American journal of physiology. Gastrointestinal and liver physiology最新文献

{"title":"Hepatic and intestinal tissue-specific <i>Fxr</i> deficiency alters bile acid homeostasis in female mice.","authors":"Jiarui Jiang, Mingjie Fan, Weian Yuan, Dawei Yue, Zhengtao Wang, Li Yang, Wendong Huang, Lihua Jin, Xu Wang, Lili Ding","doi":"10.1152/ajpgi.00387.2024","DOIUrl":"10.1152/ajpgi.00387.2024","url":null,"abstract":"<p><p>Farnesoid X receptor (FXR), predominantly expressed in the liver and intestine, plays a crucial role in regulating bile acid (BA) metabolism. However, the specific contributions of FXR in different tissues to BA homeostasis remain unclear. To elucidate the comprehensive roles of FXR, we developed a novel double tissue-specific knockout (KO) mouse model of <i>Fxr</i> in both liver and intestine (<i>Fxr</i>^ΔL/ΔIN). Notably, <i>Fxr</i>^ΔL/ΔIN mice exhibited significantly increased BA levels in the serum and liver, which were consistent with <i>Fxr</i> whole body KO mice (<i>Fxr</i>^-/-). However, <i>Fxr</i>^ΔL mice only showed elevated hepatic BA concentration, whereas <i>Fxr</i>^ΔIN displayed remarkably increased BA concentration in feces. <i>Fxr</i> deletion increased the BA synthesis genes mRNA level, such as <i>Cyp7a1</i> and <i>Cyp8b1</i>, but reduced the expression of FXR downstream target genes <i>Shp</i> and <i>Fgf15</i>. These findings provide a valuable model to underscore the pivotal functions of tissue-specific FXR in maintaining BA homeostasis. Moreover, these insights facilitate the development of FXR-targeted therapeutic strategies for the BA dysregulation disease treatment.<b>NEW & NOTEWORTHY</b> We successfully developed a double tissue-specific <i>Fxr</i> knockout (DKO) mouse model, which provides a novel tool for investigation of FXR functions in the liver and intestine. Unlike whole body KO, the DKO model excludes the FXR impact on other tissues. <i>Fxr</i>^ΔL/ΔIN mice exhibited significantly increased BA levels in the serum and liver, which were consistent with <i>Fxr</i>^-/- mice. We established a powerful tool for therapeutic strategies for bile acid metabolism disorders associated with FXR.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G774-G790"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fructooligosaccharides slow colonic motility and activate myenteric neurons via calcium sensing and 5-HT₃ receptors in the proximal colon.","authors":"Preedajit Wongkrasant, Laurie E Wallace, Wallace K MacNaughton, Keith A Sharkey","doi":"10.1152/ajpgi.00039.2025","DOIUrl":"10.1152/ajpgi.00039.2025","url":null,"abstract":"<p><p>Calcium-sensing receptors (CaSR) regulate a variety of functions in the gastrointestinal tract. Recently, prebiotic-independent effects of fructooligosaccharides (FOS) on epithelial barrier function were found to be mediated by CaSR. Here, we tested the hypothesis that FOS acts via the CaSR to regulate colonic motility and neuronal activity in the enteric nervous system. Using immunohistochemistry, we determined that CaSR were localized on the colonic epithelium of the mouse proximal colon and that a small proportion of enterochromaffin cells coexpress CaSR. We demonstrated that intraluminal administration of FOS slows colonic motility in vivo in male and female mice, an effect that is mediated by both CaSR and 5-HT₃ receptors. We assessed neuronal activity in response to luminally perfused FOS in intact segments of the proximal colon from male and female mice expressing a genetically encoded fluorescent calcium reporter in intrinsic primary afferent neurons (Calb1-GCaMP6 mice) or in all enteric neurons (Wnt1-GCaMP6 mice) using live cell confocal imaging. In both Calb1-GCaMP6 mice and Wnt1-GCaMP6 mice, intraluminal FOS perfusion induced a sustained elevation of intracellular Ca²⁺ in neurons of the myenteric plexus. This effect was sensitive to tetrodotoxin and mediated by CaSR and 5-HT₃ receptors. Serosal application of FOS was without effect. Our results demonstrate that FOS acts acutely to slow colonic motility in vivo and activates the enteric nervous system via CaSR and 5-HT₃ receptors.