Nicolas V Janto, Antoine R Gleizes, Siyang J Sun, Gurel Ari, Vivek Rao, Adam D Gracz
{"title":"<i>Tritrichomonas muris</i> sensitizes the intestinal epithelium to doxorubicin-induced apoptosis.","authors":"Nicolas V Janto, Antoine R Gleizes, Siyang J Sun, Gurel Ari, Vivek Rao, Adam D Gracz","doi":"10.1152/ajpgi.00242.2024","DOIUrl":"10.1152/ajpgi.00242.2024","url":null,"abstract":"<p><p>Doxorubicin (DXR) is a widely used chemotherapy drug that can induce severe intestinal mucositis. Although the influence of gut bacteria on DXR-induced damage has been documented, the role of eukaryotic commensals remains unexplored. We discovered <i>Tritrichomonas muris</i> (<i>Tmu</i>) in one of our mouse colonies exhibiting abnormal tuft cell hyperplasia, prompting an investigation into its impact on DXR-induced intestinal injury. Mice from <i>Tmu</i>-colonized and <i>Tmu</i>-excluded facilities were injected with DXR. Tissue morphology and gene expression were evaluated at acute injury (6 h) and regenerative (72 h and 120 h) phases. Changes to crypt and villus morphology were more subtle than previously reported and region-specific, with significantly shorter jejunal villi in <i>Tmu</i><sup>+</sup> mice at 72 h post-DXR compared with <i>Tmu</i><sup>-</sup> controls. Most notably, we observed elevated rates of DXR-induced apoptosis, measured by cleaved caspase 3 (CC3) staining, in <i>Tmu</i><sup>+</sup> intestinal crypts at 6 h post-DXR. <i>Tmu</i><sup>+</sup> mice also exhibited reduced expression of active intestinal stem cell (aISC) marker <i>Lgr5</i> and facultative ISC (fISC) marker <i>Ly6</i>a at 6 h post-DXR compared with <i>Tmu</i><sup>-</sup> controls. <i>Tmu</i>, but not DXR, was associated with increased inflammation and expression of type 2 cytokines IL-5 and IL-13. <i>Tmu</i><sup>+</sup> mice also exhibited a decreased fecal abundance of <i>Lactobacillus</i>, which promotes gut barrier integrity, and reduced claudin expression, indicating potential barrier dysfunction that could explain the increase in DXR-induced apoptosis. These findings highlight the significant influence of commensal microbiota, particularly eukaryotic organisms like <i>Tmu</i>, on intestinal biology and response to chemotherapy, underscoring the complexity of gut microbiota interactions in drug-induced mucositis.<b>NEW & NOTEWORTHY</b> Our study found that the eukaryotic commensal <i>Tritrichomonas muris</i> (<i>Tmu</i>) significantly increases DXR-induced intestinal apoptosis in mice. <i>Tmu</i> also reduces <i>Lgr5</i> expression post-DXR injury and elevates inflammation and type 2 cytokine expression in the absence of injury. 16S sequencing identifies decreased abundance of protective <i>Lactobacillus</i> in <i>Tmu</i> colonized mice, as well as decreased expression of barrier-forming claudins, which may explain increased apoptosis. These findings emphasize the complex role of microbiota in drug-induced intestinal damage.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":"328 5","pages":"G594-G609"},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shefaa AlAsfoor, Erik Jessen, Suraj R Pullapantula, Jennifer R Voisin, Linda C Hsi, Kevin D Pavelko, Samera Farwana, Jack A Patraw, Xin-Yi Chai, Sihan Ji, Michael A Strausbauch, Gianluca Cipriani, Lai Wei, David R Linden, Ruixue Hou, Richard Myers, Yogesh Bhattarai, Jill Wykosky, Alan J Burns, Surendra Dasari, Gianrico Farrugia, Madhusudan Grover
{"title":"Mass cytometric analysis of circulating monocyte subsets in a murine model of diabetic gastroparesis.","authors":"Shefaa AlAsfoor, Erik Jessen, Suraj R Pullapantula, Jennifer R Voisin, Linda C Hsi, Kevin D Pavelko, Samera Farwana, Jack A Patraw, Xin-Yi Chai, Sihan Ji, Michael A Strausbauch, Gianluca Cipriani, Lai Wei, David R Linden, Ruixue Hou, Richard Myers, Yogesh Bhattarai, Jill Wykosky, Alan J Burns, Surendra Dasari, Gianrico Farrugia, Madhusudan Grover","doi":"10.1152/ajpgi.00229.2024","DOIUrl":"10.1152/ajpgi.00229.2024","url":null,"abstract":"<p><p>Circulating monocytes (Mo) are precursors to a subset of gastric resident muscularis macrophages. Changes in muscularis macrophages (MMs) result in delayed gastric emptying (DGE) in diabetic gastroparesis. However, the dynamics of Mo in the development of DGE in an animal