Dextran Sulfate Research Articles

Exploring the potential use of Caenorhabditis elegans as an animal model for evaluating chemical-induced intestinal dysfunction

Evaluating intestinal toxicity is crucial for identifying and preventing the harmful effects of environmental chemicals. Owing to the limitations of existing models in evaluating intestinal toxicity, the development of alternative models is urgently needed. This study explored the potential use of the nematode Caenorhabditis elegans as a model animal for assessing chemical-induced intestinal dysfunction. Changes in intestinal permeability and nutrient absorption in C. elegans individuals exposed to four intestine-disrupting chemicals (sodium dodecyl sulfate (SDS), dextran sulfate sodium (DSS), lipopolysaccharide (LPS) and ethanol) were examined using dye stain assays, an enzymatic photometric assay, and fluorescent probe uptake assays. Additionally, epigallocatechin-3-gallate (EGCG), an intestine-protecting phytochemical, was chosen to prevent ethanol-induced intestinal damage. The results indicated that SDS, DSS, LPS, and ethanol compromised the intestinal barrier in C. elegans. SDS had no effect on glucose absorption, but LPS, DSS, and ethanol inhibited or tended to inhibit glucose absorption. SDS, DSS, LPS, and ethanol reduced fatty acid absorption. LPS increased peptide absorption at a low dose but decreased it at a high dose; SDS, DSS, and ethanol attenuated peptide absorption. EGCG protected against the disruption of the intestinal barrier that was induced by ethanol treatment. These results suggest that C. elegans is a suitable surrogate model animal for evaluating chemical-induced intestinal dysfunction. These findings also provide new insights into the effects of SDS, DSS, LPS, and ethanol on intestinal function and highlight the potential of EGCG as a natural dietary intervention to protect individuals who use excess alcohol from intestinal injury.

Colon-targeted self-assembled nanoparticles loaded with berberine double salt ameliorate ulcerative colitis by improving intestinal mucosal barrier and gut microbiota

Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease marked by disturbances in intestinal mucosal barriers, persistent inflammation, oxidative stress, and dysbiosis of the intestinal microbiota. Traditional treatments often fail to adequately address these issues, primarily targeting inflammation. To address these limitations, this study developed an innovative approach using self-assembled nanoparticles for oral administration that target colonic inflammation. Berberine hydrochloride and ursodeoxycholic acid were combined to form a double salt (BeU), enhancing solubility and encapsulation. An amphiphilic polymer (FU-PA) was created by esterifying fucoidan with palmitic acid. FU-PA/BeU nanoparticles were prepared using the nanoprecipitation method and further encapsulated in acid-resistant sodium alginate microspheres (FU-PA/BeU NPs@MS) for targeted delivery to colonic lesions. The aggregation rate of nanoparticles with mucus was significantly reduced to 59 % of free berberine, while the apparent permeability coefficient increased by 2.4 times. In vitro, FU-PA/BeU NPs effectively targeted inflammatory macrophages, reducing IL-6 and NO levels while increasing IL-10 level (to 42.5 %, 26.8 %, and 539 % of the LPS-treated group, respectively). Additionally, the ABTS and DPPH radical scavenging capabilities of FU-PA/BeU NPs were 177.8 % and 151.7 % of BeU, respectively. In dextran sulphate sodium-induced UC mice, oral FU-PA/BeU NPs@MS significantly improved epithelial and mucosal barriers, restored gut microbiota diversity, reduced inflammation and oxidative stress. Remarkably, the mean colon length in the FU-PA/BeU NPs@MS group was 1.2 times longer than that in the sulfasalazine group. These dual-targeted FU-PA/BeU NPs@MS show great potential for UC treatment.