<b>NEW & NOTEWORTHY</b> Calcium-sensing receptors regulate a variety of functions in the gastrointestinal tract. Here, we demonstrate a novel action of fructooligosaccharides to regulate colonic motility in vivo and activate the enteric nervous system. These effects are mediated by calcium-sensing and 5-HT₃ receptors.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G734-G745"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ion transport and epithelial barrier dysfunction in experimental models of ulcerative colitis.","authors":"Geoffrey I Sandle, Vazhaikkurichi M Rajendran","doi":"10.1152/ajpgi.00204.2024","DOIUrl":"10.1152/ajpgi.00204.2024","url":null,"abstract":"<p><p>The global prevalence of ulcerative colitis (UC) and Crohn's disease (CD) is increasing, placing greater burdens on national health systems. The pathophysiology of diarrhea, the commonest debilitating symptom in patients with UC and CD, has been studied more extensively in UC, where it reflects defective colonic Na⁺ absorption combined with changes in colonic Cl^- and K⁺ transport, which significantly reduce colonic water absorption. Dysfunctional ion transport in patients with UC is accompanied by abnormalities in tight junctional protein distribution and function, which cause the inflamed colonic epithelium to become \"leakier.\" Progress in understanding how abnormal colonic ion transport in UC might be influenced pharmacologically has been hampered by the low availability of clinical material. To counter this, various animal models of acute colitis have been developed, but differ in the way mucosal inflammation is induced. Identifying models that closely mimic human UC in terms of pathology and ion transport abnormalities remains challenging. However, the introduction of human colonic epithelial organoids (colonoids) has added a new and exciting dimension to research in this area. Here, we review current knowledge about abnormal colonic ion transport and barrier function in experimental and human colitis as well as the use and potential of human colonoids to better understand the pathophysiology of UC, which may ultimately lead to novel approaches to the treatment of diarrhea in this disease.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G811-G830"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Costimulation with high-fat diet and acidic bile salts may promote Warburg effect in gastric carcinogenesis around the squamocolumnar junction in Gan mice.","authors":"Koichiro Sudo, Kaname Uno, Toru Tamahara, Naoki Asano, Keisuke Kusano, Mizuki Tanabe, Kouya Ogasawara, Takeshi Kanno, Tomoyuki Koike, Ritsuko Shimizu, Atsushi Masamune","doi":"10.1152/ajpgi.00305.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00305.2024","url":null,"abstract":"<p><p>Epidemiological studies demonstrated relationships between gastric cardia adenocarcinoma (GCA) and metabolic syndrome (MetS). We aimed to clarify the mechanism underlying their relationship. To investigate whether systemic inflammation against high-fat diet (HFD)-related dysbiosis promotes the Warburg effect in tumors at the squamocolumnar junction (SCJ), we applied K19-Wnt1/C2mE (Gan) mice, fed either HFD or control diet ± acidic bile salts (ABS) with/without clodronate liposomes (CLs), and in vitro studies using MKN7 cells with/without THP1-derived macrophages. Then, we assessed the involvement of oxidative stress (OS) in the Warburg effect by comparing nuclear factor-erythroid 2-related factor 2 (Nrf2) knockout Gan mice with Gan mice. Tumors with macrophage infiltration in the HFD + ABS group were larger than in the control group. Gene Set Enrichment Analysis revealed enhancement of the OS signaling in tumor of the HFD + ABS group. The HFD + ABS group mice demonstrated induction of OS, Nqo1, tumor necrosis factor alpha (TNFα), and the Warburg effect in tumors and mucosal barrier dysfunction of dysbiotic gut. All of them were abolished with diminishing macrophage infiltration by additional CL treatment. Stimulation with TNFα, but not ABS nor lipopolysaccharide, on MKN7 cells activated the Warburg effect. In MKN7 cells cocultured with the macrophages whose TNFα expression was induced by the lipopolysaccharide pretreatment, the Warburg effect was enhanced in TNFα concentration-dependent manners. In Nrf2 knockout Gan mice, tumors shrank with reducing OS, TNFα, and Warburg effect, along with decreasing macrophage infiltration. Accordingly, MetS may develop GCA through the Nrf2-related Warburg effect under the TNFα stimulation from the macrophages activated by both local ABS exposure and systemic lipopolysaccharide exposure from leaky gut with HFD-related dysbiosis.