Cellular and Molecular Gastroenterology and Hepatology最新文献

{"title":"Enteric Nervous System Striped Patterning and Disease: Unexplored Pathophysiology","authors":"Lori B. Dershowitz ,&nbsp;Julia A. Kaltschmidt","doi":"10.1016/j.jcmgh.2024.03.004","DOIUrl":"10.1016/j.jcmgh.2024.03.004","url":null,"abstract":"<div><p>The enteric nervous system (ENS) controls gastrointestinal (GI) motility, and defects in ENS development underlie pediatric GI motility disorders. In disorders such as Hirschsprung’s disease (HSCR), pediatric intestinal pseudo-obstruction (PIPO), and intestinal neuronal dysplasia type B (INDB), ENS structure is altered with noted decreased neuronal density in HSCR and reports of increased neuronal density in PIPO and INDB. The developmental origin of these structural deficits is not fully understood. Here, we review the current understanding of ENS development and pediatric GI motility disorders incorporating new data on ENS structure. In particular, emerging evidence demonstrates that enteric neurons are patterned into circumferential stripes along the longitudinal axis of the intestine during mouse and human development. This novel understanding of ENS structure proposes new questions about the pathophysiology of pediatric GI motility disorders. If the ENS is organized into stripes, could the observed changes in enteric neuron density in HSCR, PIPO, and INDB represent differences in the distribution of enteric neuronal stripes? We review mechanisms of striped patterning from other biological systems and propose how defects in striped ENS patterning could explain structural deficits observed in pediatric GI motility disorders.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"18 2","pages":"Article 101332"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000560/pdfft?md5=cf202a674057981018c678e8581f1c1d&pid=1-s2.0-S2352345X24000560-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Of Sugar and Fat: How Protein Glycosylation in Sinusoidal Cells Controls Lipid Metabolism in Liver","authors":"Frédéric P. Lemaigre","doi":"10.1016/j.jcmgh.2024.03.010","DOIUrl":"10.1016/j.jcmgh.2024.03.010","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"17 6","pages":"Pages 1064-1065"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000626/pdfft?md5=178d449b36e20ab409c6a3ae600c6cbd&pid=1-s2.0-S2352345X24000626-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140793676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial Sphingolipids Exacerbate Colitis by Inhibiting ILC3-derived IL-22 Production","authors":"Bin Bao ,&nbsp;Youyuan Wang ,&nbsp;Pavl Boudreau ,&nbsp;Xinyang Song ,&nbsp;Meng Wu ,&nbsp;Xi Chen ,&nbsp;Izabel Patik ,&nbsp;Ying Tang ,&nbsp;Jodie Ouahed ,&nbsp;Amit Ringel ,&nbsp;Jared Barends ,&nbsp;Chuan Wu ,&nbsp;Emily Balskus ,&nbsp;Jay Thiagarajah ,&nbsp;Jian Liu ,&nbsp;Michael R. Wessels ,&nbsp;Wayne Isaac Lencer ,&nbsp;Dennis L. Kasper ,&nbsp;Dingding An ,&nbsp;Bruce Harold Horwitz ,&nbsp;Scott B. Snapper","doi":"10.1016/j.jcmgh.2024.04.007","DOIUrl":"10.1016/j.jcmgh.2024.04.007","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>Gut bacterial sphingolipids, primarily produced by Bacteroidetes, have dual roles as bacterial virulence factors and regulators of the host mucosal immune system, including regulatory T cells and invariant natural killer T cells. Patients with inflammatory bowel disease display altered sphingolipids profiles in fecal samples. However, how bacterial sphingolipids modulate mucosal homeostasis and regulate intestinal inflammation remains unclear.</p></div><div><h3>Methods</h3><p>We used dextran sodium sulfate (DSS)-induced colitis in mice monocolonized with <em>Bacteroides fragilis</em> strains expressing or lacking sphingolipids to assess the influence of bacterial sphingolipids on intestinal inflammation using transcriptional, protein, and cellular analyses. Colonic explant and organoid were used to study the function of bacterial sphingolipids. Host mucosal immune cells and cytokines were profiled and characterized using flow cytometry, enzyme-linked immunosorbent assay, and Western blot, and cytokine function in vivo was investigated by monoclonal antibody injection.</p></div><div><h3>Results</h3><p><em>B fragilis</em> sphingolipids exacerbated intestinal inflammation. Mice monocolonized with <em>B fragilis</em> lacking sphingolipids exhibited less severe DSS-induced colitis. This amelioration of colitis was associated with increased production of interleukin (IL)-22 by ILC3. Mice colonized with <em>B fragilis</em> lacking sphingolipids following DSS treatment showed enhanced epithelial STAT3 activity, intestinal cell proliferation, and antimicrobial peptide production. Protection against DSS colitis associated with <em>B fragilis</em> lacking sphingolipids was reversed on IL22 blockade. Furthermore, bacterial sphingolipids restricted epithelial IL18 production following DSS treatment and interfered with IL22 production by a subset of ILC3 cells expressing both IL18R and major histocompatibility complex class II.</p></div><div><h3>Conclusions</h3><p><em>B fragilis</em>–derived sphingolipids exacerbate mucosal inflammation by impeding epithelial IL18 expression and concomitantly suppressing the production of IL22 by ILC3 cells.