic injury through modulating intestinal aryl hydrocarbon receptor and innate lymphoid cells in mice with dextran sodium sulfate-induced acute colitis

This study investigated the effects of fermented rice bran (FRB) on modulating intestinal aryl hydrocarbon receptor (AhR) expression, innate lymphoid cell (ILC)3 populations, the fecal microbiota distribution, and their associations with dextran sodium sulfate (DSS)-induced acute colitis. C57BL/6 mice were assigned to four groups: 1) NC group, normal mice fed the AIN-93M diet; 2) FRB group, normal mice fed a diet supplemented with 5% FRB; 3) NCD group, DSS-treated mice fed AIN-93M; 4) FRBD group, DSS-treated mice fed a 5% FRB-supplemented diet. DSS was administered for 5 d and followed by 5 d for recovery. At the end of the experiment, mice were sacrificed. Their blood and intestinal tissues were collected. Results showed that there were no differences in colonic biological parameters and function between the NC and FRB groups. Similar fecal microbiota diversity was noted between these two groups. Compared to the non-DSS-treated groups, DSS administration led to increased intestinal permeability, enhanced inflammatory cytokine production and disease severity, whereas tight junctions and AhR, interleukin (IL)-22 expressions were downregulated, and the ILC3 population had decreased. Also, gut microbiota diversity differs from the non-DSS-treated groups and more detrimental bacterial populations exist when compared to the FRBD group. FRB supplementation in DSS-treated mice attenuated fecal microbial dysbiosis, decreased intestinal permeability, improved the barrier integrity, upregulated AhR and IL-22 expression, maintained the ILC3 population, and pathologically mitigated colonic injury. These findings suggest enhanced ILC3- and AhR-mediated functions may be partly responsible for the anti-colitis effects of FRB supplementation in DSS-induced colitis.

Lactoferrin improves symptoms of dextran sulfate sodium-induced colitis in mice through modulation of cellular senescence

The multifaceted effects of lactoferrin (LF) on the digestive and immune systems make it an attractive therapeutic option in inflammatory bowel diseases. In this study, we aimed to explore the anti-inflammatory effects of LF in colitis, particularly in relation to cellular senescence. We hypothesize that LF has the potential to modulate the senescence process. The effects of LF on senescence were tested in vitro using HCT116 and SW480 cell lines, and in vivo, the dextran sulfate sodium–induced mouse model of colitis. LF (500 mg/kg) alleviated symptoms of colitis in mice with a significant decrease in colon damage (P < .0001 vs. control) and microscopic (P < .05 vs. control) scores. Cellular senescence markers p16 and p21 were significantly upregulated in the mouse colon during inflammation (both P < .01 vs. control), and LF at 500 mg/kg decreased these markers (both P < .05 vs. dextran sulfate sodium–treated mice). In vitro, LF significantly affected the expression of p16 and p21 (P < .05–P < .0001 vs. control), senescence associated secretory phenotype (P < .01–P < .0001 vs. control), and telomere-specific proteins: telomeric repeat binding factor 1 and 2 (P < .05–P < .0001 vs. control) in a concentration-dependent manner. LF modulates the expression of cellular senescence markers and shows hallmarks of senolytic and pro-senescent activity, depending on dose. Further studies are needed to fully understand the anti-inflammatory effect of LF in the context of senescence and safe utilization in patients with inflammatory bowel diseases.