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

{"title":"Dietary 3-aminobenzoic acid enhances intestinal barrier integrity and attenuates experimental colitis.","authors":"Miho Tanaka, Takahiko Toyonaga, Fumiyuki Nakagawa, Takeo Iwamoto, Yudai Hasegawa, Akira Komatsu, Natsuki Sumiyoshi, Naoki Shibuya, Ayaka Minemura, Tadashi Ariyoshi, Asami Matsumoto, Kentaro Oka, Masayuki Shimoda, Masayuki Saruta","doi":"10.1152/ajpgi.00406.2024","DOIUrl":"10.1152/ajpgi.00406.2024","url":null,"abstract":"<p><p>Disruption of intestinal epithelial integrity and increased permeability is central to the pathogenesis of ulcerative colitis (UC). In this study, we identified 3-aminobenzoic acid (3-ABA), a dietary component abundant in azuki beans, soybeans, and chickpeas as a regulator of epithelial permeability and inflammation in the colon. Screening 119 gut microbial metabolites revealed the ability of 4-ABA, a structural isomer of 3-ABA, to enhance barrier function in Caco2 cells. Further analysis of structural isomers identified 3-ABA as the most effective, significantly increasing transepithelial electrical resistance and reducing epithelial permeability. Using liquid chromatography-mass spectrometry, 3-ABA was detected in dietary beans and human fecal samples. Fecal 3-ABA levels were significantly lower in patients with UC compared with healthy individuals. Metagenomic and functional prediction analyses revealed dysbiosis in patients with UC, characterized by an enrichment of bacterial genes involved in ABA degradation. Gene expression analysis of 3-ABA-stimulated Caco2 cells demonstrated upregulation of tight junction molecules, such as CLDN1 and TJP1, enhancing epithelial barrier integrity. In a dextran sodium sulfate-induced colitis mouse model, rectal 3-ABA administration ameliorated colitis by enhancing epithelial barrier function and reducing inflammation. These findings highlight 3-ABA's potential as a dietary therapeutic agent for UC, offering a novel strategy to enhance intestinal integrity and mitigate inflammation.<b>NEW & NOTEWORTHY</b> Increased intestinal epithelial permeability is central to the pathogenesis of ulcerative colitis (UC). 3-Aminobenzoic acid (3-ABA), a dietary component abundant in beans, decreased epithelial permeability and attenuated colonic inflammation in a mouse experimental colitis model. Reduced fecal 3-ABA levels in patients with UC were associated with dysbiosis-driven accelerated degradation. These findings highlight the therapeutic potential of 3-ABA in UC by targeting colonic epithelium.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G801-G810"},"PeriodicalIF":3.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955911","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":"Dynamic functional luminal imaging probe analysis of the anal sphincter opening function during straining in healthy volunteers.","authors":"Charlotte Desprez, Anne-Marie Leroi, Guillaume Gourcerol, Ali Zifan, Thomas Duflot","doi":"10.1152/ajpgi.00369.2024","DOIUrl":"10.1152/ajpgi.00369.2024","url":null,"abstract":"<p><p>The objective of the present study was to introduce a novel method of assessing anal canal opening in healthy volunteers (HV) using the EndoFLIP system. By analyzing dynamic loops during push maneuvers, the study aimed to identify the most reliable markers of anal canal opening function during this maneuver. Forty HV women were recruited and underwent anal canal assessments with the EndoFLIP system, both at rest and during push maneuvers. Cross-sectional area (CSA)-pressure loops were constructed for each HV at distension volumes of 40 mL and 50 mL. Key parameters (pressure and CSA) derived from these loops were identified as potential markers of anal function to reduce dimensionality. Anal opening function during push maneuver was quantified in both percentage (relative variation) and absolute (absolute variation) values for pressure and CSA. The direction of the CSA-pressure loops during the push maneuver at 40 mL and 50 mL of distension was upward and to the right, indicating an increase in both pressure and CSA during straining. None of the demographic data were significant predictors of any characteristics of the CSA-pressure loops at 40 mL and 50 mL of distension. The mean relative variation in pressure and CSA at 50 mL of distension and, to a lesser extent, the maximal relative variation pressure and CSA, were identified as markers with the lowest variability. This pilot study points to potential markers for assessing anal opening function during push maneuvers. Further confirmatory studies are necessary to establish the clinical utility of these markers.