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

{"title":"Farnesoid X receptor inhibits proinflammatory cytokine-induced epithelial necroptosis in vitro: implications for preservation of intestinal barrier function.","authors":"Caitriona E Curley, Natalia K Lajczak-McGinley, Luciano Adorini, Triona Ní Chonghaile, Stephen J Keely","doi":"10.1152/ajpgi.00086.2025","DOIUrl":"10.1152/ajpgi.00086.2025","url":null,"abstract":"<p><p>Epithelial cell death and compromised barrier function are key features of inflammatory bowel disease pathogenesis. Previous studies suggest that the nuclear bile acid receptor, farnesoid X receptor (FXR), promotes intestinal barrier function and protects against inflammation. Here, we investigated potential mechanisms involved. T₈₄ cell monolayers were treated with a combination of IFNγ and TNFα to model cytokine-induced barrier dysfunction in vitro. Apoptosis and necroptosis were assessed by measuring caspase 3/PARP cleavage and RIP3 phosphorylation, respectively. Epithelial permeability was determined by measuring 4-kDa fluorescein isothiocyanate-dextran (FD4) flux. Effects of FXR on barrier function in dextran sulfate sodium (DSS)-treated mice were assessed by measuring plasma levels of orally administered FD4. Treatment with IFNγ and TNFα enhanced FD4 flux and increased apoptosis in T₈₄ monolayers, as evidenced by increased cleaved PARP and caspase 3 levels. Pretreatment with the FXR agonist, GW4064, significantly inhibited cytokine-induced FD4 flux, but not apoptosis. Treatment with IFNγ and TNFα in the presence of the apoptosis inhibitor, Q-VD-OPh, induced necroptosis, as evidenced by increased RIP3 phosphorylation and enhanced FD4 flux, whereas a necroptosis inhibitor, necrostatin, inhibited these effects. GW4064 also inhibited cytokine-induced RIP3 phosphorylation and FD4 flux in the presence of Q-VD-OPh. In mice, treatment with the FXR agonist, obeticholic acid, attenuated DSS-induced disease activity and mucosal FD4 flux, but not levels of cleaved caspase 3 or phospho-RIP3. FXR activation inhibits cytokine-induced barrier dysfunction by inhibiting epithelial necroptosis rather than apoptosis in vitro. How such effects contribute to the protective actions of FXR in vivo requires further elucidation.<b>NEW & NOTEWORTHY</b> These studies demonstrate for the first time that FXR activation inhibits cytokine-induced necroptosis in vitro, an effect that may underlie protection against dysregulated barrier function in the setting of intestinal inflammation. These data support the potential for targeting FXR to promote epithelial barrier function in treatment of IBD.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G261-G269"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493457","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>Lactiplantibacillus plantarum</i> strengthens the intestinal barrier: involvement of the endocannabinoidome.","authors":"Bénédicte Allam-Ndoul, Elena Cristina Pulido-Mateos, Frédéric Bégin, Gabrielle St-Arnaud, Briscia Anaid Tinoco Mar, Thomas Mayer, Elizabeth Dumais, Nicolas Flamand, Frederic Raymond, Denis Roy, Yves Desjardins, Vincenzo Di Marzo, Alain Veilleux","doi":"10.1152/ajpgi.00142.2024","DOIUrl":"10.1152/ajpgi.00142.2024","url":null,"abstract":"<p><p>Probiotics have been suggested to ameliorate intestinal epithelial homeostasis and barrier function. They also modulate several mediators and receptors of the expanded endocannabinoid system, or endocannabinoidome (eCBome), potentially explaining their beneficial effects on intestinal function. We aimed to study the effects of probiotic strains on gut barrier functions and the possible involvement of the eCBome in these effects. We cocultured three strains of <i>Lactiplantibacillus plantarum</i> with murine small intestine epithelial organoids and explored the involvement of eCBome signaling and inflammation in mediating the beneficial effects of the probiotics on the epithelial barrier function. All three <i>L. plantarum</i> strains reduced the transepithelial permeability of organoids and increased mRNA expression of several tight junction proteins (<i>Clnd1</i>, <i>Clnd2</i>, <i>Ocln</i>, <i>Tjp1</i>, and <i>Cdh1</i>) and intestinal barrier proteins (<i>Muc2</i>, <i>Lyz1</i>, <i>Reg3a</i>, and <i>Defa20</i>). Concomitantly, the three strains increased the expression of genes encoding eCBome receptors while decreasing the expression of two catabolic enzymes (<i>Faah</i> and <i>Naaa</i>), and increasing one anabolic enzyme (<i>Daglb</i>). Altogether, these changes led to an overall increase in levels of eCBome mediators, namely <i>N</i>-acyl-ethanolamines (NAEs) and, particularly, 2-monoacylglycerols (2-MAGs), as measured by LC-MS/MS. URB 597 and JZL 184, two selective inhibitors of NAE and 2-MAG catabolism, reduced the transepithelial permeability of organoids, as observed with <i>L. plantarum</i> strains. Interestingly, both inhibitors also reversed inflammation-induced transepithelial permeability in organoids. Elevated endogenous levels of NAEs or 2-MAGs promote improvement in small intestine transepithelial permeability, and <i>L. plantarum</i> strains may exploit this mechanism to exert this same beneficial effect.