美国生理学杂志-胃肠和肝脏生理学发表原创文章，涉及胃肠道、肝胆系统和胰腺的正常或异常功能研究的各个方面。鼓励作者提交涉及与这些器官相关的生长和发育、消化、分泌、吸收、代谢和运动的手稿，以及涉及免疫和炎症过程以及影响神经、内分泌和循环控制机制的研究报告。这些器官。

The American Journal of Physiology - Gastrointestinal and Liver Physiology publishes original research articles covering all aspects of normal and abnormal functions of the gastrointestinal tract, hepatobiliary system, and pancreas. Authors are encouraged to submit manuscripts related to the growth and development, digestion, secretion, absorption, metabolism, and motility of these organs, as well as research reports involving immune and inflammatory processes and studies affecting neural, endocrine, and circulatory control mechanisms.

《American Journal of Physiology - Gastrointestinal and Liver Physiology》发表原创研究文章，涵盖胃肠道、肝胆系统和胰腺的正常与异常功能。我们鼓励作者提交与这些器官相关的生长与发育、消化、分泌、吸收、代谢和运动的研究稿件，同时也欢迎涉及免疫和炎症过程，以及影响神经、内分泌和循环控制机制的研究报告。

American Journal of Physiology - Gastrointestinal and Liver Physiology

Enteroendocrine L cells and glucagon-like peptide 2 (GLP-2) secretion are activated in the intestinal adaptation process following bowel resection in patients with short bowel syndrome. We hypothesized that enteral activation of Takeda G protein-coupled receptor 5 (TGR5), expressed in enteroendocrine L cells, could augment endogenous GLP-2 secretion and the intestinal adaptation response. Our aim was to assess the efficacy of different TGR5 agonists to stimulate GLP-2 secretion and intestinal adaptation in a piglet short-bowel model. In study 1, parenterally fed neonatal pigs ( n = 6/group) were gavaged with vehicle, olive extract (OE; 10 or 50 mg/kg), or ursolic acid (UA; 10 mg/kg), and plasma GLP-2 was measured for 6 h. In study 2, neonatal pigs ( n = 6–8/group) were subjected to transection or 80% mid-small intestine resection and, after 2 days, assigned to treatments for 10 days as follows: 1) transection + vehicle (sham), 2) resection + vehicle (SBS), 3) resection + 30 mg UA (SBS + UA), and 4) resection + 180 mg/kg OE (SBS + OE). We measured plasma GLP-2, intestinal histology, cell proliferation, and gene expression, as well as whole body citrulline-arginine kinetics and bile acid profiles. In study 1, GLP-2 secretion was increased by UA and tended to be increased by OE. In study 2, SBS alone, but not additional treatment with either TGR5 agonist, resulted in increased mucosal thickness and crypt cell proliferation in remnant jejunum and ileum sections. SBS increased biliary and ileal concentration of bile acids and expression of inflammatory and farnesoid X receptor target genes, but these measures were suppressed by UA treatment. In conclusion, UA is an effective oral GLP-2 secretagogue in parenterally fed pigs but is not capable of augmenting GLP-2 secretion or the intestinal adaptation response after massive small bowel resection. NEW &amp; NOTEWORTHY Therapeutic activation of endogenous glucagon-like peptide 2 (GLP-2) secretion is a promising strategy to improve intestinal adaptation in patients with short bowel syndrome. This study in neonatal pigs showed that oral supplementation with a selective Takeda G protein-coupled receptor 5 (TGR5) agonist is an effective approach to increase GLP-2 secretion. The results warrant further study to establish a more potent oral TGR5 agonist that can effectively improve intestinal adaptation in pediatric patients with SBS.

Sen Lin

Barbara Stoll

Jason Robinson

Jose J. Pastor

Juan C. Marini

Ignacio R. Ipharraguerre

Bolette Hartmann

Jens J. Holst

Stephanie Cruz

Patricio Lau

Oluyinka Olutoye

Zhengfeng Fang

Douglas G. Burrin

AJP Gastrointestinal and Liver Physiology

Differential action of TGR5 agonists on GLP-2 secretion and promotion of intestinal adaptation in a piglet short bowel model

