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

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Cyclic infusion mitigates liver dysfunction associated with continuous total parenteral nutrition in a novel murine model. 在一种新的小鼠模型中,循环输注减轻了与持续全肠外营养相关的肝功能障碍。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-01 Epub Date: 2025-08-11 DOI: 10.1152/ajpgi.00033.2025
Nathaniel B Willis, Tahliyah S Mims, Karen Antunes, Hubert Peng, Mei-I Yen, Chi-Liang Eric Yen, Joseph F Pierre
{"title":"Cyclic infusion mitigates liver dysfunction associated with continuous total parenteral nutrition in a novel murine model.","authors":"Nathaniel B Willis, Tahliyah S Mims, Karen Antunes, Hubert Peng, Mei-I Yen, Chi-Liang Eric Yen, Joseph F Pierre","doi":"10.1152/ajpgi.00033.2025","DOIUrl":"10.1152/ajpgi.00033.2025","url":null,"abstract":"<p><p>Parenteral nutrition (PN) is a lifesaving intervention for patients unable to feed enterally but is often associated with parenteral nutrition-associated liver disease (PNALD), also called intestinal failure-associated liver disease (IFALD). This disease is characterized by steatosis, cholestasis, and elevated liver stress markers. Continuous PN induces hepatic injury through mechanisms including insulin resistance, lipotoxicity, systemic inflammation, and oxidative stress. Infusion cycling is known to ameliorate clinical markers of liver injury, but metabolic underpinnings have not been thoroughly investigated. Therefore, we modeled PN-induced liver injury in mice to investigate how differential infusion patterns impacted hepatic metabolism. Intermittent infusions protected against increased circulating alanine aminotransferase levels and improved histopathology to more closely resemble chow controls. Transcriptomic analyses revealed 804 differentially expressed genes between PN groups, highlighting pathways related to peroxisome proliferator-activated receptor signaling, fatty acid metabolism, and peroxisomes. Relative to the continuous group, intermittent PN infusion specifically downregulated <i>Acaa1b</i>, <i>Aldh3a2</i>, <i>Inmt</i>, and <i>Acot4</i>; transcripts involved in peroxisomal lipid oxidation, dicarboxylic acid synthesis, and one-carbon metabolism. This study suggests that infusion cycling may attenuate metabolic burden induced by alternate lipid oxidation pathways. Future work can therapeutically leverage these metabolic pathways to deepen our understanding of PNALD/IFALD and guide PN treatments to improve patient outcomes.<b>NEW & NOTEWORTHY</b> This work demonstrated that the infusion schedule, independent of nutrient and caloric concentration, is a modulator of hepatic lipid metabolism in a novel murine model of parenteral nutrition. This cyclic infusion paradigm attenuated transcripts involved in microsomal and peroxisomal lipid oxidation, which were upregulated in the continuous infusion group. These data support the clinical use of cyclic infusion to improve hepatic parameters known to be adversely affected by parenteral nutrition.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G536-G545"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820389","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}
引用次数: 0
Neural control of goblet cells in the gastrointestinal tract. 胃肠道杯状细胞功能的神经控制。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-01 Epub Date: 2025-08-18 DOI: 10.1152/ajpgi.00191.2025
Matthew C Rowe, Victor L Pettersson, Simona E Carbone, Jenny K Gustafsson, Daniel P Poole
