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

{"title":"Preferential neurogenesis of nitrergic neurons in the myenteric plexus of the DSS-induced colitis mouse colon causes colonic dysmotility in colitis.","authors":"Kana Miyata, Takeshi Yamamoto, Ryo Kato, Shusaku Hayashi, Makoto Kadowaki","doi":"10.1152/ajpgi.00219.2023","DOIUrl":"10.1152/ajpgi.00219.2023","url":null,"abstract":"<p><p>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 dextran sodium sulfate (DSS)-induced colitis mouse colon. Male C57BL/6N mice (12-wk-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. In the motility study, veratridine-induced colonic contractions were significantly suppressed in DSS-induced colitis mice compared with 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 with 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 with normal mice. In addition, NOS inhibitor significantly enhanced veratridine-induced colonic contractions in DSS-induced colitis mice compared with normal mice. 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.<b>NEW & NOTEWORTHY</b> ENS continues to be exposed to various disturbances throughout life, which causes adult apoptosis in the ENS. In this study, the frequency of adult neurogenesis was not altered by colitis, whereas colitis selectively induced adult neurogenesis of nNOS-positive inhibitory motor neurons in the myenteric plexus of the colon by preferential adult neurogenesis, indicating that colitis caused an imbalance in the enteric neural circuit composed of excitatory neurons and inhibitory neurons, which resulted in colonic dysmotility.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G17-G28"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724380","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-heart axis: cardiac remodeling and heart failure in the context of inflammatory bowel disease and dysbiosis.","authors":"Thierry Kochkarian, Hania I Nagy, Qingjie Li","doi":"10.1152/ajpgi.00016.2025","DOIUrl":"10.1152/ajpgi.00016.2025","url":null,"abstract":"<p><p>Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are debilitating and complex chronic gastrointestinal disorders that affect not only the gut but also extraintestinal organs, including the heart. The gut-heart cross talk has garnered increasing attention in recent years; however, the molecular mechanisms underlying this complex interplay remain poorly understood. This review explores the gut-heart axis, focusing on how IBD disrupts gut microbiota homeostasis and promotes cardiac remodeling through systemic inflammation and various mediators, ultimately contributing to the onset or progression of heart failure. IBD compromises the integrity of the intestinal barrier, allowing microbial metabolites such as trimethylamine N-oxide and phenylacetylglutamine, along with inflammatory cytokines and microRNAs (miRNAs) (e.g., miR-155, miR-21, and let-7a), to enter the circulation and contribute to cardiac remodeling and heart failure. We identify dysfunction of nucleotide-binding oligomerization domain-containing protein 2 as a critical link between gut immunity and cardiovascular pathology. In addition, we discuss emerging microbiome-based therapeutic strategies, including fecal microbiota transplantation and IL-23 inhibitors, aimed at restoring gut homeostasis and mitigating cardiovascular risk. By integrating molecular mechanisms, clinical evidence, and therapeutic approaches, this review underscores the pivotal role of gut dysbiosis in cardiac dysfunction and offers new perspectives for managing cardiac dysfunction in patients with IBD.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G122-G137"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092416","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":"Crural and costal diaphragm function during emesis.","authors":"Jasmine J Park, Giovanni Tagliabue, Michael Ji, Ravinder K Mittal, Paul A Easton","doi":"10.1152/ajpgi.00354.2024","DOIUrl":"10.1152/ajpgi.00354.2024","url":null,"abstract":"<p><p>Together, the costal and crural diaphragm constitute the primary respiratory muscle in mammals, but functionally, they are distinct. The crural segment has additional gastrointestinal function, wrapped around the esophagus at the esophagogastric junction, contributing to the esophageal sphincter. Emesis is an expulsive process that requires the coordinated action of multiple muscles to rapidly force out gastric contents. The simultaneous mechanical action and neural activation of the diaphragm segments during the process of emesis, especially expulsion, is uncertain. Detailed divergence of the crural diaphragm to sphincter function during emesis has not been studied. In six awake, spontaneously