Chronic stress plays an important role in the development and exacerbation of symptoms in functional gastrointestinal disorders. To better understand the mechanisms underlying this relationship, we aimed to characterize changes in visceral and somatic nociception, colonic motility, anxiety-related behavior, and mucosal immune activation in rats exposed to 10 days of chronic psychological stress. Male Wistar rats were submitted daily to either 1-h water avoidance (WA) stress or sham WA for 10 consecutive days. The visceromotor response to colorectal distension, thermal somatic nociception, and behavioral responses to an open field test were measured at baseline and after chronic WA. Fecal pellets were counted after each WA stress or sham WA session as a measure of stress-induced colonic motility. Colonic samples were collected from both groups and evaluated for structural changes and neutrophil infiltration, mast cell number by immunohistochemistry, and cytokine expression by quantitative RT-PCR. Rats exposed to chronic WA (but not sham stress) developed persistent visceral hyperalgesia, whereas only transient changes in somatic nociception were observed. Chronically stressed rats also exhibited anxiety-like behaviors, enhanced fecal pellet excretion, and small but significant increases in the mast cell numbers and the expression of IL-1beta and IFN-gamma. Visceral hyperalgesia following chronic stress persisted for at least a month. Chronic psychological stress in rats results in a robust and long-lasting alteration of visceral, but not somatic nociception. Visceral hyperalgesia is associated with other behavioral manifestations of stress sensitization but was only associated with minor colonic immune activation arguing against a primary role of mucosal immune activation in the maintenance of this phenomenon.

Sylvie Bradesi

Ines Schwetz

Helena S Ennes

Christophe M R Lamy

Gordon Ohning

Michael Fanselow

Charalabos Pothoulakis

James A McRoberts

Emeran A Mayer

Repeated exposure to water avoidance stress in rats: a new model for sustained visceral hyperalgesia

In this review we summarize the role of inflammasomes in pancreatic physiology and disease with a focus on acute pancreatitis where much recent progress has been made. New findings have identified inducers of and cell specificity of inflammasome component expression in the pancreas, the contribution of inflammasome-regulated effectors to pancreatitis, and metabolic regulation of inflammasome activation, which are strong determinants of injury in pancreatitis. New areas of pancreatic biology will be highlighted in the context of our evolving understanding of gut microbiome- and injury-induced inflammasome priming, pyroptosis, and innate immune-mediated regulation of cell metabolism.

Rafaz Hoque

Wajahat Z. Mehal

American Journal of Physiology-Gastrointestinal and Liver Physiology

Inflammasomes in pancreatic physiology and disease

The gallbladder is conventionally regarded as an absorptive organ such that dilute hepatic bile is both stored and concentrated. We studied 35 patients who had recovered from a percutaneous transhepatic gallbladder drainage performed for acute cholecystitis. After an overnight fast, gallbladder bile was dark brown in color and had a wide scatter in the lipid composition. Two hours after a meal, the gallbladder bile was opalescent white in color and had the composition of an extracellular fluid. This phenomenon was uniformly observed in all 35 patients and was also consistently reproducible when five patients were repeatedly studied. We used normal dog gallbladder epithelial cell monolayers grown in culture and examined sodium flux. Control gallbladder cells absorbed sodium. When secretin (0.5-2.5 x 10(-7) M) was added, there was a prompt reversal of sodium flux, resulting in net secretion. We conclude that secretion is a physiological function of the gallbladder mucosa. After feeding, the neural and humoral factors divert stored and newly secreted bile into the duodenum and induce active de novo secretion thus producing a gallbladder bile that is opalescent white with no lipids. Our results also have important implications on the origin of the pathological "white bile," the pathogenesis and treatment of gallbladder sludge, as well as the kinetic analysis of compounds undergoing enterohepatic recirculation.

H. Igimi

F. Yamamoto

S. P. Lee

Gallbladder mucosal function: studies in absorption and secretion in humans and in dog gallbladder epithelium

胆囊黏膜功能：人类与狗胆囊上皮吸收与分泌的研究

The nuclear envelope and lamina regulate lipid metabolism and susceptibility to nonalcoholic steatohepatitis (NASH), but the role of the nuclear lamin-binding protein LAP2α in NASH has not been explored. Our data demonstrate that hepatocyte-specific loss of LAP2α protects against diet-induced hepatic steatosis, NASH, and fibrosis in male mice, with downregulation of pro-steatotic, pro-inflammatory, and pro-fibrotic lamin-regulated genes. These findings suggest that targeting LAP2α could have future potential as a novel therapeutic avenue in NASH.