model are unknown. Using cytometry by time-of-flight and computational approaches, we show a high heterogeneity within the Mo population. In DGE mice, via unbiased clustering, we identified two reduced Mo clusters that exhibit migratory phenotype (Ly6C<sup>hi</sup>CCR2<sup>hi-int</sup>CD62L<sup>hi</sup>Ly6G<sup>hi</sup>CD45R<sup>hi</sup>MERTK<sup>hiint</sup>LGALS3<sup>int</sup>CD14<sup>int</sup>CX3CR1<sup>low</sup>Siglec-H<sup>int-low</sup>) resembling classical Mo (CMo-like). All markers enriched in these clusters are known to regulate cell differentiation, proliferation, adhesion, and migration. Trajectory inference analysis predicted these Mo as precursors to subsequent Mo lineages. In gastric muscle tissue, we demonstrated an increase in the gene expression levels of chemokine receptor C-C chemokine receptor type 2 (<i>Ccr2</i>) and its C-C motif ligand 2 (<i>Ccl2</i>), suggesting increased trafficking of classical-Mo. These findings establish a link between two CMo-like clusters and the development of the DGE phenotype and contribute to a better understanding of the heterogenicity of the Mo population.<b>NEW & NOTEWORTHY</b> Using 32 immune cell surface markers, we identified 23 monocyte clusters in murine blood. Diabetic gastroparesis was associated with a significant decrease in two circulating classical monocyte-like clusters and an upregulation of the <i>Ccr2-Ccl2</i> axis in the gastric muscularis propria, suggesting increased tissue monocyte migration. This study offers new targets by pointing to a possible role for two classical monocyte subsets connected to the <i>Ccr2</i>-<i>Ccl2</i> axis.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G323-G341"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12282717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unique properties of proximal and distal colon reflect distinct motor functions.","authors":"Wilmarie Morales-Soto, Kristen M Smith-Edwards","doi":"10.1152/ajpgi.00215.2024","DOIUrl":"10.1152/ajpgi.00215.2024","url":null,"abstract":"<p><p>The gastrointestinal tract is made up of specialized organs that work in tandem to facilitate digestion. The colon regulates the final steps in this process where complex motor patterns in proximal regions facilitate the formation of fecal pellets that are propelled along the distal colon via self-sustaining neural peristalsis and temporarily stored before defecation. Historically, our understanding of colonic motility has focused primarily on distal regions, and the intrinsic reflex circuits of the enteric nervous system involved in neural peristalsis have been defined, but we do not yet have a clear grasp on the mechanisms orchestrating motor function in proximal regions. New approaches have brought to the forefront the unique structural, neurochemical, and functional characteristics that exist in distinct regions of the mouse and human colon. In this mini-review, we highlight key differences along the proximal-distal colonic axis and discuss how these differences relate to region-specific motor function.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G448-G454"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12295705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum for Öhnstedt et al., volume 327, 2024, p. G140-G153.","authors":"","doi":"10.1152/ajpgi.00022.2024_COR","DOIUrl":"10.1152/ajpgi.00022.2024_COR","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":"328 4","pages":"G455"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810188","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}
Gaojue Wu, Fei Li, Yan Li, Shiying Li, Md Jahangir Alam, Jiande D Z Chen
