Article
Gastroenterology & Hepatology
Daria Krzikalla, Alena Laschtowitz, Lisa Leypoldt, Cornelia Gottwick, Pia Averhoff, Soren Weidemann, Ansgar W. Lohse, Samuel Huber, Christoph Schramm, Dorothee Schwinge, Johannes Herkel, Antonella Carambia
Summary: This study investigated the immune mechanisms that establish liver tolerance. It was found that MBP-specific T cells were activated to produce IFN-gamma in the liver, which induced the up-regulation of recruitment molecules and redirected the T cells into the liver parenchyma. Some of the translocated T cells converted into regulatory T cells producing IL-10 and up-regulated the expression of immune checkpoint molecules. The up-regulation of IFN gamma and immune checkpoint molecules, including CTLA-4, were essential for tolerance induction in the liver.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2024)
Article
Gastroenterology & Hepatology
Quan Pan, Mingming Gao, Dami Kim, Weiqi Ai, Wanbao Yang, Wen Jiang, Wesley Brashear, Yujiao Dai, Sha Li, Yuxiang Sun, Yajuan Qi, Shaodong Guo
Summary: This study investigates the role of hepatocyte FoxO1 in liver fibrosis and finds that it mediates CCL4-induced liver fibrosis through upregulating hepatocyte TGF-beta 1 expression, stimulating hepatic inflammation, and TGF-beta 1-mediated HSC activation.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2024)
Article
Gastroenterology & Hepatology
Yueqi Zhang, Yue Luo, Xinhui Liu, Matti Kiupel, Aimin Li, Hongbing Wang, Qing-Sheng Mi, Hua Xiao
Summary: This study reveals a novel mechanism for the onset of NAFLD/NASH and HCC initiated by NCOA5-deficient macrophages, suggesting the NCOA5-PF4 axis in macrophages as a potential target for developing preventive and therapeutic interventions against NAFLD/NASH and HCC.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2024)
Review
Gastroenterology & Hepatology
Hyun Young Kim, Sadatsugu Sakane, Alvaro Eguileor, Raquel Carvalho Gontijo Weber, Wonseok Lee, Xiao Liu, Kevin Lam, Kei Ishizuka, Sara Brin Rosenthal, Karin Diggle, David A. Brenner, Tatiana Kisseleva
Summary: Liver fibrosis is a serious global health problem with no effective therapy currently available. Studies have shown that liver fibrosis is reversible and regression can occur when the underlying cause is removed. This review discusses the research progress in understanding the molecular mechanisms underlying the development and reversibility of liver fibrosis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2024)
Article
Gastroenterology & Hepatology
Nadege Bossuet, Cecile Guyonnet, Camille Chagneau, Min Tang-Fichaux, Marie Penary, Dorian Loubet, Priscilla Branchu, Eric Oswald, Jean-Philippe Nougayrede
Summary: Up to 25% of healthy human feces-derived E. coli strains carry the pks genomic island, which is responsible for synthesizing colibactin, a genotoxic compound implicated in colorectal cancer. However, the expression conditions of colibactin in the gut remain poorly understood. In this study, it is demonstrated that colibactin production is highest under anoxic conditions and decreases with increased oxygen concentration. The positive regulation of colibactin production and genotoxicity by the aerobic respiration control (ArcA) in response to oxygen availability suggests that the pks biosynthetic pathway is adapted for the anoxic intestinal lumen and hypoxic infected or tumor tissue.
Article
Gastroenterology & Hepatology
Antonio Francavilla, Giulio Ferrero, Barbara Pardini, Sonia Tarallo, Laura Zanatto, Gian Paolo Caviglia, Sabina Sieri, Sara Grioni, Giulia Francescato, Francesco Stalla, Cristina Guiotto, Lucia Crocella, Marco Astegiano, Mauro Bruno, Pier Luigi Calvo, Paolo Vineis, Davide Giuseppe Ribaldone, Alessio Naccarati
Summary: Current treatment for celiac disease is adhering to a gluten-free diet, but its long-term molecular effects are still unknown. This study explored fecal small non-coding RNAs and gut microbiome profiles in celiac disease subjects and found altered miRNA and microbial profiles in treated celiac disease subjects.
