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Search Results (2,705)

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13 pages, 718 KiB  
Review
Are Small Molecules Effective in Treating Inflammatory Pouch Disorders Following Ileal Pouch-Anal Anastomosis for Ulcerative Colitis? Here Is Where We Stand
by Antonietta Gerarda Gravina, Raffaele Pellegrino, Giovanna Palladino, Giuseppe Imperio, Francesco Calabrese, Andrea Pasta, Edoardo Giovanni Giannini, Alessandro Federico and Giorgia Bodini
Biomolecules 2024, 14(9), 1164; https://doi.org/10.3390/biom14091164 (registering DOI) - 17 Sep 2024
Viewed by 118
Abstract
Ulcerative colitis (UC) management encompasses conventional and advanced treatments, including biological therapy and small molecules. Surgery, particularly in the form of ileal pouch-anal anastomosis (IPAA), is indicated in cases of refractory/severe disease. IPAA can lead to acute complications (e.g., acute pouchitis) as well [...] Read more.
Ulcerative colitis (UC) management encompasses conventional and advanced treatments, including biological therapy and small molecules. Surgery, particularly in the form of ileal pouch-anal anastomosis (IPAA), is indicated in cases of refractory/severe disease. IPAA can lead to acute complications (e.g., acute pouchitis) as well as late complications, including chronic inflammatory disorders of the pouch. Chronic pouchitis, including the antibiotic-dependent (CADP) and antibiotic-refractory (CARP) forms, represents a significant and current therapeutic challenge due to the substantial need for evidence regarding viable treatment options. Biological therapies have shown promising results, with infliximab, adalimumab, ustekinumab, and vedolizumab demonstrating some efficacy in chronic pouchitis; however, robust randomized clinical trials are only available for vedolizumab. This narrative review focuses on the evidence concerning small molecules in chronic pouchitis, specifically Janus kinase (JAK) inhibitors and sphingosine-1-phosphate receptor (S1P-R) modulators. According to the preliminary studies and reports, Tofacitinib shows a potential effectiveness in CARP. Upadacitinib presents variable outcomes from the case series, necessitating further evaluation. Filgotinib and ozanimod demonstrate anecdotal efficacy. This review underscores the need for high-quality studies and real-world registries to develop robust guidelines for advanced therapies in post-IPAA inflammatory disorders, supported by vigilant clinical monitoring and ongoing education from international IBD specialist societies. Full article
(This article belongs to the Special Issue Molecular Advances in Inflammatory Bowel Disease)
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<p>Rates of clinical response (<b>A</b>) and remission (<b>B</b>) reported in studies exploring the efficacy of tofacitinib in treating inflammatory pouch disorders. The data are expressed as a percentage rate and as the number of patients who achieved the outcome of interest (i.e., clinical response or remission) out of the total number of patients included in the analysis. The rate of 50% is indicated on the <span class="html-italic">x</span>-axis by a vertical dashed grey line. The superscripts related to each study explain the interpretation provided by each study regarding the rates of clinical response and clinical remission, and, specifically: (1) Clinical remission was defined as being steroid-free and antibiotic-free at week 8 (±4 weeks) and week 52 (±8 weeks) with a modified pouchitis disease activity index (mPDAI) &lt;5 and, in cases where endoscopic control was lacking, as having an isolated clinical subscore &lt;2. Clinical response was defined at week 8 (±4 weeks) and week 52 (±8 weeks) as being steroid-free with a reduction in mPDAI &gt;4 at week 8 compared to baseline, with a reduction in mPDAI &gt;1. In cases where endoscopic assessment was lacking, clinical response was indicated by a clinical subscore &gt;1 at week 8 with a reduction of at least 1 point from the baseline score. (2) Clinical response at three months was defined as steroid- and antibiotic-free with a reduction in mPDAI of at least one point from baseline. Clinical response was defined at twelve months as a reduction in mPDAI of at least two points compared to baseline. Remission, both at three months and twelve months, was defined as an mPDAI score of 0. (3) Clinical response, assessed at month 3 (±2 months) and month 12 (±2 months), was evaluated as an improvement of at least two points from the baseline mPDAI. (4) Clinical response at 8 weeks was defined as a reduction of at least two points in the mPDAI compared to baseline with at least a one-point reduction in the endoscopic subscore. Clinical remission was defined as an mPDAI &lt;5 compared to baseline with a reduction of at least two points compared to baseline and changes in clinical and endoscopic scores of the PDAI subscores, faecal calprotectin, and the 10-point Cleveland global quality of life scores. (5) Clinical response was defined as a reduction of at least two points in the clinical PDAI compared to baseline at week 8. Clinical remission was defined as an mPDAI &lt;5 compared to baseline. The references related to the studies shown in the figure are as follows: Uzzan et al. (2023) [<a href="#B31-biomolecules-14-01164" class="html-bibr">31</a>], Ribaldone et al. (2023) [<a href="#B32-biomolecules-14-01164" class="html-bibr">32</a>], Akiyama et al. (2023) [<a href="#B33-biomolecules-14-01164" class="html-bibr">33</a>], Syal et al. (2023) [<a href="#B34-biomolecules-14-01164" class="html-bibr">34</a>], Khoo et al. (2024) [<a href="#B35-biomolecules-14-01164" class="html-bibr">35</a>].</p>
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25 pages, 2070 KiB  
Systematic Review
The Diagnostic Accuracy of Colon Capsule Endoscopy in Inflammatory Bowel Disease—A Systematic Review and Meta-Analysis
by Ian Io Lei, Camilla Thorndal, Muhammad Shoaib Manzoor, Nicholas Parsons, Charlie Noble, Cristiana Huhulea, Anastasios Koulaouzidis and Ramesh P. Arasaradnam
Diagnostics 2024, 14(18), 2056; https://doi.org/10.3390/diagnostics14182056 - 16 Sep 2024
Viewed by 213
Abstract
Colon capsule endoscopy (CCE) has regained popularity for lower gastrointestinal investigations since the COVID-19 pandemic. While there have been systematic reviews and meta-analyses on colonic polyp detection using CCE, there is a lack of comprehensive evidence concerning colonic inflammation. Therefore, this systematic review [...] Read more.