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"18 2","pages":"Article 101350"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001048/pdfft?md5=59a34194ef86160c5f3532ad4c9dd497&pid=1-s2.0-S2352345X24001048-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay Between Drug-Induced Liver Injury and Gut Microbiota: A Comprehensive Overview","authors":"Guolin Li ,&nbsp;Yifu Hou ,&nbsp;Changji Zhang ,&nbsp;Xiaoshi Zhou ,&nbsp;Furong Bao ,&nbsp;Yong Yang ,&nbsp;Lu Chen ,&nbsp;Dongke Yu","doi":"10.1016/j.jcmgh.2024.05.003","DOIUrl":"10.1016/j.jcmgh.2024.05.003","url":null,"abstract":"<div><p>Drug-induced liver injury is a prevalent severe adverse event in clinical settings, leading to increased medical burdens for patients and presenting challenges for the development and commercialization of novel pharmaceuticals. Research has revealed a close association between gut microbiota and drug-induced liver injury in recent years. However, there has yet to be a consensus on the specific mechanism by which gut microbiota is involved in drug-induced liver injury. Gut microbiota may contribute to drug-induced liver injury by increasing intestinal permeability, disrupting intestinal metabolite homeostasis, and promoting inflammation and oxidative stress. Alterations in gut microbiota were found in drug-induced liver injury caused by antibiotics, psychotropic drugs, acetaminophen, antituberculosis drugs, and antithyroid drugs. Specific gut microbiota and their abundance are associated closely with the severity of drug-induced liver injury. Therefore, gut microbiota is expected to be a new target for the treatment of drug-induced liver injury. This review focuses on the association of gut microbiota with common hepatotoxic drugs and the potential mechanisms by which gut microbiota may contribute to the pathogenesis of drug-induced liver injury, providing a more comprehensive reference for the interaction between drug-induced liver injury and gut microbiota.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"18 3","pages":"Article 101355"},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001097/pdfft?md5=7d0a80349d59da5cc87143fa65f5ff6b&pid=1-s2.0-S2352345X24001097-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Protein Complex of Liver Origin Activates a Pro-inflammatory Program That Drives Hepatic and Intestinal Injury in Alcohol-Associated Liver Disease","authors":"Xiaodong Ge ,&nbsp;Hui Han ,&nbsp;Romain Desert ,&nbsp;Sukanta Das ,&nbsp;Zhuolun Song ,&nbsp;Sai Santosh Babu Komakula ,&nbsp;Wei Chen ,&nbsp;Dipti Athavale ,&nbsp;Daniel Lantvit ,&nbsp;Natalia Nieto","doi":"10.1016/j.jcmgh.2024.05.010","DOIUrl":"10.1016/j.jcmgh.2024.05.010","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>There is limited information on how the liver-to-gut axis contributes to alcohol-associated liver disease (AALD). We previously identified that high-mobility group box-1 (HMGB1) undergoes oxidation in hepatocytes and demonstrated elevated serum levels of oxidized HMGB1 ([O] HMGB1) in alcoholic patients. Since interleukin-1 beta (IL-1B) increases in AALD, we hypothesized hepatocyte-derived [O] HMGB1 could interact with IL-1B to activate a pro-inflammatory program that, besides being detrimental to the liver, drives intestinal barrier dysfunction.</p></div><div><h3>Results</h3><p>Alcohol-fed <em>Rage</em>^ΔMye mice exhibited decreased nuclear factor kappa B signaling, a pro-inflammatory signature, and reduced total intestinal permeability, resulting in protection from AALD. In addition, [O] HMGB1 bound and signaled through the receptor for advanced-glycation end-products (RAGE) in myeloid cells, driving hepatic inflammation, intestinal permeability, and increased portal blood lipopolysaccharide in AALD. We identified that [O] HMGB1 formed a complex with IL-1B, which was found in the livers of patients with acute alcoholic hepatitis and mice with AALD. This complex originated from the liver, because it was absent in the intestine when hepatocytes did not produce [O] HMGB1. Mechanistically, the complex bound RAGE in Kupffer cells and macrophages induced a pro-inflammatory program. Moreover, it bound RAGE in intestinal macrophages and epithelial cells, leading to intestinal inflammation, altered intestinal epithelial cell tight junction protein expression, increased intestinal permeability, and elevated portal blood lipopolysaccharide, enhancing AALD pathogenesis.</p></div><div><h3>Conclusions</h3><p>We identified a protein complex of liver origin that amplifies the pro-inflammatory feedback loop in AALD; therefore, targeting this complex could have significant therapeutic potential.