Therapeutic efficacy of jeoryeong-tang in dextran sulfate sodium-induced mouse model of inflammatory bowel disease

BackgroundJeoryeong-tang (JRT) was first recorded in Shanghanlun. It is composed of Polyporus Sclerotium, Poria, Asini Corii Colla, Alisma Rhizome, and Talcum at the same weight ratio. These medicinal materials are known for diuretic and hemostatic effects and have been traditionally used to treat kidney and bladder diseases. However, their potential therapeutic effects on colon diseases, particularly inflammatory bowel disease (IBD), have not been extensively studied. Therefore, this study aimed to investigate the therapeutic efficacy of JRT in IBD and explore its underlying anti-inflammatory mechanisms using a murine model of colitis induced by dextran sulfate sodium (DSS). MethodsMice were treated with 3.0 % or 2.5 % DSS for 6 days to induce colitis and JRT extract was then administered at a low level of 40 mg/kg (JRT-L), a medium level of 120 mg/kg (JRT-M), or a high level of 400 mg/kg (JRT-H) once a day. During the administration period, clinical disease activity index (DAI) reflecting survival rate, diarrhea, bloody stool, and weight loss rate was evaluated. The degree of colonic tissue damage was scored and evaluated through hematoxylin and eosin staining. Cyclooxygenase-2 (COX-2), p-STAT3 and p-ERK expression were examined with immunohistochemistry. Tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and -1β levels were analyzed using a cytokine enzyme-linked immunosorbent assay. ResultsAmong mice treated with 3.0 % DSS, JRT-M significantly improved the survival rate compared to other treatments as a result of observation for a total of 14 days. While, in the 2.5 % DSS-treated model, the average body weights of mice in both of JRT-M and JRT-H groups were significantly higher than that in the DSS group. In addition, the JRT-M group showed significantly lower DAI score than that in the DSS group. As a result of evaluating the extent of colon tissue damage, JRT-M and JRT-H groups both showed significantly lower inflammatory index and thinner muscular externa thickness than the DSS group. The expression of COX-2, p-STAT3 and p-ERK in colon tissue were significantly suppressed in JRT-M and JRT-H groups compared to that in the DSS group. Moreover, serum TNF-α was significantly suppressed in the JRT-H group compared to that in the DSS group. ConclusionsJeoryeong-tang has a promising therapeutic potential for treating IBD through its anti-inflammatory properties. Findings of this study suggest that JRT could be a valuable candidate for further clinical investigations in the treatment of IBD.

Curcumin alleviated dextran sulfate sodium-induced ulcerative colitis via inhibition of the Wnt/β-catenin signaling pathway and regulation of the differentiation of intestinal stem cells

In this study, we investigated the regulatory role of curcumin in the differentiation of intestinal stem cells (ISCs) in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) model mice and explored whether this effect was mediated by the Wnt/β-catenin signaling pathway. We conducted experiments in DSS-induced UC model mice to observe changes in intestinal morphology through HE staining and detect the expression of key proteins in the Wnt/β-catenin signaling pathway. According to these findings, curcumin was found to have a significant impact on the differentiation of ISCs. These results indicated that curcumin inhibited the Wnt/β-catenin signaling pathway and restored ISC differentiation. The effects of curcumin on the Wnt/β-catenin signaling pathway were further confirmed using Wnt/β-catenin agonists. These findings provide a new perspective for understanding the behavior of ISCs in the context of inflammation and offer new insights into the development of novel therapeutic strategies and drugs for UC.

Poria cocos polysaccharides alleviate dextran sulphate sodium-induced ulcerative colitis in mice by modulating intestinal inflammatory responses and microbial dysbiosis