{"title":"Neural control of goblet cells in the gastrointestinal tract.","authors":"Matthew C Rowe, Victor L Pettersson, Simona E Carbone, Jenny K Gustafsson, Daniel P Poole","doi":"10.1152/ajpgi.00191.2025","DOIUrl":"10.1152/ajpgi.00191.2025","url":null,"abstract":"<p><p>The mucus layer is an essential physical barrier that protects and lubricates mucosal surfaces in the body. The semipermeable nature of the mucus layer limits bacterial interactions with the epithelium while allowing nutrient absorption. Goblet cells (GCs) are specialized epithelial cells with a classical role to synthesize and secrete mucus to maintain the mucus layer. Emerging research has revealed the diverse nature of GC functions, including their interaction with the immune system through goblet cell-associated antigen passages to promote tolerance to dietary and bacterial antigens. Dysfunction of GCs or the mucus layer leaves the epithelium vulnerable to infection and is commonly associated with digestive disease. As such, there is a growing appreciation for the importance of GCs and the mucus layer to regulate mucosal homeostasis and protect against disease. Long-standing anatomical and pharmacological evidence indicates that the nervous system is a key regulator of GC function. However, the relative contribution from each division of the nervous system to the control of GC function is poorly defined. This is partly due to conflicting evidence from the literature and differences in experimental methods used. Furthermore, whether neurotransmitters influence GC functions and the associated mucus barrier directly or via indirect mechanisms, such as enhanced fluid secretion, remains unclear. The emergence of highly specific genetic approaches provides new opportunities to examine how specific nerve types can influence GC function. In this review, we consolidate the literature to date, with a focus on the stomach and lower gastrointestinal tract, and outline how current technologies may be useful to progress our fundamental understanding of neural-GC control.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G513-G535"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870823","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}
引用次数: 0
Probiotic-mediated regulation of arginine metabolism to improve intestinal barrier function: a metabolic makeover for IBD? 益生菌介导的精氨酸代谢调节改善肠屏障功能:IBD的代谢改造?
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-01 Epub Date: 2025-09-15 DOI: 10.1152/ajpgi.00277.2025
Yevheniya Shevchenko, Michael A Schumacher
{"title":"Probiotic-mediated regulation of arginine metabolism to improve intestinal barrier function: a metabolic makeover for IBD?","authors":"Yevheniya Shevchenko, Michael A Schumacher","doi":"10.1152/ajpgi.00277.2025","DOIUrl":"10.1152/ajpgi.00277.2025","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G557-G558"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068889","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}
引用次数: 0
Pioglitazone Reduces Hepatic Alpha-1 Antitrypsin Accumulation Through Autophagy and AMPK Activation in Alpha-1 Antitrypsin Deficient Mice. 吡格列酮通过自噬和AMPK激活减少α -1抗胰蛋白酶缺陷小鼠肝脏α -1抗胰蛋白酶积累。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-09-29 DOI: 10.1152/ajpgi.00272.2025
Yuanqing Lu, Regina Oshins, Nesmine R Maptue, Qingyang Shen, Chalermchai Khemtong, Kenneth Cusi, Mark Brantly, Nazli Khodayari
{"title":"Pioglitazone Reduces Hepatic Alpha-1 Antitrypsin Accumulation Through Autophagy and AMPK Activation in Alpha-1 Antitrypsin Deficient Mice.","authors":"Yuanqing Lu, Regina Oshins, Nesmine R Maptue, Qingyang Shen, Chalermchai Khemtong, Kenneth Cusi, Mark Brantly, Nazli Khodayari","doi":"10.1152/ajpgi.00272.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00272.2025","url":null,"abstract":"<p><p><b>Background:</b> Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterized by accumulation of misfolded Z α-1 antitrypsin (ZAAT) in hepatocytes, leading to liver injury and metabolic dysfunction. There is no therapy to reduce ZAAT accumulation and restore proteostasis. Pioglitazone activates AMP-activated protein kinase (AMPK), enhance autophagy, and modulate ER stress responses, suggesting a potential effect on ZAAT clearance. Our objective is to examine whether pioglitazone can protect against AATD-mediated liver disease. <b>Methods:</b> Huh7.5 cells expressing ZAAT (HuhZ) and Pi*Z transgenic mice were used to investigate pioglitazone treatment on hepatic ZAAT accumulation, autophagy