Colon capsule endoscopy (CCE) has regained popularity for lower gastrointestinal investigations since the COVID-19 pandemic. While there have been systematic reviews and meta-analyses on colonic polyp detection using CCE, there is a lack of comprehensive evidence concerning colonic inflammation. Therefore, this systematic review and meta-analysis aimed to assess the diagnostic accuracy of CCE for colonic inflammation, predominantly ulcerative colitis (UC) and Crohn’s disease (CD). Methods: We systematically searched electronic databases (EMBASE, MEDLINE, PubMed Central, and Cochrane Library) for studies comparing the diagnostic accuracy between CCE and optical endoscopy as the standard reference. A bivariate random effect model was used for the meta-analysis. Results: From 3797 publications, 23 studies involving 1353 patients were included. Nine studies focused on UC, and ten focused on CD. For UC, CCE showed a pooled sensitivity of 92% (95% CI, 88–95%), a specificity of 71% (95% CI, 35–92%), and an AUC of 0.93 (95% CI, 0.89–0.97). For CD, the pooled sensitivity was 92% (95% CI, 89–95%), and the specificity was 88% (95% CI, 84–92%), with an AUC of 0.87 (95% CI, 0.76–0.98). Overall, for inflammatory bowel disease, the pooled sensitivity, specificity, and AUC were 90% (95% CI, 85–93%), 76% (95% CI, 56–90%), and 0.92 (95% CI, 0.94–0.97), respectively. Conclusions: Despite the challenges around standardised disease scoring and the lack of histological confirmation, CCE performs well in diagnosing inflammatory bowel disease. It demonstrates high sensitivity in both UC and Crohn’s terminal ileitis and colitis and high specificity in Crohn’s disease. Further studies are needed to evaluate the diagnostic accuracy of other colonic inflammatory conditions. Full article
(This article belongs to the Special Issue Inflammatory Pathologies)
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<p>PRISMA flow chart [<a href="#B1-diagnostics-14-02056" class="html-bibr">1</a>].</p>
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<p>The forest plot of sensitivity (left) and specificity (right) of IBD (including both UC and CD disease activity) detection using CCE. Leighton 2017 [<a href="#B46-diagnostics-14-02056" class="html-bibr">46</a>], Ye C. A. 2013 [<a href="#B28-diagnostics-14-02056" class="html-bibr">28</a>], Juan-Acosta 2014 [<a href="#B29-diagnostics-14-02056" class="html-bibr">29</a>], Shi 2017 [<a href="#B30-diagnostics-14-02056" class="html-bibr">30</a>], Adler 2019 [<a href="#B31-diagnostics-14-02056" class="html-bibr">31</a>], Oliva 2014 [<a href="#B32-diagnostics-14-02056" class="html-bibr">32</a>] Sung 2012 [<a href="#B33-diagnostics-14-02056" class="html-bibr">33</a>], Meister 2013 [<a href="#B34-diagnostics-14-02056" class="html-bibr">34</a>], Hosoe 2013 [<a href="#B35-diagnostics-14-02056" class="html-bibr">35</a>], Hosoe 2018 [<a href="#B36-diagnostics-14-02056" class="html-bibr">36</a>], Oliva 2016 [<a href="#B37-diagnostics-14-02056" class="html-bibr">37</a>], Brodersen 2022 [<a href="#B38-diagnostics-14-02056" class="html-bibr">38</a>], Hausmann 2017 [<a href="#B39-diagnostics-14-02056" class="html-bibr">39</a>], Bruining 2020 [<a href="#B40-diagnostics-14-02056" class="html-bibr">40</a>], Yamada 2021 [<a href="#B41-diagnostics-14-02056" class="html-bibr">41</a>], Papalia 2021 [<a href="#B42-diagnostics-14-02056" class="html-bibr">42</a>], Brodersen 2023 [<a href="#B43-diagnostics-14-02056" class="html-bibr">43</a>], Hall 2015 [<a href="#B47-diagnostics-14-02056" class="html-bibr">47</a>], D’Haens 2015 [<a href="#B44-diagnostics-14-02056" class="html-bibr">44</a>].</p>
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<p>Summary receiver operating characteristic (sROC) curves of CCE for the diagnosis of (<b>a</b>) IBD overall, (<b>b</b>) ulcerative colitis, and (<b>c</b>) Crohn’s disease utilising the generalised linear mixed model (GLMM) from the “glmer” function in the R package “lme4”.</p>
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<p>Risk-of-bias assessment using the QUADAS 2 and QUADAS-C tools. Leighton 2017 [<a href="#B46-diagnostics-14-02056" class="html-bibr">46</a>], Ye 2013 [<a href="#B28-diagnostics-14-02056" class="html-bibr">28</a>], Juan-Acosta 2014 [<a href="#B29-diagnostics-14-02056" class="html-bibr">29</a>], Shi 2017 [<a href="#B30-diagnostics-14-02056" class="html-bibr">30</a>], Adler 2019 [<a href="#B31-diagnostics-14-02056" class="html-bibr">31</a>], Oliva 2014 [<a href="#B32-diagnostics-14-02056" class="html-bibr">32</a>] Sung 2012 [<a href="#B33-diagnostics-14-02056" class="html-bibr">33</a>], Meister 2013 [<a href="#B34-diagnostics-14-02056" class="html-bibr">34</a>], Oliva 2016 [<a href="#B37-diagnostics-14-02056" class="html-bibr">37</a>], Brodersen 2022 [<a href="#B38-diagnostics-14-02056" class="html-bibr">38</a>], Hausmann 2017 [<a href="#B39-diagnostics-14-02056" class="html-bibr">39</a>], Bruining 2020 [<a href="#B40-diagnostics-14-02056" class="html-bibr">40</a>], Yamada 2021 [<a href="#B41-diagnostics-14-02056" class="html-bibr">41</a>], D’Haens 2015 [<a href="#B44-diagnostics-14-02056" class="html-bibr">44</a>], Ismail 2021 [<a href="#B53-diagnostics-14-02056" class="html-bibr">53</a>], Akyuz 2016 [<a href="#B54-diagnostics-14-02056" class="html-bibr">54</a>], Eliakim 2006 [<a href="#B55-diagnostics-14-02056" class="html-bibr">55</a>], Herrerias-Gutierrez 2011 [<a href="#B56-diagnostics-14-02056" class="html-bibr">56</a>].</p>
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<p>Funnel plot for diagnostic odds ratios—Deeks’ regression test for publication bias. Test result: t = −1.26; df = 11; <span class="html-italic">p</span>-value = 0.2329. Bias estimate: −6.4309 (standard error = 5.0937); multiplicative residual heterogeneity variance (tau<sup>2</sup> = 66.0431).</p>
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<p>Scatterplots showing variations in the cut-off points as well as the accuracy of CCE in overall IBD diagnosis.</p>
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27 pages, 1079 KiB  
Review
Intercellular Adhesion Molecule 1 (ICAM-1): An Inflammatory Regulator with Potential Implications in Ferroptosis and Parkinson’s Disease
by Matthew R. Miller, Harold E. Landis, Robert E. Miller and Yousef Tizabi
Cells 2024, 13(18), 1554; https://doi.org/10.3390/cells13181554 - 15 Sep 2024
Viewed by 340
Abstract
Intercellular adhesion molecule 1 (ICAM-1/CD54), a transmembrane glycoprotein, has been considered as one of the most important adhesion molecules during leukocyte recruitment. It is encoded by the ICAM1 gene and plays a central role in inflammation. Its crucial role in many inflammatory diseases [...] Read more.
Intercellular adhesion molecule 1 (ICAM-1/CD54), a transmembrane glycoprotein, has been considered as one of the most important adhesion molecules during leukocyte recruitment. It is encoded by the ICAM1 gene and plays a central role in inflammation. Its crucial role in many inflammatory diseases such as ulcerative colitis and rheumatoid arthritis are well established. Given that neuroinflammation, underscored by microglial activation, is a key element in neurodegenerative diseases such as Parkinson’s disease (PD), we investigated whether ICAM-1 has a role in this progressive neurological condition and, if so, to elucidate the underpinning mechanisms. Specifically, we were interested in the potential interaction between ICAM-1, glial cells, and ferroptosis, an iron-dependent form of cell death that has recently been implicated in PD. We conclude that there exist direct and indirect (via glial cells and T cells) influences of ICAM-1 on ferroptosis and that further elucidation of these interactions can suggest novel intervention for this devastating disease. Full article
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<p>ICAM-1 has been implicated in and associated with an array of diseases.</p>
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<p>ICAM-1, glial cells, T cells, and ferroptosis may have bidirectional interactions to influence the pathophysiology of Parkinson’s disease.</p>
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13 pages, 386 KiB  
Article
Nutrients, Diet Quality, and Dietary Patterns in Patients with Inflammatory Bowel Disease: A Comparative Analysis
by Tingting Yin, Wenjing Tu, Yiting Li, Lina Huang, Yamei Bai and Guihua Xu
Nutrients 2024, 16(18), 3093; https://doi.org/10.3390/nu16183093 - 13 Sep 2024
Viewed by 367
Abstract
(1) Background: Diet plays an important role in the development of inflammatory bowel disease (IBD). There are a number of methods available to assess the diets of patients with IBD, including nutrients, dietary patterns, and various appraisal tools of diet quality. However, research [...] Read more.
