American Journal of Physiology-Gastrointestinal and Liver Physiology Podcast

In this podcast, authors Maria A. Ilomäki and Lauri Polari (both at Åbo Akademi University) discuss their recently published research titled “Defining a timeline of colon pathologies after keratin 8 loss: Rapid crypt elongation and diarrhea are followed by epithelial erosion and cell exfoliation.”

New and Noteworthy:

Understanding the order in which physiological and molecular events occur helps to recognize the onset of diseases and improve their preclinical models. We utilized Cre-Lox-based inducible keratin 8 deletion in mouse intestinal epithelium to characterize the earliest events after keratin 8 loss leading to colitis. These include diarrhea and crypt elongation, followed by erosion and neutrophil activity. The authors results also support noninvasive methodology for monitoring colon diseases in preclinical models.

Article Citation: 

American Journal of Physiology-Gastrointestinal and Liver Physiology 0 0:0

In this episode authors Katherine L. Prowse,, and Elyanne M. Ratcliffe of McMaster University, discuss their recently published article titled “Effects of in utero exposure to fluoxetine on the gastrointestinal tract of rat offspring.”

NEW & NOTEWORTHY There is increasing recognition of the relevance of in utero and early postnatal exposures in the developmental programming of the gastrointestinal tract. Perinatal exposure to selective serotonin reuptake inhibitors and antidepressant medications is of particular relevance as they are commonly prescribed during pregnancy, and serotonergic pathways play key roles during gastrointestinal development and in postnatal homeostasis. Here, we provide a comprehensive evaluation of clinically relevant outcomes of gastrointestinal motility and susceptibility to colitis in fluoxetine-exposed offspring and highlight changes in colonic serotonergic neurons at the peak of perinatal fluoxetine exposure with sex-dependent changes in serotonin signaling and colonic motility in adulthood.

Article Citation:

Effects of in utero exposure to fluoxetine on the gastrointestinal tract of rat offspring

Katherine L. Prowse, Harriet Law, Sergio Raez-Villanueva, Filip Markovic, Megan Wang, Rajka Borojevic, Sean P. Parsons, Alexander D. Vincent, Alison C. Holloway, and Elyanne M. Ratcliffe

American Journal of Physiology-Gastrointestinal and Liver Physiology

 2023 325:6, G528-G538

Diego Alvarez de la Rosa of the University of La Laguna discusses the recently published manuscript titled “Decaying kidney function during cirrhosis correlates with remodeling of distal colon aldosterone target gene expression.”

NEW & NOTEWORTHY Liver cirrhosis progression significantly alters ion transporter subunit expression in the rat distal colon, a change that correlated well with declining kidney function and the severity of the disease. Natalia Serrano-Morillas et al. data suggests that the steroid hormone aldosterone participates in this homeostatic response to maintain electrolyte balance.

Article Citation:

Decaying kidney function during cirrhosis correlates with remodeling of distal colon aldosterone target gene expression

Natalia Serrano-Morillas, Carlos González-Alayón, Arianna Vastola-Mascolo, Ana E. Rodríguez-Rodríguez, Guadalberto Hernández, Esteban Porrini, Manuel Hernández-Guerra, and Diego Alvarez de la Rosa

American Journal of Physiology-Gastrointestinal and Liver Physiology 2023 325:4, G306-G317

In this podcast lead author Dr. Stella Liong of RMIT University, discusses the recently published manuscript titled “Influenza A virus infection during pregnancy causes immunological changes in gut-associated lymphoid tissues of offspring mice.”

NEW & NOTEWORTHY Influenza A virus (IAV) infection during pregnancy is associated with changes in gut-associated lymphoid tissue (GALT) in the offspring in a region-dependent manner. Neutrophils and monocytes/macrophages were elevated in the cecal patch of offspring from infected dams. This increase in innate immune cell infiltration was not observed in the Peyer’s patches. T cells were also elevated in the cecal patch but not in the Peyer’s patches.

Article Citation:

Influenza A virus infection during pregnancy causes immunological changes in gut-associated lymphoid tissues of offspring mice

Stella Liong, Mark A. Miles, Mitra Mohsenipour, Felicia Liong, Elisa L. Hill-Yardin, and Stavros Selemidis

American Journal of Physiology-Gastrointestinal and Liver Physiology 2023 325:3, G230-G238

First author, Dr. Kalidas Ramamoorthy of the University of California, Irvine discusses the recently published paper titled “miR-122-5p is involved in posttranscriptional regulation of the mitochondrial thiamin pyrophosphate transporter (SLC25A19) in pancreatic acinar cells.”

