Review
Pediatrics
Shuo Yang, Xin Wei, Yuting Zhong, Conglu Guo, Xinzhu Liu, Zhibin Wang, Ye Tu
Summary: Necrotizing enterocolitis (NEC) is a fatal disease commonly found in premature infants, characterized by damage to the intestinal epithelial barrier (IEB). The death and regenerative repair of intestinal epithelial cells (IECs) play important roles in maintaining IEB function in response to microbial invasion. However, excessive death of IECs leads to increased intestinal permeability and dysfunction. This review focuses on the known death modes of IECs in NEC, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and abnormal autophagy, and discusses the potential of targeting IECs death as a treatment for NEC based on animal and clinical studies.
FRONTIERS IN PEDIATRICS
(2023)
Article
Pediatrics
Shan He, Gang Liu, Xueping Zhu
Summary: This study demonstrates the beneficial effects of human breast milk-derived exosomes in preventing necrotizing enterocolitis by reducing inflammation and injury, and restoring intestinal tight-junction proteins.
PEDIATRIC RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Jie Wang, Nan Zhou, Peijun Shen, Fangmin Li, Qian Zhao, Dandan Zang, Liu Zhang, Wen Lu, Wenjing Tian, Ling Jing, Ying Chen
Summary: Necrotizing enterocolitis (NEC) is a leading cause of death in preterm infants, and breastfeeding can protect infants from NEC. In this study, the concentration of a secreted protein called MANF in breast milk was investigated, and its immune-regulatory function in protecting the intestinal epithelial barrier was evaluated. The results showed that MANF was secreted in human milk but not in infant formulas. MANF was mainly expressed in intestinal macrophages and could induce apoptosis and reduce inflammation in both NEC intestinal tissues and BMDMs. Mechanistically, MANF protein inhibited the apoptosis of intestinal epithelial cells and protected epithelial tight junctions by downregulating the NF-kappa B pathway in pro-inflammatory macrophages. These findings highlight the importance of human milk-derived MANF in intestinal macrophages, which contributes to downregulating the intestinal inflammatory response and protecting the homeostasis of intestinal epithelial cells. This study not only reveals the potential mechanism underlying the protective effects of breastfeeding in NEC but also provides new insights for clinical translation and the development of nutritional interventions for the prevention of NEC.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Peng Lu, Yukihiro Yamaguchi, William B. Fulton, Sanxia Wang, Qinjie Zhou, Hongpeng Jia, Mark L. Kovler, Andres Gonzalez Salazar, Maame Sampah, Thomas Prindle, Peter Wipf, Chhinder P. Sodhi, David J. Hackam
Summary: NEC, a disease of prematurity, is associated with AHR signaling. Administration of AHR ligands during pregnancy and postnatally can prevent NEC. AHR signaling plays a crucial role in the development of NEC and may be a potential therapeutic target for NEC.
NATURE COMMUNICATIONS
(2021)
Article
Pediatrics
Yasser Elsayed, Mary Seshia
Summary: Clinical management of gut injury remains challenging due to the lack of defined diagnostic criteria. This report introduces an integrated approach using intestinal ultrasound as the primary assessment tool along with other clinical and biochemical markers. This algorithm improves the quality of care, provides more accurate diagnosis of NEC, and differentiates other types of gut injury.
EUROPEAN JOURNAL OF PEDIATRICS
(2022)
Article
Biochemistry & Molecular Biology
Dan Dang, Zhaoli Meng, Chuan Zhang, Zhenyu Li, Jiaqi Wei, Hui Wu
Summary: This study discovered the mechanism of ferroptosis in transfusion-associated necrotising enterocolitis (TANEC) and identified heme as a trigger for ferroptosis in intestinal epithelial cells through mitochondrial dysfunction. Heme-induced ferroptosis may be a potential therapeutic target for TANEC.
Article
Ecology
Anders Brunse, Ling Deng, Xiaoyu Pan, Yan Hui, Josue L. Castro-Mejia, Witold Kot, Duc Ninh Nguyen, Jan Bojsen-Moller Secher, Dennis Sandris Nielsen, Thomas Thymann
Summary: This study demonstrated that fecal filtrate transplantation (FFT) is more effective in preventing NEC compared to fecal microbiota transplantation (FMT), without any recognizable side effects. Oro-gastric FFT completely prevented NEC, increased viral diversity, and reduced the relative abundance of specific bacteria phylum in the ileal mucosa.