Poria cocos polysaccharide (PCP), one of the main active components of P. cocos, is extensively used worldwide and exhibits strong pharmacological effects. However, whether PCP can attenuate inflammatory bowel disease remains unclear. In this study, we assessed the effects of PCP supplementation on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice. We found that PCP supplementation mitigated UC symptoms in DSS-treated mice, as evidenced by reductions in body weight loss, colon length shortening and disease activity index score. Importantly, PCP supplementation enhanced colonic barrier integrity by increasing tight junction protein abundance and exerted anti-inflammatory effects by suppressing nuclear factor-κB (NF-κB) activation in DSS-treated mice. Furthermore, PCP supplementation reversed DSS-induced dysbiosis in colonic microbiota by increasing the colonic abundance of beneficial bacteria (e.g. Akkermansiaceae) and decreasing the colonic abundance of harmful bacteria (e.g. Erysipelotrichaceae) in DSS-treated mice. Although PCP supplementation failed to ameliorate DSS-induced UC in antibiotic-treated mice, faecal microbiota transplantation from PCP-administered mice ameliorated DSS-induced UC in antibiotic-treated mice. In summary, PCP alleviates UC in mice by attenuating intestinal inflammation via the inhibition of NF-κB activation and modulating the intestinal microbiota.

Extracellular Vesicles Derived from Lipopolysaccharide-Pretreated Periodontal Ligament Stem Cells Ameliorate Inflammatory Responses in Experimental Colitis via the PI3K/AKT Signaling Pathway.

Inflammatory bowel disease is a complex chronic inflammatory condition characterized by dysbiosis of the gut microbiota and dysregulation of immune system. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells have garnered significant attention for their beneficial potentials in immune modulation and tissue repair. This study aims to evaluate the therapeutic effects and underlying mechanisms of EVs derived from lipopolysaccharide (LPS)-pretreated periodontal ligament stem cells (PDLSCs) in mice with colitis. A mouse model of colitis was established using 3.0% dextran sulfate sodium (DSS). Following the induction of colitis, mice were treated via tail vein injection with either conventional PDLSC-derived EVs (P-EVs) or LPS-pretreated PDLSC-derived EVs (LPS pre-EVs). The EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. The therapeutic effects and mechanisms were evaluated through a combination of small animal live imaging, disease activity index (DAI) scoring, histopathological staining, qRT-PCR, 16S rRNA gene sequencing, and mass spectrometry analysis. The LPS pre-EVs exhibited typical EVs characteristics in terms of morphology, particle size distribution, and marker protein expression. Compared to P-EVs, LPS pre-EVs significantly ameliorated weight loss, DAI scores, colon length, and perianal symptoms in DSS-induced murine colitis. Additionally, LPS pre-EVs up-regulated the expression of Arginase-1, a typical M2 macrophage marker, and tight junction proteins, including ZO-1, Occludin, and Claudin-1, enhanced gut microbial diversity, and significantly regulated intestinal protein expression and activation of the PI3K/AKT signaling pathway. LPS pre-EVs exhibit significant anti-inflammatory and tissue repair effects in a mouse model of colitis. The underlying mechanisms may involve the regulation of macrophage polarization, maintenance of intestinal barrier function, modulation of the gut microbiota, and activation of the PI3K/AKT signaling pathway.

Eurotium-Cristatum fermented black tea alleviates ulcerative colitis through the PPARγ-NF-κB signaling axis

Ulcerative colitis (UC) is a chronic inflammatory bowel condition that significantly impairs patient quality of life and remains incurable. Effective dietary management is crucial for both prevention and treatment. This study investigates the effects and mechanisms of Eurotium cristatum-fermented black tea (FBT) in a dextran sulfate sodium (DSS)-induced UC mouse model using transcriptome sequencing, immunofluorescence, and flow cytometry. Our results demonstrate that FBT significantly protects intestinal integrity by suppressing NF-κB-dependent inflammatory genes through the activation of peroxisome proliferator-activated receptor gamma (PPARγ) and modulation of the NF-κB signaling pathway. FBT enhances intestinal barrier integrity by limiting microbial penetration and metabolite translocation into systemic circulation, thereby reducing systemic inflammation risk. Additionally, FBT promotes intestinal mucosa repair and maintains microecological homeostasis by regulating intestinal flora and enhancing the biosynthesis of short-chain fatty acids and amino acids. These findings suggest that FBT has promising prophylactic potential for preventing and alleviating UC by modulating multiple biological pathways, including reducing inflammation, mitigating oxidative stress, and strengthening intestinal barrier integrity. This study lays the groundwork for future research on dietary interventions for UC prevention and management.

