Article
Immunology
Nicholas O. Markham, Sarah C. Bloch, John A. Shupe, Erin N. Laubacher, Audrey K. Thomas, Heather K. Kroh, Kevin O. Childress, F. Christopher Peritore-Galve, M. Kay Washington, Robert J. Coffey, D. Borden Lacy
Summary: Clostridioides difficile is associated with nearly 225,000 antibiotic-associated diarrheal infections and almost 13,000 deaths per year in the United States. The intrarectal instillation mouse model with purified recombinant TcdA and TcdB provides flexibility to better understand structure/function relationships in different stages of CDI pathogenesis.
INFECTION AND IMMUNITY
(2021)
Article
Biochemistry & Molecular Biology
Jinglue Song, Xia Shen, Zhenyu Huang, Yun Liu, Long Cui, Xuewei Cui, Chen-Ying Liu
Summary: Toxins A and B of Clostridium difficile disrupt the Hippo pathway, leading to sequestration and inactivation of YAP and TAZ in colonic epithelial cells. Overexpression of YAP restores cell function and may serve as a potential therapeutic strategy for treating CDI.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2021)
Article
Oncology
Julia L. Drewes, Jie Chen, Nicholas O. Markham, Reece J. Knippel, Jada C. Domingue, Ada J. Tam, June L. Chan, Lana Kim, Madison McMann, Courtney Stevens, Christine M. Dejea, Sarah Tomkovich, John Michel, James R. White, Fuad Mohammad, Victoria L. Campodonico, Cody N. Heiser, Xinqun Wu, Shaoguang Wu, Hua Ding, Patricia Simner, Karen Carroll, Martha J. Shrubsole, Robert A. Anders, Seth T. Walk, Christian Jobin, Fengyi Wan, Robert J. Coffey, Franck Housseau, Ken S. Lau, Cynthia L. Sears
Summary: This study reveals the role of toxigenic Clostridioides difficile in promoting colorectal cancer, suggesting that chronic colonization with this pathogenic bacteria may drive tumor development through the induction of Wnt signaling, reactive oxygen species, and protumorigenic mucosal immune responses.
Article
Biochemistry & Molecular Biology
Jianhua Luo, Qi Yang, Xiaofeng Zhang, Yuanyuan Zhang, Li Wan, Xiechao Zhan, Yao Zhou, Liuqing He, Danyang Li, Dazhi Jin, Ying Zhen, Jing Huang, Yanyan Li, Liang Tao
Summary: The study identified tissue factor pathway inhibitor (TFPI) as the receptor for TcdB4, a dominant virulence factor of hypervirulent clade 2 Clostridioides difficile. TFPI is highly expressed in the intestinal glands and protects the colonic epithelium from TcdB2/4. These findings reveal new mechanisms for CDI pathogenesis.
Article
Pharmacology & Pharmacy
Giuseppe Esposito, Chiara Corpetti, Marcella Pesce, Luisa Seguella, Giuseppe Annunziata, Alessandro Del Re, Martina Vincenzi, Roberta Lattanzi, Jie Lu, Walter Sanseverino, Giovanni Sarnelli
Summary: The newly designed PEA-producing probiotic showed therapeutic potential in inhibiting colonic inflammation and restoring tight junction protein expression in a mouse model of CDI.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Srijita Basak, Debashrito Deb, Utkarsh Narsaria, Tamalika Kar, Filippo Castiglione, Indraneel Sanyal, Pratap D. Bade, Anurag P. Srivastava
Summary: Clostridium difficile infection is a major health-associated infection with high incidence and mortality rates. A chimeric vaccine candidate was designed using immunoinformatics, which showed stability and reliability in silico and molecular dynamics simulations. Docking studies demonstrated stable interactions with immune receptors, and in silico modeling indicated competent expression in E. coli system for potential immune response.
SCIENTIFIC REPORTS
(2021)
Article
Gastroenterology & Hepatology
Steven J. Mileto, Melanie L. Hutton, Sarah L. Walton, Antariksh Das, Lisa J. Ioannidis, Don Ketagoda, Kylie M. Quinn, Kate M. Denton, Diana S. Hansen, Dena Lyras
Summary: This study investigated the systemic complications of C. difficile infection using a mouse model, focusing on thymic damage and serum markers. The efficacy of bezlotoxumab in preventing systemic disease complications was also examined. The study found that C. difficile infection causes thymic damage, depletion of thymocytes, and changes in liver and kidney function markers. Administration of bezlotoxumab prevented systemic disease and thymic atrophy without blocking gut damage.