Article
Immunology
Yan-Chun Ji, Qian Sun, Chun-Yan Fu, Xiang She, Xiao-Chen Liu, Yu He, Qing Ai, Lu-Quan Li, Zheng-Li Wang
Summary: The study found that in a mouse model of necrotizing enterocolitis (NEC), exogenous AI-2 partially reversed flora disorder and reduced inflammation levels.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Liying Dai, Shuangshuang Jie, Shaohua Bi, Qing Qing, Jun Chen, Le Wang
Summary: In this study, it was found that the expression of ANGPT2 was significantly increased after LPS induction. Silencing of ANGPT2 significantly reduced apoptosis, inflammatory response, barrier dysfunction, and endoplasmic reticulum stress in LPS-induced IEC-6 cells. Additionally, ANGPT2 knockdown could block the Notch signaling pathway.
Article
Gastroenterology & Hepatology
Saravanan Subramanian, Hua Geng, Chao Du, Pauline M. Chou, Heng-Fu Bu, Xiao Wang, Suchitra Swaminathan, Stephanie C. Tan, Jason M. Ridlon, Isabelle G. De Plaen, Xiao-Di Tan
Summary: This study investigated the impact of feeding modes on the gut microbiome, physiological inflammation, and susceptibility to intestinal injury in neonatal mice. The results showed that formula feeding altered the gut microbiome, increased inflammatory activity, and predisposed the mice to intestinal injury. These findings contribute to a better understanding of gastrointestinal diseases in infants.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Nutrition & Dietetics
Ilse H. de Lange, Charlotte van Gorp, Kimberly R. I. Massy, Lilian Kessels, Nico Kloosterboer, Ann Bjornshave, Marie Stampe Ostenfeld, Jan G. M. C. Damoiseaux, Joep P. M. Derikx, Wim G. van Gemert, Tim G. A. M. Wolfs
Summary: Many whey proteins, peptides, and protein-derived amino acids can improve gut health through their anti-oxidant, anti-microbial, barrier-protective, and immune-modulating effects. This study investigated the effects of whey protein fractions with different degrees of enzymatic hydrolysis on the intestinal epithelium, as well as their anti-microbial and immune effects. The results highlight the importance of hydrolysis degree in influencing the biological effects of whey protein fractions, and provide new insights for improving immune tolerance and promoting intestinal health.
Article
Pediatrics
Bo Shi, Cheng-Jie Lyu, Zhen-Kai Le, Hao-Sen Ji, Yi Xiao, Yuan-Yuan Zhang, Shou-Jiang Huang, Lin-Jun Yu, Qiang Shu, Jin-Fa Tou, Deng-Ming Lai
Summary: This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis (NEC). The results showed that NEC patients had high levels of macrophage infiltration and NLRP3, caspase-1, and IL-1β expression in the intestinal lamina propria compared to healthy patients. In the mouse model, NEC mice with Nlrp3 gene knockout showed improved survival rate, reduced intestinal macrophage proportion, and decreased intestinal injury. Macrophage-derived NLRP3, caspase-1, and IL-1β, as well as macrophage-epithelial cell co-culture supernatant, also caused intestinal epithelial cell injuries. Macrophage activation and NLRP3/caspase-1/IL-1β cellular signals may be crucial in NEC development and serve as potential therapeutic targets for NEC treatment.
WORLD JOURNAL OF PEDIATRICS
(2023)
Article
Pediatrics
Ming Yue, Heying Yang, Mingxia Cui, Yuhang Yuan, Ning Zhang, Xiangyu Zhang, Yan Li
Summary: Santulli enterostomy is a simple and safe surgical procedure that provides early restoration of intestinal continuity without formal laparotomy. Compared to traditional ostomy procedures, Santulli enterostomy has shorter operative time, shorter hospital stay, and lower incidence of postoperative complications.
FRONTIERS IN PEDIATRICS
(2023)
Article
Gastroenterology & Hepatology
Li Lu, Weijue Xu, Jiangbin Liu, Liping Chen, Shaohua Hu, Qingfeng Sheng, Minghua Zhang, Zhibao Lv
Summary: The study showed that DRG1 plays a crucial role in maintaining cell junctions in the intestine, especially adherens junctions, by regulating RAC1 activity. DRG1 deficiency leads to disruption of E-cadherin and occludin proteins, increasing epithelial cell permeability, while DRG1 overexpression helps maintain cell monolayer integrity. Inhibiting RAC1 with NSC23766 was found to attenuate intestinal injury and improve barrier integrity in experimental NEC.