{"title":"Progressive impairment in gastric and duodenal slow waves and autonomic function during progression of type 2 diabetes in rats.","authors":"Gaojue Wu, Fei Li, Yan Li, Shiying Li, Md Jahangir Alam, Jiande D Z Chen","doi":"10.1152/ajpgi.00278.2024","DOIUrl":"10.1152/ajpgi.00278.2024","url":null,"abstract":"<p><p>The abnormalities of gastrointestinal (GI) slow waves play key roles in the pathophysiology of diabetic gastroparesis, which is highly prevalent in type 2 diabetes (T2D). Although relatively well-investigated in diabetic enteric neuropathy, abnormalities and progressive impairments of gastric slow waves (GSWs) and duodenal slow waves (DSWs) are underinvestigated during the progression of T2D. The aim of this study was to explore alterations in GSW and DSW during the development of diabetes induced by high-fat diet (HFD) followed by a low dose of streptozotocin (STZ). Weekly recordings of slow waves from healthy, prediabetic to diabetes stages exhibited a progressively decreased percentage of normal slow waves (%NSW) starting after HFD feeding (prediabetic stage) in the fasting state and starting after STZ injection (diabetic stage) in the postprandial state. The postprandial increase in the power of slow waves observed in normal control rats was absent starting from 2 wk after HFD and persisted after STZ. The mechanism might be attributed to both progressively increased blood glucose (BG) and impaired autonomic function in view of the following results: <i>1</i>) the %NSW was negatively correlated with the fasting BG; <i>2</i>) during the oral glucose tolerance test, %NSW of DSW and BG exhibited a positive correlation in rats with hemoglobin A1C (HbA1C) < 5.0%, but a negative correlation in rats with HbA1C ≥ 5.0%; and <i>3</i>) in comparison with baseline (healthy stage) of the same cohort, plasma pancreatic polypeptide (reflecting vagal activity) was progressively decreased, whereas plasma norepinephrine (reflecting sympathetic activity) was progressively increased.<b>NEW & NOTEWORTHY</b> This study recorded the progressive impairment in the regularity of gastric and duodenal slow waves in a rat model mimicking the progression to type 2 diabetes including the stage of health, prediabetic stage, and diabetes. The progressive impairment in gastric/duodenal slow waves might be attributed to the progressive increase in blood glucose and impairment in autonomic function.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G386-G398"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nikhil Y Patil, Iulia Rus, Felix Ampadu, Hassan M Abu Shukair, Sarah Bonvicino, Richard S Brush, Elena Eaton, Martin-Paul Agbaga, Tae Gyu Oh, Jacob E Friedman, Aditya D Joshi
{"title":"Cinnabarinic acid protects against metabolic dysfunction-associated steatohepatitis by activating aryl hydrocarbon receptor-dependent AMPK signaling.","authors":"Nikhil Y Patil, Iulia Rus, Felix Ampadu, Hassan M Abu Shukair, Sarah Bonvicino, Richard S Brush, Elena Eaton, Martin-Paul Agbaga, Tae Gyu Oh, Jacob E Friedman, Aditya D Joshi","doi":"10.1152/ajpgi.00337.2024","DOIUrl":"10.1152/ajpgi.00337.2024","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by the accumulation of fats in the liver, chronic inflammation, hepatocytic ballooning, and fibrosis. This study investigates the significance of hepatic aryl hydrocarbon receptor (AhR) signaling in cinnabarinic acid (CA)-mediated protection against MASH. Here, we report that livers of high-fat, high-fructose, high-cholesterol diet-fed hepatocyte-specific aryl hydrocarbon receptor knockout mice (AhR-hKO) exhibited aggravated steatosis, inflammation, and fibrosis compared with control AhR-floxed livers. Moreover, treatment with a tryptophan catabolite, CA, reduced body weight gain and significantly attenuated hepatic steatosis, inflammation, ballooning, fibrosis, and liver injury only in AhR-floxed but not in AhR-hKO mice, strongly indicating that the CA-mediated protection against steatohepatitis is AhR-dependent. Furthermore, protection against lipotoxicity by CA-activated AhR signaling was confirmed by utilizing an in vitro human hepatocyte model of MASLD. Mechanistically, CA-induced AhR-dependent signaling augmented AMP-activated protein kinase (AMPK), leading to the upregulation of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1α) and attenuation of sterol regulatory element-binding protein-1 (SREBP1) to regulate hepatic lipid metabolism. Collectively, our findings indicate that CA-mediated protection against MASH is dependent on hepatic AhR signaling, and selective endogenous AhR agonists that regulate lipogenesis can serve as promising future therapeutics against MASLD.<b>NEW & NOTEWORTHY</b> The study showed that the absence of AhR in hepatocytes results in exacerbated metabolic dysfunction-associated steatohepatitis (MASH) in mice subjected to a Western-style high-fat, high-fructose, high-cholesterol diet. Moreover, treatment with a tryptophan catabolite, cinnabarinic acid (CA), mitigated hallmarks of MASH in an AhR-dependent manner. In conclusion, the study delineates the significance of hepatic AhR-dependent AMPK signaling in CA-mediated protection against MASH.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G433-G447"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sharun Kuhar, Jung-Hee Seo, Pankaj Jay Pasricha, Michael Camilleri, Rajat Mittal