Diallyl trisulfide alleviates dextran sulphate sodium-induced colitis in mice by inhibiting NLRP3 inflammasome activation via ROS/Trx-1 pathway.

Diallyl trisulfide (DATS), a sulphur-containing compound isolated from the medicinal food plant garlic, has been previously reported to attenuate experimental colitis induced by either dextran sodium sulphate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) in mice; however, the underlying mechanism remains to be identified. In this study, we deciphered the key mechanism by which DATS alleviates ulcerative colitis (UC). We showed that oral administration of DATS for 10 consecutive days greatly restrained the infiltration of macrophages and the pathological changes in colonic tissues of mice with DSS-induced colitis. DATS treatment notably dampened the content of IL-1β and IL-18 and suppressed NLRP3 inflammasome activation in colon. Mechanistically, DATS effectively diminished the generation of ROS in macrophages. The suppressive effect of DATS on the activation of NLRP3 inflammasome and downregulation of IL-18 and IL-1β levels was blunted by xanthine oxidase. Further studies revealed that DATS inhibited NF-κB pathway activation by suppressing the expression of Trx-1, thereby inhibiting NLRP3 inflammasome activation. Trx-1 overexpression and interference in macrophages promoted and diminished NLRP3 inflammasome activation, respectively. In summary, garlic and its main active ingredient DATS have potentials to prevent and treat UC, and DATS functions by inhibiting NLRP3 inflammasome activation via Trx-1/ROS pathway.

Tarm1 may affect colitis by regulating macrophage M1 polarization in a mouse colitis model.

In this study, we aimed to explore the role of Tarm1 in juvenile mice with dextran sulfate sodium (DSS)-induced colitis and elucidate the mechanisms that affect intestinal barrier function. A DSS-induced pediatric inflammatory bowel disease mouse model was established using 4-week-old juvenile mice. Disease activity index and histopathological damage scores were determined using hematoxylin and eosin (H&E) staining. Tarm1, F4/80, CD68, and CD86 levels were detected using qPCR, western blotting, and immunofluorescence. Trans epithelial electric resistance (TEER) was detected using the transwell assay. Results revealed that juvenile colitis mice fed 4% DSS drinking water had increased Tarm1 expression in the colon tissue, increased macrophage M1 polarization, higher expression of pro-inflammatory cytokines, and an impaired intestinal mucosal barrier, compared with the control group. Tarm1-knockdown RAW264.7 cells inhibited lipopolysaccharide (LPS)-induced M1 polarization and attenuated barrier damage in co-cultured intestinal epithelial cells. Tarm1 expression was increased in colonic tissues of juvenile mice with colitis, and LPS-induced M1 polarization and intestinal barrier damage were attenuated in Tarm1-knockdown RAW264.7 cells. This suggests that attenuation of Tarm1 expression is a potential target for pediatric inflammatory bowel disease therapy.

Liubao insect tea polyphenols ameliorate DSS-induced experimental colitis by protecting intestinal barrier and regulating intestinal microbiota

Liubao insect tea (LIT) is a traditional tea produced from the excreta of Hydrillodes repugnalis that are fed with Liubao tea. In this study, LIT polyphenols (LITP) were extracted and identified, mainly consisting of brevifolin carboxylic acid, brevifolin, ellagic acid. The study aimed to explore the therapeutic potential of LITP in experimental colitis induced by dextran sulfate sodium in mice. LITP treatment effectively mitigated colitis symptoms, including body weight loss, diarrhoea and haematochezia, etc. Furthermore, LITP treatment significantly increased colon length, attenuated inflammatory cell infiltration and mucosal damage, safeguarded the integrity of the epithelial cell barrier, and reduced proinflammatory cytokines levels. Noteworthy alterations in the abundance of gut microbiota community were also observed, with increases in beneficial bacteria Akkermansia, Clostridia_UCG-014, and decreases in harmful bacteria Turicibacter and Erysipelatoclostridium. In conclusion, LITP exerted alleviative effects on colitis via fortifying intestinal barrier and modulating the intestinal microbiota.