<b>NEW & NOTEWORTHY</b> In the present study, we generated a bioinformatics pipeline for analyzing anal EndoFLIP data in healthy volunteers using automated data reprocessing to identify potential markers of anal opening function during the push maneuver. Mean relative variations in pressure and CSA at 50 mL of distension were identified as the most indicative parameters. Given that this was a pilot study, our findings warrant further confirmatory research to establish the clinical relevance of these markers.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G513-G521"},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802218","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":"Oryzanol ameliorates MCD-induced metabolic dysfunction-associated steatohepatitis in mice via gut microbiota reprogramming and TLR4/NF-κB signaling suppression.","authors":"Naqash Alam, Xinhua Ding, Yu Fu, Linying Jia, Sadiq Ali, Enqi Liu","doi":"10.1152/ajpgi.00190.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00190.2024","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) has emerged as a major global health concern that affects about a quarter of the global population. Recently, host-gut microbiota metabolic interactions have emerged as key mechanistic pathways in MASH development. Oryzanol (ORY), a rice bran bioactive compound, exhibits antioxidant, anti-inflammatory, hypolipidemic, and hypoglycemic properties. Here, we investigated the potential of ORY in alleviating MASH and its association with gut microbiota and MASH progression. Male C57BL/6J mice were fed normal chow diet or methionine-choline-deficient diet and received ORY supplementation at 300 mg/kg/day via gavage for 4 wk. Liver injury, inflammation, lipid accumulation, and TLR4/NF-κB signaling protein levels were assessed. In addition, changes in gut microbiota diversity and abundance across groups were evaluated using 16S rDNA sequencing. Our results demonstrated that ORY significantly reduced lipid accumulation and liver enzymes, ameliorated liver and ileum damage, and restored intestinal barrier function in MASH mice. Furthermore, ORY decreased plasma lipopolysaccharide levels, and inflammatory cytokines and downregulated TLR4, MyD88, and NF-κB protein levels in the liver. ORY enhanced tight junction protein level (ZO-1, occludin) in the gut. Microbial analysis revealed that ORY positively impacted Firmicutes and Bacteroidetes abundance, promoted beneficial bacteria like <i>Lactobacillus</i> and <i>Lachnospiraceae_NK4A136_group</i>, and inhibited harmful bacteria such as <i>Mucispirillum</i>, <i>Bacteroides</i>, and <i>Colidextribacter</i>. Notably, ORY increased <i>Akkermansia</i> abundance, potentially modulating metabolic and inflammatory pathways. ORY exerted restorative and reversible effects on the pathophysiological damage within the gut-liver axis in MASH mice. The therapeutic mechanism may be related to the modulation of the gut microbiota and TLR4/NF-κB signaling pathway.<b>NEW & NOTEWORTHY</b> This study demonstrates that oryzanol (ORY), a bioactive rice bran compound, alleviates metabolic dysfunction-associated steatohepatitis (MASH) in mice by reducing lipid accumulation and inflammation. ORY beneficial effects are associated to the modulation of gut microbiota, enhancing gut barrier integrity, and lowering endotoxemia and TLR4/NF-κB signaling pathway. These findings suggest ORY potential in MASH prevention and treatment, highlighting its influence on gut-liver axis dynamics.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":"328 5","pages":"G578-G593"},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The spatiotemporal development of mesenteric lymphatic changes in the <i>TNF</i>^ΔARE/+ mouse model of terminal ileitis.","authors":"Keith Keane, Matthew Stephens, Simon Roizes, Jingna Xue, Shan Liao, Pierre-Yves von der Weid","doi":"10.1152/ajpgi.00334.2024","DOIUrl":"10.1152/ajpgi.00334.2024","url":null,"abstract":"<p><p>Crohn's disease (CD) is a chronic inflammatory bowel disease, which also encompasses significant alterations of the mesenteric lymphatic system. Whether these changes are a mere consequence of or directly contribute to the inflammation is unknown. Here, we characterized the spatial and temporal development of these events in the <i>TNF</i>^ΔARE/+ mouse, which develops CD-like ileitis and significant mesenteric lymphatic alterations. At 8, 12, 20, and 28 wk of age, specific pathogen-free (SPF), germ-free (GF) <i>TNF</i>^ΔARE/+ and wild-type (WT) mice were assessed for ileitis via myeloperoxidase (MPO) activity while mesenteric lymphatic alterations were assessed by confocal immunofluorescence imaging. Lymphatic alterations in the SPF <i>TNF</i>^ΔARE/+ occurred in a stepwise manner between 8 and 28 wk of age beginning with the development of mesenteric lymphadenopathy at 8 wk despite no significant ileitis. By 12-wk ileal MPO significantly elevates concomitantly with lymphangiectasia of the mesenteric collecting lymphatic vessels (CLVs) and clustering of CD45⁺ immune cells around them. At 20 wk, significant lymphangiogenesis of the initials (initial lymphatic vessel) and tertiary lymphoid organs aligned along lymphatic collectors (CA-TLOs) had developed. At 28 wk, lymphangiectasia, lymphangiogenesis, and CA-TLOs increased. However, 28-wk-old GF <i>TNF</i>^ΔARE/+, while displaying no ileitis, presented with mesenteric lymphadenopathy, lymphangiectasia, and lymphangiogenesis but no immune cell clustering nor CA-TLOs. The <i>TNF</i>^ΔARE/+ mice develop terminal ileitis and lymphatic alterations in a stepwise manner beginning with mesenteric lymph node lymphadenopathy and ileal inflammation, followed by CLV dilation and lymphangiogenesis. These lymphatic alterations are exacerbated by the gut microbiome, with immune cell clustering and tertiary lymphoid organ formation being entirely dependent of its presence.<b>NEW & NOTEWORTHY</b> The mesenteric lymphatic system displays striking morphological alterations in Crohn's disease. To assess the importance of these changes in the perpetuation of the disease, we established the timeframe of their occurrence with respect to the development of ileitis in a mouse model of Crohn's disease and in the same model derived germ-free where intestinal inflammation does not occur. Although immune-related alterations seem to depend on microbiome, changes specifically affecting lymphatic vessels persist in its absence.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G624-G643"},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypobaric hypoxia exposure impairs colonic goblet cell subpopulation via the HIF-1α signaling pathway.","authors":"Shaojie Zhang, Xiufang Jiang, Wangjingyi Zhang, Fansen Meng, Jiayue Gao, Xiang Cheng, Yazhuo Hu, Jing Liu, Tong Zhao, Lingling Zhu, Gangshi Wang","doi":"10.1152/ajpgi.00372.2024","DOIUrl":"10.1152/ajpgi.00372.2024","url":null,"abstract":"<p><p>Exposure to hypobaric hypoxia during rapid ascent to high altitudes significantly impacts intestinal barrier function. Goblet cells, as one of the primary cell types in the intestinal mucosa, play a crucial role in maintaining this barrier. However, the effects of hypobaric hypoxia on goblet cell function and the underlying molecular mechanisms remain unclear. In this study, we established a mouse model of hypobaric hypoxia exposure (simulating an altitude of 6,000 m) and studied its effects on colonic goblet cells by transcriptomic analysis. In addition, the hypoxia-treated (1% O₂) goblet cell line Ls174t was used to investigate potential mechanisms underlying hypoxia-induced changes in goblet cells. In the present study, we discovered that hypobaric hypoxia exposure not only reduced the number of colonic goblet cells in mice by 27.6% but also impaired their mucus secretion. Transcriptome sequencing analysis of sorted goblet cells from the mice colon revealed significant changes in gene expression profiles, particularly in the expression of canonical goblet cell markers such as calcium-activated chloride channel regulator 1 (<i>Clca1</i>) and Fcγ-binding protein (<i>Fcgbp</i>). We confirmed the effects of hypobaric hypoxia/hypoxia exposure on CLCA1 and FCGBP expression at both mRNA and protein levels in mouse colonic tissues and in Ls174t cells. The expression of these canonical goblet cell marker genes was dependent upon hypoxia-inducible factor-1α (HIF-1α) activity; their expression decreased upon hypoxia-induced activation of HIF-1α and increased when HIF-1α was knocked down using siRNA. Thus, hypobaric hypoxia exposure regulates the distribution and function of colonic goblet cell subsets through the HIF-1α signaling pathway.<b>NEW & NOTEWORTHY</b> We investigated the role of hypoxia-inducible factor-1α (HIF-1α) in colonic goblet cell injury under hypobaric hypoxia exposure. Our results indicate that the elevation of HIF-1α caused by hypobaric hypoxia exposure can significantly reduce canonical goblet cells and disrupt intestinal mucosal barrier function. It provides a potential intervention strategy for restoring goblet cell function under hypobaric hypoxic conditions.