activation, and AMPK signaling. Histological, molecular, and metabolic analyses were conducted to assess changes in ZAAT content, autophagy markers, AMPK phosphorylation, and proteostasis. <b>Results:</b> Pioglitazone significantly reduced intracellular ZAAT and decreased lipid droplet accumulation in HuhZ cells. Pioglitazone markedly lowered hepatic ZAAT content in Pi*Z mice, suggesting enhanced degradation. This reduction was mediated through the AMPK pathway, indicated by increased phosphorylation of AMPK and ULK1. Pioglitazone induced autophagy, shown by decreased p62 and increased ATG5 and LC3B-II. This is indicative of enhanced autophagy. Although total hepatic AAT levels were reduced, PASD-positive ZAAT aggregates exhibited only a downward trend, suggesting these may be more resistant to clearance. <b>Conclusion:</b> These findings demonstrate pioglitazone reduces hepatic ZAAT accumulation by activating AMPK and inducing autophagy in AATD-associated liver disease, supporting its potential for therapeutic repurposing. As pioglitazone is FDA-approved with benefits for metabolic liver health, further studies are warranted to evaluate efficacy in restoring proteostasis and reducing hepatic ZAAT.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190615","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}
引用次数: 0
Dynamic Cholangiocyte Responses in a Murine Model of Reversible Cholestasis: Macrophage Remodeling and NF-Y Mediated TGFβ1 Expression. 可逆性胆汁淤积小鼠模型中的动态胆管细胞反应:巨噬细胞重塑和NF-Y介导的tgf - β1表达。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-09-29 DOI: 10.1152/ajpgi.00243.2025
Kirsta E Olson, Anuradha Krishnan, Patrick Splinter, Alexander Q Wixom, Maria Eugenia Guicciardi, Nidhi Jalan-Sakrikar, Adiba Azad, Nicholas F LaRusso, Gregory J Gores
{"title":"Dynamic Cholangiocyte Responses in a Murine Model of Reversible Cholestasis: Macrophage Remodeling and NF-Y Mediated TGFβ1 Expression.","authors":"Kirsta E Olson, Anuradha Krishnan, Patrick Splinter, Alexander Q Wixom, Maria Eugenia Guicciardi, Nidhi Jalan-Sakrikar, Adiba Azad, Nicholas F LaRusso, Gregory J Gores","doi":"10.1152/ajpgi.00243.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00243.2025","url":null,"abstract":"<p><p>During cholestasis, cholangiocytes become activated, promoting macrophage-associated periductal infiltration and fibrosis. The cholangiocyte specific mechanisms responsible for these processes are unclear. To gain insight into the cholangiocyte signaling mechanisms contributing to these pathophysiologic processes, mice were fed a DDC diet for 10 days to induce liver injury and then switched to a chow diet to permit recovery, designated as R days. Profiling of isolated intrahepatic leukocytes by mass spectrometry revealed an abundant CX3CR1<sup>+</sup> macrophage population on the DDC diet which declined during the recovery period. This observation was confirmed using <i>Cx3cr1</i><sup>GFP</sup> mice. Next, cholangiocytes were isolated from control, DDC, and R15 mice, and RNA-seq performed. Cholangiocyte CX3CL1 expression, the cognate ligand for CX3CR1, increased in DDC fed mice and returned to basal values by R15, implicating cholangiocytes in CX3CR1<sup>+</sup> macrophage recruitment. Ingenuity pathway analysis (IPA) of the RNAseq data revealed upregulation of the pathogen induced cytokine storm pathway in cholangiocytes activated from DDC fed mice, and resolution of this pathway in R15 isolated cholangiocytes. SCENIC regulon analysis identified that NF-Y, a transcription factor complex, was activated only on the DDC diet, but not in control or R15 mice. Finally, siRNA targeted suppression of NF-YA in normal human cholangiocytes (NHC) reduced cholangiocyte expression of the profibrogenic ligand <i>TGFβ1</i>. Consistent with this observation, <i>Tgfβ1</i> was increased in cholangiocytes from DDC fed animals which returned to control values at day R15. Collectively, these observations provide mechanistic insights into cholangiocyte pathobiology during cholestasis.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190640","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}