<b>NEW & NOTEWORTHY</b> <i>Lactiplantibacillus plantarum</i> strains improve transepithelial permeability and concomitantly increase the levels of eCBome mediators in murine small intestine epithelial organoids. Pharmacological elevation of NAE or 2-MAG levels enhances the expression of intestinal epithelial barrier genes and reduces the transepithelial permeability of murine small intestine epithelial organoids, suggesting that <i>L. plantarum</i> may exploit eCBome signaling to exert its beneficial effects.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G245-G260"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309380","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":"Integrating anorectal manometry, balloon expulsion, and defecography: insights into diagnosing pelvic floor dysfunction.","authors":"Narmin Zoabi, Dorit Zelikovich, Fahim Kanani, Edward Ram, Amina Issa, Dan Carter","doi":"10.1152/ajpgi.00100.2025","DOIUrl":"10.1152/ajpgi.00100.2025","url":null,"abstract":"<p><p>Defecatory dysfunction (DD) is a common cause of chronic constipation resulting from functional abnormalities or structural pelvic pathologies. Accurate diagnosis requires combining anorectal manometry (ARM), balloon expulsion test (BET), and defecography. This study evaluates the diagnostic utility of these modalities and explores uncertainties in their performance and interpretation. This retrospective study included 325 adult patients assessed for DD between 2020 and 2023. All patients went through ARM, BET in the left lateral position, and defecography. Statistical associations between test outcomes were analyzed to assess diagnostic concordance and significance. A strong correlation was observed between ARM and defecography, with 65% of patients with normal anal relaxation on ARM achieving normal rectal evacuation on defecography (<i>P</i> < 0.0001). Conversely, patients with paradoxical contraction during ARM demonstrated a higher likelihood of evacuation failure. BET demonstrated high specificity but limited sensitivity in association with relaxation on ARM and evacuation on defecography. BET failure did not demonstrate a significant association with the presence of pelvic floor pathologies. Combining ARM, BET, and defecography provides a comprehensive framework for diagnosing DD, addressing its functional and structural components. This integrated approach facilitates targeted interventions, ultimately improving clinical outcomes.<b>NEW & NOTEWORTHY</b> This study demonstrates that anal relaxation on anorectal manometry significantly correlates with rectal evacuation on defecography, supporting its physiological relevance. Balloon expulsion in the left lateral position shows high specificity but low sensitivity for defecatory dysfunction. Notably, balloon expulsion test (BET) failure was not associated with anatomical abnormalities. An integrated diagnostic approach using anorectal manometry (ARM), BET, and defecography enhances accuracy in distinguishing functional from structural causes of pelvic floor dysfunction.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G270-G275"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493459","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":"Mechanistic Insights into Intestinal Stem Cell Disruption during Infection.","authors":"Naomi Chege, Constance A M Finney","doi":"10.1152/ajpgi.00352.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00352.2024","url":null,"abstract":"<p><p>The intestinal epithelium is in continual flux. It must balance maintaining a healthy microbiota with detecting and destroying intestinal pathogens. Intestinal stem cells (ISCs), which sit in the crypts below the intestinal villi, control this process. Depending on the molecular signals they receive, ISCs rapidly differentiate into the different intestinal epithelial cell subsets, making the intestine a remarkably adaptable organ. However, pathogens can hijack ISC functions to their advantage and establish infections. In this review, we explore the mechanisms used by pathogens to exploit ISCs.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635915","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":"Energy status alters intestinal function and the gut microbiota during consecutive days of high energy demands.","authors":"Cassandra Suther, Adrienne Hatch-McChesney, Jillian T Allen, Nabarun Chakraborty, Alexander B Lawrence, Candace Moyler, George I Dimitrov, Aarti Gautam, Rasha Hammamieh, Jess A Gwin, Lee M Margolis, Stephen R Hennigar, James P McClung, Stefan M Pasiakos, J Philip Karl","doi":"10.1152/ajpgi.00130.