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

{"title":"<i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> targets M cells in enteroid-derived monolayers through interactions with β1 integrins.","authors":"Grace Baruta, Kyle L Flannigan, Laurie Alston, Andrew Thorne, Hong Zhang, Jeroen De Buck, Pina Colarusso, Simon A Hirota","doi":"10.1152/ajpgi.00250.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00250.2024","url":null,"abstract":"<p><p>Paratuberculosis is an infectious disease caused by the bacterium, <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> (MAP). MAP infection of ruminants triggers progressive wasting disease characterized by granulomatous lymphadenitis, enteritis, and severe intestinal pathology that often requires early culling of the animal. The resulting economic burden is significant and MAP exposure in the workplace constitutes a significant zoonotic risk. While it has been established the MAP propagates within resident immune cells, less is known about how it traverses the epithelium. It's currently thought that MAP infects the small intestinal epithelium by targeting both enterocytes and M cells, with a potential tropism for the latter. In the current study, we developed and validated an enteroid-based in vitro assay containing functional M cells to identify the target cells for MAP's entry. Upon exposure to MAP, the bacteria were detected within both enterocytes and M cells, however quantitative image analysis revealed significant tropism for the latter. Complementary studies using the Caco-2/Raji-B co-culture system provided similar results. Since other mycobacteria have been shown to initiate cell attachment and entry by using a fibronectin-bridging process, we tested whether these interactions were involved in MAP's targeting of M cells. We found that MAP's M cell tropism was enhanced by fibronectin and that this effect was abolished when monolayers were pretreated with an integrin blocking peptide. Our data demonstrate that MAP preferentially targets M cells and that this involves a fibronectin-bridging process. Furthermore, our study supports the utility of M cell containing enteroids to study host-pathogen interaction at the intestinal epithelium.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668903","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":"Unique properties of proximal and distal colon reflect distinct motor functions.","authors":"Wilmarie Morales-Soto, Kristen Smith-Edwards","doi":"10.1152/ajpgi.00215.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00215.2024","url":null,"abstract":"<p><p>The gastrointestinal (GI) tract is made up of specialized organs that work in tandem to facilitate digestion. The colon regulates the final steps in this process where complex motor patterns in proximal regions facilitate formation of fecal pellets that are propelled along the distal colon via self-sustaining neural peristalsis and temporarily stored prior to defecation. Historically, our understanding of colonic motility has focused primarily on distal regions, and the intrinsic reflex circuits of the enteric nervous system (ENS) involved in neural peristalsis have been defined, but we do not yet have a clear grasp on the mechanisms orchestrating motor function in proximal regions. New approaches have brought to the forefront the unique structural, neurochemical, and functional characteristics that exist in distinct regions of the mouse and human colon. In this mini-review, we highlight key differences along the proximal-distal colonic axis and discuss how these differences relate to region-specific motor function.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646792","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":"The Spatiotemporal Development of Mesenteric Lymphatic Changes in the TNF^ΔARE/+ Mouse Model of Terminal Ileitis.","authors":"Keith Keane, Matthew Stephens, Simon Roizes, Jingna Xue, Shan Liao, Pierre-Yves von der Weid","doi":"10.1152/ajpgi.00334.