(1) Background: Diet plays an important role in the development of inflammatory bowel disease (IBD). There are a number of methods available to assess the diets of patients with IBD, including nutrients, dietary patterns, and various appraisal tools of diet quality. However, research on diet quality and dietary patterns in IBD populations is limited, and comparative evaluations of dietary intake in patients with IBD have not been performed. (2) Objectives: The aim of this study was to assess nutrients, the dietary patterns, and diet quality of patients with IBD and to investigate the relationship between dietary patterns, diet quality, and the adequacy of nutrient intake. (3) Methods: Three-day food records of 268 patients with ulcerative colitis (UC) and 126 patients with Crohn’s disease (CD) were collected to estimate nutrients and food groups, while dietary quality was assessed using the Dietary Inflammation Index (DII) and Mediterranean Diet Score (MDS). Dietary patterns were derived using principal component analysis (PCA). Participants’ nutrient intake, diet quality, and dietary patterns were compared. We used binary logistic regression to assess the relationship between dietary patterns (independent variable) and nutritional adequacy (dependent variable). (4) Results: In our sample, patients had inadequate energy, protein, and dietary fiber intake compared with Reference Nutrient Intake (RNI). Regarding micronutrients, intakes of potassium, zinc, selenium, vitamin A, vitamin C, vitamin E, sodium, calcium, iron, niacin, thiamin, and riboflavin were inadequate. Regarding food groups, the highest intakes were fruits, legumes, dairy products, and nuts. PCA revealed four dietary patterns, namely DP1, DP2, DP3, and DP4. Among UC patients, 96, 55, 69, and 48 patients adhered to DP1, DP2, DP3, and DP4 dietary patterns, respectively. Among CD patients, 41, 31, 34, and 20 patients complied with the dietary patterns of DP1, DP2, DP3, and DP4, respectively. There was no significant difference in dietary patterns between UC and CD patients. Compared with DP4 (high intake of mixed legumes and low intake of tubers), DP1 (high intake of cereals, tubers, vegetables and eggs) was more likely to ensure adequate intake of energy (OR, 2.96; 95% CI, 1.55, 5.62), protein (OR, 2.05; 95% CI, 1.06, 3.96), carbohydrates (OR, 3.55; 95% CI, 1.51, 6.59), thiamine (OR, 2.59; 95% CI, 1.36,4.93), niacin (OR, 2.75; 95% CI, 1.39, 5.42), phosphorus (OR, 2.04; 95% CI, 1.08, 3.85), zinc (OR, 2.43; 95% CI, 1.28, 4.63), and manganese (OR, 3.10; 95% CI, 1.60, 5.90), and DP2 (high intake of fruits, poultry, aquatic products, and nuts) was more likely to meet niacin requirements than DP4 (OR, 2.65; 95% CI, 1.28, 5.48). (5) Conclusion: This study clarifies our understanding of dietary intake, diet quality, and dietary patterns in adult patients with IBD. Future attention is needed to improve diet quality, emphasizing the importance of assessing and understanding patient dietary habits and increasing understanding of the factors that influence dietary intake in IBD in order to achieve optimal outcomes for patients with IBD. Full article
(This article belongs to the Topic Ways to Achieve Healthy and Sustainable Diets)
9 pages, 434 KiB  
Article
Long-Term Follow Up of Patients Treated for Inflammatory Bowel Disease and Cytomegalovirus Colitis
by Gurtej Singh, Clarissa Rentsch, William Beattie, Britt Christensen, Finlay Macrae and Jonathan P. Segal
Diagnostics 2024, 14(18), 2030; https://doi.org/10.3390/diagnostics14182030 - 13 Sep 2024
Viewed by 324
Abstract
Background: Pathological reactivation of latent Cytomegalovirus (CMV) is triggered by inflammation and immunosuppression; both present in the pathogenesis and treatment of Inflammatory Bowel Disease (IBD). Whether CMV reactivation is associated with escalating medical therapy, further hospital admissions, or worse clinical outcomes remains controversial. [...] Read more.
Background: Pathological reactivation of latent Cytomegalovirus (CMV) is triggered by inflammation and immunosuppression; both present in the pathogenesis and treatment of Inflammatory Bowel Disease (IBD). Whether CMV reactivation is associated with escalating medical therapy, further hospital admissions, or worse clinical outcomes remains controversial. This study aimed to follow up IBD patients with an index episode of CMV colitis and analyse the clinical outcomes. Methods: A retrospective study of patients with IBD treated for CMV colitis was completed. The outcome results were collected at 6-month and 12-month time points after the first episode of CMV colitis. A total of 13 patients with Ulcerative Colitis and 1 with Crohn’s Disease were included. Results: CMV colitis recurrence occurred in 29% of patients at 12 months. A total of 43% of patients had changed their biologic dose at 6 months and 29% had escalated their biologic dose at 12 months. At 12 months, 36% of patients had been re-hospitalised, including three colectomies. Disease remission was only achieved by 29% of patients at 12 months. Conclusions: IBD patients with CMV colitis have substantial rates of re-hospitalisation, failed medical therapy, and colectomy. These risks may be greater at <6 months from an index episode of CMV colitis. Full article
(This article belongs to the Special Issue Inflammatory Pathologies)
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<p>Consort flowchart showing inclusion and exclusion of patients included in final analysis.</p>
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15 pages, 4199 KiB  
Article
Exposure of Colon-Derived Epithelial Monolayers to Fecal Luminal Factors from Patients with Colon Cancer and Ulcerative Colitis Results in Distinct Gene Expression Patterns
by Maria K. Magnusson, Anna Bas Forsberg, Alexandra Verveda, Maria Sapnara, Julie Lorent, Otto Savolainen, Yvonne Wettergren, Hans Strid, Magnus Simrén and Lena Öhman
Int. J. Mol. Sci. 2024, 25(18), 9886; https://doi.org/10.3390/ijms25189886 - 13 Sep 2024
Viewed by 232
Abstract
Microbiota and luminal components may affect epithelial integrity and thus participate in the pathophysiology of colon cancer (CC) and inflammatory bowel disease (IBD). Therefore, we aimed to determine the effects of fecal luminal factors derived from patients with CC and ulcerative colitis (UC) [...] Read more.