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00130.2025","url":null,"abstract":"<p><p>Host-gut microbiota interactions may impact intestinal function during sustained periods of high energy demands. Whether energy status, reflecting the balance between energy intake and expenditure, impacts those interactions is unknown. This study determined the effects of energy status during sustained high energy demands on intestinal function and the gut microbiota. Ten healthy men completed a randomized, crossover study that included baseline (BL) testing, and two 72-hour periods of high physical activity-induced energy demands (HPA; ~2300kcal/d physical activity energy expenditure) followed by a 7-day recovery period (REC). During HPA, diets designed to elicit a ~45% energy deficit (DEF; -2047±920kcal/d) or maintain energy balance within ±10% total daily energy expenditure (BAL; 689±852kcal/d) were provided. Intestinal permeability and transit time, fecal microbiota composition and gene content, fecal short chain fatty acids (SCFA) and gastrointestinal symptoms were measured. Intestinal permeability was 17% higher during HPA-DEF versus HPA-BAL (P=0.02) and colonic transit time was slower during HPA-DEF versus HPA-BAL (mean difference [95%CI] =-764 min [- 1345, -183]) and BL (-643min [-1178, -108]) (P=0.02). Fecal microbiota species richness (-40 species [-66, -13], P=0.01) and relative abundances of multiple species (log₂ fold difference< -5, P<0.02) were lower during HPA-BAL versus HPA-DEF but did not differ between conditions during REC. Small bowel transit time, gastrointestinal symptoms, fecal microbiota gene pathways, and fecal SCFA did not differ between conditions. Findings suggest that increasing dietary intake to prevent energy deficit may benefit intestinal health and function during short term periods of high energy demands without sustained impacts on the gut microbiota.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599167","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":"Maternal Western Diet Increases Inflammatory Markers and Decreases Barrier Function of Offspring in <i>Papio Anubis</i>.","authors":"Grant H Gershner, Alena Golubkova, Cody Dalton, Camille Schlegel, Chase Calkins, Darlene N Reuter, Megan Lerner, James F Papin, Sunam Gurung, Karen R Jonscher, Dean A Myers, Catherine J Hunter","doi":"10.1152/ajpgi.00342.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00342.2024","url":null,"abstract":"<p><p><b>Introduction:</b> The Western diet (WD) has been associated with various pathologies, largely due to chronic inflammatory responses triggered by insulin spikes and excess cholesterol. However, the effects of maternal WD on offspring are currently understudied. We hypothesize that maternal WD consumption in baboons induces a hyperinflammatory state in offspring, leading to compromised intestinal barrier function. <b>Methods:</b> Intestinal tissue was harvested from olive baboon (Papio anubis) 0.9 gestation fetuses and juveniles (age 2-3 years), whose mothers who were fed either a high fat/high sugar WD, or fed a control diet (CD) of standard monkey chow. RNA and protein were isolated and analyzed for markers of inflammation and apoptosis. Intestinal organoids (enteroids) were generated from these bowel samples, and subsequently subjected to hypoxia and LPS to simulate NEC. RNA was extracted and similarly examined for inflammatory markers and markers of apoptosis. Enteroids were plated onto TransWellTM plates to evaluate barrier function. Immunohistochemistry and immunofluorescence were used to evaluate barrier proteins. <b>Results:</b> The intestinal tissue of baboon fetuses and juveniles of mothers fed a Western diet exhibited evidence of a hyper-inflammatory state. Although not all cytokines reached our significance set a priori at p<0.05, interleukin-8 (IL-8) and Interferon ? (IFN?) were significantly elevated. This trend was stable across generations. Offspring from the Western diet group exhibited decreased barrier function based on transepithelial resistance measurements. <b>Conclusion:</b> Maternal consumption of a Western diet during gestation in olive baboons leads to a generalized inflammatory state and weakened intestinal barrier function in offspring, with potential long-term health implications.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599168","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":"Investigating Intestinal Farnesoid X Receptor functions at the Intestinal Mucosal Barrier and in the Intestinal Microbiota in a Biliary Obstruction Mouse Model.","authors":"Yaoyao Cai, Xintong Chen, Hanfei Wang, Li Hou, Ruifei Zheng, Yue Wang, WeiWei Jiang, Weibing Tang","doi":"10.1152/ajpgi.00223.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00223.2024","url":null,"abstract":"<p><p>Intestinal barrier dysfunction and dysbiosis are critical intestinal alterations in biliary obstructive diseases, for which FXR is a potential intestinal therapeutic target, but its roles and mechanisms in the intestinal tract remain poorly defined. Using gut-specific knockout mice, we demonstrate that intestinal FXR deficiency caused intestinal barrier function impairment and dysbiosis, and in a biliary obstruction model, obeticholic acid (OCA) -dependent intestinal FXR activation protected against intestinal barrier injury and dysbiosis after bile duct ligation (BDL) surgery. Furthermore, from single-cell sequencing data, FXR may directly regulate <i>Reg3g</i> to influence intestinal functions. In conclusion, we elucidated FXR actions in the intestine under physiological and biliary obstruction conditions, and suggest possible molecular targets which provide new insights for the intestinal treatment of biliary obstructive diseases.