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G465-G478"},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707861","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>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> targets M cells in enteroid-derived monolayers through interactions with β1 integrins.","authors":"Grace Baruta, Kyle L Flannigan, Laurie Alston, Andrew Thorne, Hong Zhang, Jeroen De Buck, Pina Colarusso, Simon A Hirota","doi":"10.1152/ajpgi.00250.2024","DOIUrl":"10.1152/ajpgi.00250.2024","url":null,"abstract":"<p><p>Paratuberculosis is an infectious disease caused by the bacterium, <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> (MAP). MAP infection of ruminants triggers progressive wasting disease characterized by granulomatous lymphadenitis, enteritis, and severe intestinal pathology that often requires early culling of the animal. The resulting economic burden is significant, and MAP exposure in the workplace constitutes a significant zoonotic risk. Although it has been established that the MAP propagates within resident immune cells, less is known about how it traverses the epithelium. It is currently thought that MAP infects the small intestinal epithelium by targeting both enterocytes and M cells, with a potential tropism for the latter. In the current study, we developed and validated an enteroid-based in vitro assay containing functional M cells to identify the target cells for MAP's entry. Upon exposure to MAP, the bacteria were detected within both enterocytes and M cells; however, quantitative image analysis revealed significant tropism for the latter. Complementary studies using the Caco-2/Raji-B coculture system provided similar results. Since other mycobacteria have been shown to initiate cell attachment and entry by using a fibronectin-bridging process, we tested whether these interactions were involved in MAP's targeting of M cells. We found that MAP's M cell tropism was enhanced by fibronectin and that this effect was abolished when monolayers were pretreated with an integrin-blocking peptide. Our data demonstrate that MAP preferentially targets M cells and that this involves a fibronectin-bridging process. Furthermore, our study supports the utility of M cell-containing enteroids to study host-pathogen interaction at the intestinal epithelium.<b>NEW & NOTEWORTHY</b> We developed and validated a novel enteroid-based in vitro infection model with functional M cells and incorporated leading-edge imaging approaches to determine how MAP interacts with the intestinal epithelium. Using this model, we found that MAP preferentially enters M cells and that this process is enhanced by fibronectin opsonization and interactions with M cell-associated b1 integrins-the so-called fibronectin bridging mechanism that is used by other Mycobacterium to mediate cell attachment and entry.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G482-G501"},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of corticotropin-release hormone on duodenal permeability and immune activation in healthy volunteers in a double-blind placebo-controlled study.","authors":"Jolien Schol, I-Hsuan Huang, Lukas Balsiger, Joran Tóth, Karen Van den Houte, Annelies Verheyden, Karlien Raymenants, Bert Broeders, Tim Vanuytsel, Jan Tack","doi":"10.1152/ajpgi.00130.2024","DOIUrl":"10.1152/ajpgi.00130.2024","url":null,"abstract":"<p><p>In functional dyspepsia, increased gut permeability, low-grade inflammation, and altered sensorimotor function have been reported. Both stress and corticotropin-release hormone (CRH) have been shown to increase small bowel permeability in a mast-cell-dependent manner. Moreover, eosinophil-derived CRH has been implicated in mast cell activation. The aim of this study was to evaluate whether CRH administration alters duodenal permeability and immune activation in healthy volunteers (HVs). An intravenous bolus of 100-µg CRH or placebo was administered in HVs in a crossover, double-blind, randomized manner. Two hours later, a gastroscopy was performed to measure permeability in Ussing chambers and to count mast cells and eosinophils on duodenal biopsies. Supernatant was assessed for eosinophil-derived neurotoxin (EDN), tryptase, and chymase. In addition, CRH was administrated ex vivo to baseline biopsies pretreated with or without lodoxamide. Results are described as means ± SD. <i>P</i> values < 0.05 were considered significant. Twenty HVs completed the study. Mast cell or eosinophil counts were not significantly altered after CRH versus Placebo (respectively <i>P</i> = 0.31 and <i>P</i> = 0.069). Tryptase, but not chymase, significantly decreased after