Kapil K. Upadhyay

Eun-Young K. Choi

Roland Foisner

M. Bishr Omary

Graham F. Brady

Hepatocyte-specific loss of LAP2α protects against diet-induced hepatic steatosis, steatohepatitis, and fibrosis in male mice

LAP2α在肝细胞特异性缺失可保护雄性小鼠免受饮食诱导的肝脂肪变性、脂肪性肝炎和纤维化

Editorial FocusAugmenting anti-inflammatory macrophage function in colitis: a neuroimmune mechanism to drive intestinal wound repair.Natalie Bhesania, , M.D.Michael A. Schumacher, , Ph.D.Natalie Bhesania1. Department of Pediatrics, University of Southern California Keck School of Medicine. Los Angeles, CA 900892. Division of Gastroenterology, Hepatology, and Nutrition, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027M.D. and Michael A. SchumacherCorrespondence: Michael A. Schumacher, Ph.D. Children's Hospital Los Angeles 4650 Sunset Blvd. MS#137 Los Angeles, CA 90027 E-mail: mschumacher@chla.usc.edu1. Department of Pediatrics, University of Southern California Keck School of Medicine. Los Angeles, CA 900892. Division of Gastroenterology, Hepatology, and Nutrition, The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027Ph.D.Published Online:23 Dec 2024https://doi.org/10.1152/ajpgi.00368.2024MoreFiguresReferencesRelatedInformationPDF (94 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookXLinkedInWeChat We recommendThe anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitisGaiyan Ren, American Journal of Physiology - Gastrointestinal and Liver Physiology, 2015Nonantibiotic macrolides restore airway macrophage phagocytic function with potential anti-inflammatory effects in chronic lung diseasesSandra Hodge, American Journal of Physiology - Lung Cellular and Molecular Physiology, 2017Temporal induction of intestinal epithelial hypoxia-inducible factor (HIF)-2α is sufficient to drive colitis.Sumeet Solanki, American Journal of Physiology - Gastrointestinal and Liver Physiology, 2019Reactivation of hapten-induced colitis and its prevention by anti-inflammatory drugsC. B. Appleyard, American Journal of Physiology - Gastrointestinal and Liver Physiology, 1995Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in miceNancy M. Benight, American Journal of Physiology - Gastrointestinal and Liver Physiology, 2012RETRACTED: Anti-microbial/oxidative/inflammatory nanogels accelerate chronic wound healing Smart Materials in MedicineCholecystokinin plays a novel protective role in diabetic kidney through anti-inflammatory actions on macrophage: anti-inflammatory effect of cholecystokinin. Satoshi Miyamoto, Diabetes, 2012M2 Macrophage Polarization Mediates Anti-inflammatory Effects of Endothelial Nitric Oxide Signaling Woo Je Lee, Diabetes, 2015Reduced smooth muscle-fibroblasts transformation potentially decreases intestinal wound healing and colitis-associated cancer in ageing mice Yi Liu, Signal Transduction and Targeted Therapy, 2023Intestinal eosinophils: characterization of elusive granulocytes as anti-bacterial and immunomodulatory effector cells in colitis Tim Holland, Signal Transduction and Targeted Therapy, 2023Powered by Privacy policyGoogle Analytics settings Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationSee PDF More from this issue > Articles in PressPublished 23 Dec 2024 Crossmark Copyright & PermissionsCopyright © 2025 the American Physiological Society.https://doi.org/10.1152/ajpgi.00368.2024PubMed39716372History Received 27 November 2024 Accepted 10 December 2024 Published online 23 December 2024 KeywordsIBDmacrophagesCGRPinterleukin-4 Metrics Downloaded 0 times We recommendThe anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitisGaiyan Ren, American Journal of Physiology - Gastrointestinal and Liver Physiology, 2015Nonantibiotic macrolides restore airway macrophage phagocytic function with potential anti-inflammatory effects in chronic lung diseasesSandra Hodge, American Journal of Physiology - Lung Cellular and Molecular Physiology, 2017Temporal induction of intestinal epithelial hypoxia-inducible factor (HIF)-2α is sufficient to drive colitis.Sumeet Solanki, American Journal of Physiology - Gastrointestinal and Liver Physiology, 2019Reactivation of hapten-induced colitis and its prevention by anti-inflammatory drugsC. B. Appleyard, American Journal of Physiology - Gastrointestinal and Liver Physiology, 1995Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in miceNancy M. Benight, American Journal of Physiology - Gastrointestinal and Liver Physiology, 2012TLR-independent anti-inflammatory function of intestinal epithelial TRAF6 signalling prevents DSS-induced colitis in mice Katerina Vlantis, Gut, 2016Spermidine ameliorates colitis via induction of anti-inflammatory macrophages and prevention of intestinal dysbiosis Anna Niechcial, Journal of Crohn's and Colitis, 202316 CCL11 EXACERBATES COLITIS VIA MODULATION OF EPITHELIAL WOUND REPAIR Dina Polosukhina, Inflammatory Bowel Diseases, 2020Sequential expression of macrophage anti-microbial/inflammatory and wound healing markers following innate, alternative and classical activation F M Menzies, Clinical and Experimental Immunology, 2010Macrophage amphiregulin-pericyte TGF-β axis: a novel mechanism of the immune system that contributes to wound repair Hong Huang, Acta Biochimica et Biophysica Sinica, 2019Powered by Privacy policyGoogle Analytics settings publications0supporting0mentioning0contrasting0Smart Citations0000Citing PublicationsSupportingMentioningContrastingView CitationsSee how this article has been cited at scite.aiscite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