Facilitation of mucosal healing by estrogen receptor β in ulcerative colitis through suppression of branched-chain amino acid transport and subsequent triggering of autophagy in colonic epithelial cells

Colonic mucosal healing is the ultimate goal of ulcerative colitis (UC) treatment, but it remains difficult to realize. Given the higher incidence of UC in males and the beneficial effect of estrogen on UC, we conducted this study to examine the therapeutic potential of estrogen receptor β (ERβ), the primary ER subtype in colon, on mucosal healing in UC. Our study is the first to report that ERβ activation degree was positively correlated with mucosal healing in patients with UC. Furthermore, ERβ activation enhanced mucosal healing in mice with dextran sulfate sodium-induced and biopsy-induced colonic injuries. Mechanistically, ERβ activation promoted autophagy of colonic epithelial cells by inhibiting branched-chain amino acid transport, leading to focal adhesion kinase (FAK) activation. Activated FAK promoted focal adhesion turnover and colonic epithelial cell migration, ultimately facilitating mucosal healing. ERβ−/− colitis mice exhibited impaired mucosal healing compared to wild-type littermates, highlighting the crucial effect of ERβ. Importantly, combination with ERβ-agonist diarylpropionitrile enhanced the amelioration of 5-aminosalicylic acid, a standard UC treatment agent, against mouse colitis. These findings attest to the crucial role of ERβ activation in colonic mucosal healing and may further inform the development of novel strategies for UC treatment.

Elegant approach to intervention of homogalacturonan from the fruits of Ficus pumila L. in colitis: Unraveling the role of methyl esters and acetyl groups.

Oral administration of homogalacturonan (HG) has shown significant potential in anti-colitis activity, yet the therapeutic efficacy of naturally sourced HG still requires enhancement. Herein, HG from the fruits of Ficus pumila L. was modified by chemical methods and the intervention effect of modified HG with different degrees of methyl-esterification (DM) and acetylation (DA) on dextran sulfate sodium-induced colitis in mice was explored. Our results indicated that low-DM HG (DM3 and DM25) primarily mitigated colitis by reducing inflammation (TNF-α, IL-1β, IL-17, and IL-6), while high-DM HG (DM54 and DM94) primarily repaired the intestinal barrier. These effects may be attributed to the differential regulation of gut microbiota by HG with varying DM, such as Lachnospiraceae_NK4A136_group, Lactobacillus, Mucispirillum, Escherichia-Shigella, Bifidobacterium, and Bacteroides. Increased DA reduced the solubility of HG, showing limited anti-inflammatory response but unique advantages in intestinal barrier repair and microbiome regulation (Bifidobacterium, Candidatus_Saccharimonas, Lachnospiraceae_NK4A136_group, Mucispirillum, and Escherichia-Shigella). Furthermore, various structural parameters and substitution degrees showed no significant impact on HG's regulation of oxidative stress reactions. This study emphasized the importance of substituent effect in determining HG's functional role, providing a robust foundation for the design and development of functional polysaccharides for the prevention of intestinal inflammation and other related conditions.

Fucoidan from Stichopus chloronotus relieved DSS induced ulcerative colitis through inhibiting intestinal barrier disruption and oxidative stress.

Intestinal barrier disruption and oxidative stress are the major pathological features during the ulcerative colitis (UC). The present research aimed to explore the amelioration property of fucoidan of Stichopus chloronotus (FucSc) against dextran sulfate sodium (DSS) resulted UC. The findings from our study suggest that treating with Fuc-Sc improved the integrity of the Caco-2 monolayer through raising its TEER value, reducing LDH release, promoting the tight junction proteins (TJs) in Caco-2 cells, and shielding the cells from decreases of these proteins caused by H2O2. Besides, Fuc-Sc activated Nrf2/HO-1 pathway to facilitate the antioxidant activities of Caco-2 cells under oxidative stress through elevating the SOD and GSH, and reducing LDH and MDA. Furthermore, oral administration of Fuc-Sc attenuated DSS resulted body weights decrease, DAI score increase, colon length decrease, and structural damage of colon tissue. Fuc-Sc also promoted the barrier function and suppressed oxidative injury via activation of Nrf2/HO-1 signal path. Collectively, this research provided the theoretical foundation for fucoidan as a promising functional food for colitis.