breathing canines, electrical activity and corresponding muscle shortening of the costal and crural diaphragm were measured at five phases of emesis (rest, early prodrome, mid prodrome, late prodrome, and expulsion) induced by apomorphine. Overall, baseline muscle length decreased and baseline EMG increased progressively from rest through prodrome for both costal and crural, but at expulsion, the crural segment diverged, lengthening abruptly. Shortening and EMG activity per breath for costal changed slightly throughout emesis; crural shortening and EMG activity increased abruptly at expulsion. The divergent action of crural during expulsion developed sequentially through each breath. Also, neuromechanical coupling of the segments reversed at expulsion, with contractility of the crural surpassing that of the costal. These measurements confirm a disparate action of crural diaphragm, compared with costal, to facilitate expulsion. During the process of emesis, although the costal persists as an obligatory respiratory muscle, the crural converts from respiratory muscle to opening sphincter.<b>NEW & NOTEWORTHY</b> Although the diaphragm is known as a primary respiratory muscle, the two diaphragm sections, the costal and crural, have notably different functions. This study elucidates the essential role of the crural diaphragm during emesis, a gastrointestinal process. During emesis, the crural diaphragm abandons respiratory function and transmutes to act as an esophageal sphincter. Meanwhile, the costal diaphragm continues ventilatory function.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G69-G78"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085601","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":"Elucidation of roles of serine/threonine phosphatases PP1 and PP2A in mediating CCK-stimulated growth and enzyme secretion in pancreatic acinar cells.","authors":"Irene Ramos-Alvarez, Robert T Jensen","doi":"10.1152/ajpgi.00308.2024","DOIUrl":"10.1152/ajpgi.00308.2024","url":null,"abstract":"<p><p>Serine/threonine phosphatases, protein phosphatases 1 and 2A (PP1 and PP2A), play important roles in mediating cellular signaling in different tissues to different stimuli, including glycogen metabolism, protein synthesis/growth, and secretion. However, the roles of PP1/PP2A in pancreatic acinar cell secretion/growth are both unclear and controversial. To address this issue, in the present study, we examined the ability of gastrointestinal hormones/growth factors (GFs) to activate PP1 and PP2A and the signaling cascades involved in rat pancreatic acini and the pancreatic acinar tumor cell line, AR42J cells. PP1 and PP2A were both detected in pancreatic acini and AR42J cells. In acini, PP1 and PP2A were activated by pancreatic secretagogues-stimulating phospholipase C (bombesin, CCK-8, and carbachol) and endothelin and by pancreatic GFs (insulin, hepatocyte growth factor, epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor, and insulin-like growth factor 1). Full CCK-8 activation of PP1/PP2A required activation of both high- and low-affinity CCK1-receptor states. Using specific PP1 and PP2 assays, in both acini and AR42J cells, experimental conditions were established, where calyculin A, a known nonselective PP1/PP2A inhibitor, inhibited activation of both, whereas okadaic acid and fostriecin inhibited only PP2A activation and tautomycetin inhibited only PP1 activation. Under these conditions, CCK-stimulated enzyme secretion and stimulation of p44/42, a key mediator of growth, required PP2A activation, without activation of PP1. Using specific siRNA for PP1/PP2A in AR42J cells, similar results were found. These results establish that only PP2A activation is essential for CCK-mediated stimulation of growth and enzyme secretion in pancreatic acinar cells and pancreatic acinar AR42J tumor cells.<b>NEW & NOTEWORTHY</b> Despite more than 10 studies, the roles of the serine/threonine phosphatases, PP1/PP2A, in pancreatic acinar cell-secretion/growth remain controversial. This study demonstrates that both PP1/PP2A are present in rat pancreatic acini and in pancreatic acinar tumor-AR42J cells. Both phosphatases are activated by pancreatic secretagogues, stimulating PLC, and by pancreatic growth factors. Using specific inhibitory conditions for PP1/PP2A (inhibitors, siRNA studies), only PP2A activation is needed for CCK-8-stimulated enzyme secretion and growth signaling cascades in pancreatic acinar cells.