NEW & NOTEWORTHY This study shows that the expression and function of mitochondrial TPP transporter (MTPPT) are subject to posttranscriptional regulation by miRNA-122-5p in pancreatic acinar cells.

Article Citation:

miR-122-5p is involved in posttranscriptional regulation of the mitochondrial thiamin pyrophosphate transporter (SLC25A19) in pancreatic acinar cells

Kalidas Ramamoorthy, Subrata Sabui, Kameron I. Manzon, Appakalai N. Balamurugan, and Hamid M. Said

American Journal of Physiology-Gastrointestinal and Liver Physiology 2023 325:4, G347-G355

In this podcast  Steven Hutchens and Dr. Somshuvra Mukhopadhyay of the University of Texas at Austin discuss the recently published research titled "Hepatic and intestinal manganese excretion are both required to regulate brain manganese during elevated manganese exposure." 

NEW & NOTEWORTHY This article shows that, in contrast with expectations from prior studies and physiological conditions, excretion of manganese by the intestines and liver is equally important in controlling brain manganese during human-relevant manganese exposure. The results provide foundational insights about the interorgan mechanisms that control brain manganese homeostasis at the organism level and have important implications for the development of therapeutics to treat manganese-induced neurological disease.

Article Citation: 

American Journal of Physiology-Gastrointestinal and Liver Physiology 2023 325:3, G251-G264

In this episode, Dr. Jihane N. Benhammou of UCLA discusses the recently published article titled "Lipophilic statins inhibit YAP coactivator transcriptional activity in HCC cells through Rho-mediated modulation of actin cytoskeleton."

NEW & NOTEWORTHY Statins are widely used for the treatment of cardiovascular diseases. Recently, their use has been associated with a decrease in the incidence of hepatocellular carcinoma (HCC); however, their mechanism(s) has remained elusive. In this study, we delineate the mechanism by which statins affect the Yes-associated protein (YAP), which has emerged as a key oncogenic pathway in HCC. We investigate each step of the mevalonate pathway and demonstrate that statins regulate YAP via Rho GTPases.

Article Citation:

American Journal of Physiology-Gastrointestinal and Liver Physiology 2023 325:3, G239-G250

In this podcast coauthors Francisco Pascual, and Samuel Camilli of Morsani College of Medicine, University of South Florida discuss the recently published Perspectives titled "Mind-body connection: metabolite 4-ethylphenyl linked to anxiety behavior and oligodendrocyte modification in autism spectrum disorder."

Article Citation:

American Journal of Physiology-Gastrointestinal and Liver Physiology 2023 324:6, G422-G425

In this podcast Prof. Theo A.T.G. van Kempen of North Carolina State University and Dr. Gavin M. Boerboom of Trouw Nutrition discuss their recently published perspectives paper titled "Is the intestinal mucous layer a natural deep eutectic solvent-based digestion matrix?"

Article Citation:

American Journal of Physiology-Gastrointestinal and Liver Physiology 2023 324:6, G438-G441

In this podcast first author Dr. Jessica A. Breznik of McMaster University, discusses the recently published manuscript titled "Diet-induced obesity alters intestinal monocyte-derived and tissue-resident macrophages and increases intestinal permeability in female mice independent of tumor necrosis factor." 

NEW & NOTEWORTHY We found that diet-induced obesity in female mice has tissue- and time-dependent effects on intestinal paracellular permeability as well as monocyte-derived and tissue-resident macrophage numbers, surface marker phenotype, and intracellular production of the cytokines IL-10 and TNF. These changes were not mediated by TNF.

Article Citation: 

American Journal of Physiology-Gastrointestinal and Liver Physiology 2023 324:4, G305-G321

In this micro podcast Dr. Gene G. Lamanilao The University of Tennessee Health Science Center, College of Medicine gives the listeners an overview the recently published manuscript titled "Key hepatoprotective roles of mitochondria in liver regeneration." 

