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Search Results (914)

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Keywords = ulcerative colitis (UC)

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20 pages, 998 KiB  
Article
Health Benefits of Montmorency Tart Cherry Juice Supplementation in Adults with Mild to Moderate Ulcerative Colitis; A Placebo Randomized Controlled Trial
by Jonathan Sinclair, Graham McLaughlin, Robert Allan, Johanne Brooks-Warburton, Charlotte Lawson, Shan Goh, Terun Desai and Lindsay Bottoms
Life 2025, 15(2), 306; https://doi.org/10.3390/life15020306 - 17 Feb 2025
Abstract
Aims: Ulcerative colitis (UC) significantly impacts individuals’ self-perception, body image, and overall quality of life, while also imposing considerable economic costs. These challenges highlight the necessity for complementary therapeutic strategies with reduced adverse effects to support conventional pharmacological treatments. Among natural interventions, Montmorency [...] Read more.
Aims: Ulcerative colitis (UC) significantly impacts individuals’ self-perception, body image, and overall quality of life, while also imposing considerable economic costs. These challenges highlight the necessity for complementary therapeutic strategies with reduced adverse effects to support conventional pharmacological treatments. Among natural interventions, Montmorency tart cherries, noted for their high anthocyanin content have emerged as a natural anti-inflammatory agent for UC. The current trial aimed to investigate the effects of Montmorency tart cherries compared to placebo in patients with mild to moderate UC. Materials and methods: Thirty-five patients with UC were randomly assigned to receive either placebo or Montmorency tart cherry juice, of which they drank 60 mL per day for 6 weeks. The primary outcomes and health-related quality of life, measured via the Inflammatory Bowel Disease Quality of Life Questionnaire (IBDQ), and the secondary measures, including other health-related questionnaires, blood biomarkers, and faecal samples, were measured before and after the intervention. Linear mixed-effects models were adopted to contrast the changes from baseline to 6 weeks between trial arms. Effect sizes were calculated using Cohen’s d. Results: There were significantly greater improvements in the IBDQ (22.61 (95% CI = 5.24 to 39.99) d = 0.90) and simple clinical colitis activity index (−3.98 (95% CI = −6.69 to –1.28) d = −1.01) in the tart cherry trial arm compared to placebo. In addition, reductions in faecal calprotectin levels were significantly greater in the tart cherry trial arm compared to placebo (−136.17 µg/g (95% CI = −258.06 to –4.28) d = −1.14). Loss to follow-up (N = 1) and adverse events (N = 1) were low and compliance was very high in the tart cherry (95.8%) trial arm. Conclusions: Given the profoundly negative effects of UC on health-related quality of life and its fiscal implications for global healthcare systems, this trial indicates that twice-daily tart cherry supplementation can improve IBD-related quality of life as well as the severity of symptoms and therefore may be important in the management of UC. Full article
(This article belongs to the Collection Clinical Trials)
14 pages, 5793 KiB  
Article
Oral Microbiota and Inflammatory Bowel Diseases: Detection of Emerging Fungal Pathogens and Herpesvirus
by Manoel Marques Evangelista Oliveira, Letícia Bomfim Campos, Fernanda Brito, Flavia Martinez de Carvalho, Geraldo Oliveira Silva-Junior, Gisela Lara da Costa, Tatiane Nobre Pinto, Rafaela Moraes Pereira de Sousa, Rodrigo Miranda, Rodolfo Castro, Cyrla Zaltman and Vanessa Salete de Paula
Biomedicines 2025, 13(2), 480; https://doi.org/10.3390/biomedicines13020480 - 15 Feb 2025
Viewed by 348
Abstract
Background/Objectives: Ulcerative colitis (UC) and Crohn’s disease (CD) are the usual clinical forms of inflammatory bowel disease (IBD). Changes in the oral microbiota, especially the presence of emerging fungi and herpesviruses, have been shown to worsen the clinical aspects of IBD. The aim [...] Read more.
Background/Objectives: Ulcerative colitis (UC) and Crohn’s disease (CD) are the usual clinical forms of inflammatory bowel disease (IBD). Changes in the oral microbiota, especially the presence of emerging fungi and herpesviruses, have been shown to worsen the clinical aspects of IBD. The aim of this study was to screen for emerging pathogens in the oral yeast microbiota and the presence of herpesvirus in IBD patients. Methods: Oral swabs of seven UC or CD patients were collected. The samples were plated on Sabouraud Dextrose Agar and subcultured on CHROMagar Candida and CHROMagar Candida Plus. Polyphasic taxonomy was applied and identified using molecular tools, such as MALDI-TOF MS and ITS partial sequencing. Multiplex qPCR was used to identify the herpesvirus. Results: The mean age was 38.67 ± 14.06 years, 57.14% were female, and two had diabetes. The CD patients presented with Rhodotorula mucilaginosa, Candida orthopsilosis and Kodamaea jinghongensis, while the UC patients presented with Cutaneotrichosporon dermatis, Candida glabrata, Candida lusitanea and Candida tropicalis. Two UC individuals had at least one herpesvirus. In the first individual, a co-detection of Herpes Simplex Virus 1 (HSV-1) and C. lusitaniae was observed. The second presented with co-infections of Epstein–Barr virus (EBV), Human Herpesvirus 7 (HHV-7) and C. tropicalis. Conclusions: We identified rarely described yeasts and co-infections in IBD patients, highlighting the need to identify emerging pathogens in the oral microbiota, as they may contribute to opportunistic infections. Full article
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Figure 1
<p>Growth in Sabouraud Dextrose Agar Medium (BD Difco) incubated at 35 °C for 48 h: (<b>A</b>) <span class="html-italic">Cutaneotrichosporon dermatis</span>, (<b>B</b>) <span class="html-italic">Rhodotorula mucilaginosa</span>, (<b>C</b>) <span class="html-italic">Candida glabrata</span>, (<b>D</b>) <span class="html-italic">Candida orthopsilosis</span>, (<b>E</b>) <span class="html-italic">Kodamaea jinghongensis</span>, (<b>F</b>) <span class="html-italic">Candida lusitanea</span>, (<b>G</b>) <span class="html-italic">Kodamaea jinghongensis,</span> (<b>H</b>) <span class="html-italic">Candida orthopsilosis</span> and (<b>I</b>) <span class="html-italic">Candida tropicalis</span>.</p>
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<p>Growth in BDTM CHROMagar<sup>TM</sup> Candida Medium (BD Difco) incubated at 35 °C for 48 h: (<b>A</b>) <span class="html-italic">Cutaneotrichosporon dermatis,</span> (<b>B</b>) <span class="html-italic">Rhodotorula mucilaginosa</span>, (<b>C</b>) <span class="html-italic">Candida glabrata</span>, (<b>D</b>) <span class="html-italic">Candida orthopsilosis</span>, (<b>E</b>) <span class="html-italic">Kodamaea jinghongensis,</span> (<b>F</b>) <span class="html-italic">Candida lusitanea</span>, (<b>G</b>) <span class="html-italic">Kodamaea jinghongensis,</span> (<b>H</b>) <span class="html-italic">Candida orthopsilosis</span> and (<b>I</b>) <span class="html-italic">Candida tropicalis</span>.</p>
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<p>The phylogenetic relationships between the isolates of samples with reference strains inferred from ITS sequences. (<b>A</b>) <span class="html-italic">Kodhamaea</span> sp.: this analysis involved eight nucleotide sequences, and a total of 263 positions were obtained in the final dataset. (<b>B</b>) <span class="html-italic">Rhodotorula</span> sp.: this analysis involved nine nucleotide sequences, and a total of 602 positions were obtained in the final dataset. (<b>C</b>) <span class="html-italic">Trichosporon</span> sp.: this analysis involved 16 nucleotide sequences and a total of 560 positions were obtained in the final dataset. (<b>D</b>) <span class="html-italic">Candida</span> spp.: this analysis involved 22 nucleotide sequences and a total of 92 positions were obtained in the final dataset.</p>
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24 pages, 16534 KiB  
Article
The Diagnostic Significance of SLC26A2 and Its Potential Role in Ulcerative Colitis
by Lijuan Qian, Shuo Hu, Haizhou Zhao, Ye Han, Chenguang Dai, Xinquan Zan, Qiaoming Zhi and Chunfang Xu
Biomedicines 2025, 13(2), 461; https://doi.org/10.3390/biomedicines13020461 - 13 Feb 2025
Viewed by 317
Abstract
Background/Objectives: The solute carrier family 26, member 2 (SLC26A2) gene, which belongs to the family of SLC26 transporters, can be detected in multiple tissues. However, the studies of SLC26A2 in colon-related diseases are still limited and incompletely understood, especially in ulcerative colitis (UC). [...] Read more.