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G102-G121"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075387","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 novel human hepatocyte cell line to study PNPLA3-associated steatotic liver disease.","authors":"Gary Huang, Daniel F Wallace, V Nathan Subramaniam","doi":"10.1152/ajpgi.00193.2024","DOIUrl":"10.1152/ajpgi.00193.2024","url":null,"abstract":"<p><p>Patatin-like phospholipase domain-containing protein 3 (<i>PNPLA3</i>) p.I148M is a well-established variant associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Conflicting in vitro and in vivo data about the impact of the variant suggest that the <i>PNPLA3</i> p.I148M variant could be gain- or loss-of-function, or neomorphic. Most in vitro models used to study MASLD are cancer-derived hepatoma cell lines such as HepG2 and Huh7, which already endogenously express the homozygous <i>PNPLA3</i> p.I148M variant. This highlights the need to develop models that better reflect disease and allow comparisons with wild-type cells. Clustered regularly interspaced short palindromic repeats (CRISPR) prime editing was used to introduce the <i>PNPLA3</i> p.I148M gene variant into a healthy-derived immortalized human hepatocyte (IHH) cell line to generate a new in vitro model of MASLD that would better reflect PNPLA3-associated MASLD/MASH. Heterozygous and homozygous <i>PNPLA3</i> p.I148M IHH cell lines were generated and validated with Sanger sequencing. Mutant cell lines exhibited lipid accumulation, increased cluster of differentiation 36 (<i>CD36</i>) gene expression and a decline in carnitine palmitoyltransferase 1 alpha (<i>CPT1A</i>) gene expression compared with the wild-type control, basally or in the presence of free fatty acid (FFA)-induced steatosis. The homozygous <i>PNPLA3</i> p.I148M IHH cell line also demonstrated reduced <i>PNPLA3</i> gene and protein expression compared with the wild-type control. We have developed a new human hepatocyte cell line and in vitro model to help understand PNPLA3-associated steatotic liver disease and provide a new resource for developing potential therapeutics.<b>NEW & NOTEWORTHY</b> We have developed a novel in vitro model for studying the <i>PNPLA3</i> p.I148M variant in steatotic liver disease using a normal, healthy-derived hepatocyte cell line, which does not endogenously express the variant. We show that carrying the homozygous <i>PNPLA3</i> p.I148M variant results in reduced PNPLA3 gene and protein expression, more lipid accumulation, increased lipid uptake, and reduced mitochondrial lipid oxidation-associated gene expressions and altered expression of genes associated with lipid synthesis and transport.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G1-G16"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972988","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":"Could physical exercise improve mental health in the context of chronic liver disease?","authors":"Caroline J K Wallace, Marie-Claude Audet","doi":"10.1152/ajpgi.00038.2025","DOIUrl":"10.1152/ajpgi.00038.2025","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G138-G139"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085690","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 J Hwang, Elizabeth A H Beckett, Kenton M Sanders, Sean M Ward","doi":"10.1152/ajpgi.00400.2024","DOIUrl":"10.1152/ajpgi.00400.2024","url":null,"abstract":"<p><p>Prostaglandin E₂ (PGE₂) actions on intestinal motility are complex due to 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 a 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 tetrodotoxin (TTX) and <i>N</i>^ω-nitro-l-arginine (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, whereas 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, whereas 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.<b>NEW & NOTEWORTHY</b> Prostaglandins are lipid mediators that have complex actions on gastrointestinal motility that are highly dependent on the expression of the receptor subtypes where they exert their actions. PGE₂ has inhibitory or excitatory effects on circular or longitudinal muscle layers of the small intestine. Despite many studies of the effects of prostaglandins on tissue contractility, little is known about the specific receptors eliciting these effects. The present study examines functional receptor expression in the small intestine.