引用次数: 0
Temporal Transcriptional and Functional Dynamics of Jejunal Mucosal Response to Early Weaning in Piglets. 仔猪早期断奶时空肠黏膜反应的时间转录和功能动力学。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-09-22 DOI: 10.1152/ajpgi.00022.2025
Ty M Mitchell, Heather Ann Moeser, Adam J Moeser
{"title":"Temporal Transcriptional and Functional Dynamics of Jejunal Mucosal Response to Early Weaning in Piglets.","authors":"Ty M Mitchell, Heather Ann Moeser, Adam J Moeser","doi":"10.1152/ajpgi.00022.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00022.2025","url":null,"abstract":"<p><p>Early-life adversity, including abrupt weaning, imposes significant psychosocial and environmental stress during a critical window of gastrointestinal (GI) development, leading to long-term consequences for gut function and disease susceptibility. In piglets, early weaning profoundly disrupts GI development, altering the intestinal epithelial barrier, reshaping immune function, and inducing lasting changes in the enteric nervous system. Despite these adverse outcomes, the early molecular mechanisms that initiate these alterations and set the gut on a divergent developmental trajectory remain poorly understood. Here, we utilized RNA sequencing and bioinformatic analyses to delineate early transcriptional changes in the jejunal mucosa of early-weaned male castrates compared to unweaned littermates. Ex vivo Ussing chamber experiments validated functional changes associated with these transcriptional alterations. Weaning triggered rapid transcriptional shifts observable within 3 hours, including suppressed mitochondrial energy production and increased glucose transporter expression. Pathway analysis revealed upregulation of ion channel transport genes (KCN, SCN, TRP, SLC) and neurotransmitter receptors (cholinergic, dopaminergic, GABAergic, glutamatergic), indicating early neuronal adaptations. Functional assays confirmed enhanced SGLT-mediated glucose transport and neural-evoked secretory responses 24 hours post-weaning, supporting transcriptomic findings. These findings reveal previously unexamined early transcriptional and functional changes that may serve as inciting mechanisms altering gut trajectory during this critical developmental window, providing new insight into how psychosocial stress and early weaning contribute to long-term gut dysfunction, with broader implications for preterm birth, neonatal GI injury, and other early-life stressors that impact lifelong GI health.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111730","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}
引用次数: 0
Colon: A Likely Middleman Connecting the Liver, Adipose Tissue, and Gut Microbiota in MASLD. 结肠:MASLD中连接肝脏、脂肪组织和肠道微生物群的可能中间人。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-09-15 DOI: 10.1152/ajpgi.00248.2025
Medha Priyadarshini, Brian T Layden
{"title":"Colon: A Likely Middleman Connecting the Liver, Adipose Tissue, and Gut Microbiota in MASLD.","authors":"Medha Priyadarshini, Brian T Layden","doi":"10.1152/ajpgi.00248.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00248.2025","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068835","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}
引用次数: 0
Serotonin, a downstream effector of GLP-2, enhances lacteal contractility and lymph flow. 血清素,GLP-2的下游效应,增强乳收缩性和淋巴流动。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-09-15 DOI: 10.1152/ajpgi.00205.2025
Lili Tian, Majid Mufaqam Syed-Abdul, Gary F Lewis