Background/Objectives: The solute carrier family 26, member 2 (SLC26A2) gene, which belongs to the family of SLC26 transporters, can be detected in multiple tissues. However, the studies of SLC26A2 in colon-related diseases are still limited and incompletely understood, especially in ulcerative colitis (UC). Methods: In this study, we attempted to search and identify putative UC candidate genes within a large number of known genes by multiple bioinformatics analyses. The potential cellular characteristics and biological functions of SLC26A2 in the pathogenesis of UC were also elucidated. Results: Notably, SLC26A2 was representative and down-regulated in the intestinal mucosa of patients with active UC, compared to healthy controls. Decreased levels of SLC26A2 were proved to have a more value in diagnosis of UC patients, and closely correlated with some UC characteristics, including the Mayo score and Paediatric Ulcerative Colitis Activity Index (PUCAI). Mechanistically, subsequent results from published datasets and our validated clinical data all strongly implied that SLC26A2 was negatively correlated with the IL-17 signaling pathway, and positively associated with the tight junction, which led to abnormal immune cell infiltration and inflammatory injuries. After establishing the UC mice models in vivo by orally administration of DSS in portable water, SLC26A2 was significantly down-regulated at the mRNA or protein level, when compared to that in the control groups. Furthermore, the correlation analyses confirmed that SLC26A2 was positively associated with CLDN3, and negatively correlated with IL-17A expression in colon tissues. In addition, according to the SLC26A2 expression, UC patients were divided into different subgroups. The potential target drugs for UC treatment, such as progesterone, tetradioxin, and dexamethasone, were initially predicted and exerted anti-inflammatory effects via the common molecule-SLC26A2. Conclusions: SLC26A2 might be served as a protective candidate in the UC pathogenesis as well as a potential drug target for UC treatment. Full article
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<p>The flowchart of the analysis process.</p>
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<p>Screening of potential UC-related molecules. (<b>A</b>) Selection of the soft threshold for WGCNA (GSE87466 and GSE109142). (<b>B</b>) The heatmaps indicated the correlations between modules and UC. Red boxes indicate that magenta module in GSE87466 and purple module in GSE109142 exhibited the strongest correlations with UC. (<b>C</b>) The scatterplots showed the relationships between gene significance and module membership in the magenta module of GSE87466 and purple module of GSE109142. (<b>D</b>) The volcano plots displayed all the DEGs. (<b>E</b>) The Venn diagram illustrates the overlapping genes.</p>
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<p>Validate the clinical significance of potential UC related molecules. (<b>A</b>,<b>B</b>) The boxplots illustrated the expressing levels of 3 UC-related molecules between healthy controls and UC samples in the GSE87466 (<b>A</b>) and GSE109142 (<b>B</b>) datasets, respectively. (<b>C</b>) The ABCB1, AQP8, and SLC26A2 mRNA expressions in our collected UC samples were also determined by the RT-PCR. (<b>D</b>) ROC curves were used to evaluate the potential usages and values of tissue-derived ABCB1, AQP8, and SLC26A2 as invasive biomarkers for UC diagnosis. (<b>E</b>–<b>H</b>) The Spearman correlation analyses revealed the possible relationships between 3 UC-related genes (ABCB1, AQP8, and SLC26A2) and some significant clinical characteristics, including the Mayo and PUCAI scores in UC samples from GSE109142, GSE92415, and our collected UC samples, respectively. (**** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Single gene GSEA analysis was conducted on SLC26A2. (<b>A</b>) The heatmaps displayed the top 30 up-regulated and 30 down-regulated genes in the high-SLC26A2 expressed groups, compared to the low-expressed groups. (<b>B</b>) The KEGG pathway enrichment analyzed the DEGs in the GSE87466 and GSE109142 datasets. (<b>C</b>) The GSEA implied that SLC26A2 was negatively associated with the IL-17 signaling pathway. (<b>D</b>) The barplots illustrated the top 50% of enriched pathways in the GSE87466 and GSE109142 datasets.</p>
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<p>According to the expressing levels of SLC26A2, ssGSEA of the IL-17 signaling pathway and immune cell clusters were performed in the GSE87466 and GSE109142 datasets, respectively. (<b>A</b>) The scores of the IL-17 signaling pathway were significantly lower in the high SLC26A2 expression group, compared to the low expression group. (<b>B</b>) A strong negative correlation between the SLC26A2 expressing levels and scores of the IL-17 signaling pathway was observed by the Spearman correlation analyses. (<b>C</b>) The boxplots illustrated the differences in immune infiltration between the high and low expression groups of SLC26A2. (<b>D</b>) The correlations between immune cell infiltration and SLC26A2 were also estimated. (**** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Localization analysis of SLC26A2 in single-cell sequencing data. (<b>A</b>–<b>D</b>) tSNE plots visualized the cell clusters, original identities, cell annotation, and localization of SLC26A2 in healthy controls and individuals with UC, respectively. (<b>E</b>) The distribution of SLC26A2 in cells with annotation was visualized as a violin plot. (<b>F</b>) Integrated map of the different numbers of interactions detected between each cell and other cells was presented. (<b>G</b>) Intensity demonstration of cell populations in different pathways in healthy controls and individuals with ulcerative colitis. (<b>H</b>) Differential signaling pathways in epithelial cells between healthy controls and individuals with UC revealed the diverse biological functions of epithelial cells.</p>
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<p>hdWGCNA revealed the potential biological functions of SLC26A2 at the level of single-cell RNA-seq. (<b>A</b>) The scale-free topology model displayed the scale-free fit index and the mean connectivity for various soft-thresholding powers. (<b>B</b>) The dendrogram illustrated illustrates the different modules in which genes are clustered. (<b>C</b>) The correlations between traits and modules were are shown in the correlation heatmap. (<b>D</b>) The KEGG pathways enriched by the genes in the brown module were listed, and the tight junction pathway (marked by a red box) was enriched. (<b>E</b>) The potential correlations among modules were calculated using the Pearson method. (<b>F</b>) Gene scores of the brown module were calculated using the UCell algorithm and presented in each cell. (<b>G</b>) The correlations between the genes involved in the tight junction in the brown module and SLC26A2 (as well as the IL-17 signaling pathway), were analyzed using the Spearman method. (<b>H</b>) Similar Spearman analyses were conducted between the genes involved in the tight junction in the brown module and immune cell subtypes. (*** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>The relationship between SLC26A2 and tight junction genes. (<b>A</b>) The PPI network demonstrated the relationships among involved proteins, including SLC26A2, tight junction proteins, the IL-17 signaling pathway, and activated molecules in epithelial cells in UC. (<b>B</b>) The mRNA expressing levels of CFTR, CLDN3, CLDN7, MYL6, SLC26A3R1, and SLC26A2 were determined by the qRT-PCR. (<b>C</b>) The potential correlations between SLC26A2 and CFTR (CLDN3, CLDN7, MYL6, SLC26A3R1 and SLC26A2, respectively) were analyzed. (<b>D</b>) According to the expressing levels of SLC26A2 in GSE87466 and GSE109142 datasets, putative drugs were predicted, and the top 10 drugs were described. Progesterone CTD 00006624, tetradioxin CTD 00006848, and dexamethasone CTD 00005779 were highly co-enriched and indicated by the red, orange and blue boxes respectively. (** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001, and ns: no significance).</p>
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<p>The relationships between SLC26A2 and CLDN3 (or IL-17A) at mRNA levels in vivo. (<b>A</b>) Photos of mice colon in each group. (<b>B</b>) The colon length of mice on 7th day in the control and UC groups. (<b>C</b>,<b>D</b>) The colons were stained by H&amp;E, and the corresponding histological scores were compared. (<b>E</b>,<b>F</b>) The SLC26A2 mRNA expressions in each group were detected by qRT-PCR, and correlation analysis showed the potential relationships between SLC26A2 and histological scores. (<b>G</b>–<b>J</b>) The CLDN3 and IL-17A mRNA expressions in each group were also determined by qRT-PCR, and the relationships between SLC26A2 and CLDN3 (or IL-17A) were evaluated. (**** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>The relationships between SLC26A2 and CLDN3 (or IL-17A) at protein levels in vivo. (<b>A</b>–<b>F</b>) The protein expressions of SLC26A2, CLDN3 and IL-17A in mice colon were determined by immunofluorescence, and the fluorescence quantification was compared. (<b>G</b>,<b>H</b>) Spearman–Pearson correlation between SLC26A2 and CLDN3 (or IL-17A) fluorescence intensity in mice was analyzed. (**** <span class="html-italic">p</span> &lt; 0.0001).</p>
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21 pages, 3719 KiB  
Article
Anti-Inflammatory Potential of Wampee (Clausena lansium (Lour.) Skeels) Polyphenol Extract in Ulcerative Colitis: Gut Microbiota and TLR4-p38 MAPK/NF-κB Signaling Axis Regulation
by Kaijie Shang, Zhiheng Zhao, Hua Chen, Xiaonan Bian, Xianquan Zhong, Xiaoping Hu, Xue Lin and Lu Wang
Foods 2025, 14(4), 619; https://doi.org/10.3390/foods14040619 - 13 Feb 2025
Viewed by 428
Abstract
The consumption of wampee has traditionally been utilized to alleviate gastrointestinal inflammation and associated disorders; however, its exact mechanism has remained unknown. The aim of this study was to elucidate the therapeutic efficacy and underlying mechanism of wampee polyphenol extract (WPE) in dextran [...] Read more.