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582820","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":"Glia maturation factor-β in hepatocytes enhances liver regeneration and mitigates steatosis and ballooning in zebrafish.","authors":"Hong-Yu Li, Wei-Lan Zeng, Yi-Wen Ye, Xin Chen, Ming-Ming Zhang, Yi-Si Chen, Cui-Ting Liu, Zhun-Qiang Zhong, Jing Li, Yan Wang","doi":"10.1152/ajpgi.00407.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00407.2024","url":null,"abstract":"<p><p>Glia maturation factor-β (Gmfb), an actin filament debrancher, was initially identified in brain and recently linked to liver diseases. To investigate the role of hepatocyte Gmfb (hep-Gmfb) in liver reparative regeneration, hepatocyte-specific <i>gmfb</i> knockout (HepGKO) and overexpression (HepGOE) zebrafish strains were constructed. Both transgenic and wild-type (WT) zebrafish underwent partial hepatectomy (PHX) or were fed high fat, high cholesterol diets to model metabolism-associated steatotic liver disease (MASLD). Under physiological conditions, the HepGKO, HepGOE, and WT fish displayed similar survival, gross appearance, and liver histology. Following PHX, WT liver gmfb levels positively correlated with cell proliferation and proinflammatory cytokine levels. HepGOE showed enhanced regeneration and reduced liver steatosis compared to WT, while HepGKO exhibited opposite effects. In MASLD, WT liver gmfb increased with disease progression. HepGKO experienced worsening liver enlargement, steatosis, ballooning, inflammation, and endoplasmic reticulum stress, while HepGOE showed improvements. HepGOE liver had the highest cell proliferation, but all three groups showed similar levels of cell apoptosis. Moreover, elevated proinflammatory cytokines were observed across MASLD groups, being the highest in HepGKO and lowest in HepGOE. However, stat3 activation was the lowest in HepGKO and highest in HepGOE, while jnk and mapk/erk activation was consistent across the MASLD groups. In il6-treated primary hepatocytes, gmfb abundance influenced stat3 activation, and hep-gmfb abundance significantly affected actin filaments distribution in hepatocytes both <i>in vivo</i> and <i>vitro</i>. <i>Conclusions</i>: Hep-Gmfb boosts regenerative processes by enhancing hepatocyte proliferation, alleviating fatty liver histological abnormalities, and modulating the Il6/Stat3 signaling, potentially through remodeling of actin-filament network within hepatocytes.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551739","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":"Adolescent binge drinking disrupts hepatic lipid homeostasis leading to steatosis in rats: protective role of folic acid in cholesterol and fatty acid balance.","authors":"Maria Del Carmen Gallego Lopez, Fátima Nogales, Ines Romero Herrera, Alvaro Santana Garrido, Olimpia Carreras, María Luisa Ojeda","doi":"10.1152/ajpgi.00129.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00129.2025","url":null,"abstract":"<p><p>Alcohol liver damage (ALD) is increasing worldwide among adolescents, along with binge drinking (BD). BD is an acute alcohol consumption pattern, strongly pro-oxidant in the liver, and may be associated with steatosis, the first step in ALD. Folic acid (FA), an antioxidant crucial for liver function, shows compromised hepatic stores after BD. Therefore, this study aims to analyze the hepatic lipid changes associated with BD-induced steatosis during adolescence in rats and to evaluate the efficacy of FA supplementation in preventing these alterations. Four groups of adolescent rats were used: control, BD (intraperitoneal alcohol exposure), control FA-supplemented, and BD-FA-supplemented. FA content was 2 ppm in control diets and 8 ppm in supplemented groups. BD impaired liver function by increasing transaminases and UGT-1 expression. BD also induced dyslipidemia and an anabolic liver lipid state by increasing hepatic cholesteryl esters depots through dysregulation of cholesterol modulators (HMGCR, SREBP1, LDLR, SR-B1, ACAT-2, Ces1d) and enhancing FXR expression, which affected liver bile acid balance. Furthermore, BD promoted all sources of hepatic free fatty acids (de novo synthesis, dietary source, and adipose tissue uptake) and impaired their hepatic clearance, contributing to steatosis as confirmed by microvesicular lipid droplet accumulation. FA supplementation, mainly by improving hepatic cholesterol balance and stimulating free fatty acid mobilization, partially prevented these alterations, with beneficial effects on cardiovascular health. In conclusion, this study demonstrates for the first time that BD in adolescents disturbs hepatic lipid homeostasis, leading to steatosis, and that FA therapy could be used to mitigate these deleterious effects.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551738","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":"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}