Article
Infectious Diseases
Miad Elahi, Haruyuki Nakayama-Imaohji, Masahito Hashimoto, Ayano Tada, Hisashi Yamasaki, Tamiko Nagao, Tomomi Kuwahara
Summary: The gut symbiont Bacteroides thetaiotaomicron (BT) suppresses Clostridium difficile (CD) toxin production by inhibiting polysaccharide metabolism pathways. Polysaccharide fractions derived from BT can suppress CD toxin production, with cell wall-associated glycans playing a key role in this inhibitory effect.
Review
Public, Environmental & Occupational Health
Peng An Khun, Thomas V. Riley
Summary: This review provides an overview of Clostridium difficile infection (CDI) in southeast Asia, including its prevalence, detection methods, antimicrobial susceptibility profiles, and the potential significance of a One Health approach. CDI is a common cause of hospital-acquired gastroenteritis worldwide, with higher rates observed in high-income countries. Lack of knowledge and awareness about CDI, along with antimicrobial abuse and inadequate education on appropriate usage, contribute to its evolution. Underreporting of CDI rates and misuse of antimicrobial agents pose a significant threat in regions like Indochina, while C. difficile RT 017 strain is endemic in southeast Asia.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2022)
Article
Microbiology
Mahmoud Fayez, Waleed R. El-Ghareeb, Ahmed Elmoslemany, Saleem J. Alsunaini, Mohamed Alkafafy, Othman M. Alzahrani, Samy F. Mahmoud, Ibrahim Elsohaby
Summary: The study investigated the presence of Clostridium perfringens and Clostridioides difficile in camel minced meat samples collected from small butcher shops and supermarkets in Al-Ahsa Governorate, Saudi Arabia. It was found that most isolates exhibited resistance to at least one antimicrobial, with some showing multidrug resistance. This highlights the importance of enforcing food safety standards and conducting regular inspections in abattoirs, small butcher shops, and supermarkets.
Article
Environmental Sciences
Sen Yan, Sinuo Tian, Zhiyuan Meng, Miaomiao Teng, Wei Sun, Ming Jia, Zhiqiang Zhou, Sheng Bi, Wentao Zhu
Summary: Environmental pollutants such as nitenpyram during pregnancy can affect metabolic health in mouse offspring by increasing specific microbial strains and hydrogen sulfide concentration, leading to colonic mucosa destruction, intestinal inflammation, and NASH. These findings shed light on the crucial role of gut microbiota in the pathogenesis of NASH.
ENVIRONMENTAL POLLUTION
(2021)
Article
Chemistry, Analytical
Waleed A. Hassanain, Julia Spoors, Christopher L. Johnson, Karen Faulds, Neil Keegan, Duncan Graham
Summary: The study introduces a novel testing platform for the rapid and simultaneous detection of two specific biomarkers of Clostridium difficile infection, providing a rapid, selective, sensitive, and cost-effective clinical evaluation method for CDI.
Article
Multidisciplinary Sciences
Nuria Tubau-Juni, Josep Bassaganya-Riera, Andrew J. Leber, Sameeksha S. Alva, Ryan Baker, Raquel Hontecillas
Summary: The study analyzed the colonic and host response during Clostridioides difficile infection (CDI), revealing significant changes in gene expression kinetics during the acute infection stage that were restored during the recovery phase. The study also found an increase in glycolytic metabolism during the peak of inflammation and a predominance of mitochondrial metabolism during the recovery/healing stage. Treatment of CDI with 2-Deoxy-d-glucose (2-DG) reduced disease severity, protected against mortality, and improved colitis in vivo. Furthermore, 2-DG protected intestinal epithelial cells from C. difficile toxin damage.
SCIENTIFIC REPORTS
(2023)
Article
Gastroenterology & Hepatology
Dominika Trzilova, Mercedes A. H. Warren, Nicole C. Gadda, Caitlin L. Williams, Rita Tamayo
Summary: C. difficile exhibits heterogeneity in swimming motility and toxin production through phase variation by site-specific DNA recombination. The ability of C. difficile to phase vary flagella and toxins influences colonization and disease development, indicating that the phenotypic variants generated by flagellar switch inversion have distinct capacities for causing disease.