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"18 3","pages":"Article 101362"},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001164/pdfft?md5=7d69d746edcf32f0cd528be96ec7279b&pid=1-s2.0-S2352345X24001164-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Progress and Promise of Lineage Reprogramming Strategies for Liver Regeneration","authors":"Shuyong Wang ,&nbsp;Xuan Wang ,&nbsp;Yunfang Wang","doi":"10.1016/j.jcmgh.2024.101395","DOIUrl":"10.1016/j.jcmgh.2024.101395","url":null,"abstract":"<div><div>The liver exhibits remarkable regenerative capacity. However, the limited ability of primary human hepatocytes to proliferate <em>in vitro</em>, combined with a compromised regenerative capacity induced by pathological conditions <em>in vivo</em>, presents significant obstacles to effective liver regeneration following liver injuries and diseases. Developing strategies to compensate for the loss of endogenous hepatocytes is crucial for overcoming these challenges, and this remains an active area of investigation. Lineage reprogramming, the process of directly converting one cell type into another bypassing the intermediate pluripotent state, has emerged as a promising method for generating specific cell types for therapeutic purposes in regenerative medicine. Here, we discuss the recent progress and emergent technologies in lineage reprogramming into hepatic cells, and their potential applications in enhancing liver regeneration or treating liver disease models. We also address controversies and challenges that confront this field.</div></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"18 6","pages":"Article 101395"},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"It Takes Guts: Interactions of Intestinal Stearoyl CoA Desaturase 1 and Bile Acids","authors":"Jessica M. Ferrell","doi":"10.1016/j.jcmgh.2024.101401","DOIUrl":"10.1016/j.jcmgh.2024.101401","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"18 6","pages":"Article 101401"},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding Enterohepatic Bile Acid Pools and Their Impact on Intestinal Physiology","authors":"Shogo Takahashi,&nbsp;Frank J. Gonzalez","doi":"10.1016/j.jcmgh.2024.101400","DOIUrl":"10.1016/j.jcmgh.2024.101400","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"18 6","pages":"Article 101400"},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TOC","authors":"","doi":"10.1016/S2352-345X(23)00224-2","DOIUrl":"https://doi.org/10.1016/S2352-345X(23)00224-2","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"17 2","pages":"Pages A2-A4"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X23002242/pdfft?md5=6543da2703ddee09e39965a70aa26951&pid=1-s2.0-S2352345X23002242-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Murine Model of Maternal Micronutrient Deficiencies and Gut Inflammatory Host-microbe Interactions in the Offspring","authors":"Ravi Holani ,&nbsp;Paula T. Littlejohn ,&nbsp;Karlie Edwards ,&nbsp;Charisse Petersen ,&nbsp;Kyung-Mee Moon ,&nbsp;Richard G. Stacey ,&nbsp;Tahereh Bozorgmehr ,&nbsp;Zachary J. Gerbec ,&nbsp;Antonio Serapio-Palacios ,&nbsp;Zakhar Krekhno ,&nbsp;Katherine Donald ,&nbsp;Leonard J. Foster ,&nbsp;Stuart E. Turvey ,&nbsp;B. Brett Finlay","doi":"10.1016/j.jcmgh.2024.01.018","DOIUrl":"10.1016/j.jcmgh.2024.01.018","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>Micronutrient deficiency (MND) (ie, lack of vitamins and minerals) during pregnancy is a major public health concern. Historically, studies have considered micronutrients in isolation; however, MNDs rarely occur alone. The impact of co-occurring MNDs on public health, mainly in shaping mucosal colonization by pathobionts from the <em>Enterobacteriaceae</em> family, remains undetermined due to lack of relevant animal models.</p></div><div><h3>Methods</h3><p>To establish a maternal murine model of multiple MND (MMND), we customized a diet deficient in vitamins (A, B12, and B9) and minerals (iron and zinc) that most commonly affect children and women of reproductive age. Thereafter, mucosal adherence by <em>Enterobacteriaceae</em>, the associated inflammatory markers, and proteomic profile of intestines were determined in the offspring of MMND mothers (hereafter, low micronutrient [LM] pups) via bacterial plating, flow cytometry, and mass spectrometry, respectively. For human validation, <em>Enterobacteriaceae</em> abundance, assessed via 16s sequencing of 3-month-old infant fecal samples (n = 100), was correlated with micronutrient metabolites using Spearman’s correlation in meconium of children from the CHILD birth cohort.</p></div><div><h3>Results</h3><p>We developed an MMND model and reported an increase in colonic abundance of <em>Enterobacteriaceae</em> in LM pups at weaning. Findings from CHILD cohort confirmed a negative correlation between <em>Enterobacteriaceae</em> and micronutrient availability. Furthermore, pro-inflammatory cytokines and increased infiltration of lymphocyte antigen 6 complex high monocytes and M1-like macrophages were evident in the colons of LM pups. Mechanistically, mitochondrial dysfunction marked by reduced expression of nicotinamide adenine dinucleotide (NAD)H dehydrogenase and increased expression of <em>NAD phosphate oxidase</em> (<em>Nox</em>) <em>1</em> contributed to the <em>Enterobacteriaceae</em> bloom.</p></div><div><h3>Conclusion</h3><p>This study establishes an early life MMND link to intestinal pathobiont colonization and mucosal inflammation via damaged mitochondria in the offspring.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"17 5","pages":"Pages 827-852"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000213/pdfft?md5=2ac9ea2e4d626e38a8ad7594e501a39f&pid=1-s2.0-S2352345X24000213-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}