DIGESTIVE DISEASES AND SCIENCES
(2021)
Article
Food Science & Technology
Richard Y. Wu, Bo Li, Rachael G. Horne, Abdalla Ahmed, Dorothy Lee, Shaiya C. Robinson, Haitao Zhu, Marissa Cadete, Mashriq Alganabi, Rachel Filler, Kathene C. Johnson-Henry, Paul Delgado-Olguin, Agostino Pierro, Philip M. Sherman
Summary: Necrotizing enterocolitis (NEC) is a serious gastrointestinal emergency that affects premature infants. Breastmilk helps prevent NEC, in part due to human milk oligosaccharides (HMOs). This study found that different structural HMOs have varying effects on intestinal physiology, with unique mechanisms of action, providing a functional framework for screening and designing HMO-like compounds.
MOLECULAR NUTRITION & FOOD RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Carolina Battistini, Rafael Ballan, Marcos Edgar Herkenhoff, Susana Marta Isay Saad, Jun Sun
Summary: Inflammatory bowel disease is a chronic inflammation of the GI tract, including Crohn's disease and ulcerative colitis, associated with microbiota dysbiosis and vitamin D deficiency. Further studies are needed to explore the mechanisms and therapeutic potential related to vitamin D/VDR in gut microbiota modulation for IBD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Rong Lu, Yong-guo Zhang, Yinglin Xia, Jilei Zhang, Arthur Kaser, Richard Blumberg, Jun Sun
Summary: The study reveals that VDR in Paneth cells plays a crucial role in antibacterial activities and inflammatory responses, and the lack of VDR in Paneth cells may lead to the development of chronic inflammation.
Review
Oncology
Ikuko Kato, Jilei Zhang, Jun Sun
Summary: This review discusses the interactions between viruses and bacteria in the development of human cancers, with a focus on cancers arising from the oral cavity, stomach, intestine, liver, uterine cervix and mammary glands. The strength of existing evidence varies between different types of cancer, and there are gaps in knowledge for future research in infection and cancer.
Review
Cell Biology
Jun Sun, Yong-Guo Zhang
Summary: VDR plays a crucial role in the biological functions of vitamin D and acts as a transcriptional factor regulating the expression of target genes; Research shows that VDR regulation of intestinal barriers influences health and disease; Understanding the mechanisms by which VDR signaling regulates intestinal barrier functions can help develop efficient therapeutic strategies for human diseases.
Article
Oncology
Yongguo Zhang, Jilei Zhang, Yinglin Xia, Jun Sun
Summary: In this study, host factors such as vitamin D receptor deficiency and APC gene mutation were found to be associated with dysbiosis and disrupted barrier in colorectal cancer development. These findings provide potential applications in risk assessment, early detection, and prevention of colon cancer.
Review
Oncology
Shreya Deb, Jun Sun
Summary: SNX27 is a member of the sorting nexin (SNX) family of proteins and functions in sorting and trafficking of proteins in the endocytosis pathway. It has a unique PDZ domain, which interacts with endogenous proteins and mediates their recycling from early endosomes to the plasma membrane, avoiding lysosomal degradation. While the role of SNX27 in cancer remains poorly understood, many of its known binding partners are associated with tumorigenesis.
Article
Biochemistry & Molecular Biology
Destiny Ogbu, Yongguo Zhang, Katerina Claud, Yinglin Xia, Jun Sun
Summary: Microbial metabolites, neuroactive metabolites from the gut, and inflammation are interrelated factors in the progression of ALS.
Article
Environmental Sciences
Yong-guo Zhang, Mackenzie E. Malo, Tanya Tschirhart, Yinglin Xia, Zheng Wang, Ekaterina Dadachova, Jun Sun
Summary: The study examined the safety of using soluble melanin and melanin-producing bacteria for preventing radiation-induced injury. Mice were administered with soluble allomelanin and melanized E. coli Nissle to observe their effects on intestinal physiology and body weight. The results showed that melanized bacteria demonstrated strong colonization ability in the intestine, without causing significant changes in body weight or inflammation. These findings provide support for using melanin and melanized bacteria to treat radiation-induced injuries and restore gut dysbiosis.