{"title":"Serotonin, a downstream effector of GLP-2, enhances lacteal contractility and lymph flow.","authors":"Lili Tian, Majid Mufaqam Syed-Abdul, Gary F Lewis","doi":"10.1152/ajpgi.00205.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00205.2025","url":null,"abstract":"<p><p>Glucagon-like peptide-2 (GLP-2) is known to exert some of its biological effects via the release of neurotransmitters, and in view of the absolute requirement for the enteric nervous system (ENS) demonstrated in our recent GLP-2-induced lipid mobilization studies, we aimed to identify the neurotransmitter that mediates GLP-2's effect on intestinal lipid mobilization. We also examined the role of VEGFR3 as an intermediate in the signaling cascade. Utilizing a rat lymph fistula model, 5 hours after an intraduodenal (i.d.) lipid bolus, the following intraperitoneal (i.p.) administrations were applied in two different sets of experiments: Experiment 1: 1) Placebo, 2) GLP-2, 3) GLP-2 + Ketanserin (serotonin receptor antagonist). Experiment 2: 1) Placebo, 2) Serotonin, 3) Serotonin + MAZ-51 (a VEGFR3 inhibitor), 4) Serotonin + SAR131675 (a second VEGFR3 inhibitor). Lymph flow and triglyceride (TG) output were assessed for 60 mins (Experiment 1) or 90 mins (Experiment 2) after administration. In another set of animals, GLP-2 or serotonin were administered i.p and blood samples were collected to quantify plasma serotonin concentration. Intravital imaging of a prospero-related homeobox 1-enhanced green fluorescent protein rat model was utilized to assess lacteal contractility after placebo or serotonin administration. We demonstrated that single-dose GLP-2 administration acutely increased serotonin concentration in plasma, serotonin enhanced lymph flow, lymph TG output and lacteal contractility, antagonism of the serotonin receptor decreases GLP-2-enhanced mesenteric lymph flow and TG output and inhibition of VEGFR3 abolished serotonin-induced lymph flow and TG output.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068860","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}
引用次数: 0
The synergistic interplay between vitamin A, dietary fiber, and the microbiota-gut-brain axis: a potential mechanism for preventing Alzheimer's disease. 维生素A、膳食纤维和微生物-肠-脑轴之间的协同相互作用:预防阿尔茨海默病的潜在机制。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-09-01 Epub Date: 2025-08-12 DOI: 10.1152/ajpgi.00097.2025
Shadt Skawratananond, Grace E McCrea, Paul Lie, Matthew B Buxton, Sean P Daly, Nicholas A Vojtkofsky, Shane C Smith, Charlie Zhang, Matthew Hernandez, Ashly Hindle, Aric F Logsdon, J Josh Lawrence
{"title":"The synergistic interplay between vitamin A, dietary fiber, and the microbiota-gut-brain axis: a potential mechanism for preventing Alzheimer's disease.","authors":"Shadt Skawratananond, Grace E McCrea, Paul Lie, Matthew B Buxton, Sean P Daly, Nicholas A Vojtkofsky, Shane C Smith, Charlie Zhang, Matthew Hernandez, Ashly Hindle, Aric F Logsdon, J Josh Lawrence","doi":"10.1152/ajpgi.00097.2025","DOIUrl":"10.1152/ajpgi.00097.2025","url":null,"abstract":"<p><p>The human gastrointestinal tract harbors a vast and diverse microbial community, with the gut microbiome playing a fundamental role in numerous biological processes that influence overall health and disease progression. Emerging evidence has identified bacterial lipopolysaccharides in the hippocampus of patients with Alzheimer's disease (AD), highlighting the intricate relationship between the gastrointestinal tract, gut microbiome, and the central and enteric nervous systems-commonly referred to as the \"microbiota-gut-brain axis.\" In this review, we explore the mechanisms by which the microbiota-gut-brain axis contributes to AD pathogenesis. We propose that sufficient levels of all-trans retinoic acid (ATRA), the bioactive form of vitamin A, enhance intestinal barrier integrity by upregulating tight junction proteins and modulating immune function through the induction of regulatory T-cell differentiation, thereby mitigating inflammation. Furthermore, dietary fiber complements this process by promoting the production of short-chain fatty acids, such as butyrate, via bacterial fermentation. Butyrate, in turn, acts as a histone deacetylase inhibitor, upregulating ATRA bioavailability by elevating aldehyde dehydrogenase gene expression. Our mechanistic framework is supported by the endotoxin hypothesis of AD, which