Microbiota and luminal components may affect epithelial integrity and thus participate in the pathophysiology of colon cancer (CC) and inflammatory bowel disease (IBD). Therefore, we aimed to determine the effects of fecal luminal factors derived from patients with CC and ulcerative colitis (UC) on the colonic epithelium using a standardized colon-derived two-dimensional epithelial monolayer. The complex primary human stem cell-derived intestinal epithelium model, termed RepliGut® Planar, was expanded and passaged in a two-dimensional culture which underwent stimulation for 48 h with fecal supernatants (FS) from CC patients (n = 6), UC patients with active disease (n = 6), and healthy subjects (HS) (n = 6). mRNA sequencing of monolayers was performed and cytokine secretion in the basolateral cell culture compartment was measured. The addition of fecal supernatants did not impair the integrity of the colon-derived epithelial monolayer. However, monolayers stimulated with fecal supernatants from CC patients and UC patients presented distinct gene expression patterns. Comparing UC vs. CC, 29 genes were downregulated and 33 genes were upregulated, for CC vs. HS, 17 genes were downregulated and five genes were upregulated, and for UC vs. HS, three genes were downregulated and one gene was upregulated. The addition of FS increased secretion of IL8 with no difference between the study groups. Fecal luminal factors from CC patients and UC patients induce distinct colonic epithelial gene expression patterns, potentially reflecting the disease pathophysiology. The culture of colonic epithelial monolayers with fecal supernatants derived from patients may facilitate the exploration of IBD- and CC-related intestinal microenvironmental and barrier interactions. Full article
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<p>Fecal metabolite profiles and characterization of the RepliGut<sup>®</sup> Planar monolayers treated with fecal supernatants (FS). (<b>A</b>) A principal component analysis based on 9699 spectral features detected in FS, analyzed by untargeted liquid chromatography/mass spectrometry, for healthy subjects (HS, <span class="html-italic">n</span> = 6, green dots), patients with ulcerative colitis (UC, <span class="html-italic">n</span> = 6, red dots) and colon cancer patients (CC, <span class="html-italic">n</span> = 6, blue dots). (<b>B</b>) Primary human intestinal cells in the RepliGut<sup>®</sup> Planar system form a polarized monolayer with an apical membrane morphologically comparable with that of human intestine, as visualized by apical localization of phospho-ezrin (green), and actin filaments as detected by fluorescent phalloidin (magenta). Nuclei are visualized in blue color. The right hand and bottom panels show the orthographic view of the region, where “XY” and “XZ” indicate different cross-sections. The image was acquired with LSM700 inverted confocal microscope; 63× magnification. (<b>C</b>) Transepithelial electrical resistance was measured before and at 24 h and 48 h after addition of FS (HS: green dots, UC: red dots, CC: blue dots), TNFα (black triangles) or untreated (Media, gray triangles).</p>
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<p>Gene expression of RepliGut<sup>®</sup> Planar monolayers stimulated with fecal supernatants (FS) from healthy subjects (HS), patients with ulcerative colitis (UC), and patients with colon cancer (CC). Differentiated monolayers were stimulated apically with FS, TNFα, or left untreated (Media), for 48 h. Gene expression was analyzed by mRNA sequencing. (<b>A</b>) Principal component analysis (PCA) for monolayers treated with FS from HS, UC, CC, or with TNFα or media. (<b>B</b>) PCA for monolayers treated with FS from HS, UC, or CC. (<b>C</b>) Heatmap of distances between samples for monolayers treated with FS from HS, UC, or CC. HS <span class="html-italic">n</span> = 6 (green dots), UC <span class="html-italic">n</span> = 6 (red dots), CC <span class="html-italic">n</span> = 6 (blue dots), TNFα <span class="html-italic">n</span> = 2 (black triangles), and media <span class="html-italic">n</span> = 2 (gray triangles).</p>
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<p>Comparison of gene expression of RepliGut<sup>®</sup> Planar monolayers stimulated with fecal supernatants (FS) from patients with colon cancer (CC) and healthy subjects (HS). Differentiated monolayers were stimulated apically with FS for 48 h. Gene expression was analyzed by mRNA sequencing. (<b>A</b>) Volcano plot showing log2 fold change vs. significance. Wald test and false discovery rate analysis using the Benjamini−Hochberg method were used. Downregulated genes are shown in blue, upregulated genes in red and all the other genes in black. Horizontal dotted lines show cut-off for significance (q &lt; 0.05) and vertical dotted lines show two-fold up- and downregulation. (<b>B</b>) Gene expression of the four most significant genes from (<b>A</b>). HS <span class="html-italic">n</span> = 6 (green dots) and CC <span class="html-italic">n</span> = 6 (blue dots). Results for patients with ulcerative colitis (UC) <span class="html-italic">n</span> = 6 (pale red dots) are shown to the right of the dotted line for reference.</p>
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<p>Comparison of gene expression of RepliGut<sup>®</sup> Planar monolayers stimulated with fecal supernatants (FS) from patients with ulcerative colitis (UC) and healthy subjects (HS). Differentiated monolayers were stimulated apically with FS for 48 h. Gene expression was analyzed by mRNA sequencing. (<b>A</b>) Volcano plot showing log2 fold change vs. significance. Wald test and false discovery rate analysis using the Benjamini−Hochberg method were used. Downregulated genes are shown in blue, upregulated genes in red and all the other genes in black. Horizontal dotted lines show cut-off for significance (q &lt; 0.05) and vertical dotted lines show two-fold up- and downregulation. (<b>B</b>) Gene expression of the four significant genes from (<b>A</b>). HS <span class="html-italic">n</span> = 6 (green dots) and UC <span class="html-italic">n</span> = 6 (red dots). Results for patients with colon cancer (CC) <span class="html-italic">n</span> = 6 (pale blue dots) are shown to the right of the dotted line for reference.</p>
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<p>Comparison of gene expression of RepliGut<sup>®</sup> Planar monolayers stimulated with fecal supernatants (FS) from patients with ulcerative colitis (UC) and patients with colon cancer (CC). Differentiated monolayers were stimulated apically with FS for 48 h. Gene expression was analyzed by mRNA sequencing. (<b>A</b>) Volcano plot showing log2 fold change vs. significance. Wald test and false discovery rate analysis using the Benjamini−Hochberg method were used. Downregulated genes are shown in blue, upregulated genes in red and all the other genes in black. Horizontal dotted lines show cut-off for significance (q &lt; 0.05) and vertical dotted lines show two-fold up- and downregulation. (<b>B</b>) Gene expression of the four most significant genes from (<b>A</b>). UC <span class="html-italic">n</span> = 6 (red dots) and CC <span class="html-italic">n</span> = 6 (blue dots). Results for healthy subjects (HS) <span class="html-italic">n</span> = 6 (pale green dots) are shown to the right of the dotted line for reference.</p>
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<p>Cytokine secretion from RepliGut<sup>®</sup> Planar monolayers stimulated with fecal supernatants (FS) from patients with ulcerative colitis (UC), patients with colon cancer (CC), and healthy subjects (HS). Differentiated monolayers were stimulated apically for 48 h with FS from HS, CC, UC, or media alone (<span class="html-italic">n</span> = 3). IL1β, IL8, and TNFα levels in the basolateral compartment were analyzed by MSD<sup>®</sup> V-PLEX platform system. (<b>A</b>) Levels of IL1β, IL8, and TNFα. Dashed lines represent median cytokine concentration from monolayers cultured with media alone. (<b>B</b>) Principal component analysis based on the levels of IL1β, IL8, and TNFα. HS <span class="html-italic">n</span> = 6 (green dots), UC <span class="html-italic">n</span> = 6 (red dots), CC <span class="html-italic">n</span> = 6 (blue dots), and media <span class="html-italic">n</span> = 3 (gray triangles).</p>
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16 pages, 2697 KiB  
Review
Pulmonary Manifestations of IBD: Case Report and Review of the Literature
by Amit Herling, Tal Moshe Perluk, Ophir Freund, Nitsan Maharshak and Nathaniel Aviv Cohen
J. Clin. Med. 2024, 13(18), 5401; https://doi.org/10.3390/jcm13185401 - 12 Sep 2024
Viewed by 304
Abstract
This article explores the pulmonary complications associated with inflammatory bowel disease (IBD). It presents a detailed case study of a 22-year-old male with Crohn’s disease exhibiting pulmonary symptoms. The review delves into the spectrum of pulmonary involvement in IBD, covering clinical presentations, diagnostic [...] Read more.