The consumption of wampee has traditionally been utilized to alleviate gastrointestinal inflammation and associated disorders; however, its exact mechanism has remained unknown. The aim of this study was to elucidate the therapeutic efficacy and underlying mechanism of wampee polyphenol extract (WPE) in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). The findings revealed that WPE alleviated diverse symptoms of UC, regulated various inflammatory cytokines, and effectively protected the colon tissue structure and barrier integrity, thereby inhibiting LPS translocation. Moreover, WPE restored the richness and diversity of gut microbiota and optimized its structure at the phylum and genus levels, causing a notable improvement in short- chain fatty acid (SCFA) metabolism, particularly acetic acid, propionic acid, and butyric acid. Consequently, WPE was demonstrated to effectively suppress the LPS-induced TLR4-p38 MAPK/NF-κB signaling pathway by modulating gut microbiota and SCFA metabolism. These findings provided a theoretical basis for the use of wampee as a potential functional natural food for UC. Full article
(This article belongs to the Section Food Nutrition)
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<p>Effect of WPE on disease symptoms and colonic damage. (<b>A</b>) Changes in daily body weight; (<b>B</b>) changes in DAI score; (<b>C</b>) representative image of colon length; (<b>D</b>) colon length; (<b>E</b>) ratio of colon weight to length; (<b>F</b>) H&amp;E—stained images of colon tissues; (<b>G</b>) spleen index (ratio of spleen weight to body weight); (<b>H</b>) histological score. All data are expressed as mean ± SD (<span class="html-italic">n</span> = 7). Bars with different lowercase letters indicate statistically significant differences (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Effect of WPE on the expression of TJ proteins (ZO-1 and occludin). (<b>A</b>) Immunofluorescence staining of ZO-1; (<b>B</b>) immunofluorescence staining of occludin; (<b>C</b>) relative expression of ZO-1; (<b>D</b>) relative expression of occludin. Data are expressed as mean ± SD (<span class="html-italic">n</span> = 5). Bars with different lowercase letters indicate statistically significant differences (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Effect of WPE on the inflammatory cytokines, LPS, and key proteins related to the TLR4-p38 MAPK/NF-κB signaling pathway in serum. (<b>A</b>–<b>C</b>) The expressions of pro-inflammatory cytokines IL-1<span class="html-italic">β</span>, IL-6, and TNF-<span class="html-italic">α</span>; (<b>D</b>) the expressions of anti-inflammatory cytokine IL-10; (<b>E</b>) the contents of LPS; (<b>F</b>–<b>H</b>) the expressions of TLR4, p38 MAPK, and NF-κB p65 proteins and their corresponding WB images. Data are expressed as mean ± SD (<span class="html-italic">n</span> = 5). Bars with different lowercase letters indicate statistically significant differences (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Effect of WPE on gut microbiota diversity. (<b>A</b>) Venn diagram of OTU; (<b>B</b>) <span class="html-italic">β</span> diversity at the OTU level; (<b>C</b>) <span class="html-italic">α</span> diversity at the OTU level (richness: Chao1 index; diversity: Simpson index and Shannon index). Data are expressed as mean ± SD (<span class="html-italic">n</span> = 5). Bars with different lowercase letters indicate statistically significant differences (<span class="html-italic">p</span> &lt; 0.05).</p>
Full article ">Figure 5
<p>Effect of WPE on gut microbiota structure. (<b>A</b>) Relative abundance of gut microbiota at the phylum level; (<b>B</b>) relative abundance and ratio of Firmicutes and Bacteroidota; the score plot (<b>C</b>) and loading plot (<b>D</b>) of PCA at the genus level; (<b>E</b>) relative abundance and biological classification of the top 20 gut microbiota at the genus level; LEfSe (<b>F</b>) and its influencing factors (<b>G</b>). Data are expressed as mean ± SD (<span class="html-italic">n</span> = 5). Bars with different lowercase letters indicate statistically significant differences (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Heatmaps of Spearman’s correlation analysis. (<b>A</b>) Correlation between SCFAs and biochemical indicators; (<b>B</b>) correlation between gut microbiota with SCFAs and biochemical indicators. * means <span class="html-italic">p</span> &lt; 0.05, and ** means <span class="html-italic">p</span> &lt; 0.01. The red (or green) arrow indicates a significant increase (or decrease) in the abundance of the corresponding item, compared to the DSS group (<span class="html-italic">p</span> &lt; 0.05), whereas the slash indicates no significant difference.</p>
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<p>Mechanism of WPE in attenuating DSS-induced UC (figure created using FigDraw).</p>
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26 pages, 1185 KiB  
Review
pH-Dependent Drug Delivery Systems for Ulcerative Colitis Treatment
by Yana Gvozdeva and Radiana Staynova
Pharmaceutics 2025, 17(2), 226; https://doi.org/10.3390/pharmaceutics17020226 - 10 Feb 2025
Viewed by 411
Abstract
Inflammatory bowel diseases (IBDs), such as ulcerative colitis (UC) or Crohn’s disease, are becoming a growing global problem due to the limitations of current treatments, which fail to address the needs of patients effectively. UC is characterized by the widespread inflammation of the [...] Read more.