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00334.2024","url":null,"abstract":"<p><p>Crohn's disease (CD) is a chronic inflammatory bowel disease which also encompasses significant alterations of the mesenteric lymphatic system. Whether these changes are a mere consequence of, or directly contribute to the inflammation is unknown. Here we characterized the spatial and temporal development of these events in the TNF^ΔARE/+ mouse, which develops CD-like ileitis and significant mesenteric lymphatic alterations. At 8-, 12-, 20-, and 28 weeks of age, specific pathogen-free (SPF), germ-free (GF) TNF^ΔARE/+ and WT mice were assessed for ileitis via myeloperoxidase activity (MPO) while mesenteric lymphatic alterations were assessed by confocal immunofluorescence imaging. Lymphatic alterations in the SPF TNF^ΔARE/+ occurred in a stepwise manner between 8 and 28 weeks of age beginning with the development of mesenteric lymphadenopathy at 8 weeks despite no significant ileitis. By 12 weeks ileal MPO significantly elevates concomitantly with lymphangiectasia of the mesenteric collecting lymphatic vessels (CLV) and clustering of CD45⁺ immune cells around them. At 20 weeks, significant lymphangiogenesis of the initials (ILV) and tertiary lymphoid organs aligned along lymphatic collectors (CA-TLOs) had developed. At 28 weeks, lymphangiectasia, lymphangiogenesis, and CA-TLOs increased. However, 28-week-old GF TNF^ΔARE/+, while displaying no ileitis, presented with mesenteric lymphadenopathy, lymphangiectasia, and lymphangiogenesis but no immune cell clustering nor CA-TLOs. The TNF^ΔARE/+ mice develop terminal ileitis and lymphatic alterations in a stepwise manner beginning with MLN lymphadenopathy and ileal inflammation, followed by CLV dilation and lymphangiogenesis. These lymphatic alterations are exacerbated by the gut microbiome, with immune cell clustering and TLO formation being entirely dependent of its presence.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584378","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":"Cinnabarinic acid protects against metabolic dysfunction-associated steatohepatitis by activating Aryl hydrocarbon Receptor-dependent AMPK signaling.","authors":"Nikhil Y Patil, Iulia Rus, Felix Ampadu, Hassan M Abu Shukair, Sarah Bonvicino, Richard S Brush, Elena Eaton, Martin-Paul Agbaga, Tae Gyu Oh, Jacob E Friedman, Aditya D Joshi","doi":"10.1152/ajpgi.00337.2024","DOIUrl":"10.1152/ajpgi.00337.2024","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by accumulation of fats in liver, chronic inflammation, hepatocytic ballooning, and fibrosis. This study investigates the significance of hepatic Aryl hydrocarbon Receptor (AhR) signaling in cinnabarinic acid (CA)-mediated protection against MASH. Here, we report that livers of high-fat, high-fructose, high-cholesterol diet-fed hepatocyte-specific Aryl hydrocarbon Receptor knockout mice (AhR-hKO) exhibited aggravated steatosis, inflammation, and fibrosis compared to control AhR-floxed livers. Moreover, treatment with a tryptophan catabolite, CA reduced body weight gain and significantly attenuated hepatic steatosis, inflammation, ballooning, fibrosis, and liver injury only in AhR-floxed but not in AhR-hKO mice, strongly indicating that the CA-mediated protection against steatohepatitis is AhR-dependent. Furthermore, protection against lipotoxicity by CA-activated AhR signaling was confirmed by utilizing an <i>in vitro</i> human hepatocyte model of MASLD. Mechanistically, CA-induced AhR-dependent signaling augmented AMP-activated protein kinase (AMPK) leading to the upregulation of peroxisome proliferator-activated receptor-c coactivator-1a (PGC1α) and attenuation of sterol regulatory element-binding protein-1 (SREBP1) to regulate hepatic lipid metabolism. Collectively, our findings indicate that CA-mediated protection against MASH is dependent on hepatic AhR signaling and selective endogenous AhR agonists that regulate lipogenesis can serve as promising future therapeutics against MASLD.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584376","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":"DIFFERENTIAL RESPONSES TO PROSTAGLANDINS IN THE CIRCULAR AND LONGITUDINAL MUSCLE LAYERS OF THE MURINE ILEUM.","authors":"Joong Goo Kwon, Sung Jin Hwang, Elizabeth A H Beckett, Kenton M Sanders, Sean Ward","doi":"10.1152/ajpgi.00400.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00400.2024","url":null,"abstract":"<p><p>Prostaglandin E₂ (PGE₂) actions on intestinal motility are complex due the differential expression of the PGE₂ receptors EP1-EP4. We sought to determine the actions of PGE₂ on electrical pacemaker and contractile activity of the circular and longitudinal muscle layers of the murine small intestine. Intracellular microelectrode and isometric force measurements were performed to examine the effects of PGE₂ receptor activation on circular and longitudinal muscle layers. In the two muscle layers PGE₂ produced differential responses. In the circular muscle layer PGE₂ caused dose-dependent membrane hyperpolarization and reduction in slow wave amplitude, accompanied by a decrease in the amplitude