<b>NEW & NOTEWORTHY</b> In K19-Wnt1/C2mE (Gan) mice, a high-fat diet accompanied by orally taking acidic bile salts (ABS) promoted inflammation-associated carcinogenesis at the squamocolumnar junction (SCJ), maybe due to transudates from dysbiotic gut into systemic circulation. Systemic lipopolysaccharide exposure and local ABS exposure at the SCJ activate macrophages to induce the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) and TNFα, which might promote Warburg effect in cancer cells. These phenomena were abolished in the Nrf2-knockout Gan mice.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":"328 6","pages":"G645-G662"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota dysbiosis in a novel mouse model of colitis potentially increases the risk of colorectal cancer.","authors":"Abrory A C Pramana, Guanying Bianca Xu, Siyuan Liang, Erick Omar Garcia Vazquez, Jacob M Allen, Brett R Loman, Wenyan Mei, Yuan-Xiang Pan, Hong Chen","doi":"10.1152/ajpgi.00040.2025","DOIUrl":"10.1152/ajpgi.00040.2025","url":null,"abstract":"&lt;p&gt;&lt;p&gt;This research investigates the gut microbiota profile in a novel mouse model of colitis with a specific knockout (KO) of the &lt;i&gt;hnRNPI&lt;/i&gt; gene in intestinal epithelial cells. This KO mouse model is characterized by activation of the NF-κB pathway and early-onset colitis. Although the influence of gut microbiota on colitis pathophysiology is well established, its role in &lt;i&gt;hnRNPI&lt;/i&gt; KO mice remains unexplored. To address this, we used 16S rRNA gene amplicon sequencing to compare the gut microbiota between &lt;i&gt;hnRNPI&lt;/i&gt; KO and wild-type (WT) mice at baseline and following a dextran sodium sulfate (DSS) challenge. Untargeted metabolomics was also used to profile bacterial metabolites identified in the 16S rRNA analysis. Fecal DNA was extracted and analyzed to determine gut microbiota composition. Body weight and the disease activity index (DAI) were measured, while organ samples, including liver, spleen, and colon, were collected during necropsy for analysis. Representative bacteria identified from 16S-rRNA gene sequencing were cultured in designated media to further characterize their metabolite profiles. Initial findings on 16S-rRNA gene analysis revealed significant disparities in the gut microbiota between KO and WT mice. Notably, KO mice exhibited lower levels of &lt;i&gt;Dubosiella&lt;/i&gt; sp. but higher levels of &lt;i&gt;Paraclostridium bifermentans&lt;/i&gt; and &lt;i&gt;Enterococcus faecalis&lt;/i&gt; compared with WT mice. The DSS challenge exacerbated colitis in KO mice and led to further alterations in gut microbiota diversity and composition. After DSS treatment, significant shifts were observed in five bacterial species. Specifically, &lt;i&gt;Dubosiella&lt;/i&gt; sp. remained consistently low, whereas &lt;i&gt;P. bifermentans&lt;/i&gt; persisted at high levels in DSS-treated KO mice. In addition, elevated levels of &lt;i&gt;Clostridium paraputrificum&lt;/i&gt; and &lt;i&gt;Lactococcus garvieae&lt;/i&gt; were detected in KO mice, whereas &lt;i&gt;Malacoplasma muris&lt;/i&gt; was significantly higher in WT mice. The metabolomic analysis highlighted distinct bacterial metabolic profiles between &lt;i&gt;P. bifermentans&lt;/i&gt; and &lt;i&gt;Dubosiella newyorkensis&lt;/i&gt;. &lt;i&gt;P. bifermentans&lt;/i&gt; were found to produce higher levels of glycocholate, urocanate, and deoxycholate, whereas &lt;i&gt;D. newyorkensis&lt;/i&gt; predominantly produced N-formyltryptophan, indole-3-carboxaldehyde, and glycyl-l-norleucine. Importantly, an imbalance in the abundance of &lt;i&gt;Dubosiella&lt;/i&gt; sp. and &lt;i&gt;P. bifermentans&lt;/i&gt; was observed in KO mice, suggesting a potential role in colitis pathogenesis. Comprehensive pathway analysis based on 16S rRNA gene sequences revealed disturbances in several pathways, including those related to human diseases such as cancer, which were notably increased in &lt;i&gt;hnRNPI&lt;/i&gt; KO mice after the DSS challenge. These findings underscore the disrupted microbiome balance in KO mice, particularly the altered levels of &lt;i&gt;Dubosiella&lt;/i&gt; sp., which may play a pivotal role in gut health and colitis development.