This article explores the pulmonary complications associated with inflammatory bowel disease (IBD). It presents a detailed case study of a 22-year-old male with Crohn’s disease exhibiting pulmonary symptoms. The review delves into the spectrum of pulmonary involvement in IBD, covering clinical presentations, diagnostic challenges, underlying pathophysiology, and management strategies. It highlights the significance of these extraintestinal manifestations on patient outcomes and quality of life. The article underscores the need for heightened clinical awareness and a systematic approach to diagnosis and management, integrating the expertise of multiple specialists. The review identifies gaps in current research, suggesting avenues for future investigation to enhance the understanding and treatment of these complex manifestations. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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<p>(<b>A</b>)—Chest CT scan revealed subtle opacities in a tree-in-bud pattern in the lower and right middle lobes of the lungs (red arrows), along with minute, non-specific nodules in the lingula and upper lobes. (<b>B</b>)—Follow-up chest CT scan, four months post-treatment initiation, indicated complete resolution of the previously noted nodular opacities (green arrow) and other abnormal findings.</p>
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<p>(<b>A</b>)—Chest CT scan revealed subtle opacities in a tree-in-bud pattern in the lower and right middle lobes of the lungs (red arrows), along with minute, non-specific nodules in the lingula and upper lobes. (<b>B</b>)—Follow-up chest CT scan, four months post-treatment initiation, indicated complete resolution of the previously noted nodular opacities (green arrow) and other abnormal findings.</p>
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11 pages, 265 KiB  
Review
An Overview of Nutritional Interventions in Inflammatory Bowel Diseases
by Ramit Magen-Rimon, Andrew S. Day and Ron Shaoul
Nutrients 2024, 16(18), 3055; https://doi.org/10.3390/nu16183055 - 10 Sep 2024
Viewed by 623
Abstract
Food is an important environmental factor in the development of inflammatory bowel diseases, chronic immune-mediated diseases of the gastrointestinal tract. Consequently, there is significant focus on the role that dietary approaches might have in the management of these diseases. The introduction of exclusive [...] Read more.
Food is an important environmental factor in the development of inflammatory bowel diseases, chronic immune-mediated diseases of the gastrointestinal tract. Consequently, there is significant focus on the role that dietary approaches might have in the management of these diseases. The introduction of exclusive enteral nutrition (EEN) as a treatment option for induction of remission in Crohn’s disease was a breakthrough in disease pathophysiology understanding and has paved the way for dietary options based on this understanding. This review aims to summarize the current data on the effect of different available diets on disease symptoms and the inflammatory process. Full article
(This article belongs to the Special Issue The Role of Nutrition in Pediatric Gastrointestinal Diseases)
22 pages, 14482 KiB  
Article
Key Disease-Related Genes and Immune Cell Infiltration Landscape in Inflammatory Bowel Disease: A Bioinformatics Investigation
by Kawthar S. Alghamdi, Rahaf H. Kassar, Wesam F. Farrash, Ahmad A. Obaid, Shakir Idris, Alaa Siddig, Afnan M. Shakoori, Sallwa M. Alshehre, Faisal Minshawi and Abdulrahman Mujalli
Int. J. Mol. Sci. 2024, 25(17), 9751; https://doi.org/10.3390/ijms25179751 - 9 Sep 2024
Viewed by 474
Abstract
Inflammatory Bowel Diseases (IBD), which encompass ulcerative colitis (UC) and Crohn’s disease (CD), are characterized by chronic inflammation and tissue damage of the gastrointestinal tract. This study aimed to uncover novel disease-gene signatures, dysregulated pathways, and the immune cell infiltration landscape of inflamed [...] Read more.
Inflammatory Bowel Diseases (IBD), which encompass ulcerative colitis (UC) and Crohn’s disease (CD), are characterized by chronic inflammation and tissue damage of the gastrointestinal tract. This study aimed to uncover novel disease-gene signatures, dysregulated pathways, and the immune cell infiltration landscape of inflamed tissues. Eight publicly available transcriptomic datasets, including inflamed and non-inflamed tissues from CD and UC patients were analyzed. Common differentially expressed genes (DEGs) were identified through meta-analysis, revealing 180 DEGs. DEGs were implicated in leukocyte transendothelial migration, PI3K-Akt, chemokine, NOD-like receptors, TNF signaling pathways, and pathways in cancer. Protein–protein interaction network and cluster analysis identified 14 central IBD players, which were validated using eight external datasets. Disease module construction using the NeDRex platform identified nine out of 14 disease-associated genes (CYBB, RAC2, GNAI2, ITGA4, CYBA, NCF4, CPT1A, NCF2, and PCK1). Immune infiltration profile assessment revealed a significantly higher degree of infiltration of neutrophils, activated dendritic cells, plasma cells, mast cells (resting/activated), B cells (memory/naïve), regulatory T cells, and M0 and M1 macrophages in inflamed IBD tissue. Collectively, this study identified the immune infiltration profile and nine disease-associated genes as potential modulators of IBD pathogenesis, offering insights into disease molecular mechanisms, and highlighting potential disease modulators and immune cell dynamics. Full article
(This article belongs to the Special Issue Immunoanalytical and Bioinformatics Methods in Immunology Research)
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<p>Differential expression analysis of Crohn’s disease (CD). (<b>a</b>) Volcano plots across four CD datasets. The colored dots represent the significant DEGs identified at |log2FC| ≥ 1 and an adjusted <span class="html-italic">p</span>-value of ≤0.05. The top 10 genes within each dataset are shown. (<b>b</b>) The upset plots depict DEG distribution across CD datasets. (<b>c</b>) Heatmap of top 10 DEGs identified by meta-analysis. The expression heatmap depicts expression levels of significantly different upregulated and downregulated genes. The color indicates high expression (red) and low expression (green).</p>
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<p>Differential expression analysis of ulcerative colitis (UC). (<b>a</b>) Volcano plots across four UC datasets. The colored dots represent the significant DEGs identified at |log2FC| ≥ 1 and an adjusted <span class="html-italic">p</span>-value of ≤0.05. The top 10 genes within each dataset are shown. (<b>b</b>) The upset plots depict DEG distribution across UC datasets. (<b>c</b>) Heatmap of top 10 DEGs identified by meta-analysis. The expression heatmap depicts expression levels of significantly different upregulated and downregulated genes. The color indicates high expression (red) and low expression (green).</p>
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<p>Enrichment analysis of DEGs. Bubble plot of top 20 gene ontology (GO) and KEGG signaling pathways for (<b>a</b>) CD and (<b>b</b>) UC. The bubble color scaled the enrichment score. The size of the bubbles represents the level of DEG enrichment within each pathway. (<b>c</b>) The Sankey plot represents both shared and distinct pathways between CD and UC.</p>
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<p>Characterization of IBD-DEGs. (<b>a</b>) Venn diagram illustrates shared DEGs between CD and UC, identifying 180 IBD-DEGs with 106 upregulated and 74 downregulated. (<b>b</b>) Tissue specificity enrichment analysis of IBD-DEGs shows predominant enrichment in tissues such as the small intestine, appendix, colon, duodenum, and rectum. (<b>c</b>) PPI network of IBD-DEGs, displaying top genes with their centrality parameters obtained from network analysis. Node size corresponds to the degree of connectivity. (<b>d</b>) Hub genes identified from the PPI network were ranked based on their degree of connectivity.</p>
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<p>Potential key IB-DEGs. (<b>a</b>) PPI network with clusters identified using MCODE and BiCoN clustering methods in Cytoscape. Nodes with lavender color indicate the genes in the clusters and the cluster regions in the PPI network (<b>b</b>) 14 key IBD-DEGs identified through the intersection of clusters identified by both methods. (<b>c</b>) Heatmap showing the validation of the candidate IBD-DEGs across eight external validation datasets (GSE117993, GSE4183, GSE13367, GSE16879, GSE36807, GSE38713, GSE6731, and GSE59071). Consistent expression patterns of the identified genes were observed across these datasets. Red signifies upregulation, and blue signifies downregulation of expression levels.</p>
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<p>Disease modules of key IBD-DEGs and mechanistic pathways. (<b>a</b>) An illustration of IBD-related genes recovered through the Get Disease Genes function in NeDRex platform. (<b>b</b>) Disease module obtained from IBD-related genes and potential key IBD genes using DIAMOnD algorithm. Nine out of 14 key IBD-DEGs are present in the subnetwork highlighted in yellow. (<b>c</b>) Enriched pathways for key IBD-DEGs.</p>
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<p>Immune cell infiltration fraction between inflamed and non-inflamed IBD tissues. Violin plots of the proportion of 22 immune cells in inflamed (<span class="html-italic">n</span> = 397, red) vs. non-inflamed (<span class="html-italic">n</span> = 370, blue) IBD tissues. The red boxplot represents inflamed, and the blue boxplot represents non-inflamed tissues. Significance levels are indicated as follows: ns = non-significant, * <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.</p>
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<p>Workflow used in this study.</p>
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15 pages, 2928 KiB  
Review
Lactic Acid Bacteria–Gut-Microbiota-Mediated Intervention towards Inflammatory Bowel Disease
by Diantong Li, Zhenjiang Liu, Xueni Fan, Tingting Zhao, Dongxu Wen, Xiaodan Huang and Bin Li
Microorganisms 2024, 12(9), 1864; https://doi.org/10.3390/microorganisms12091864 - 9 Sep 2024
Viewed by 424
Abstract
Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), arises from intricate interactions involving genetics, environment, and pharmaceuticals with an ambiguous pathogenic mechanism. Recently, there has been an increasing utilization of lactic acid bacteria (LAB) in managing IBD, attributed to [...] Read more.
Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), arises from intricate interactions involving genetics, environment, and pharmaceuticals with an ambiguous pathogenic mechanism. Recently, there has been an increasing utilization of lactic acid bacteria (LAB) in managing IBD, attributed to their ability to enhance intestinal barrier function, mitigate inflammatory responses, and modulate gut microbiota. This review initiates by elucidating the pathogenesis of IBD and its determinants, followed by an exploration of the mechanisms underlying LAB therapy in UC and CD. Special attention is directed towards their influence on intestinal barrier function and homeostasis regulated by gut microbiota. Furthermore, the review investigates the complex interplay among pivotal gut microbiota, metabolites, and pathways associated with inflammation. Moreover, it underscores the limitations of LAB in treating IBD, particularly in light of their varying roles in UC and CD. This comprehensive analysis endeavors to offer insights for the optimized application of LAB in IBD therapy. Full article
(This article belongs to the Topic Probiotics: New Avenues)
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<p>Types of Inflammatory Bowel Disease. The red areas indicate inflammation, with CD (<b>A</b>) showing segmental distribution and UC (<b>B</b>) presenting as a continuous lesion.</p>
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<p>Inflammatory bowel disease pathogenesis. Risk factors trigger microbial dysbiosis in IBD, reducing SCFA-producing bacteria and increasing Proteobacteria. Intestinal barrier integrity is compromised by decreased E-cadherin, altered goblet cell function (Muc2, RELMβ), and Paneth cell dysfunction (NOD2, ATG16L1). Innate immune dysregulation involves reduced CD14+ macrophages and impaired autophagy. An imbalance between effector and Treg leads to uncontrolled T cell activation and abnormal leukocyte migration in the inflamed intestine. Abbreviations: NOD2: nucleotide-binding oligomerization domain 2; ATG16L1: autophagy related 16 like; Muc2: mucin 2; RELMβ: resistin-like molecule β; TNF-α: tumor necrosis factor-α; IL: interleukin; TGF-β: transforming growth factor-β; Th: helper T cell; Treg: regulatory T cell; NK-T: natural killer/T cell.</p>
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<p>The role of LAB in UC. LAB treats and ameliorates UC primarily by improving the intestinal barrier, inhibiting the expression of cytokines, and modulating the gut microbiota. Abbreviations: ROS: reactive oxygen species; NO: nitric oxide; COX-2: cyclooxygenase-2; NF-κB: nuclear factor κ-light-chain-enhancer of activated B cells; IFN-γ: interferon-γ; MPO: myeloperoxidase; Nrf2: nuclear factor erythroid 2-related factor 2; HO-1: heme oxygenase-1; sMaf: small Maf transcription factor; ARE: antioxidant response element.</p>
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<p>Differences between UC and CD pathogenesis. In UC (<b>A</b>), lesions are primarily confined to the mucosal layer, characterized by superficial ulcers and crypt abscesses. Conversely, CD (<b>B</b>) is marked by segmental inflammation with transmural involvement, presenting as deep fissuring ulcers and granulomatous inflammation.</p>
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9 pages, 1145 KiB  
Article
Food-Protein-Induced Proctocolitis in Pre-Term Newborns with Bloody Stools in a Neonatal Intensive Care Unit
by Enza D’Auria, Francesco Cavigioli, Miriam Acunzo, Paola Azzurra La Verde, Anna Di Gallo, Carolina Piran, Lodovico Sterzi, Gian Vincenzo Zuccotti and Gianluca Lista
Nutrients 2024, 16(17), 3036; https://doi.org/10.3390/nu16173036 - 9 Sep 2024
Viewed by 542
Abstract
The bloody stools of newborns may be a clue for several clinical entities of varying severity, ranging from idiopathic neonatal transient colitis to food-protein-induced allergic proctocolitis (FPIAP) or necrotizing enterocolitis (NEC). Distinguishing among them at an early stage is challenging but crucial, as [...] Read more.
The bloody stools of newborns may be a clue for several clinical entities of varying severity, ranging from idiopathic neonatal transient colitis to food-protein-induced allergic proctocolitis (FPIAP) or necrotizing enterocolitis (NEC). Distinguishing among them at an early stage is challenging but crucial, as the treatments and prognoses are different. We conducted a monocentric retrospective study including all pre-term infants with bloody stools admitted to the Neonatal Intensive Care Unit (NICU) of the Vittore Buzzi Children’s Hospital (Milan) from December 2022 to May 2024. Patients diagnosed with NEC exhibited significantly lower eosinophil counts and higher procalcitonin levels than both patients with FPIAP and patients with idiopathic neonatal transient colitis, as well as a statistically significant increase in pathological features from abdomen ultrasounds and abdominal X-rays. In contrast, no lab markers or imaging techniques have been demonstrated to be useful in distinguishing between idiopathic neonatal transient colitis and FPIAP. Thus, after excluding a diagnosis of NEC, the only way to confirm FPIAP is through the oral food challenge, which can be performed in premature newborns presenting with bloody stools who are otherwise healthy and under medical supervision, in order to identify infants who may benefit from a cow’s-milk-free diet. Full article
(This article belongs to the Special Issue Nutrition and Immunity in Early Childhood)
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<p>Boxplots of the eosinophil (<b>on the left</b>) and platelet (<b>on the right</b>) levels in the patient population. The <span class="html-italic">p</span>-values of pairwise comparisons between the groups performed via Mann–Whitney U test are shown on top.</p>
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<p>Boxplots of PCR (<b>on the left</b>) and neutrophils levels (<b>on the right</b>) in the patient population. The <span class="html-italic">p</span>-values of pairwise comparisons between the groups performed via Mann–Whitney U test are shown on top.</p>
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<p>ROC curve of eosinophils.</p>
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15 pages, 3356 KiB  
Article
Anti-Inflammatory Effect of Dietary Pentadecanoic Fatty Acid Supplementation on Inflammatory Bowel Disease in SAMP1/YitFc Mice
by Drishtant Singh, Paola Mehghini, Alexander Rodriguez-Palacios, Luca Di Martino, Fabio Cominelli and Abigail Raffner Basson
Nutrients 2024, 16(17), 3031; https://doi.org/10.3390/nu16173031 - 8 Sep 2024
Viewed by 614
Abstract
Background/Objectives: Dietary fats have been linked to the increasing incidence of chronic diseases, including inflammatory bowel diseases (IBD), namely, Crohn’s disease (CD). Methods: This study investigated the impact of pentadecanoic acid (C15:0), a type of an odd-numbered chain saturated fatty acid, for its [...] Read more.