{"title":"Duodenogastric reflux in health and disease: insights from a computational fluid dynamics model of the stomach.","authors":"Sharun Kuhar, Jung-Hee Seo, Pankaj Jay Pasricha, Michael Camilleri, Rajat Mittal","doi":"10.1152/ajpgi.00241.2024","DOIUrl":"10.1152/ajpgi.00241.2024","url":null,"abstract":"<p><p>The stomach is responsible for physically and chemically processing the ingested meal before controlled emptying into the duodenum through the pyloric sphincter. An incompetent pylorus allows reflux from the duodenum back into the stomach, and if the amount of reflux is large enough, it could alter the low-pH environment of the stomach and erode the mucosal lining of the lumen. In some cases, the regurgitated contents can also reach the esophagus, leading to additional complications. In this work, \"StomachSim\", an in silico model of the fluid dynamics of the stomach, is used to study the mechanism of duodenogastric reflux. The effects of variations in food properties and motility disorders on reflux are investigated. The simulations show that the primary driver of reflux is the relaxation of the antrum after a stomach contraction terminates near the pylorus. The region of the stomach walls exposed to the regurgitated contents depends significantly on the density of the stomach contents. For stomach contents of higher viscosity, the increased pressure required to maintain gastric emptying reduces the amount of duodenogastric reflux. Concomitant stomach motility disorders that weaken the relaxation of the walls also affect the amount of reflux. The study illustrates the utility of in silico models in analyzing the factors at play in gastrointestinal diseases.<b>NEW & NOTEWORTHY</b> An in silico model of the stomach is presented to study the phenomenon of duodenogastric reflux. We use the model to investigate the role of pyloric incompetence, food properties, and gastroparesis on reflux. This first-ever in silico study of duodenogastric reflux provides new insights into the mechanisms and factors implicated in this reflux and the sequelae of conditions that result from the exposure of the stomach lumen to bile.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G411-G425"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051372","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":"Dynamics of circulatory monocytes trafficking and transitioning to gastric resident macrophages in diabetic gastroparesis.","authors":"Rajan Singh","doi":"10.1152/ajpgi.00053.2025","DOIUrl":"10.1152/ajpgi.00053.2025","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G429-G432"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539965","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}
Srikanth Iyer, Mohammad Tarique, Preeti Sahay, Sagnik Giri, Ejas P Bava, JiaShiung Guan, Tejeshwar Jain, Utpreksha Vaish, Xiuwen Jin, Sabrina Moon, David K Crossman, Vikas Dudeja
{"title":"Inhibition of hedgehog signaling ameliorates severity of chronic pancreatitis in experimental mouse models.","authors":"Srikanth Iyer, Mohammad Tarique, Preeti Sahay, Sagnik Giri, Ejas P Bava, JiaShiung Guan, Tejeshwar Jain, Utpreksha Vaish, Xiuwen Jin, Sabrina Moon, David K Crossman, Vikas Dudeja","doi":"10.1152/ajpgi.00212.2024","DOIUrl":"10.1152/ajpgi.00212.2024","url":null,"abstract":"<p><p>Chronic pancreatitis (CP) is a fibro-inflammatory disease of the pancreas with no specific cure. Research highlighting the pathogenesis and especially the therapeutic aspect remains limited. Aberrant activation of developmental pathways in adults has been implicated in several diseases. Hedgehog pathway is a notable embryonic signaling pathway, known to promote fibrosis of various organs when overactivated. The aim of this study is to explore