Inflammatory bowel diseases (IBDs), such as ulcerative colitis (UC) or Crohn’s disease, are becoming a growing global problem due to the limitations of current treatments, which fail to address the needs of patients effectively. UC is characterized by the widespread inflammation of the mucosal lining, affecting both the rectum and the entire length of the colon. Over the past forty years, traditional treatments for IBDs have primarily relied on anti-inflammatory drugs and immunosuppressive medications. Treatment could be more effective if drugs could be specifically targeted to act directly on the colon. Conventional drug delivery systems for IBDs encounter numerous challenges on their way to the colon, such as physiological barriers and disease severity. To address these issues, pH-dependent carriers have emerged as a promising advancement, offering a more effective and tolerable treatment for UC. These carriers enable localized, targeted action, reducing side effects and preventing the premature clearance of drugs from inflamed colon tissues. pH-responsive systems are a leading approach for targeted drug release in colitis treatment as they take advantage of the varying pH levels throughout the gastrointestinal tract (GIT). By incorporating pH-sensitive polymers, they ensure drug protection and controlled release in the lower GIT. This review will discuss the advantages and limitations of pH-dependent drug delivery systems for colon-targeted drug delivery. Full article
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<p>Colon-targeted drug delivery to the UC area. Created at <a href="https://BioRender.com" target="_blank">https://BioRender.com</a> (accessed on 20 December 2024). Note: The arrows indicate the transition of particulate colon-specific drug delivery systems to the target site affected by UC; The circles represent particulate CDDS.</p>
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<p>pH-dependent polymers and their pH-threshold of dissolution. Created in <a href="https://BioRender.com" target="_blank">https://BioRender.com</a> (accessed on 20 December 2024).</p>
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17 pages, 6914 KiB  
Article
Investigating the Alleviating Effect of Fucoidan from Apostichopus japonicus on Ulcerative Colitis by Mice Experiments and In Vitro Simulation of Human Fecal Fermentation
by Lingyan Xue, Yuchen Huan, Yaoguang Chang, Yuming Wang and Qingjuan Tang
Foods 2025, 14(4), 574; https://doi.org/10.3390/foods14040574 - 9 Feb 2025
Viewed by 570
Abstract
Background: Fucoidan from Apostichopus japonicus (Aj-FUC) is a marine polysaccharide extracted from the high-quality sea cucumber, which has received increasing attention for its multiple biological activities. Methods: In this study, Aj-FUC was extracted, and its basic structure was characterized, while the alleviating efficacy [...] Read more.
Background: Fucoidan from Apostichopus japonicus (Aj-FUC) is a marine polysaccharide extracted from the high-quality sea cucumber, which has received increasing attention for its multiple biological activities. Methods: In this study, Aj-FUC was extracted, and its basic structure was characterized, while the alleviating efficacy of Aj-FUC on ulcerative colitis (UC) was investigated using C57BL/6 mice. The improvement of Aj-FUC on the fecal gut microbiota in healthy individuals and inflammatory bowel disease (IBD) patients was explored using in vitro simulated fecal fermentation. Results: The results reflected that Aj-FUC treatment attenuated the histopathological damage associated with colitis, reduced the levels of IL-6, IL-1β, and TNF-α. Aj-FUC treatment also upregulated the expression of ZO-1 and occludin, thereby aiding in the repair of the intestinal barrier. Furthermore, Aj-FUC enhanced the levels of short-chain fatty acids (SCFAs) and helped restore the balance of gut microbiota, particularly by increasing the relative abundance of Akkermansia. In vitro simulation of fecal fermentation showed that Aj-FUC could modulate the gut microbiota of IBD patients and increase the relative abundance of beneficial bacteria. Conclusions: In conclusion, this study highlights that Aj-FUC can alleviate UC by modulating the levels of inflammatory factors, improving the intestinal barrier, and regulating the intestinal flora in a variety of ways. Full article
(This article belongs to the Section Food Nutrition)
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<p>Structural characterization of Aj-FUC. (<b>A</b>) FT-IR spectra; (<b>B</b>) UV spectrum; (<b>C</b>) molecular weight measurement; (<b>D</b>) monosaccharide composition.</p>
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<p>Effect of Aj-FUC on basic indicators of pathologic histology in mice with DSS-induced colitis. (<b>A</b>) Experimental design; (<b>B</b>) disease activity index (DAI); (<b>C</b>) representative colonic images of mice; (<b>D</b>) length of mice colon; (<b>E</b>) HE stained section of mice colon; (<b>F</b>) pathohistological scores. ### <span class="html-italic">p</span> &lt; 0.001, #### <span class="html-italic">p</span> &lt; 0.0001 vs. N; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 vs. M.</p>
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<p>Effect of Aj-FUC on tissue inflammatory factors in mice with DSS-induced colitis. (<b>A</b>) IL-6; (<b>B</b>) IL-1β; (<b>C</b>) TNF-α. ## <span class="html-italic">p</span> &lt; 0.01, ### <span class="html-italic">p</span> &lt; 0.001 vs. N; * <span class="html-italic">p</span> &lt; 0.05 vs. M.</p>
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<p>Effect of Aj-FUC on DSS-induced intestinal mucosal barrier in mice. (<b>A</b>) Pictures of AB-PAS-stained colon sections; (<b>B</b>) the protein levels of ZO-1; (<b>C</b>) the protein levels of occludin; (<b>D</b>) the mRNA levels of muc-2; (<b>E</b>) the mRNA levels of ZO-1; (<b>F</b>) the mRNA levels of occludin. # <span class="html-italic">p</span> &lt; 0.05, ## <span class="html-italic">p</span> &lt; 0.01 vs. N; * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001 vs. M.</p>
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<p>Effect of Aj-FUC treatment on SCFA concentration in DSS-induced mice in the contents of the cecum: (<b>A</b>) acetate; (<b>B</b>) propionate; (<b>C</b>) isobutyrate; (<b>D</b>) butyrate; (<b>E</b>) isovalerate; (<b>F</b>) valerate. # <span class="html-italic">p</span> &lt; 0.05 vs. N; * <span class="html-italic">p</span> &lt; 0.05 vs. M.</p>
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<p>Regulation of intestinal microbiota in mice with DSS-induced colitis by Aj-FUC. (<b>A</b>) Principal Coordinate Analysis; (<b>B</b>) effect of Aj-FUC on the composition and structure of intestinal microbiota in mice; (<b>C</b>) relative abundance of Akkermansia, Lachnospiraceae_NK4A136_group, Prevotellaceae UCG-00l, Clostridia UCG-014; (<b>D</b>) LDA scores based on LEfSe analysis. ### <span class="html-italic">p</span> &lt; 0.001 vs. N; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. M.</p>
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<p>Aj-FUC alters human gut microbiota diversity through in vitro fermentation. (<b>A</b>) Chao1 index; (<b>B</b>) Shannon index; (<b>C</b>) Simpson index; (<b>D</b>) principal coordinate analysis.</p>
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<p>Alterations in human gut microbiota after 48 h of Aj-FUC fermentation. (<b>A</b>) Relative abundance of microbial communities at the phylum level; (<b>B</b>) relative abundance of microbial communities at the genus level; (<b>C</b>) description of LEfSe analysis for microbial characterization; (<b>D</b>) LDA scores based on LEfSe analysis.</p>
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15 pages, 1252 KiB  
Article
Impact of Vitamins, Antibiotics, Probiotics, and History of COVID-19 on the Gut Microbiome in Ulcerative Colitis Patients: A Cross-Sectional Study
by Zane Straume, Nikola Krūmiņa, Ilze Elbere, Maija Rozenberga, Renārs Erts, Dace Rudzīte, Anna Proskurina and Angelika Krumina
Medicina 2025, 61(2), 284; https://doi.org/10.3390/medicina61020284 - 7 Feb 2025
Viewed by 392
Abstract
Background and Objectives: The human gut microbiome is essential for the health of the host and is affected by antibiotics and coronavirus disease 2019 (COVID-19). The gut microbiome is recognized as a contributing factor in the development of ulcerative colitis. Specific vitamins [...] Read more.