Bacteroides uniformis ameliorates pro-inflammatory diet-exacerbated colitis by targeting endoplasmic reticulum stress-mediated ferroptosis

IntroductionA pro-inflammatory diet is positively associated with the risk and progression of inflammatory bowel diseases (IBD). Recently, ferroptosis has been observed in patients with different dietary patterns-associated intestinal inflammation, while the mechanisms underlying the effects of a pro-inflammatory diet and whether it mediates ferroptosis are unknown. ObjectivesThis study aims to elucidate the mechanisms underlying pro-inflammatory diet-mediated colitis and explore potential intervention strategies. MethodsMice were fed a dietary inflammatory index-based pro-inflammatory diet for 12 weeks. Subsequently, colitis was chemically induced using 2.5 % dextran sulfate sodium. The body weight, pathological score, immune response and mucosal barrier function were evaluated to assess intestinal inflammation. Intestine tissue transcriptomics, fecal microbiome analysis and serum metabolomics were applied to identify diet–microbe–host interactions. Additionally, the dietary inflammatory index (DII) scores and intestinal specimens of 32 patients with Crohn’s disease were evaluated. The biological functions of Bacteroides uniformis were observed in vitro and in vivo. ResultsPro-inflammatory diet induces low-grade intestinal inflammation in mice and exacerbates colitis by activating glutathione peroxidase 4-associated ferroptosis in the endoplasmic reticulum stress-mediated pathway. These effects are reversed by ferrostatin-1 treatment. Additionally, the pro-inflammatory diet triggers colitis by modulating the gut microbiota and metabolites. Notably, supplementation with B. uniformis improves the pro-inflammatory diet-aggravated colitis by inhibiting endoplasmic reticulum stress-mediated ferroptosis. Moreover, B. uniformis is non-enterotoxigenic and non-enteroinvasive in co-cultures with intestinal epithelial cells. ConclusionsPro-inflammatory diet drives colitis by targeting endoplasmic reticulum stress-mediated ferroptosis, possibly in a gut microbiota-dependent manner. Pro-inflammatory diet restriction and microbial-based therapies may be effective strategies for preventing and treating IBD.

A new strategy for pharmacodynamic substance screening and research on gut microbiota pathway mechanisms based on UPLC-Q-orbitrap-MS and 16S rRNA

ObjectiveTo establish a progressive research strategy for “colonic components analysis - efficacy verification and mechanism exploration - gut microbiota”, screen pharmacodynamic substances, and investigate their mechanism via gut microbiota. MethodsThe pharmacodynamics of Gegen Qinlian decoction (GQD) were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis (UC). Ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC. To analyze the structure and function of characteristic genera of GQD and its active components, 16S rRNA sequencing was performed. ResultsWe identified 67 prototypic and 14 metabolic components of GQD in the UC colon. The primary prototype components are flavonoids and alkaloids, including puerarin (PUE), baicalin (BAI), and berberine (BER). The metabolism was predominantly sulfonation. Efficacy verification showed that the main active components, puerarin, baicalin, and berberine, had good therapeutic effects on UC. The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota. The abundance of gut microbiota involved in the metabolism of the prototype components was influenced by the corresponding components. The function prediction results showed that PUE was the most comparable to GQD, with 24 consistent pathways. BAI and BER showed comparable gut microbiota regulation pathways. Characteristic pathways of BER include glucometabolic processes. ConclusionThis study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components. This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC, as well as changes in the structure and function of the gut microbiota, clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.