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G29-G44"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","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":"The multifaceted role of sirtuins in inflammatory bowel diseases.","authors":"Sadhana A Samant, Sanjiv K Hyoju, John C Alverdy, Mahesh P Gupta","doi":"10.1152/ajpgi.00311.2024","DOIUrl":"10.1152/ajpgi.00311.2024","url":null,"abstract":"<p><p>Inflammatory bowel diseases (IBDs), mainly involving the disease states of ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic, relapsing inflammation of the gastrointestinal tract. IBD has an unclear etiology and likely develops from a complex interaction between the host's genetic predisposition, the gut microbiota, the immune system, and elements within the environment. In the United States alone, the estimated health care cost for IBD, according to a recent study, exceeds $25 billion. More than 200 genetic loci have been identified to be associated with IBD, highlighting its complex pathophysiology. Although existing treatments for IBD are generally supportive, they are not curative, underscoring the need to identify the causative agents that drive disease pathogenesis. Several studies have reported metabolic alterations in the pathogenesis of IBD. In all living cells, the central action of nicotinamide adenine dinucleotide (NAD⁺) plays a pivotal role in the regulation of energy metabolism and cell signaling. Dysregulated NAD⁺ metabolism is reported in patients with IBD. Sirtuins, a protein family of posttranslational modifiers, need NAD⁺ as a cofactor to perform enzymatic reactions such as deacylation and ADP-ribosylation of not only histones, but also of various other key cellular proteins. Therefore, sirtuins play a vital and central role as stress-responsive metabolic sensors in cells. In this review, we address novel mechanisms by which sirtuins play a role in IBD pathogenesis, thus exposing a potential therapeutic role of this group of enzymes that might be useful in curtailing IBD and several other debilitating gastrointestinal inflammatory disorders.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G58-G68"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956300","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":"Blame skewed neurogenesis for an inflamed askew gut.","authors":"Srinivas N Puttapaka, Subhash Kulkarni","doi":"10.1152/ajpgi.00077.2025","DOIUrl":"10.1152/ajpgi.00077.2025","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G189-G190"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965838","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":"<i>Lacticaseibacillus rhamnosus GG</i>-driven remodeling of arginine metabolism mitigates gut barrier dysfunction.","authors":"Jayson M Antonio, Yue Liu, Panan Suntornsaratoon, Abigail Jones, Jayanth Ambat, Ajitha Bala, Joshua Joby Kanattu, Juan Flores, Sheila Bandyopadhyay, Ravij Upadhyay, Jagannatham Naidu Bhupana, Xiaoyang Su, Wei Vivian Li, Nan Gao, Ronaldo P Ferraris","doi":"10.1152/ajpgi.00366.2024","DOIUrl":"10.1152/ajpgi.00366.2024","url":null,"abstract":"<p><p>Inflammatory bowel diseases (IBDs) and gut barrier impairment are associated with changes in dietary tryptophan and arginine metabolism, but mechanisms of barrier perturbation and restoration are unclear. We show here that the widely consumed probiotic <i>Lacticaseibacillus rhamnosus</i> GG (LGG) enhances gut barrier functions in part through stimulating the intestinal arginine metabolic pathway, and this mechanism depends on the sufficiency of dietary tryptophan in the host. Specifically, LGG markedly upregulates argininosuccinate lyase (ASL), the enzyme that breaks down argininosuccinate into arginine. ASL expression is markedly reduced during experimental colitis with an accumulation of serum argininosuccinate. LGG colonization in mice reduces serum argininosuccinate, a metabolite that inversely correlates with tight junction gene expression, impairs barrier function, and exacerbates dextran sodium sulfate colitis. We show that LGG-derived indoles as well as arginine metabolites enhanced argininosuccinate lyase (ASL) and nitric oxide synthase (NOS2) expression, linking microbial metabolism to nitric oxide production and epithelial homeostasis. Patients with IBD have increased ASS1 and decreased ASL expression, suggesting a metabolic bottleneck driving ASA accumulation. We propose that signaling pathways underlying LGG and tryptophan-mediated ASL upregulation can be useful therapeutic targets to normalize arginine metabolism in select patients with IBD.<b>NEW & NOTEWORTHY</b> This study identifies a novel probiotic-driven mechanism linking dietary tryptophan and host arginine metabolism. <i>Lacticaseibacillus rhamnosus</i> GG, in synergy with tryptophan, enhances gut barrier integrity by upregulating argininosuccinate lyase (ASL), a critical enzyme in arginine biosynthesis. Furthermore, we uncover ASL downregulation and serum argininosuccinate elevation in experimental colitis in mice, suggesting a target to guide precision probiotics.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G162-G185"},"PeriodicalIF":3.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148876","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}