CRH (respectively <i>P</i> = 0.037 and <i>P</i> = 0.44) with a trend for a decrease in EDN (<i>P</i> = 0.053). Permeability was unaltered comparing both conditions. Ex vivo, transepithelial electrical resistance significantly decreased after CRH exposure compared with baseline (<i>P</i> = 0.010), which was not prevented by pretreatment with lodoxamide. In vivo CRH administration reduced tryptase levels in the supernatant of duodenal biopsies without affecting permeability, whereas ex vivo duodenal permeability increased regardless of mast cell stabilization. These results suggest the involvement of mast cells in regulating gut permeability in HVs in response to CRH, possibly influenced by in vivo compensatory mechanisms.<b>NEW & NOTEWORTHY</b> Our investigation breaks new ground by directly examining the effects of corticotropin-release hormone (CRH) on duodenal alterations, including permeability and immune activation, in healthy subjects. Intriguingly, our findings highlight disparities between ex vivo and in vivo pathways affecting duodenal permeability, offering novel insights into the potential pathophysiology of CRH on the duodenum.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G457-G464"},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750730","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":"Optogenetic activation of the gut-brain axis in freely moving mice using a fully implantable wireless battery-free device.","authors":"Timothy J Hibberd, Andrew Efimov, Yue Wang, Mingzheng Wu, Lee Travis, Kaila Ting, Min-Kyu Lee, Joohee Kim, Jiheon Kang, Mohammad Riahi, Melinda Kyloh, Vladimir Zagorodnyuk, Hongzhen Hu, John A Rogers, Nick J Spencer, Abraham Vázquez-Guardado","doi":"10.1152/ajpgi.00330.2024","DOIUrl":"10.1152/ajpgi.00330.2024","url":null,"abstract":"<p><p>Considerable evidence suggests that the gut-brain axis can influence behavior. However, there has been a conspicuous lack of technology to provide targeted wireless activation of the gut-brain axis in conscious freely moving animals. We utilized a miniature fully implantable battery-free device to apply highly controlled optogenetic stimuli to the terminal region of gastrointestinal tract, in conscious freely moving mice. The optical stimulator was implanted and secured on the serosal surface of the distal colon and rectum to characterize the behavioral responses evoked by optogenetic stimulation of axons expressing channelrhodopsin (ChR2) driven by the Trpv1 promoter (Trpv1^Cre+ChR2 mice). In freely moving Trpv1^Cre+ChR2 mice, trains of blue light pulses to the distal colon and rectum induced increased abdominal grooming and reduced movement. In contrast to stimulation of the gut, trains of stimuli applied to the peritoneal cavity evoked writhing and abdominal contraction. Anterograde labeling from nodose ganglia revealed sparse vagal afferent axons and endings in the proximal and mid colon, with no labeled axons caudal of the mid colon (within 30 mm of the anus). The distal colon and rectum were densely innervated by spinal afferents. The findings demonstrate that wireless optogenetic stimulation of the gut-brain axis can induce specific behavioral patterns in conscious freely moving rodents, using fully implantable battery-free technology.<b>NEW & NOTEWORTHY</b> The findings demonstrate that distinct behavioral changes can be induced by wireless activation of the terminal region of the large intestine (distal colon and rectum) in freely moving rodents, using fully implantable battery-free devices.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G545-G557"},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802222","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":"Effects of potassium on laryngeal-induced swallowing rate in rats.","authors":"Satomi Kawada, Titi Chotirungsan, Charng-Rong Pan, Yuhei Tsutsui, Keiichiro Okamoto, Jin Magara, Takanori Tsujimura, Makoto Inoue","doi":"10.1152/ajpgi.00012.2025","DOIUrl":"10.1152/ajpgi.00012.2025","url":null,"abstract":"<p><p>The swallowing reflex can be induced by peripheral stimulation of the larynx. Although previous studies have suggested that potassium ions exert facilitatory effects on the initiation of swallowing, little information is available on the mechanism underlying the potassium ion-evoked swallowing reflex. In this study, we evaluated the effects of potassium ions on peripheral afferent responses and the initiation of swallowing in conscious and anesthetized rats. Furthermore, the possible receptors involved were explored. The topical application of potassium chloride (KCl) significantly