Background/Objectives: Dietary fats have been linked to the increasing incidence of chronic diseases, including inflammatory bowel diseases (IBD), namely, Crohn’s disease (CD). Methods: This study investigated the impact of pentadecanoic acid (C15:0), a type of an odd-numbered chain saturated fatty acid, for its potential anti-inflammatory properties in different mouse models of experimental IBD using the SAMP1/YitFc (SAMP) mouse line (14- or 24-week-old), including chronic ileitis and DSS-induced colitis. To quantitively assess the effect of C:15, we tested two dosages of C:15 in selected experiments in comparison to control mice. Intestinal inflammation and intestinal permeability were used as primary outcomes. Results: In ileitis, C:15 supplementation showed an anti-inflammatory effect in SAMP mice (e.g., a reduction in ileitis severity vs. control p < 0.0043), which was reproducible when mice were tested in the DSS model of colitis (e.g., reduced permeability vs. control p < 0.0006). Of relevance, even the short-term C:15 therapy prevented colitis in mice by maintaining body weight, decreasing inflammation, preserving gut integrity, and alleviating colitis signs. Conclusions: Collectively, the findings from both ileitis and colitis in SAMP mice indicate that C:15 may have therapeutic effects in the treatment of IBD (colitis in the short term). This promising effect has major translational potential for the alleviation of IBD in humans. Full article
(This article belongs to the Section Lipids)
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<p>Overview of the Experimental Design (SAMP1/YitFc, a sub-strain of AKR/J mice produced through a program of selective breeding; DSS, Dextran Sulfate Sodium; MPO, myeloperoxidase; FITC, fluorescein isothiocyanate).</p>
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<p>C:15 given for 3 weeks reduces the severity of acute chemical colitis in 14 wk old SPF SAMP. Values are mean ± SD, <span class="html-italic">n</span> = 7. (<b>A</b>) Effect of C:15 diet on body weight of DSS-treated mice, (<b>B</b>) colon length, (<b>C</b>) colonoscopy score, (<b>D</b>) intestinal permeability assay—FITC-Dextran before DSS treatment, and (<b>E</b>) intestinal permeability after DSS treatment; (<b>F</b>) fecal MPO activity before the start of diet, and after (<b>G</b>) 1 week and (<b>H</b>) 2 weeks of diet administration; (<b>I</b>) fecal MPO activity before DSS and (<b>J</b>) after DSS treatment; (<b>K</b>) colon histology scores (FITC, fluorescein isothiocyanate; MPO, myeloperoxidase; M-W, Mann–Whitney <span class="html-italic">U</span> test).</p>
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<p>Effect of six weeks of C:15 supplementation on SPF-SAMP mice DSS colitis. Values are mean ± SD, <span class="html-italic">n</span> = 6. (<b>A</b>) Percentage change from original body weight (defined as day 0 and as 100%) after induction of DSS-colitis, (<b>B)</b> colon length, (<b>C</b>) colonoscopy score, (<b>D</b>) colon histology score, (<b>E</b>) fecal MPO activity before DSS and (<b>F</b>) after DSS treatment, and (<b>G</b>) FITC-Dextran before DSS and (<b>H</b>) after DSS treatment (FITC, fluorescein isothiocyanate; MPO, myeloperoxidase; KW—Kruskal–Wallis ANOVA, ANOVA—Analysis of Variance).</p>
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<p>Treatment of older SPF-SAMP mice with C:15 for six weeks reduces the severity of established ileitis. Values are mean ± SD, <span class="html-italic">n</span> = 6. (<b>A</b>) Effect of C:15 diet on body weight over six weeks (percentage change from original body weight defined as week 0 and as 100% after the start of diet). (<b>B</b>) Fecal MPO activity before the start of diet. (<b>C</b>) Fecal MPO activity after 1 week, (<b>D</b>) 2 weeks, (<b>E</b>) 3 weeks, (<b>F</b>) 4 weeks, (<b>G</b>) 5 weeks, and (<b>H</b>) 6 weeks of diet administration. (<b>I</b>) Intestinal permeability assay—FITC-Dextran before sacrifice (FITC, fluorescein isothiocyanate; MPO, myeloperoxidase; M-W, Mann–Whitney <span class="html-italic">U</span> test).</p>
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<p>C:15 supplementation alters expression of various genes related to different immunological pathways in SAMP mice. (<b>A</b>) Heatmap and (<b>B</b>) volcano plot of the normalized data revealed connections among genes with differential expression * in the colon tissues of DSS-treated mice upon C:15 supplementation for 3 weeks in comparison to control. Each row in the heatmap represents a specific probe, and each column represents a specific sample (green bar represents upregulated gene clusters, and purple bar represents downregulated gene clusters). * Criteria for genes with differential expression in volcano plot were fold-change &gt; ±1.5 and <span class="html-italic">p</span> &lt; 0.05.</p>
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23 pages, 1465 KiB  
Review
Insights into Gut Dysbiosis: Inflammatory Diseases, Obesity, and Restoration Approaches
by Andy Acevedo-Román, Natalia Pagán-Zayas, Liz I. Velázquez-Rivera, Aryanne C. Torres-Ventura and Filipa Godoy-Vitorino
Int. J. Mol. Sci. 2024, 25(17), 9715; https://doi.org/10.3390/ijms25179715 - 8 Sep 2024
Viewed by 1045
Abstract
The gut microbiota is one of the most critical factors in human health. It involves numerous physiological processes impacting host health, mainly via immune system modulation. A balanced microbiome contributes to the gut’s barrier function, preventing the invasion of pathogens and maintaining the [...] Read more.
The gut microbiota is one of the most critical factors in human health. It involves numerous physiological processes impacting host health, mainly via immune system modulation. A balanced microbiome contributes to the gut’s barrier function, preventing the invasion of pathogens and maintaining the integrity of the gut lining. Dysbiosis, or an imbalance in the gut microbiome’s composition and function, disrupts essential processes and contributes to various diseases. This narrative review summarizes key findings related to the gut microbiota in modern multifactorial inflammatory conditions such as ulcerative colitis or Crohn’s disease. It addresses the challenges posed by antibiotic-driven dysbiosis, particularly in the context of C. difficile infections, and the development of novel therapies like fecal microbiota transplantation and biotherapeutic drugs to combat these infections. An emphasis is given to restoration of the healthy gut microbiome through dietary interventions, probiotics, prebiotics, and novel approaches for managing gut-related diseases. Full article
(This article belongs to the Special Issue New Molecular Insights into the Gut Microbiome)
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<p>Overview of factors that affect the gut microbiota and current available therapies for IBD, namely ulcerative colitis and Crohn’s disease, as well as in <span class="html-italic">Clostridioides difficile</span> infection. Panel (<b>A</b>) summarizes the factors that induce dysbiosis in the microbial gut communities, such as microbiome/host interaction, environmental factors, high-fat diet, and genetic predisposition leading to a reduction in gut alpha diversity. Panel (<b>B</b>) shows available microbiota restoration therapies for UC and CD and treatments against <span class="html-italic">C. difficile</span> colonization (probiotic supplementation, Rebyota/SER-109 Partial Enteral Nutrition, high-fiber prebiotic diet, and fecal microbiota transplants). Created with Biorender.</p>
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<p>Overview of how diet and the consumption of fiber and fermented foods change the gut microbiota. Panel (<b>A</b>) shows how a high-fat diet induces a reduction in IgA and permeability as well as a reduction in probiotic Bifidobacteria. Panel (<b>B</b>) shows how fiber and fermented foods such as kimchi increase protective bacteria and lean phenotypes. Panel (<b>C</b>) shows how combining diet and probiotics helps decrease inflammation and obese phenotype markers. In the figure, upward green arrows indicate an increase in specific taxa, while red downward arrows indicate a decrease. Created with Biorender.</p>
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17 pages, 1109 KiB  
Review
Advancements in Inflammatory Bowel Disease Management: From Traditional Treatments to Monoclonal Antibodies and Future Drug Delivery Systems
by Annalisa Di Rienzo, Lisa Marinelli, Marilisa Pia Dimmito, Eleonora Chiara Toto, Antonio Di Stefano and Ivana Cacciatore
Pharmaceutics 2024, 16(9), 1185; https://doi.org/10.3390/pharmaceutics16091185 - 7 Sep 2024
Viewed by 525
Abstract
Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with two main subtypes: ulcerative colitis (UC) and Crohn’s disease (CD). The pathogenesis involves genetic predisposition, dysbiosis, and immune dysregulation. Complications include perianal lesions, strictures, fistulas, perforations, and an increased risk of colon [...] Read more.
Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with two main subtypes: ulcerative colitis (UC) and Crohn’s disease (CD). The pathogenesis involves genetic predisposition, dysbiosis, and immune dysregulation. Complications include perianal lesions, strictures, fistulas, perforations, and an increased risk of colon cancer. Clinical classification ranges from mild to fulminant and recurrent disease, with common symptoms such as abdominal discomfort, rectal bleeding, diarrhea, and weight loss. Extraintestinal manifestations include arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis. Conventional treatments using aminosalicylates, corticosteroids, and immunomodulators have limitations. Biologics, introduced in the 1990s, offer improved efficacy and specificity, targeting factors like TNF-α, integrins, and cytokines. Monoclonal antibodies play a crucial role in IBD management, aiming to reduce relapses, hospitalizations, and surgeries. In conclusion, this review is aimed at summarizing the latest knowledge, advantages, and drawbacks of IBD therapies, such as small molecules, biologics, and monoclonal antibodies, to provide a basis for further research in the IBD field. Full article
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<p>Main targets of biological drugs in the treatment of IBD.</p>
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<p>Different mechanisms of nanoparticle targeting.</p>
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16 pages, 16701 KiB  
Article
Yellow Teas Protect against DSS-Induced Ulcerative Colitis by Inhibiting TLR4/NF-κB/NLRP3 Inflammasome in Mice
by Dawei Xing, Tao Zheng, Xiaoju Chen and Zhongwen Xie
Foods 2024, 13(17), 2843; https://doi.org/10.3390/foods13172843 - 7 Sep 2024
Viewed by 444
Abstract
Yellow tea (YT), a slightly fermented tea with a unique yellowing process and mellow taste, is becoming widely popular. Currently, the YT includes bud yellow tea (BYT), small-leaf yellow tea (SYT), and large-leaf yellow tea (LYT) based on maturity of raw materials. Previous [...] Read more.
Yellow tea (YT), a slightly fermented tea with a unique yellowing process and mellow taste, is becoming widely popular. Currently, the YT includes bud yellow tea (BYT), small-leaf yellow tea (SYT), and large-leaf yellow tea (LYT) based on maturity of raw materials. Previous studies have shown that YT has outstanding potential in preventing metabolic syndrome. However, the distinct effects and mechanisms of different types of YT on ulcerative colitis (UC) are still unclear. This study investigated the effects and mechanisms of continuous or intermittent intervention of three yellow tea water extracts (YTEs) on dextran sulfate sodium (DSS)-induced ulcerative colitis in CD-1 mice. The results showed that YTE intervention significantly improves the syndrome of DSS-induced UC in mice. Mechanistic studies reveal that YTEs increase the expression levels of tight junction (TJ) proteins and reduce the levels of pro-inflammatory cytokines in the colon by inactivating TLR4/NF-κB/NLRP3. YTE treatment protected intestinal barrier integrity and reduced serum lipopolysaccharide (LPS) levels. Interestingly, our results indicate that large-leaf yellow tea (LYT) has a better alleviating effect than BYT and SYT. YTE intervention before DSS administration has a certain degree of preventive effect on ulcerative colitis, while continuous YTE intervention after DSS induction has a significant reversing effect on the damage caused by DSS. Our results indicated that drinking YT may have preventive and therapeutic effect on UC, especially drinking LYT. Full article
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<p>Experimental design. (<b>a</b>) Dry samples and water infusion of three YTs used in this study; (<b>b</b>) schematic of experimental design.</p>
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<p>Effects of YTs on the symptom of DSS-induced ulcerative colitis. (<b>a</b>) Hematochezia of mices; (<b>b</b>) disease activity index; (<b>c</b>) body weight; (<b>d</b>) food consumption; (<b>e</b>) water consumption across various group of mice (n = 6).</p>
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<p>Effects of YTs on TJ protein expression in colon of DSS-induced ulcerative colitis in mice. (<b>a</b>) Representative immunofluorescence images of ZO-1 in colon sections (magnification of 100×, scale bar:50 μm); (<b>b</b>) representative immunofluorescence staining of claudin-1 in colon section (magnification of 100×, scale bar:50 μm); arrows indicate loss of TJ protein fluorescence; (<b>c</b>,<b>d</b>) Quantitative data of a (ZO-1) and b (claudin-1), respectively; **** <span class="html-italic">p</span> &lt; 0.0001 when compared to NC group; # <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 when compared to DSS group. <span class="html-italic">p</span> value on the bars represents the significant analysis between continued and stopped administration of YT groups (n = 6, data are the means ± SEM).</p>
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<p>Colonic pathological changes in DSS-induced UC in mice. (<b>a</b>) Representative images of colonic in each group (n = 3); (<b>b</b>) statistical analysis of colonic length; (<b>c</b>) histopathological score; (<b>d</b>) H&amp;E staining of colons across various group of mice. Arrows indicate disruption of intestinal epithelial integrity; **** <span class="html-italic">p</span> &lt; 0.0001 when compared to NC; # <span class="html-italic">p</span> &lt; 0.05, ## <span class="html-italic">p</span> &lt; 0.01 when compared to DSS. <span class="html-italic">p</span> value on the bars represents the significant analysis between continued and stopped administration of YT groups (n = 6, data are the means ± SEM).</p>
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<p>Effect of different types of YT on LPS and cytokines levels in DSS-induced ulcerative colitis mice. (<b>a</b>) LPS level; (<b>b</b>) TNF-α level; (<b>c</b>) IL-1β level; (<b>d</b>) IL-6 level in serum, respectively; (<b>e</b>) <span class="html-italic">TNF-α</span>; (<b>f</b>) <span class="html-italic">IL-1β</span>; (<b>g</b>) <span class="html-italic">IL-6</span>; (<b>h</b>) <span class="html-italic">IL-10</span>; (<b>i</b>) <span class="html-italic">IL-17</span>; (<b>j</b>) <span class="html-italic">IL-18</span>; (<b>k</b>) <span class="html-italic">MCP-1</span>; (<b>l</b>) <span class="html-italic">TLR4</span>; (<b>m</b>) <span class="html-italic">NLRP3</span> expression level in the colon across various groups of mice, respectively. * <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 when compared to NC; # <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 compared to DSS. <span class="html-italic">p</span> value on the bars represents the significant analysis between continued and stopped administration of YT groups (n = 4–6, data are the means ± SEM).</p>
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<p>Effects of YTs on NF-κB/ NLRP3 pathway in DSS-induced ulcerative colitis mice. (<b>a</b>) The protein levels of NF-κB /NLRP3 inflammasome-associated proteins (NLRP3, caspase-1, ASC, p-NF-κB p65, NF-κB p65, p-IκBα, IκBα) were detected by Western blot; (<b>b</b>–<b>h</b>) statistical analysis of NLRP3, ASC, p-NF-κB p65, NF-κB p65, p-IκBα, IκBα expression levels, respectively. ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 when compared to NC; # <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 when compared to DSS. <span class="html-italic">p</span> value on the bars represents the significant analysis between continued and stopped administration of YT groups (n = 4–6, data are the means ± SEM), ns indicates that there is no significant difference between the groups.</p>
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<p>The schematic diagram for this study.</p>
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