Article
Microbiology
Carmen Saenz, Qing Fang, Thiyagarajan Gnanasekaran, Samuel Addison Jack Trammell, Jesse Arnold Buijink, Paola Pisano, Michael Wierer, Frederic Moens, Bettina Lengger, Asker Brejnrod, Manimozhiyan Arumugam
Summary: Clostridioides difficile infection (CDI) is challenging to treat due to antibiotic resistance. Recent studies have shown that bile acids (BAs) can be a promising approach to treat CDI. This research found that Clostridium scindens and BAs can inhibit the growth and toxin expression of C. difficile.
MICROBIOLOGY SPECTRUM
(2023)
Article
Surgery
Lisa T. Zhang, Lars F. Westblade, Fatima Iqbal, Michael R. Taylor, Alice Chung, Michael J. Satlin, Matthew Magruder, Emmanuel Edusei, Shady Albakry, Brittany Botticelli, Amy Robertson, Tricia Alston, Darshana M. Dadhania, Michelle Lubetzky, Simon A. Hirota, Steven C. Greenway, John R. Lee
Summary: The study found that kidney transplant recipients with post-transplant diarrhea had decreased gut microbial diversity and decreased relative gut abundances of 12 genera. Additionally, patients with higher fecal beta-glucuronidase activity in diarrhea patients had a more prolonged course of diarrhea. This suggests that fecal beta-glucuronidase activity could be a novel biomarker for gastrointestinal-related MMF toxicity.
CLINICAL TRANSPLANTATION
(2021)
Article
Gastroenterology & Hepatology
Aito Ueno, Humberto B. Jijon, Richard Peng, Steven Sparksman, Barbara Mainoli, Alexis Filyk, Yan Li, Stephanie Wilson, Kerri Novak, Remo Panaccione, Simon Hirota, Antoine Dufour, Cathy Lu, Paul L. Beck
Summary: This study provides evidence supporting a potential role of fibrocytes in collagen deposition in Crohn's disease strictures and suggests that fibrocyte numbers may predict the need for therapy escalation.
INFLAMMATORY BOWEL DISEASES
(2022)
Review
Gastroenterology & Hepatology
Kristoff M. Nieves, Simon A. Hirota, Kyle L. Flannigan
Summary: Microbial metabolites regulate physiological and immunological processes in the intestinal environment through the activation of AhR and PXR.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Immunology
Fernando A. Vicentini, Jake C. Szamosi, Laura Rossi, Lateece Griffin, Kristoff Nieves, Dominique Bihan, Ian A. Lewis, Quentin J. Pittman, Mark G. Swain, Michael G. Surette, Simon A. Hirota, Keith A. Sharkey
Summary: Inflammatory bowel diseases (IBD) are associated with cognitive and emotional comorbidities. This study found that alterations in the gut microbiota, which are influenced by intestinal inflammation, may contribute to the development of behavioral abnormalities in colitis.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Gastroenterology & Hepatology
Huey-Miin Chen, Justin A. MacDonald
Summary: This study verifies pancolitis as a conduit for ulcerative colitis advancement to dysplasia and identifies key molecular determinants for disease progression. The study also highlights the dysregulation of actin reorganization as an important aspect of disease progression.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Immunology
Nina L. Cluny, Kewir D. Nyuyki, Wagdi Almishri, Lateece Griffin, Benjamin H. Lee, Simon A. Hirota, Quentin J. Pittman, Mark G. Swain, Keith A. Sharkey
Summary: In experimental colitis, monocytes expressing α4β7 integrin direct the recruitment of neutrophils to cerebral vasculature, leading to elevated cytokine levels and subsequently anxiety-like behavior.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Anatomy & Morphology
Huey-Miin Chen, Justin A. MacDonald
Summary: This review highlights the importance of the family of death-associated protein kinases (DAPKs) and DAPK-related apoptosis-inducing protein kinases (DRAKs) in regulating cellular processes in the intestinal epithelium. It discusses their role in tumor suppression, programmed cell death, inflammation-mediated tumor growth, and wound healing. The review also provides insights into the biochemical properties of each family member and the ongoing efforts to develop pharmacologic effectors for specific DAPKs.