of phasic contractions. Membrane hyperpolarization and the reduction in slow wave amplitude and phasic contractions were insensitive to TTX and L-NNA, but inhibited by the K_ATP channel antagonist, glibenclamide. The actions of PGE₂ on the circular muscle layer were mimicked by the selective EP₂ and EP₄ agonists ONO AE1-259 and ONO AE1-329, respectively. The actions of PGE₂ were partially inhibited by the EP4 antagonist ONO AE3-208. The EP₁ agonist ONO DI-004 produced little effect while the EP3 agonist ONO AE-248 caused dose-dependent membrane depolarization. In comparison, PGE₂ produced increased tone and phasic contractions in the longitudinal muscle layer that was mimicked by ONO DI-004 and ONO AE-248, while EP₂ and EP₄ agonists had little effect on contractile activity. These data suggest that differential expression of PGE₂ receptors on intestinal muscle layers can produce antagonistic actions on intestinal motility.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565583","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":"Dynamics of circulatory monocytes trafficking and transitioning to gastric resident macrophages in diabetic gastroparesis.","authors":"Rajan Singh","doi":"10.1152/ajpgi.00053.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00053.2025","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539965","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":"Diet-microbiome-ENS connection: impact of the cafeteria diet.","authors":"Arun Balasubramaniam, Shanthi Srinivasan","doi":"10.1152/ajpgi.00391.2024","DOIUrl":"10.1152/ajpgi.00391.2024","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G179-G181"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051370","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":"Prenatal lipopolysaccharide stimulation modulates gastrointestinal immunity and oxidative status in weaned pigs.","authors":"Ty M Mitchell, Nicole C Burdick Sanchez, Jeff A Carroll, Paul R Broadway, Jerrad F Legako, Brooke M Bowen, Amy L Petry","doi":"10.1152/ajpgi.00268.2024","DOIUrl":"10.1152/ajpgi.00268.2024","url":null,"abstract":"<p><p>Gastrointestinal immunity and antioxidant defenses may be bolstered in young animals through prenatal immune stimulation (PIS), but this is largely uninvestigated in swine. This study tested the hypothesis that PIS could regulate offspring's gastrointestinal immune response and oxidative stress profile. To this end, a PIS model was utilized in sows, delivering low-dose lipopolysaccharide (LPS) during the final third of gestation to target the developing immune system. On day 78 ± 1.8 of gestation, 14 Camborough sows (parity = 2.6 ± 1.4) received either saline (Control, CON) or LPS from <i>Escherichia coli</i> O111:B4 (2.5 µg/kg of body wt). A subset of 34 weaned barrows (<i>n</i> = 17 CON, PIS), weaned at 21 ± 1.3 days, were anesthetized for subcutaneous temperature loggers and jugular catheter placement. Following recovery, all pigs received an intravenous injection of LPS (10 µg/kg·body wt) from <i>E. coli</i> O111:B4. Our findings demonstrate that PIS enhances the gut immune response by upregulating key inflammatory cytokines, indicative of a proinflammatory profile. Consistently across the jejunum and ileum, stem cell factor was modulated with heightened expression in PIS than CON (<i>P</i> ≤ 0.05). In the ileum alone, PIS exhibited heightened expression of proinflammatory cytokines and chemokines, including TNFα, IL-6, IL-1β, and CCL3L1, compared with CON (<i>P</i> ≤ 0.05). Exposure to PIS resulted in reduced systemic total antioxidant capacity at <i>hours 2</i> and <i>4</i> postchallenge (<i>P</i> = 0.004). Piglets exposed to PIS had decreased jejunal tissue malondialdehyde concentrations (<i>P</i> = 0.049). Together, these data indicate that exposure to PIS alters the inflammatory profile of the gastrointestinal immune response and oxidative status in weaned pigs.<b>NEW & NOTEWORTHY</b> These studies represent novel investigations into the influence of prenatal immune stimulation (PIS) in swine on the gastrointestinal immune response and oxidative status of offspring following subsequent immune challenge. Notable alterations were observed in gut protein biomarkers, particularly the upregulation of proinflammatory cytokines TNFα, IL-6, and IL-1β in PIS-exposed pigs, but has variable effects on oxidative status. Altered intestinal immune development may contribute to an increased risk for inflammatory disease associated with prenatal immune stimulation.