Article
Biochemistry & Molecular Biology
Danika S. Bakke, Jilei Zhang, Yongguo Zhang, Destiny Ogbu, Yinglin Xia, Jun Sun
Summary: Cross talk between immune cells and the intestinal crypt is critical in maintaining intestinal homeostasis. Recent studies have found that vitamin D receptor (VDR) signaling plays a direct role in intestinal and microbial homeostasis, but the specific role of immune VDR signaling is still not well understood. This study used a myeloid-specific VDR knockout mouse model and a macrophage/enteroids coculture system to investigate the tissue-specific VDR signaling in intestinal homeostasis. The findings showed that myeloid VDR regulates crypt differentiation and the microbiota in a VDR-dependent mechanism, and dysregulation of myeloid VDR increases the risk of colitis-associated diseases.
Meeting Abstract
Physiology
Jilei Zhang, Shreya Deb, Yongguo Zhang, Shari Garrett, Yinglin Xia, Paul Slesinger, Jun Sun
Article
Gastroenterology & Hepatology
Yong-Guo Zhang, Yinglin Xia, Jilei Zhang, Shreya Deb, Shari Garrett, Jun Sun
Summary: The microbiota plays a critical role in regulating intestinal and extraintestinal health. This study investigates the potential connection between the intestinal microbiome and breast cancer. Through the examination of mice with VDR deficiency and dysbiosis, the researchers found that VDR deficiency leads to an increased susceptibility to breast cancer. Moreover, they identified the mechanisms by which VDR deficiency disrupts gut health and increases the risk of breast tumorigenesis. Treatment with beneficial bacteria or their metabolites showed promising results in reducing breast tumors and improving gut health.
Article
Biochemistry & Molecular Biology
Anita Sharma, Yueyue Yu, Jing Lu, Lei Lu, Yong-Guo Zhang, Yinglin Xia, Jun Sun, Erika C. C. Claud
Summary: Vitamin D Receptor (VDR) signaling has a protective effect against intestinal inflammation. The interaction between intestinal VDR and the microbiome suggests the potential of probiotics in modulating VDR expression. Although probiotics have been shown to reduce necrotizing enterocolitis (NEC) in preterm infants, their use is not currently recommended by the FDA due to potential risks. This study explores the effect of maternally administered probiotics on intestinal VDR expression in early life using an infancy mouse model, finding that probiotic exposure enhances VDR expression and suggests the potential role of microbiome-modulating therapies in preventing NEC.
Article
Gastroenterology & Hepatology
Jun Sun, M. Nedim Ince, Clara Abraham, Terrence Barrett, Lisa A. Brenner, Yingzi Cong, Reza Dashti, Pradeep K. Dudeja, David Elliott, Thomas S. Griffith, Peter S. Heeger, Andrew Hoisington, Kaikobad Irani, Tae Kon Kim, Neeraj Kapur, Joseph Leventhal, Mansour Mohamadzadeh, Ece Mutlu, Rodney Newberry, Jonathan U. Peled, Israel Rubinstein, Salyka Sengsayadeth, Chen Sabrina Tan, Xiao-Di Tan, Eric Tkaczyk, Jason Wertheim, Zheng Jenny Zhang
Summary: This report summarizes a field-based meeting held by the United States Department of Veterans Affairs (VA), focusing on modulating the microbiome-immune axis in deployment-related chronic diseases of veterans. The meeting discussed various research areas, including interactions between microbiome and immune cells, intestinal inflammation and modification, microbiome-neuron-immunity interplay in mental and physical health, and microbiome-micronutrient-immune interactions during homeostasis and infectious diseases.
Article
Gastroenterology & Hepatology
Jilei Zhang, Yongguo Zhang, Callum J. McGrenaghan, Vincent P. Kelly, Yinglin Xia, Jun Sun
Summary: This study found that the expression of QTRT1 was significantly downregulated in patients with inflammatory bowel disease (IBD). The 4 Q-tRNA-related tRNA synthetases were also decreased in IBD patients. These changes were associated with alterations in epithelial cell proliferation and junction formation. Further investigation revealed that queuine treatment enhanced cell proliferation and junction activity, and reduced inflammation in epithelial cells. These findings uncover a novel role for tRNA modifications in the pathogenesis of IBD.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Shari Garrett, Yong-Guo Zhang, Yinglin Xia, Jun Sun