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
(2023)
Article
Cell Biology
Istvan Tamas, Evelin Major, Daniel Horvath, Ilka Keller, Adam Ungvari, Timothy A. Haystead, Justin A. MacDonald, Beata Lontay
Summary: This study provides evidence for the insulin-sensitizing role of SMTNL1 in skeletal muscle. SMTNL1 regulates the phosphorylation of IRS1 and the insulin-signaling cascade, contributing to improved insulin sensitivity and glucose disposal.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Holly E. Szczepanski, Kyle L. Flannigan, Barbara Mainoli, Laurie Alston, Grace M. Baruta, Joshua W. Lee, Vivek Krishna Pulakazhi Venu, Jane Shearer, Antoine Dufour, Simon A. Hirota
Summary: Stricture formation is a common complication of Crohn's disease, and the orphan nuclear receptor NR4A1 plays a role in regulating intestinal smooth muscle cell proliferation and muscle thickening. Loss of NR4A1 leads to increased proliferation and alterations in cellular metabolism, while activation of NR4A1 attenuates proliferation. By targeting NR4A1, it may be possible to regulate intestinal smooth muscle phenotype and limit excessive proliferation contributing to stricture development in Crohn's disease.
Article
Gastroenterology & Hepatology
Kyle L. Flannigan, Kristoff M. Nieves, Holly E. Szczepanski, Alex Serra, Joshua W. Lee, Laurie A. Alston, Hena Ramay, Sridhar Mani, Simon A. Hirota
Summary: The pregnane X receptor (PXR) plays an important role in regulating intestinal inflammation and fibrosis. Microbiota-derived indole-3-propionic acid (IPA) influences PXR signaling. Deletion of PXR exacerbates fibrosis, suggesting that microbiota metabolites may be a vital determinant in the progression of fibrotic complications in inflammatory bowel diseases (IBDs).
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Pharmacology & Pharmacy
Megha Murali, Sara R. Turner, Darrell D. Belke, William C. Cole, Justin A. MacDonald
Summary: This study found a novel sex-dimorphic role for SMTNL1 in modulating cardiac structure and function in mice, with male Smtnl1-/- mice showing significant changes in cardiac morphology and function.
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
(2022)
Article
Physiology
Sara R. Turner, Abdulhameed Al-Ghabkari, David A. Carlson, Mona Chappellaz, Cindy Sutherland, Timothy A. J. Haystead, William C. Cole, Justin A. MacDonald
Summary: This study provides the first evidence linking DAPK3 to the myogenic response of cerebral arteries in rats and humans. DAPK3 is involved in regulating the actin cytoskeleton and plays a role in the myogenic reaction. This finding suggests DAPK3 as a potential therapeutic target for the cerebrovascular system.
EXPERIMENTAL PHYSIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Megha Murali, Sara R. Turner, Darrell D. Belke, William C. Cole, Justin A. MacDonald
Summary: Smoothelin-like 1 (SMTNL1) plays a crucial role in the contractile performance of smooth muscle and vascular homeostasis. This study investigated the impact of SMTNL1 deletion on cardiac morphology and function in mice. Male Smtnl1-/- mice showed distinct changes in cardiac morphology, increased ejection fraction and fractional shortening, as well as elevated aortic and pulmonary flow velocities. Under cardiac stress, Smtnl1-/- mice displayed impaired relaxation, higher LV filling pressure, and altered myocardial performance indices. These findings highlight a novel, sex-dimorphic role of SMTNL1 in modulating cardiac structure and function.
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
(2023)
Proceedings Paper
Gastroenterology & Hepatology
Fernando A. Vicentini, Tanner Fahlman, Stephanie G. Raptis, Laurie E. Wallace, Simon A. Hirota, Keith A. Sharkey
Summary: Propulsive gastrointestinal motility is crucial for digestion and defense. It is regulated by the intramural reflex pathways of the enteric nervous system (ENS), which is influenced by luminal factors, including the gut microbiota. The gut microbiota not only regulates ENS motor programs, but also plays a critical role in the structure and function of the ENS.
ENTERIC NERVOUS SYSTEM II
(2022)
Article
Biochemical Research Methods
Huey-Miin Chen, Justin A. Macdonald
Summary: Advancements in high-throughput sequencing technologies have enabled the generation of extensive volumes of OMICs data, allowing for systematic data analysis and the discovery of novel biological insights. This study presents protocols for analyzing differentially expressed genes in TCGA and GTEx RNA-Seq data from human cancers, conducting comprehensive integrative GO and network analyses with a focus on clinical and survival data, as well as identifying differential correlations of trait-associated biomarkers.