Background and Objectives: The human gut microbiome is essential for the health of the host and is affected by antibiotics and coronavirus disease 2019 (COVID-19). The gut microbiome is recognized as a contributing factor in the development of ulcerative colitis. Specific vitamins and probiotics have been demonstrated to positively influence the microbiome by enhancing the prevalence of expected beneficial microorganisms. Materials and Methods: Forty-nine ulcerative colitis (UC) outpatients from Riga East Clinical University Hospital were enrolled in this cross-sectional study from June 2021 to December 2021. All patients were divided into groups based on history of COVID-19 (COVID-19 positive vs. COVID-19 negative) in the last six months. Information about antibiotic, probiotic, and vitamin intake were outlined, and faecal samples were collected. The MetaPhlAn v.2.6.0 tool was used for the taxonomic classification of the gut microbiome metagenome data. Statistical analysis was performed using R 4.2.1. Results: Of the 49 patients enrolled, 31 (63%) were male and 18 (37%) were female. Coronavirus disease 2019 was found in 14 (28.6%) patients in the last 6 months. Verrucomicrobia was statistically significantly lower in the COVID-19 positive group (M = 0.05; SD = 0.11) compared to the COVID-19 negative group (M = 0.5; SD = 1.22), p = 0.03. Antibiotic non-users had more Firmicutes in their microbiome than antibiotic users (p = 0.008). The most used vitamin supplement was vitamin D (N = 18), fifteen (42.9%) of the patients were COVID-19 negative and 3 (21.4%) were COVID-19 positive over the last six months (p > 0.05). Vitamin C users had more Firmicutes in their gut microbiome compared to non-users (Md = 72.8 [IQR: 66.6; 78.7] vs. Md = 60.1 [IQR: 42.4; 67.7]), p = 0.01. Conclusions: Antibiotic non-users had more Firmicutes than antibiotic users in their gut microbiome. Only vitamin C had statistically significant results; in users, more Firmicutes were observed. A mild course of COVID-19 may not influence ulcerative colitis patients’ gut microbiome. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
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<p>Relationship between Age (years) and Proteobacteria abundance. The blue line represents the fitted regression line showing the trend of Proteobacteria abundance with increasing age. The shaded gray area represents the 95% confidence interval of the regression line. Individual gray dots represent data points for Proteobacteria abundance for each individual. Histograms at the top and right indicate the distribution of Age (years) and Proteobacteria abundance, respectively.</p>
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<p>Vitamin supplement use by COVID-19 status.</p>
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<p>Boxplot showing the distribution of Actinobacteria abundance between antibiotic non-users and antibiotic users. The horizontal line within each box represents the median, and the box indicates the interquartile range (IQR). Whiskers extend to 1.5 times the IQR. Individual dots represent outliers, defined as values that fall outside 1.5 times the IQR above or below the box. The <span class="html-italic">p</span>-value (0.011) indicates a significant difference in Actinobacteria abundance between the two groups.</p>
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<p>Amount of <span class="html-italic">Bacteroidetes</span> in active antibiotic users and non-users.</p>
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12 pages, 235 KiB  
Article
Quality of Life in Patients with Inflammatory Bowel Diseases Is Associated with Affective Temperament Traits: A Cross-Sectional Survey of a Polish Clinical Sample
by Anna Mokrowiecka, Magdalena Kopczynska, Alina Borkowska and Ewa Malecka-Wojciesko
J. Clin. Med. 2025, 14(3), 1018; https://doi.org/10.3390/jcm14031018 - 5 Feb 2025
Viewed by 296
Abstract
Background: Affective temperaments can be considered the subclinical manifestations of affective and stress-related disorders, which could have a relationship with many chronic diseases. The purpose of this study was to explore the influence of affective temperament traits on disease-specific quality of life in [...] Read more.
Background: Affective temperaments can be considered the subclinical manifestations of affective and stress-related disorders, which could have a relationship with many chronic diseases. The purpose of this study was to explore the influence of affective temperament traits on disease-specific quality of life in patients with ulcerative colitis (UC) and Crohn’s disease (CD), two types of inflammatory bowel disease (IBD). Methods: The patients completed the Temperament Evaluation of the Memphis, Pisa, Paris, San Diego-Auto-questionnaire (TEMPS-A), which is the 110-item self-reported assessment for five dimensions of temperament: depressive, cyclothymic, hyperthymic, irritable, and anxious, already validated in Poland. For comprehensive assessment of the health-related quality of life (HRQoL), the Inflammatory Bowel Disease Questionnaire (IBDQ) was applied. Results: The study included 116 patients with IBD-61 with UC and 55 with CD, with mean age 43 years, in remission, without serious mental or medical co-morbidities. Mean HRQoL in patients with IBD was poor and mean IBDQ scores were 145, despite clinical remission. A significant negative correlation was found between HRQoL in all the IBDQ domains and TEMPS-A traits: D (p < 0.001), C (p < 0.01), I (p < 0.05), and A (p < 0.001). No significant correlation between hyperthymic temperament and IBDQ scores was found. Conclusions: Poor quality of life in IBD could be associated with affective temperament. Affective temperament traits should be taken into account when identifying patients at risk of worse IBD course and further introducing personalized therapy. Full article
(This article belongs to the Special Issue Inflammatory Bowel Diseases: Clinical Advances and Emerging Therapies)
13 pages, 414 KiB  
Article
Evaluation of Tryptophan and Its Metabolites in Predicting Disease Activation in Inflammatory Bowel Disease
by Ali Karataş, Tarkan Karakan, Nergiz Ekmen, Yasemin Ünsal, Gülsüm Feyza Türkeş, Özlem Gülbahar, Mehmet Cindoruk, Mustafa Ergin, Güner Kılıç, Mehmet İbiş, Mehmet Arhan, İbrahim Doğan and Hasan Dağlı
J. Clin. Med. 2025, 14(3), 1016; https://doi.org/10.3390/jcm14031016 - 5 Feb 2025
Viewed by 438
Abstract
Background and Aim: Inflammatory bowel disease (IBD), which comprises ulcerative colitis (UC) and Crohn’s disease (CD), is characterized by chronic inflammation and fluctuating disease activity. This study aimed to evaluate serum tryptophan (TRP) and its metabolites as potential biomarkers for predicting disease [...] Read more.
Background and Aim: Inflammatory bowel disease (IBD), which comprises ulcerative colitis (UC) and Crohn’s disease (CD), is characterized by chronic inflammation and fluctuating disease activity. This study aimed to evaluate serum tryptophan (TRP) and its metabolites as potential biomarkers for predicting disease activation in comparison to fecal calprotectin (FC). Methods: This prospective study included 115 patients (77 with UC and 38 with CD). Disease activity was assessed based on clinical and endoscopic findings. Serum TRP levels and their metabolites were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS), whereas FC levels were analyzed using an enzyme-linked immunosorbent assay (ELISA). Results: Serum TRP levels ≤ 11,328.41 ng/mL predicted disease activation with 72.1% sensitivity and 62.7% specificity, whereas FC levels ≥ 89.60 µg/g showed 84.2% sensitivity and 67.6% specificity. The TRP-to-C-reactive protein (CRP) ratio (TRP/CRP) demonstrated superior diagnostic accuracy, with an area under the curve (AUC) of 0.847. Conclusions: The TRP/CRP ratio is a novel and comprehensive approach for predicting disease activation in IBD patients. Although FC remains the gold standard, TRP and its metabolites provide valuable complementary insights. Further research is required to validate these findings in larger cohorts. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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<p>Receiver operating characteristic (ROC) curves for calprotectin (larger results of calprotectin indicate more predictive for disease activation).</p>
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<p>Receiver operating characteristic (ROC) curves for tryptophan (smaller results of tryptophan indicate more predictive for disease activation).</p>
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19 pages, 1149 KiB  
Review
Dual Therapy in Inflammatory Bowel Disease
by Gabriele Altieri, Alessandra Zilli, Tommaso Lorenzo Parigi, Mariangela Allocca, Federica Furfaro, Gionata Fiorino, Clelia Cicerone, Laurent Peyrin-Biroulet, Silvio Danese and Ferdinando D’Amico
Biomolecules 2025, 15(2), 222; https://doi.org/10.3390/biom15020222 - 3 Feb 2025
Viewed by 573
Abstract
Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic and complex autoimmune conditions. Despite the advancements in biologics and small molecules, the therapeutic ceiling persists, posing significant treatment challenges and contributing to the concept of difficult-to-treat IBD. Dual-targeted [...] Read more.
Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic and complex autoimmune conditions. Despite the advancements in biologics and small molecules, the therapeutic ceiling persists, posing significant treatment challenges and contributing to the concept of difficult-to-treat IBD. Dual-targeted therapy (DTT), combining two biologic agents or biologics with small molecules, has emerged as a novel approach to address this unmet need by targeting multiple inflammatory pathways simultaneously. Evidence suggests that DTT holds promise in improving clinical and endoscopic outcomes, especially in patients with refractory disease or extraintestinal manifestations. Safety data, while consistent with monotherapy profiles, highlight the importance of vigilant monitoring for infections and other adverse events. Continued research and high-quality trials are crucial to defining optimal DTT regimens and broadening its clinical applicability. This review explores the efficacy and safety of DTT in IBD, reporting data from clinical trials, systematic reviews, and real-world studies. Full article
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<p>Key benefits of DTT in overcoming the therapeutic ceiling in IBD.</p>
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32 pages, 697 KiB  
Review
Drug Development in Inflammatory Bowel Diseases: What Is Next?
by Lorenzo Petronio, Arianna Dal Buono, Roberto Gabbiadini, Giulia Migliorisi, Giuseppe Privitera, Matteo Ferraris, Laura Loy, Cristina Bezzio and Alessandro Armuzzi
Pharmaceuticals 2025, 18(2), 190; https://doi.org/10.3390/ph18020190 - 30 Jan 2025
Viewed by 483
Abstract
Background/Objectives: Inflammatory bowel diseases (IBDs), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic conditions requiring long-term therapy to maintain remission and improve quality of life. Despite the approval of numerous drugs, IBD continues to present treatment challenges. This review [...] Read more.
Background/Objectives: Inflammatory bowel diseases (IBDs), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic conditions requiring long-term therapy to maintain remission and improve quality of life. Despite the approval of numerous drugs, IBD continues to present treatment challenges. This review aims to summarize novel therapeutic target agents in phases II and III of development, including sphingosine-1-phosphate receptor modulators (S1P), anti-interleukin-23 (IL-23), and other small molecules and monoclonal antibodies currently under investigation (e.g., anti-TL1A, obefazimod, NX-13, RIPK-inhibitors). Methods: A comprehensive literature search was conducted up to December 2024 to identify relevant articles published in English over the past three–five years, focusing on phase II/III studies for UC and CD. The search included databases such as PubMed, Google Scholar, and the ClinicalTrials.gov portal. Results: Clinical trials underline the potential of novel immunomodulators, including anti-TL1A, obefazimod, NX-13, RIPK inhibitors, and anti-IL-23p19 agents, as promising therapeutic options for IBD. Anti-IL23p19 therapies, such as risankizumab and mirikizumab, alongside guselkumab, exemplify this class’s growing clinical relevance. While some are already in clinical use, others are nearing approval. Conclusions: Ongoing research into long-term safety and the development of personalized treatment strategies remains pivotal to enhance outcomes. Patient stratification and the strategic positioning of these therapies within the expanding treatment landscape are critical for optimizing their clinical impact. Full article
(This article belongs to the Special Issue Pharmacotherapy of Inflammatory Bowel Disease)
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<p>Mechanism of action of NX-13.</p>
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13 pages, 1755 KiB  
Article
Efficacy of Serum BDNF for the Evaluation of Depressive Neurological Symptoms in Patients with Refractory Ulcerative Colitis
by Kei Moriya, Shinsaku Nagamatsu, Yuya Nishio, Yusuke Komeda, Shoma Kikukawa, Kyohei Matsuura, Hideki Matsuo, Masakazu Uejima, Takamichi Kitagawa and Fumihiko Nakamura
J. Clin. Med. 2025, 14(3), 874; https://doi.org/10.3390/jcm14030874 - 28 Jan 2025
Viewed by 660
Abstract
Background/Aims: Numerous patients with ulcerative colitis (UC) become mentally unstable after experiencing a long-standing, physically painful life, and their long-term prognosis is poorer than that of those who are mentally stable. The current study aimed to evaluate serum biomarkers for predicting mental instability, [...] Read more.
Background/Aims: Numerous patients with ulcerative colitis (UC) become mentally unstable after experiencing a long-standing, physically painful life, and their long-term prognosis is poorer than that of those who are mentally stable. The current study aimed to evaluate serum biomarkers for predicting mental instability, which is challenging to objectively quantify. Methods: In total, 29 refractory UC patients newly treated with filgotinib underwent measurements of blood parameters associated with depression and a quantitative assessment of quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ) before and after treatment initiation with a 12-week interval. The data collected were examined in relation to each other. Results: The induction of remission treatment with filgotinib resulted in a clinical response rate of 89.7% and a clinical remission rate of 86.2%, with all eight extraintestinal manifestations resolved. No adverse events were observed. The serum zinc, high-density lipoprotein cholesterol, mature brain-derived neurotrophic factor (BDNF) concentrations, and the IBDQ psychiatric subscores increased significantly after treatment (p < 0.05). Among these parameters, the mature-BDNF concentration and the IBDQ psychiatric subscore had the strongest positive correlation (R = 0.29, p = 0.08). Based on the logistic regression analysis, the mature-BDNF concentration (cutoff value: 20.5 ng/mL) had a sensitivity of 68.2%, specificity of 64.7%, and area under the curve of 0.67 for predicting psychiatric remission (subscore > 42.5) (p = 0.04). Conclusions: While it is not easy to objectively predict the degree of psychiatric instability in patients with refractory UC, serum mature-BDNF levels can be a useful biomarker. Full article
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<p>Proportions of patients treated with filgotinib (200 mg per day) who achieved clinical response, clinical remission, and clinical relapse.</p>
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<p>Changes in the IBDQ score before and after filgotinib induction. (<b>A</b>) The total IBDQ score and (<b>B</b>) the IBDQ subscores. The arrow indicates the minimum level of IBDQ remission (170 points). The Mann–Whitney U test was adopted to examine significant differences between two groups. <span class="html-italic">p</span> values of &lt;0.05 indicated statistically significant differences. *, <span class="html-italic">p</span> &lt; 0.05. IBDQ, Inflammatory Bowel Disease Questionnaire.</p>
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<p>Association between the IBDQ psychiatric subscores and depression-related clinical parameters. (<b>A</b>) IBDQ subscore and serum HDL (mg/dL) concentration. (<b>B</b>) IBDQ subscore and serum zinc (μg/dL) concentration. (<b>C</b>) IBDQ subscore and serum mature-BDNF (ng/mL) concentration. (<b>D</b>) IBDQ subscore and serum pro-BDNF (ng/mL) concentration. Correlation was evaluated using Spearman’s rank correlation coefficients. <span class="html-italic">p</span> values of &lt;0.05 indicated statistically significant differences. BDNF, brain-derived neurotrophic factor; HDL, high-density lipoprotein; IBDQ, Inflammatory Bowel Disease Questionnaire.</p>
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<p>Efficacy of the mature-BDNF concentration in predicting depressive neurological symptoms (IBDQ psychiatric subscores &lt; 42.5) in patients with refractory UC. ROC curve analysis. (<b>A</b>) Bivariate analysis between the serum mature-BDNF (ng/mL) concentration and the IBDQ subscore (points). (<b>B</b>) ROC curves for depressive neurological symptoms (AUC = 0.67, sensitivity = 68.2%, and specificity = 64.7%). <span class="html-italic">p</span> values of &lt;0.05 indicated statistically significant differences. AUC, area under the curve; BDNF, brain-derived neurotrophic factor; ROC, receiver operating characteristic.</p>
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11 pages, 757 KiB  
Article
Is There Any Association Between Fat Body Mass and Bone Mineral Density in Patients with Crohn’s Disease and Ulcerative Colitis?
by Alicja Ewa Ratajczak-Pawłowska, Michał Michalak, Aleksandra Szymczak-Tomczak, Anna Maria Rychter, Agnieszka Zawada, Kinga Skoracka, Agnieszka Dobrowolska and Iwona Krela-Kaźmierczak
Nutrients 2025, 17(3), 466; https://doi.org/10.3390/nu17030466 - 28 Jan 2025
Viewed by 493
Abstract
Background: The study aimed to investigate the association between fat body mass and bone mineral density (BMD) of the lumbar spine (L1–L4), femoral neck, and total body. Methods: We studied 95 patients with Crohn’s disease (CD), 68 with ulcerative colitis (UC), [...] Read more.