PET biodistribution study of subcutaneous and intravenous administration of adalimumab in an inflammatory bowel disease model

Monoclonal antibodies targeting tumor necrosis factor-alpha (antiTNF-α) are used for patients with immuno-mediated illness as inflammatory bowel disease (IBD). However, 20–40 % of IBD patients do not respond to these therapies, and increasing knowledge of biodistribution could optimize their use and consequently their effectiveness. The aim of this study is to compare the biodistribution of adalimumab after intravenous (IV) and subcutaneous (SC) administration using Positron Emission Tomography (PET) imaging in IBD animal models. IBD was induced in mice using oral dextran sulfate sodium (DSS) and each induced animal was individually confirmed using [18F]FDG PET/CT scans, weight monitoring and histopathological analysis of colon tissue samples. The SC and IV biodistribution pharmacokinetics profiles and in vivo biodistribution of adalimumab labeled with 89Zr were evaluated using a dedicated PET/CT scanner. Mean standardized uptake values (SUV) were estimated from the colon, liver, and blood over seven days. Blood analysis revealed faster elimination of adalimumab in IBD models compared to controls, and after IV compared to SC administration (SUV 168 h p.i. SC-IBD = 0.06 ± 0.02, SC-Control = 1.08 ± 0.11, IV-IBD = 0.02 ± 0.01, IV-Control = 0.26 ± 0.13). Furthermore, IBD models exhibited faster whole-body clearance than controls and an earlier and higher concentration peak of adalimumab in the colon after IV (SUV 6 h p.i. IBD-IV = 2.11 ± 0.18) compared to SC administration (SUV 24 h p.i. IBD-SC = 1.49 ± 0.27). Our findings demonstrate the significant influence of the administration route and the TNF-α expression (local and also systemic) on the amount of adalimumab reaching the colon over time.

Effects of Centella asiatica-isolated pectic polysaccharide on dextran sulfate sodium-induced colitis

Dietary supplementation of polysaccharides demonstrates strong therapeutic actions on inflammatory bowel disease (IBD). Centella asiatica (CA) has traditionally been used in Ayurveda and Chinese medicine. However, the effects of CA-isolated pectic polysaccharides on IBD remain unknown. This study determined the effect of a CA-isolated pectic polysaccharide on IBD. The crude polysaccharide (CA-CP), isolated from a hot-water extract of CA, is a typical pectic polysaccharide composed mainly of galacturonic acid (40.6 %), galactose (27.6 %), arabinose (13.5 %), and rhamnose (8.5 %). CA-CP improved clinical symptoms in a DSS-induced colitis murine model, including weight change (9.9–12.0 %), disease activity index (31.6–51.9 %), colon length (13.2–21.5 %), and spleen weight (21.8–26.3 %). CA-CP effectively regulated the levels of inflammatory and junctional factors by mediating the MAPK and NF-κB pathways. CA-CP partially alleviated DSS-induced crypt destruction, submucosal edema, inflammatory infiltration, and mucin secretion. The content of total short-chain fatty acids increased substantially (cecum 29.8–53.7 %, feces 75.4–109.3 %) with oral CA-CP administration compared to the DSS group. Cecal microbial community analysis revealed that CA-CP administration regulated DSS-induced colitis by reducing the abundance of Escherichia (5.0–10.9 %) and Clostridium (0.3–0.4 %), while increasing the abundance of Bacteroidetes (6.8–8.5 %), Ligilactobacillus (2.7–6.0 %), and Bilophilia (0.3–0.6 %). The findings provide fundamental data for developing novel functional therapeutic agents for the prevention and treatment of colitis, using CA-isolated pectic polysaccharides. Furthermore, to the best of our knowledge, our study is the first to demonstrate the effects of pectic polysaccharides isolated from CA on IBD.

Segmental regulation of intestinal motility by colitis and the adaptive immune system in the mouse ileum and colon.