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G197-G205"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031841","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":"A menu for microbes: unraveling appetite regulation and weight dynamics through the microbiota-brain connection across the lifespan.","authors":"Gabriela Ribeiro, Harriët Schellekens, Cristina Cuesta-Marti, Ivie Maneschy, Shámila Ismael, Amanda Cuevas-Sierra, J Alfredo Martínez, Marta P Silvestre, Cláudia Marques, André Moreira-Rosário, Ana Faria, Luis A Moreno, Conceição Calhau","doi":"10.1152/ajpgi.00227.2024","DOIUrl":"10.1152/ajpgi.00227.2024","url":null,"abstract":"<p><p>Appetite, as the internal drive for food intake, is often dysregulated in a broad spectrum of conditions associated with over- and under-nutrition across the lifespan. Appetite regulation is a complex, integrative process comprising psychological and behavioral events, peripheral and metabolic inputs, and central neurotransmitter and metabolic interactions. The microbiota-gut-brain axis has emerged as a critical mediator of multiple physiological processes, including energy metabolism, brain function, and behavior. Therefore, the role of the microbiota-gut-brain axis in appetite and obesity is receiving increased attention. Omics approaches such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics in appetite and weight regulation offer new opportunities for featuring obesity phenotypes. Furthermore, gut-microbiota-targeted approaches such as pre-, pro-, post-, and synbiotic, personalized nutrition, and fecal microbiota transplantation are novel avenues for precision treatments. The aim of this narrative review is <i>1</i>) to provide an overview of the role of the microbiota-gut-brain axis in appetite regulation across the lifespan and <i>2</i>) to discuss the potential of omics and gut microbiota-targeted approaches to deepen understanding of appetite regulation and obesity.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G206-G228"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982495","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":"Carbon monoxide produced by HO-1 upregulation is the main factor behind the abnormal motility seen in experimental ulcerative colitis in mice.","authors":"Mengchao Zhao, Yaru Lei, Mengyuan Wang, Yixin Chen, Shaozhang Hou, Xinyuan Dai, Di Gao, Yudan Liu, Bruno Mazet, Lei Sha","doi":"10.1152/ajpgi.00179.2023","DOIUrl":"10.1152/ajpgi.00179.2023","url":null,"abstract":"<p><p>The colonic motility is altered in patients with ulcerative colitis (UC), but the mechanism is not clear. Carbon monoxide (CO) is the molecule regulating the resting membrane potential (RMP) gradient across colonic smooth muscle wall. Changes in RMP will affect the contractility of smooth muscle. In this study, we investigated the altered colonic motility in dextran sodium sulfate-induced UC mice and the role of CO. The results showed that in the UC group, the frequency of spontaneous colonic contractions was increased while the AUC was decreased compared with the control group. HO-1-, but not HO-2-, positive cells were increased in the colonic smooth muscle wall of the UC group. These HO-1-positive cells were mainly in the myenteric plexus and PGP9.5 positive, suggesting neuronal overproduction of CO. The RMP of circular smooth muscle cells (SMCs) in the colon of UC group was hyperpolarized compared with that of control group. In control group, application of CORM-3, a CO donor, altered colonic spontaneous contractions by increasing their frequency and decreasing amplitude. In the UC group, ZnPPIX, a HO-1 inhibitor, reduced the frequency and increased the amplitude. CORM-3 hyperpolarized the RMP of colonic SMCs and abolished its gradient in the control group, while ZnPPIX depolarized the RMP of colonic SMCs and restored its gradient in the UC group. CO produced by HO-1 upregulation is the main factor behind the altered colonic motility seen in UC mice. CO is a potential candidate as a therapeutic target for patients with UC who suffer from abnormal colonic motility.<b>NEW & NOTEWORTHY</b> Carbon monoxide (CO) produced by HO-1 upregulation in myenteric plexus is the main factor that abolishes the RMP gradient across colonic muscle wall causing the altered colonic motility seen in experimental ulcerative colitis (UC) mice. CO is a potential candidate as a therapeutic target for patients with UC who suffer from abnormal colonic motility.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G311-G322"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381562","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}