Article
Gastroenterology & Hepatology
Hui Xu, Haidan Luo, Jiayu Zhang, Kai Li, Mong-Hong Lee
Summary: The probiotic Clostridium butyricum (C.B) plays a role in regulating disease and cancers, but the mechanisms underlying these roles are largely unknown. This study reveals that C.B can reprogram the behavior of CRC cells by regulating crucial signaling molecules, such as MYC. By destabilizing MYC, C.B supplementation suppresses cancer cell proliferation and metastasis, enhances sensitivity to 5-FU treatment, and improves the efficacy of anti-PD1 immunotherapy.
Article
Gastroenterology & Hepatology
Yannouck F. van Lier, Jael Vos, Bianca Blom, Mette D. Hazenberg
Summary: Patients with hematological malignancies often undergo allogeneic hematopoietic cell transplantation (HCT) to cure their condition. HCT can disrupt the intestinal microbiota, leading to poor transplant outcomes and graft-versus-host disease (GvHD). Strategies such as dietary interventions, antibiotic stewardship, and fecal microbiota transplantation are being explored to prevent or treat microbiota injury and GvHD. This review provides insights into the role of microbiome in GvHD pathogenesis and summarizes interventions for microbiota injury prevention and treatment.
Article
Gastroenterology & Hepatology
Da-Jung Jung, Ledia Gebremedhin, Byoungsook Goh, Ji-Sun Yoo, Francesca Gazzaniga, Dennis L. Kasper, Sungwhan F. Oh
Summary: Symbiotic microbiota play a critical role in maintaining host immune homeostasis in a cell-specific manner. Germ-free animals have been the gold standard for excluding microbial components but complete removal of gut microbiota from birth can impair physiological development. Using an improved regimen, we were able to rapidly remove gut microbiota and maintain sterility in animals without any adverse reactions. This method allowed us to observe kinetic differences among colonic lymphocyte subsets that are not observed in traditional germ-free animal models. Additionally, we were able to distinguish between direct stimulation and homeostatic cues of microbiota contribution to effector cell function.
Article
Gastroenterology & Hepatology
Yu Shimizu, Ryodai Yamamura, Yuki Yokoi, Tokiyoshi Ayabe, Shigekazu Ukawa, Koshi Nakamura, Emiko Okada, Akihiro Imae, Takafumi Nakagawa, Akiko Tamakoshi, Kiminori Nakamura
Summary: Sleep is crucial for our health, and insufficient sleep can increase the risk of diseases due to imbalanced intestinal microbiota. However, the mechanisms through which short sleep leads to dysbiosis remain unknown. This study aims to investigate the effects of short sleep on HD5 secretion and the intestinal microbiota.
Review
Gastroenterology & Hepatology
Yi-han Wei, Xi Ma, Jiang-Chao Zhao, Xiu-Qi Wang, Chun-Qi Gao
Summary: This review focuses on the role of succinate, a metabolite produced by both host cells and gut microbes, in activating intestinal mucosal cells and regulating the gut-immune tissue axis. It also explores its function as a mediator of microbiota-host crosstalk and its potential in regulating intestinal microbiota homeostasis. The review provides insights into feasible ways to modulate succinate levels and highlights succinate as a potential target for microbial therapeutics for humans.
Article
Gastroenterology & Hepatology
Yali Liu, Harry Cheuk-Hay Lau, Jun Yu
Summary: Trillions of microbes in the human gastrointestinal tract form an ecological community known as the gut microbiota, which plays a crucial role in dietary digestion and produces various metabolites. However, these microbial metabolites have been found to be correlated with the development of colorectal cancer (CRC) and can also impact the efficacy of cancer treatments. This review discusses the role of metabolites derived from microbes-mediated metabolism of dietary components and their influence on CRC development, as well as their impacts on chemotherapy and immunotherapy. Targeting metabolites may be a promising therapeutic approach for improving patient outcome in CRC.