Background: The study aimed to investigate the association between fat body mass and bone mineral density (BMD) of the lumbar spine (L1–L4), femoral neck, and total body. Methods: We studied 95 patients with Crohn’s disease (CD), 68 with ulcerative colitis (UC), and 40 healthy adults (control group—CG) aged 18–50 years old. The BMD of lumbar spine and femoral neck was assessed as well as body composition. Results: A lower fat mass percentage was observed in about 8% of CD, 13% of UC, and 3% of CG. An increased percentage of fat mass was common, and occurred above 50% of CD, 40% of UC, and about 60% of CG. Body fat mass and fat mass percentage were significantly lower among UC compared with the CG (p-value < 0.001) and CD (p-value < 0.01) in women. Body fat mass correlated positively with the BMD and T-score of L1–L4 and total body mass in men with UC. We found a positive correlation between the fat body mass and BMD and T-score of L1–L4, femoral neck, and total body in women with IBD. Among CG, positive correlations occurred between the fat body mass and BMD of L1–L4, BMD of total body, and T-score of total body, but only in men. CRP (C-reactive protein) correlated negatively with fat body mass only in men with CD. Conclusions: A higher fat mass percentage is common among IBD patients and healthy adults despite a normal body mass index. Body fat mass is a predictor of nutritional status and likely influences the course of the disease, as it correlated positively with BMD, T-score, and Z-score. The association between fat tissue and bone health appears to be stronger in women. Further studies are needed to investigate additional factors that may affect bone health in IBD. Full article
(This article belongs to the Special Issue Advances in Nutrition and Dietetics in Gastroenterology)
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<p>Methodology of the study (DXA—Dual-energy X-ray absorptiometry).</p>
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24 pages, 14052 KiB  
Article
Identification of DDR1 Inhibitors from Marine Compound Library Based on Pharmacophore Model and Scaffold Hopping
by Honghui Hu, Jiahua Tao and Lianxiang Luo
Int. J. Mol. Sci. 2025, 26(3), 1099; https://doi.org/10.3390/ijms26031099 - 27 Jan 2025
Viewed by 464
Abstract
Ulcerative colitis (UC) is a chronic inflammatory condition that affects the intestines. Research has shown that reducing the activity of DDR1 can help maintain intestinal barrier function in UC, making DDR1 a promising target for treatment. However, the development of DDR1 inhibitors as [...] Read more.
Ulcerative colitis (UC) is a chronic inflammatory condition that affects the intestines. Research has shown that reducing the activity of DDR1 can help maintain intestinal barrier function in UC, making DDR1 a promising target for treatment. However, the development of DDR1 inhibitors as drugs has been hindered by issues such as toxicity and poor binding stability. As a result, there are currently no DDR1-targeting drugs available for clinical use, highlighting the need for new inhibitors. In a recent study, a dataset of 85 DDR1 inhibitors was analyzed to identify key characteristics for effective inhibition. A pharmacophore model was constructed and validated to screen a library of marine natural products for potential DDR1 inhibitors. Through high-throughput virtual screening and precise docking, 17 promising compounds were identified from a pool of over 52,000 molecules in the marine database. To improve binding affinity and reduce potential toxicity, scaffold hopping was employed to modify the 17 compounds, resulting in the generation of 1070 new compounds. These new compounds were further evaluated through docking and ADMET analysis, leading to the identification of three compounds—39713a, 34346a, and 34419a—with superior predicted activity and drug-like properties compared to the original 17 compounds. Further analysis showed that the binding free energy values of the three candidate compounds were less than −12.200 kcal/mol, which was similar to or better than −12.377 kcal/mol of the known positive compound VU6015929, and the drug-like properties were better than those of the positive compounds. Molecular dynamics simulations were then conducted on these three candidate compounds, confirming their stable interactions with the target protein. In conclusion, compounds 39713a, 34346a, and 34419a show promise as potential DDR1 inhibitors for the treatment of ulcerative colitis. Full article
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<p>A flowchart of the strategy employed in the identification of potential inhibitors of DDR1. By constructing a pharmacophore model with multi-ligand common features to screen a compound library composed of three marine compound libraries to distinguish between active and inactive compounds, and through high-throughput virtual screening and precise docking, 17 promising potential DDR1 inhibitors were identified from the marine compound library. In order to improve the binding affinity and reduce the potential toxicity, we modified the 17 compounds by fragment substitution and re-evaluated the fragment-replaced compounds by precise docking and ADMET. Three potential DDR1 inhibitors were identified that were superior to the positive compounds, and their molecular dynamics simulations were carried out. The potential DDR1 inhibitors 39713a, 34346a, and 34419a with advantages were screened out through a comprehensive analysis of the above multiple perspectives.</p>
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<p>Comparative analysis of pharmacophore model interactions. (<b>A</b>) Successful alignment of pharmacophore model ADHRR_3 with active molecule 71624791; (<b>B</b>) ineffective alignment of pharmacophore model AARR_2 with inactive molecule 89884371; (<b>C</b>) receiver operating characteristic (ROC) curve for pharmacophore model ADHRR_3.</p>
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<p>Binding pattern of DI1 and 89884371 to the protein DDR1. (<b>A</b>) Two-dimensional images of DDR1 interacting with DI1. (<b>B</b>) Three-dimensional images of DDR1 interacting with DI1. (<b>C</b>) Two-dimensional images of DDR1 interacting with 89884371. (<b>D</b>) Three-dimensional images of DDR1 interacting with 89884371.</p>
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<p>Identification of 17 marine compounds superior to positive compound VU6015929 by high-throughput virtual screening and precision docking.</p>
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<p>Three-dimensional visualization of binding patterns in protein–ligand complexes (hydrogen bond interactions in violet, cation–π interactions in red, π-π interactions in green). (<b>A</b>) Binding pattern of compound 39713a; (<b>B</b>) binding pattern of compound 34346a; (<b>C</b>) binding pattern of compound 34419a; (<b>D</b>) binding pattern of positive control compound VU6015929.</p>
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<p>Two-dimensional images of DDR1 interacting with different compounds. (<b>A</b>) DDR1 and compound 39713a; (<b>B</b>) DDR1 and compound 34346a; (<b>C</b>) DDR1 and compound 34419a; (<b>D</b>) DDR1 and positive control compound VU6015929.</p>
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<p>Intestinal absorption models (red ellipses represent 95% confidence intervals for the HIA model; green ellipses represent 99% confidence intervals for the HIA model. Blue dots depict the values of ADMET_PSA_2D and ADMET_AlogP98 for the three active molecules, positive control compound, and negative compound) (A: 39713-a, B: 34346-a, C: 34419-a, D: VU6015929, E: 89884371).</p>
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<p>Molecular dynamics simulations of 3 ligand–protein complexes, positive control compound, and negative control compound. (<b>A</b>) RMSD values of the 3 ligand–protein complexes, positive control compound, and negative control compound over time; (<b>B</b>) schematic of the RMSF of the 3 ligand–protein complexes, positive control compound, and negative control compound; (<b>C</b>) schematic of the protein radius of gyration of the 3 ligand–protein complexes, positive control compound, and negative control compound; (<b>D</b>) overall potential energy of the 3 ligand–protein complexes, positive control compound, and negative control compound over time.</p>
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<p>Statistical analysis of interaction numbers for three ligand–protein complexes. (<b>A</b>) Time-dependent hydrogen bond formation in the 34419a–DDR1 complex; (<b>B</b>) time-dependent hydrogen bond formation in the 37913a–DDR1 complex; (<b>C</b>) time-dependent hydrogen bond formation in the 34346a–DDR1 complex; (<b>D</b>) time-dependent interaction counts in the 34419a–DDR1 complex; (<b>E</b>) time-dependent interaction counts in the 37913a–DDR1 complex; (<b>F</b>) time-dependent interaction counts in the 34346a–DDR1 complex.</p>
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<p>Schematic representation of principal component distributions and variance ratios of the different ligand and protein systems in the molecular dynamics simulation. Blue dots indicate early stages of the simulation, red dots indicate later stages of the simulation, and the blue to red colour gradient can help to observe the molecular trend over time during the simulation process. (<b>A</b>) Two-dimensional plot of PC1 versus PC2 for the 34419a–protein system; (<b>B</b>) 2D plot of PC2 versus PC3 for the 34419a–protein system; (<b>C</b>) 2D plot of PC1 versus PC3 for the 34419a–protein system; (<b>D</b>) plot of the eigenvalues versus the proportion of variance of the 34419a–protein system; (<b>E</b>) 2D plot of PC1 versus PC2 for the 37913a–protein system; (<b>F</b>) 2D plot of PC2 versus PC3 for the 37913a–protein system; (<b>G</b>) 2D plot of PC1 versus PC3 for the 37913a–protein system; (<b>H</b>) plot of eigenvalues versus variance scaling for the 37913a–protein system; (<b>I</b>) 2D plot of PC1 versus PC2 for the 34346a–protein system; (<b>J</b>) 2D plot of PC2 versus PC3 for the 34346a–protein system; (<b>K</b>) two-dimensional plot of PC1 versus PC3 for the 34346a–protein system; (<b>L</b>) plot of eigenvalues versus variance scaling for the 34346a–protein system.</p>
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<p>Graph of energy breakdown of protein residues at equilibrium for systems with different ligand and protein compositions. (<b>A</b>) 34419a; (<b>B</b>) 37913a; (<b>C</b>) 34346a.</p>
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28 pages, 12568 KiB  
Article
Lactobacillus fermentum 016 Alleviates Mice Colitis by Modulating Oxidative Stress, Gut Microbiota, and Microbial Metabolism
by Huachun Pan, Shumin Yang, Md. F. Kulyar, Hongwei Ma, Kewei Li, Lihong Zhang, Quan Mo and Jiakui Li
Nutrients 2025, 17(3), 452; https://doi.org/10.3390/nu17030452 - 26 Jan 2025
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Abstract
Ulcerative colitis (UC) is a chronic and progressive inflammatory gastrointestinal disease closely associated with gut microbiota dysbiosis and metabolic homeostasis disruption. Although targeted microbial therapies are an emerging intervention strategy for inflammatory bowel disease (IBD), the mechanisms by which specific probiotics, such as [...] Read more.