Treatment of advanced liver disease using surgical modalities is possible due to the liver’s innate ability to regenerate following resection. Several key cellular events in the regenerative process converge at the mitochondria, implicating their crucial roles in liver regeneration. Mitochondria enable the regenerating liver to meet massive metabolic demands by coordinating energy production to drive cellular proliferative processes and vital homeostatic functions. Mitochondria are also involved in terminating the regenerative process by mediating apoptosis. Studies have shown that attenuation of mitochondrial activity results in delayed liver regeneration, and liver failure following resection is associated with mitochondrial dysfunction. Emerging mitochondria therapy (i.e., mitotherapy) strategies involve isolating healthy donor mitochondria for transplantation into diseased organs to promote regeneration. This review highlights mitochondria’s inherent role in liver regeneration.

Article Citation: 

American Journal of Physiology-Gastrointestinal and Liver Physiology 2023 324:3, G207-G218

Take a listen to our latest podcast with coauthor Dr. Yoshi Sei as he discusses the recently published manuscript "Tissue- and cell-specific properties of enterochromaffin cells affect the fate of tumorigenesis toward nonendocrine adenocarcinoma of the small intestine" with Editor in Chief Professor Mark Frey. Small intestinal neuroendocrine tumors are of putative enterochromaffin (EC) cell origin and are the most common malignancy in the small intestine, followed by adenocarcinoma. Dr Sei, explains how tissue- and cell-specific properties of EC cells such as cell turnover, migration, and dedifferentiation, affect their fate of tumorigenesis.

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Take a listen to our latest podcast where the magnificent Dr. Karen Edelblum, chair of the GI and Liver Section discusses what's happening at our first ever American Physiology Summit, April 20-23rd in Long Beach California.

Registration Deadline for American Physiology Summit is March 31, 2023

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Get to know author Dr. Rodger Liddle (Duke University) in this latest podcast as he goes over his recently published manuscript "Initiation and severity of experimental pancreatitis are modified by phosphate" with Editor in Chief Professor Mark Frey. 

New and Noteworthy-Impaired ATP synthesis disrupts acinar cell homeostasis and is an early step in pancreatitis. We report that reduced phosphate availability impairs mitochondrial function and worsens pancreatic injury. Phosphate supplementation improves mitochondrial function and protects against experimental pancreatitis, raising the possibility that phosphate supplementation may be useful in treating pancreatitis.

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In this podcast authors Prof D. Mark Pritchard and Dr. Carrie Duckworth of the University of Liverpool, discuss their recently published manuscript “Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa” with Editor-in-Chief Prof. Mark Frey. Novel transcriptomic analysis of murine proximal intestinal mucosa revealed an unexpected B cell signature in Nfkb2-/- mice. In depth analysis revealed a defect in the CD38+ B cell population and a gut-specific dysregulation of immunoglobulin levels. Take a listen to this latest podcast today!

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In our latest podcast senior author Dr. Rhonda Souza discusses her latest published research “A Human Barrett's Esophagus Organoid System Reveals Epithelial-Mesenchymal Plasticity Induced by Acid and Bile Salts” with Editor-in-Chief Prof. Mark Frey. Using Barrett's esophagus (BE) biopsies, the authors established organoids recapitulating key BE features. During early stages of organoid development, a GERD-like wound environment induced features of epithelial-mesenchymal plasticity (EMP) in Barrett's progenitor cells, suggesting that reflux-induced EMP can enable Barrett's cells to migrate underneath squamous epithelium to form subsquamous intestinal metaplasia, a condition that may underlie Barrett's cancers that escape detection by endoscopic surveillance, and recurrences of Barrett's metaplasia following endoscopic eradication therapy.

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In this podcast, coauthors Dr. Huajun Han, and Prof. Robert S. Chapkin of Texas A&M University, discuss their recently published research "Loss of aryl hydrocarbon receptor suppresses the response of colonic epithelial cells to IL22 signaling by upregulating SOCS3" with Editor-in-Chief Prof. Mark Frey. Data from their preclinical orthogonal models indicate that AhR signaling modulates the response of colonic epithelial cells to IL22, resulting in the suppression of carcinogen-associated colon tumorigenesis. These findings provide rationale for targeting AhR as a means of ameliorating IBD and reducing colon cancer risk. Take a listen today! 