the role of the hedgehog pathway in the progression of CP and evaluate its inhibition as a novel therapeutic strategy against CP. CP was induced in mice by repeated injections of l-arginine or caerulein in two separate models. Mice were administered with the FDA-approved pharmacological hedgehog pathway inhibitor, vismodegib during or after establishing the disease condition to inhibit hedgehog signaling. Various parameters of CP were analyzed to determine the effect of hedgehog pathway inhibition on the severity and progression of the disease. Our study shows that hedgehog signaling was overactivated during CP and its inhibition was effective in improving the histopathological parameters associated with CP. Vismodegib administration not only halted the progression of CP but was also able to resolve already-established fibrosis. In addition, inhibition of hedgehog signaling resulted in the reversal of pancreatic stellate cell activation ex vivo. Findings from our study justify conducting clinical trials using vismodegib against CP and, thus, could lead to the development of a novel therapeutic strategy for the treatment of CP.<b>NEW & NOTEWORTHY</b> Hedgehog signaling is activated in human and experimental models of CP. Inhibition of hedgehog signaling using an FDA-approved inhibitor, vismodegib, leads to the resolution of fibrosis and improves CP. This study has immense and immediate translational benefits.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G342-G363"},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Artemiy Kovynev, Mikołaj M Charchuta, Amina Begtašević, Quinten R Ducarmon, Patrick C N Rensen, Milena Schönke
{"title":"Combination of dietary fiber and exercise training improves fat loss in mice but does not ameliorate MASLD more than exercise alone.","authors":"Artemiy Kovynev, Mikołaj M Charchuta, Amina Begtašević, Quinten R Ducarmon, Patrick C N Rensen, Milena Schönke","doi":"10.1152/ajpgi.00317.2024","DOIUrl":"10.1152/ajpgi.00317.2024","url":null,"abstract":"<p><p>Lifestyle interventions, such as diet and exercise, are currently the main therapies against metabolic dysfunction-associated steatotic liver disease (MASLD). However, not much is known about the combined impact of fiber and exercise on the modulation of gut-liver axis and MASLD amelioration. Here, we studied the impact of the combination of exercise training and a fiber-rich diet on the amelioration of MASLD. Male APOE*3-Leiden.CETP mice were fed a high-fat high-cholesterol diet with or without the addition of fiber (10% inulin) and exercise trained on a treadmill, or remained sedentary. Exercise training and fiber supplementation reduced fat mass gain and lowered plasma glucose levels. Only the combination treatment, however, induced fat loss and decreased plasma triglyceride and cholesterol levels compared with sedentary control mice. Exercise training with and without the addition of fiber had a similar ameliorating effect on the MASLD score. Only exercise without fiber decreased the hepatic expression of inflammatory markers. Fiber diet was mainly responsible for remodeling the gut microbial composition, with an increase in the relative abundance of the short-chain fatty acid (SCFA)-producing genera <i>Anaerostipes</i> and <i>Muribaculaceae</i>, whereas, surprisingly, exercise training alone and with fiber resulted in the highest increase of SCFA production. Overall, the combination of exercise training and dietary fiber decreases fat mass and improves glucose and lipid homeostasis but does not have an additional synergistic positive effect on liver health compared with exercise training alone.<b>NEW & NOTEWORTHY</b> The combination of dietary fiber intake and exercise training has a synergetic beneficial effect on the metabolic health, resulting in fat loss, lowered blood glucose, and lowered plasma lipid levels in mice with steatotic liver disease. However, fiber supplementation, despite a positive remodulation of the gut-liver axis, does not have an additional positive effect on liver health compared with exercise training alone.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G399-G410"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539852","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}