Ulcerative colitis (UC) is a chronic and progressive inflammatory gastrointestinal disease closely associated with gut microbiota dysbiosis and metabolic homeostasis disruption. Although targeted microbial therapies are an emerging intervention strategy for inflammatory bowel disease (IBD), the mechanisms by which specific probiotics, such as Lactobacillus fermentum 016 (LF), alleviate UC remain unclear. The current study evaluated the effects of LF supplementation on gut health in a basal model using C57BL/6 mice. Subsequently, the preventive effects and mechanisms of LF supplementation on DSS-induced UC were systematically investigated. According to our findings, LF supplementation revealed immunoregulatory capabilities with significantly altered gut the composition of microbiota and metabolic activities, particularly enhancing tryptophan metabolism. In the UC model, LF supplementation effectively mitigated weight loss, increased the disease activity index (DAI), and alleviated diarrhea, rectal bleeding, and colon shortening. Moreover, it reduced colonic pathological damage and histological injury scores. LF intervention improved antioxidant markers and intestinal mucosal barrier function with the activation of the Nrf2–Keap1 signaling pathway and regulation of systemic inflammatory markers, i.e., IL-1β, IL-6, TNF-α, IFN-γ, IL-4, and IL-10. Importantly, LF supplementation reversed metabolic disturbances by significantly increasing the abundance of beneficial genera (e.g., g_Dubosiella, g_Faecalibaculum, g_Odoribacter, g_Candidatus_saccharimonas, g_Roseburia, and g_Eubacterium_xylanophilum_group) and elevating tryptophan metabolites (e.g., melatonin, kynurenic acid, 3-indoleacetic acid, 5-methoxytryptophan, and 5-hydroxyindoleacetic acid). In conclusion, Lactobacillus fermentum 016 exhibits potential for regulating gut microbiota homeostasis, enhancing tryptophan metabolism, and alleviating UC, providing critical insights for developing probiotic-based precision therapeutic strategies for IBD. Full article
(This article belongs to the Special Issue Effect of Dietary Components on Gut Homeostasis and Microbiota)
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Figure 1
<p>Modulatory effects of LF supplementation in the diet on gut health and immune factors in C57 mice. (<b>a</b>) Schematic plan of the experimental design. (<b>b</b>) Body weight change curve of mice during the experiment. (<b>c</b>,<b>d</b>) Measurement and statistical analysis of colon length. (<b>e</b>,<b>f</b>) Histopathological sections of colon tissue and tissue damage scores (scale bar: 200 μm). (<b>g</b>) ELISA detection of serum cytokine levels. Data are presented as mean ± SEM. ns statistically insignificant, * <span class="html-italic">p</span> &lt; 0.05, ns non-significant.</p>
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<p>Effects of LF supplementation in the diet on the colonic microbiota and microbial metabolism in C57 mice. (<b>a</b>) α-diversity index analysis, including Simpson index and Ace index. (<b>b</b>) Venn diagram analysis. (<b>c</b>) β-diversity analysis, displayed by PCoA. (<b>d</b>) Community bar plot analysis (at the genus level). (<b>e</b>) Community heatmap analysis (at the genus level). (<b>f</b>) LefSe analysis showing microbial taxonomic differences. (<b>g</b>) Partial least squares discriminant analysis (PLS-DA). (<b>h</b>) Volcano plot analysis of differential metabolites. (<b>i</b>) Heatmap analysis of differential metabolites (averaged values). (<b>j</b>) KEGG pathway enrichment analysis. (<b>k</b>) Bar chart of inter-group metabolite differences. Data are presented as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001, ns non-significant.</p>
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<p>The ameliorative effects of preventive LF supplementation on DSS-induced colitis symptoms. (<b>a</b>) Experimental design schematic. (<b>b</b>) Body weight change curve of mice during DSS induction. (<b>c</b>) Phenotypes of diarrhea and rectal bleeding in mice. (<b>d</b>) Disease activity index (DAI). (<b>e</b>) Spleen index analysis. Data are expressed as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Effects of preventive supplementation of LF on colonic damage. (<b>a</b>) Colonic length images. (<b>b</b>) Bar graph analysis of colonic length. (<b>c</b>) Histological sections of colonic tissue. (<b>d</b>) Histopathological damage scores. Data are presented as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Effects of preventive supplementation of LF on oxidative stress, immune cytokines, and MPO. (<b>a</b>) Analysis of oxidative stress-related physiological and biochemical indicators. (<b>b</b>) Serum immune cytokine analysis. (<b>c</b>) MPO activity in colonic tissue. Data are presented as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, ns non-significant.</p>
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<p>Effects of preventive supplementation of LF on intestinal mucosal barrier function and the Nrf2–Keap1 pathway. (<b>a</b>) Immunohistochemistry (IHC) analysis of colonic tissue. (<b>b</b>) Immunofluorescence (IFC) analysis of colonic tissue. (<b>c</b>) Western blot analysis of intestinal tight junction proteins. (<b>d</b>) Western blot analysis of the Nrf2–Keap1 pathway. Data are presented as mean ± SEM. The blue arrows indicate the expression of tight junction proteins in colon epithelial cells.</p>
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<p>Effects of preventive supplementation of LF on the gut microbiota structure and composition in colitis mice. (<b>a</b>) α-diversity index analysis, including Shannon index and Ace index. (<b>b</b>) Venn diagram showing the overlap of microbiota among different treatment groups. (<b>c</b>) β-diversity analysis, displaying group differences in microbiota through PCoA. (<b>d</b>) Bar plots of microbiota composition at the phylum and genus levels. (<b>e</b>) Cluster heatmap of microbiota communities at the genus level. (<b>f</b>) LefSe analysis showing microbial taxonomic differences. Data are presented as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Effects of preventive supplementation of LF on the gut microbiota metabolite profile in colitis mice. (<b>a</b>) Partial least squares discriminant analysis (PLS-DA) showing metabolite differences between groups. (<b>b</b>) Venn diagram illustrating the overlap of metabolites among different treatment groups. (<b>c</b>) Volcano plot highlighting significantly altered metabolites. (<b>d</b>) Heatmap analysis of metabolites in the tryptophan metabolism pathway. (<b>e</b>) Bar chart of metabolite differences between groups. (<b>f</b>) KEGG pathway enrichment analysis of metabolites. Data are presented as mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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