Gastrointestinal motility disturbances are a hallmark of inflammatory bowel disease (IBD); however, their mechanisms remain unclear. This study utilized a dextran sulfate sodium (DSS)-induced colitis mouse model, deficient in mature B and T lymphocytes, to assess intestinal motility and the role of the adaptive immune system in health and IBD. In healthy mice, the absence of adaptive lymphocytes reduced acetylcholine (ACh) sensitivity in the ileum. During colitis, it decreases motility by reducing the intensity and frequency of spontaneous contractions while increasing cholinergic responsiveness. In the proximal colon, adaptive immunity deficiency led to increased contractility and reduced ACh sensitivity in homeostasis, while colitis reduced contractile capacity. In the mid-colon, immune-deficient mice have reduced ACh sensitivity in homeostasis and exacerbated contractile responses during colitis. In the distal colon, adaptive immunity loss reduced contractility in health and cholinergic responsiveness during colitis. These motility alterations were associated with altered acetylcholinesterase and M2/M3 muscarinic receptor expression. Notably, adaptive lymphocyte deficiency resulted in reduced tissue damage and lower TNF-α expression in the colon during colitis paralleling intestinal motility changes. Overall, the adaptive immune system critically regulates motility and inflammation across different intestinal segments in IBD.

Leucine-Enriched Diet Reduces Fecal MPO but Does Not Protect Against DSS Colitis in a Mouse Model of Crohn's Disease-like Ileitis.

Understanding the complex link between inflammation, gut health, and dietary amino acids is becoming increasingly important in the pathophysiology of inflammatory bowel disease (IBD). This study tested the hypothesis that a leucine-rich diet could attenuate inflammation and improve gut health in a mouse model of IBD. Specifically, we investigated the effects of a leucine-rich diet on dextran sulfate sodium (DSS)-induced colitis in germ-free (GF) SAMP1/YitFC (SAMP) mice colonized with human gut microbiota (hGF-SAMP). hGF-SAMP mice were fed one of four different diets: standard mouse diet (CHOW), American diet (AD), leucine-rich AD (AD + AA), or leucine-rich CHOW diet (CH + AA). Body weight, myeloperoxidase (MPO) activity, gut permeability, colonoscopy scores, and histological analysis were measured. Mice on a leucine-rich CHOW diet showed a decrease in fecal MPO prior to DSS treatment as compared to those on a regular diet (p > 0.05); however, after week five, prior to DSS, this effect had diminished. Following DSS treatment, there was no significant difference in gut permeability, fecal MPO activity, or body weight changes between the leucine-supplemented and control groups. These findings suggest that while a leucine-rich diet may transiently affect fecal MPO levels in hGF-SAMP mice, it does not confer protection against DSS-induced colitis symptoms or mitigate inflammation in the long term.

Osa-miR168a, a Plant miRNA That Survives the Process of In Vivo Food Digestion, Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice by Oral Administration.

Previous studies showed that osa-miR168a, a plant miRNA rich in fruits and vegetables, had cross-kingdom biological effects on immunocytes, silkworms, and rodents. In this study, the effects of miR168a on mouse colitis induced by dextran sulfate sodium (DSS) were investigated. The results showed that miR168a oligomers were resistant during the process of food digestion, ending up with a residual concentration of 67.8 ± 11.2 fM in mouse intestines 4 h after oral gavage. More importantly, direct oral administration of the miRNA to the colitis mice significantly ameliorated the progression of the disease, as evidenced by the reduction in DAI score, histopathological lesions, and proinflammatory cytokines. Repairing intestinal barrier function by promoting the regeneration of TJ proteins and the mucus layer, suppressing oxidative stress and colonic inflammation via modulating Nrf2 and NF-κB signaling pathways, and restoring the imbalanced gut microbiota caused by DSS are proposed mechanisms behind the anticolitis activity of miR168a. This study provided new evidence of the cross-kingdom regulatory effects of dietary miRNAs, suggesting the potential of the plant miRNA for the prevention and treatment of inflammatory bowel diseases.