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In today’s episode Dr. Stephen Keely from the Royal College of Surgeons in Ireland and Prof Kim Barrett of the University of California, Davis talk about their recent review article “Mechanisms of Secretory Diarrhea” with Prof Mark Frey. They discuss why it is we need to talk more about diarrheal diseases, lift the lid on the complex cellular and molecular mechanisms involved, and look to where new therapeutics are likely to arise in the future.

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In a rapidly evolving era of single cell technologies, the authors of "Stiffness is associated with hepatic stellate cell heterogeneity during liver fibrosis" explain the mechanism of an amplification loop during liver fibrosis. By deciphering how stiffness macro and microscopic heterogeneity promote differential gene expression in hepatic stellate cell sub-populations, the authors find a novel stiffness-promoted molecule involved in liver fibrosis progression. Get to know authors Dr. Enis Kostallari and Dr. Vijay Shah of the Mayo Clinic as they discuss their recently published manuscript and what life is like as a researcher with Editor-in-Chief Professor Mark Frey. 

https://journals.physiology.org/journal/ajpgi 

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Get to know senior author Dr. Liara M. Gonzalez of North Carolina State University as she discusses the recently published paper entitled "HOPX+ injury-resistant intestinal stem cells drive epithelial recovery after severe intestinal ischemia" with EIC Prof. Mark Frey.  This paper supports that rISCs are resistant to ischemic injury and likely an important source of cellular renewal following near-complete epithelial loss. Furthermore, the authors have evidence that HOPX controls ISC activity state and may be a critical signaling pathway during ISC-mediated repair. Finally, they use multiple novel methods to evaluate ISCs in a translationally relevant large animal model of severe intestinal injury and provide evidence for the potential role of rISCs as therapeutic targets. 

Amy Stieler Stewart, Cecilia Renee Schaaf, Jennifer A. Luff, John M. Freund, Thomas C. Becker, Sara R. Tufts, James B. Robertson, and Liara M. Gonzalez

https://doi.org/10.1152/ajpgi.00165.2021

Looking for a new pharmacological approach to treat gastrointestinal motility disorders?

In this podcast authors Dr. Daniel Poole and Dr. Simona Carbone of Monash University discuss their recent paper, where they investigated the therapeutic potential of a positive allosteric modulator to enhance endogenous delta-opioid receptor signaling in the gut. Take a listen today! 

Jesse J. DiCello, Simona E. Carbone, Ayame Saito, Vi Pham, Agata Szymaszkiewicz, Arisbel B. Gondin, Sadia Alvi, Kiliana Marique, Priyank Shenoy, Nicholas A. Veldhuis, Jakub Fichna, Meritxell Canals, Arthur Christopoulos, Celine Valant, and Daniel P. Poole 

https://doi.org/10.1152/ajpgi.00297.2021

Three investigators at Children's Hospital Los Angeles, Nandini Girish, Dr. Cambrian Liu, and Dr. Brent Polk, talk about their recent work to visualize the fates and functions of epithelial stem cells in models of inflammatory bowel disease with Editor-in-Chief Professor Mark Frey. The investigators discuss their diverse backgrounds, reveal how they started the work, and begin a spirited debate on the relative values of minivans and dogs and cats.

Check out the manuscript associated with this podcast here:

https://doi.org/10.1152/ajpgi.00248.2020

Many times we read a manuscript but don’t really get to know the amazing author behind the great science.  Behind those black typewritten letters that spell a scientists name lies a person that is usually creative, intelligent, quirky, and fun.  This is certainly the case with the author of “Use of human tissue stem cell-derived organoid cultures to model enterohepatic circulation”, Dr. Sarah Blutt.  Please listen in as we learn a little bit about one of the fields Organoid Divas and what makes her tick as we discuss organoids as a biological toll booth and other topics.

Check out the manuscript associated with this podcast here: https://doi.org/10.1152/ajpgi.00177.2021 

Welcome to AJP- Gastrointestinal Liver’s Physiology’s Podcast series, Got Guts? Our first episode is a  joint effort with Dr. Pradeep Dudeja, Chair of the GI and Liver Section and Dr. Karen Edelblum, Chair of GI and Liver Program Committee with host Editor-In-Chief, Professor Mark Frey. In this podcast we will be talking about all things Experimental Biology 2022. For more information on Experimental Biology 2022 please go to www.experimentalbiology.org . To learn more about the journal and section please go to www.physiology.org. If you are interested in submitting a manuscript and have questions, please email Jami Jones at jjones@physiology.org