maintains that the movement of infectious pathogens across the blood-brain barrier causes a vicious cycle of inflammation, a key factor of AD pathogenesis, leading to amyloid-β deposition, microglial activation, and CYP26A1-mediated ATRA degradation. Finally, we discuss microbiome-based therapeutic strategies and dietary interventions, including prebiotic compounds, probiotic bacteria, fecal microbiota transplantation, the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, and a combined approach featuring vitamins A/D and dietary fiber, as potential approaches to prevent progression to AD via the microbiota-gut-brain axis.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G484-G499"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833715","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}
引用次数: 0
Liquid nutrient drink testing induces gastric myoelectrical abnormalities that correlate with gastroduodenal symptoms. 液体营养饮料试验诱发与胃十二指肠症状相关的胃肌电异常。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-09-01 DOI: 10.1152/ajpgi.00070.2025
Hassan Shaaban, Chris Varghese, Gabriel Schamberg, India Wallace, Mikaela Law, Nooriyah Poonawala, William Xu, Christopher N Andrews, Armen Gharibans, Jan Tack, Gregory O'Grady, Stefan Calder
{"title":"Liquid nutrient drink testing induces gastric myoelectrical abnormalities that correlate with gastroduodenal symptoms.","authors":"Hassan Shaaban, Chris Varghese, Gabriel Schamberg, India Wallace, Mikaela Law, Nooriyah Poonawala, William Xu, Christopher N Andrews, Armen Gharibans, Jan Tack, Gregory O'Grady, Stefan Calder","doi":"10.1152/ajpgi.00070.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00070.2025","url":null,"abstract":"<p><p>Chronic gastroduodenal symptoms experienced in functional dyspepsia, chronic nausea and vomiting syndromes, and gastroparesis affect over 10% of the global population and impose a significant healthcare burden. The relationship between aberrant gastric myoelectrical activity and symptom genesis remains incompletely defined. In this study, we evaluated the effects of gastric distension induced by a liquid nutrient drink test (LNDT) on gastric myoelectrical activity in healthy volunteers using noninvasive body surface gastric mapping (BSGM) with the Gastric Alimetry system (Auckland, New Zealand). Twenty healthy participants (10 females) underwent BSGM with 30-min fasting baseline, LNDT with Ensure administered at 30 mL/min until maximal toleration, and 4-h postprandial recording. Gastric Alimetry Rhythm Index (GA-RI), principal gastric frequency (PGF), and BMI-adjusted amplitude were analyzed across time and in relation to symptoms using mixed models. During LNDT, PGF decreased significantly (2.7 ± 0.2 vs. an overall average 3.0 ± 0.2 cycles/min, <i>P</i> < 0.001) and GA-RI declined (β = -0.11, 95% CI -0.21 to -0.002, <i>P</i> = 0.047) with a concurrent increase in nausea ratings. In the first postprandial hour, bloating, nausea, and overall symptom burden were elevated, with sustained reductions in GA-RI and PGF correlating with higher symptom scores. Spectral analyses revealed transient abnormalities temporally aligned with symptom genesis. These findings indicate that excessive gastric distension provokes aberrant gastric myoelectrical activity that is closely associated with foregut symptoms, supporting the role of these abnormalities in the pathophysiology of neurogastroduodenal disorders.<b>NEW & NOTEWORTHY</b> Body surface gastric mapping with liquid nutrient drink test found that excessive gastric distension provokes dysrhythmias that are closely associated with foregut symptoms, supporting the role of disrupted gastric myoelectrical function in the pathophysiology of neurogastroduodenal disorders.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":"329 3","pages":"G363-G370"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939482","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}
引用次数: 0
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