&lt;b&gt;NEW & NOTEWORTHY&lt;/b&gt; Ablation of &lt;i&gt;hn","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G831-G847"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum for Yang et al., volume 328, 2025, p. G243-G251.","authors":"","doi":"10.1152/ajpgi.00279.2024_COR","DOIUrl":"https://doi.org/10.1152/ajpgi.00279.2024_COR","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":"328 6","pages":"G872-G873"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut neuropeptide involvement in Parkinson's disease.","authors":"Hayley N Templeton, Stuart A Tobet, Luke A Schwerdtfeger","doi":"10.1152/ajpgi.00383.2024","DOIUrl":"10.1152/ajpgi.00383.2024","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disorder affecting over 10 million people. A key pathological feature of PD is the accumulation of misfolded α-synuclein (aSyn) protein in the substantia nigra pars compacta. Aggregation of aSyn can form Lewy bodies that contribute to dopaminergic neuron degeneration and motor symptoms, such as tremor, rigidity, and bradykinesia. Beyond the central nervous system, aSyn aggregates have been detected in the gastrointestinal (GI) tract, suggesting a link between peripheral aSyn and nonmotor PD symptoms. GI symptoms, often preceding motor symptoms by up to 20 years, highlight the bidirectional communication between the central nervous system and the enteric nervous system (gut-brain axis) in PD. Although microbiome alterations and intestinal inflammation have been associated with PD, functional impacts on gut-brain signaling or aSyn aggregation remain unclear. Intestinal neuropeptides are key modulators of gut-brain communication, alter immune response to pathogens and environmental toxins, and may contribute to the function of the luminal gut barrier. Dysregulation of gut neuropeptide signaling, including vasoactive intestinal peptide, neuropeptide Y, calcitonin gene-related peptide, ghrelin, cholecystokinin, glucagon-like peptide 1, and substance P, have been associated with pathologic effects of PD in animal models. Despite their potential role in pathogenesis and disease modulation, gut neuropeptide roles in PD are underexplored. This article reviews current knowledge surrounding microbial metabolite and immune influences on gut neuropeptide signaling, aSyn aggregation in the enteric nervous system, and downstream neuroimmune pathway alterations within the context of PD and its mouse models.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G716-G733"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host-microbial interactions in the esophagus.","authors":"Nonyelum Ebigbo, Rhonda F Souza","doi":"10.1152/ajpgi.00079.2025","DOIUrl":"10.1152/ajpgi.00079.2025","url":null,"abstract":"<p><p>Host-microbial interactions within the gastrointestinal tract are increasingly recognized as contributors to health and disease, yet our understanding of these interactions in the esophagus remains limited. Dysbiosis of the esophageal microbiome has been linked to esophageal disorders, but the precise mechanisms underlying microbial contributions to esophageal pathophysiology remain speculative. This review explores the mechanisms by which the esophageal microbiome modulates mucosal immunity, epithelial barrier integrity, and inflammatory responses. We highlight key host receptors that mediate these interactions and microbial metabolites that influence the local immune environment and epithelial function. By synthesizing current knowledge on how the microbiome impacts esophageal health, we identify significant knowledge gaps and propose areas for future research.