Natalie Bhesania

Michael A. Schumacher

Augmenting anti-inflammatory macrophage function in colitis: a neuroimmune mechanism to drive intestinal wound repair.

增强结肠炎中抗炎巨噬细胞功能：驱动肠道伤口修复的神经免疫机制。

The intestinal microenvironment represents a complex and dynamic ecosystem, comprising a diverse range of epithelial and non-epithelial cells, a protective mucus layer, and a diverse community of gut microbiota. Understanding the intricate interplay between these components is essential for uncovering the mechanisms underlying intestinal health and disease. The development of intestinal organoids, 3D mini-intestines that closely mimic the architecture, cellular diversity, and functionality of the intestine, offers a powerful platform for investigating different aspects of intestinal physiology and pathology. However, current intestinal organoid models, mainly adult stem cell-derived organoids, lack the non-epithelial and microbial components of the intestinal microenvironment. As such, several co-culture systems have been developed to co-culture intestinal organoids with other intestinal elements including microbes (bacteria and viruses) and immune, stromal, and neural cells. These co-culture models allow researchers to recreate the complex intestinal environment and study the intricate crosstalk between different components of the intestinal ecosystem under healthy and pathological conditions. Currently, there are several approaches and methodologies to establish intestinal organoid co-cultures, and each approach has its own strengths and limitations. This review discusses the existing methods for co-culturing intestinal organoids with different intestinal elements, focusing on the methodological approaches, strengths and limitations, and future directions.

Ghanyah Al-Qadami

Anita Raposo

Chia-Chi Chien

Chenkai Ma

Ilka Priebe

Maryam Hor

Kim Fung

Intestinal organoid co-culture systems: current approaches, challenges, and future directions

肠道类器官共培养系统：当前方法、挑战与未来方向

Background: The goal of this study was to determine whether the influence of high-fat high-sugar diet (Western diet) on intestinal function and health was reversible. Methods: We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from male C57Bl/6J mice randomly assigned to one of the following groups for the study duration: high-fat high-sugar diet for 24-weeks (HFHS), HFHS diet for 12-weeks then switched to standard chow and water for a further 12 weeks (Std), and lean controls (standard chow and water for 24-weeks). At the completion of the study, segments of jejunum were frozen for western blot determination of key proteins involved in secretory and absorptive functions, as well as senescence. Intestinal morphology was assessed. Serum and tissue assays were performed. Results: Basal Isc was significantly decreased (by 42%, P&lt;0.05) in HFHS versus leans. This decrease in I sc was fully reversed by switching to Std diet. The HFHS-induced decrease in Isc was attributed to a significant loss of ClC2 expression. Changes in inflammatory state (TNF-Alpha) and intestinal health (MPO activity) were associated with body weight changes. Conclusions: Our data suggests that the reduced basal jejunal I sc in HFHS mice is reversible. Better understanding of Western diet-mediated intestinal disturbances may permit for improved treatment options for gastrointestinal disturbances in obese individuals.