facilitated the swallowing reflex; these facilitatory effects were more prominent than those of distilled water (DW) or sodium chloride (NaCl). This phenomenon depended not on the concentrations of anions but on those of potassium ions. The potassium ion-induced response in the superior laryngeal nerve was most prominent after treatment with KCl, especially at the early stage. In chronic rats, without differences in licking behavior between DW, NaCl, and KCl, the intervals between swallows were the smallest during KCl-associated licking. Inward rectifier potassium channel (Kir)3.1- and Kir6.2-positive cells were detected in the nodose ganglion and vocal folds. The rate of expression of these molecules in immunoreactive cells was relatively high at 74.1% for Kir3.1 and 75.3% for Kir6.2. Kir3.1 and Kir6.2 blockers significantly decreased the number of KCl-induced swallows. Possible mechanisms underlying potassium ion-induced swallowing are discussed. Our findings suggest that Kir3.1 and Kir6.2 are involved in K ion-induced swallowing in rats.<b>NEW & NOTEWORTHY</b> Potassium ion-containing solutions readily induce responses in the superior laryngeal nerve and swallowing reflexes, particularly at an early stage. Inward rectifier potassium channel (Kir)3.1 and Kir6.2 channel-positive cells were detected in the nodose ganglion and vocal folds. Kir3.1 and Kir6.2 blockers significantly decreased the number of KCl-induced swallows. Kir3.1 and Kir6.2 are involved in potassium ion-induced swallowing in rats.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G502-G512"},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778849","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":"Dimethyl fumarate attenuates bile acid retention and liver fibrosis in a mouse model of cholestasis.","authors":"Hana Lastuvkova, Ester Dohnalkova, Dina Faeq Manna, Jolana Cermanova, Jaroslav Mokry, Jaroslav Pejchal, Petra Hirsova, Petr Nachtigal, Ivona Pavkova, Maria Bajnokova, Lucie Smutna, Alzbeta Stefela, Rajamanikkam Kamaraj, Lenka Jandova, Martin Uher, Petr Pavek, Stanislav Micuda, Milos Hroch","doi":"10.1152/ajpgi.00262.2024","DOIUrl":"10.1152/ajpgi.00262.2024","url":null,"abstract":"<p><p>Cholestatic liver diseases are characterized by intrahepatic accumulation of bile acids (BAs), exacerbating liver inflammation, and fibrosis. Dimethyl fumarate (DMF) is a clinically approved anti-inflammatory drug that demonstrated protective effects in several experimental models of liver injury. Still, its effect on BA homeostasis and liver fibrosis has not been thoroughly studied. Herein, we hypothesized that DMF could improve BA homeostasis and mitigate the progression of cholestasis-induced liver fibrosis. The DMF was administered to mice with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholestasis for 4 wk. The content of individual BAs in the plasma, liver, bile, intestine, and feces was measured using the LC-MS method alongside the analysis of liver phenotype and related executive and regulatory pathways. The DMF slowed down the progression of DDC-induced liver fibrosis by suppressing hepatic stellate cell and macrophage activation and by reducing c-Jun N-terminal kinase phosphorylation. Notably, DMF reduced BA cumulation in the plasma and liver of cholestatic mice by increasing BA fecal excretion via their reduced <i>Bacteroidetes</i> phyla-mediated deconjugation in the intestine. In addition, DMF was identified as the antagonist of the mouse farnesoid X receptor in enterocytes. In conclusion, DMF alleviates DDC-induced cholestatic liver injury through pleiotropic action leading to significant anti-inflammatory and antifibrotic activity of the agent. In addition, DMF mitigates BA retention in the liver and plasma by increasing their fecal excretion in cholestatic mice. These findings suggest that DMF warrants further investigation as a potential therapeutic agent for human chronic fibrosing cholestatic liver disorders.<b>NEW & NOTEWORTHY</b> Chronic cholestatic cholangiopathies present a therapeutic challenge due to their complex pathophysiology, where the accumulation of bile acids plays a crucial role. In this study, we found that dimethyl fumarate attenuated cholestatic liver damage in a murine model through its significant anti-inflammatory and antifibrotic activity supported by reduced bile acid accumulation in the plasma and liver via their increased fecal excretion.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":"328 5","pages":"G558-G577"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956550","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}