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G848-G860"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous ileitis and postsurgical murine models of enteric hyperoxaluria.","authors":"Karim Jaber, Nadim Zaidan, Melody Ho, Xiaozhong Xiong, Rashmi Mishra, Ambika Nair, Arnav Mishra, Yi Chu, Mohamad Mokadem, Lama Nazzal","doi":"10.1152/ajpgi.00043.2025","DOIUrl":"10.1152/ajpgi.00043.2025","url":null,"abstract":"<p><p>Enteric hyperoxaluria, a risk factor for kidney stone disease, often arises from malabsorptive bariatric surgeries or inflammatory bowel diseases. Current murine models for studying this condition are limited, necessitating new approaches. This study aims to establish two novel and distinct mouse models to investigate enteric hyperoxaluria: one simulating Roux-en-Y gastric bypass surgery and the other Crohn's ileitis. In the first model, diet-induced obese C57BL/6J male mice underwent either sham or bypass surgery, followed by 3 wk on a high-fat, oxalate-enriched diet. In the second model, SAMP1/YitFc and AKR mice were gradually introduced to high-fat diets, later supplemented with oxalate while reducing fat content. Samples of urine, blood, and feces were collected to assess oxalate, creatinine, and fecal lipid profiles. Results showed hyperoxaluria and increased stool fat content, indicating fat malabsorption, in both SAMP1 and bypass mice compared with controls. Kidney injury was also observed. These findings confirm the successful establishment of enteric hyperoxaluria in both models, highlighting the role of dietary oxalate, intestinal inflammation, and fat malabsorption in disease progression. These models provide valuable tools for exploring cellular and molecular mechanisms in enteric hyperoxaluria and may inform future therapeutic strategies.<b>NEW & NOTEWORTHY</b> This study is among the first to establish an enteric hyperoxaluria (EH) phenotype in two different and novel mouse models secondary to Roux-en-Y gastric bypass and ileitis. It also elucidates key factors affecting EH using the SAMP1 mice, revealing the significant roles of GI tract inflammation, fat malabsorption, and dietary fat in developing hyperoxaluria.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G760-G773"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver bypass in the development of pathogen-associated pulmonary vascular disease: contribution of mesocaval and portosystemic shunts.","authors":"Claudia Lucia Martins Silva, Prasanth N Puthanveetil, Suellen Darc Oliveira","doi":"10.1152/ajpgi.00409.2024","DOIUrl":"10.1152/ajpgi.00409.2024","url":null,"abstract":"<p><p>Portosystemic and mesocaval shunts are aberrant vascular connections that bypass hepatic detoxification process, directly linking the portal to the systemic circulation. These shunts, whether congenital or acquired, might play a pivotal role in the pathogenesis of systemic inflammatory diseases, such as schistosomiasis-associated pulmonary hypertension (Sch-PH) by facilitating the dissemination of pathogen-derived eggs and antigens from the gut and mesentery into the lungs. Beyond the translocation of <i>Schistosoma mansoni</i> eggs, emerging evidence implicates that gut-lung microbiome dysbiosis contributes to the development of pulmonary hypertension (PH) in the preclinical animal model of Sch-PH. Sch-PH emerges as a chronic complication of schistosomiasis and evolves silently, progressively increasing the mean pulmonary arterial pressure and vascular resistance, leading to right heart hypertrophy, failure, and significant morbidity and mortality. Chronic schistosomiasis is often linked to the development of portal hypertension, which significantly contributes to the formation of the porto/mesocaval shunt as a compensatory response that can have far-reaching implications on pulmonary vascular physiology. In addition, portal hypertension compromises the integrity of the intestinal barrier, exacerbating peritoneal and mesenteric inflammation, potentially facilitating microbial and metabolite entrance into the systemic circulation. This article briefly discusses the mechanisms by which porto/mesocaval shunts contribute to PH, especially Group I PH, focusing on the interplay between portosystemic shunting, microbial translocation, and systemic dissemination of proinflammatory metabolites.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G791-G800"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}