Sarah Carpinelli

John Ahlert

Maxwell Rubin

Alex Aratani

Emma Smith

Dana Floyd

Ross M Potter

Layla Al-Nakkash

Deleterious Impacts of Western diet on Jejunum Function and Health are Reversible

西方饮食对空肠功能与健康的有害影响是可逆的

Membrane proteins, such as the Cystic Fibrosis Transmembrane-conductance Regulator (CFTR), play a crucial role in gastrointestinal functions and heath. Endoplasmic reticulum (ER) membrane protein complex (EMC), a multi-subunit insertase, mediates the incorporation of membrane segments into lipid bilayers during protein synthesis. Whether EMC regulates membrane proteins’ processing and function in intestinal epithelial cells remains unclear. To investigate the role of EMC in the intestinal epithelium, we generated mice in which EMC subunit 3 (EMC3) was deleted in intestinal epithelial cells (EMC3ΔIEC). EMC3ΔIEC mice were viable but notable smaller compared to their wildtype littermates. While intestinal structure was generally maintained, EMC3ΔIEC crypts exhibited altered morphology, particularly at the base of the crypts with decreased goblet cells and paneth cells. Levels of multiple polytopic membrane proteins, including CFTR, were decreased in EMC3-deficient epithelial cells. Several calcium ATPase pumps were downregulated, and calcium mobilization was impaired in EMC3ΔIEC enteroids. CFTR-mediated organoid swelling in EMC3ΔIEC mice was impaired in response to both cAMP-dependent signaling and calcium-secretagogue stimulation. Our study demonstrated that EMC plays a critical role in maintaining intestinal epithelium homeostasis by regulating membrane protein biogenesis and intracellular calcium homeostasis. Maintaining intracellular calcium homeostasis may be a universal cellular function regulated by EMC.

Sarah Penrod

Xiaofang Tang

Changsuk Moon

Jeffrey A. Whitsett

Anjaparavanda P. Naren

Yunjie Huang

EMC3 is critical for CFTR function and calcium mobilization in the mouse intestinal epithelium

EMC3 对小鼠肠上皮细胞中CFTR功能和钙动员至关重要

The enteric nervous system (ENS) continues to be exposed to various disturbances throughout life, which causes apoptosis in the ENS. Therefore, it is assumed that neurogenesis is induced to maintain the neuronal network in the adult ENS. However, these underlying mechanisms are largely unknown. We aimed to investigate adult neurogenesis in the DSS-induced colitis mouse colon. Methods: male C57BL/6N mice (12-week-old) were administered 2% DSS in their drinking water for 8 days. After DSS treatment, cross-sections and longitudinal muscle and myenteric plexus preparations from the colon were used for immunohistochemistry. The segments of colons were mounted in organ baths and then exposed to a voltage-gated sodium channel activator veratridine. Results: in the motility study, veratridine-induced colonic contractions were significantly suppressed in DSS-induced colitis mice compared to normal mice. Immunohistochemical analyses revealed that the proportion of nitrergic neurons per ganglion was significantly increased in the colons of DSS-induced colitis mice compared to normal mice. Furthermore, the proportion of Sox2 (new-born neuron marker)-positive neurons per ganglion was not significantly different between normal mice and DSS-induced colitis mice, whereas the proportion of Sox2-positive nitrergic neurons to Sox2-positive neurons per ganglion was significantly increased in the colons of DSS-induced colitis mice compared to normal mice. In addition, NOS inhibitor significantly enhanced veratridine-induced colonic contractions in DSS-induced colitis mice compared with normal mice. Conclusions: these findings suggested that colitis caused an imbalance in the enteric neural circuit composed of excitatory neurons and inhibitory neurons in the myenteric plexus of the colon, which resulted in colonic dysmotility.

Kana Miyata

Takeshi Yamamoto

Ryo Kato

Shusaku Hayashi

Makoto Kadowaki

Preferential Neurogenesis of Nitrergic Neurons in the Myenteric Plexus of the DSS-induced Colitis Mouse Colon Causes Colonic Dysmotility in Colitis

DSS诱导的结肠炎小鼠结肠肌间神经丛中一氧化氮能神经元优先神经发生导致结肠炎性运动障碍

Abbreviation	Am. J. Physiol. Liver Physiol.
Journal Impact	4.02
Quartiles(Global)	PHYSIOLOGY(Q1)

ISSN	0193-1857, 1522-1547
h-index	191

Publication Information	Publisher: American Physiological Society，Publishing cycle: Monthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1980，Proportion of original research papers: 84.54%，Self Citation Rate:0.00%， Gold OA Rate: 6.18%
Average review cycle	网友分享经验：平均1月
Average recruitment ratio	网友分享经验：较易

American Journal of Physiology - Gastrointestinal and Liver Physiology

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