Article
Gastroenterology & Hepatology
Jing Lu, Xiaobing Fan, Lei Lu, Yueyue Yu, Erica Markiewicz, Jessica C. Little, Ashley M. Sidebottom, Erika C. Claud
Summary: Maternal immune activation (MIA) derived from late gestational infection increases the risk of neurodevelopmental deficits in offspring. This study shows that MIA induced underdevelopment and dysfunction of the blood-brain barrier (BBB) in prewean mice, leading to impaired spatial learning later in life. Maternal supplementation of Limosilactobacillus reuteri (L. reuteri) rescued BBB development and cognitive function associated with BBB dysfunction.
Article
Gastroenterology & Hepatology
Seung-Ho Seo, Chang-Su Na, Seong-Eun Park, Eun-Ju Kim, Woo-Seok Kim, ChunKyun Park, Seungmi Oh, Yanghee You, Mee-Hyun Lee, Kwang-Moon Cho, Sun Jae Kwon, Tae Woong Whon, Seong Woon Roh, Hong-Seok Son
Summary: Age-related changes in gut microbes and urine metabolites were studied in 568 healthy individuals. The richness and evenness of fecal microbiota increased with age, and 16 genera showed significant abundance differences between young and old groups. Additionally, 17 urine metabolites contributed to the age-related differences. Bacteroides and Prevotella 9 were found to be correlated with some urine metabolites. The machine learning algorithm XGBoost achieved the best age prediction performance, with a mean absolute error of 5.48 years. Including urine metabolite data improved the accuracy to 4.93 years. This study highlights the potential of using gut microbiota and urine metabolic profiles for age prediction in healthy individuals.
Article
Gastroenterology & Hepatology
Meixia Li, Yeqing Wang, Ciliang Guo, Sheng Wang, Liangzhen Zheng, Yifan Bu, Kan Ding
Summary: A demonstration of cellulose degrading bacterium from human gut challenged the belief that humans cannot degrade cellulose. However, research on the molecular level of cellulose degradation by human gut microbiota is still incomplete. Using cellobiose as a model, we investigated the molecular mechanism behind cellulose degradation by key members of the human gut microbiota, such as Bacteroides ovatus (BO). Our results showed that a new polysaccharide utilization locus (PUL) from BO was involved in cellobiose capturing and degradation, and two new cellulases on the cell surface, BACOVA_02626 (GH5) and BACOVA_02630 (GH5), were responsible for cellobiose degradation into glucose. Studies on mice also revealed that cellobiose reshaped the gut microbiota composition and potentially modified bacterial metabolic functions. These findings provide further evidence of cellulose degradation by human gut microbes and contribute new insights to cellulose research.
Article
Gastroenterology & Hepatology
Laila Silamikele, Rihards Saksis, Ivars Silamikelis, Patricija Pauline Kotovica, Monta Briviba, Ineta Kalnina, Zane Kalnina, Davids Fridmanis, Janis Klovins
Summary: This study investigated the spatial variation of the gut microbiome in a mouse model of type 2 diabetes induced by a high-fat diet. The results showed that metformin treatment significantly altered the gut microbiome diversity in different intestinal parts, with the most pronounced effect in the small intestine. The abundance of Lactococcus increased remarkably, while the abundance of Lactobacillus was lower in male mice compared to female mice. Diet type and intestinal layer also had significant effects on microbiome composition.
Article
Gastroenterology & Hepatology
Alba Santiago, Amber Hann, Marco Constante, Sara Rahmani, Josie Libertucci, Kyle Jackson, Gaston Rueda, Laura Rossi, Ramachandran Rithwick, Wolfram Ruf, Jon Schertzer, Alberto Caminero, Premysl Bercik, Heather Jean Galipeau, Elena Francisca Verdu
Summary: Emerging evidence suggests that microbial proteolytic activity is implicated in ulcerative colitis (UC), but its role in Crohn's disease (CD) remains unclear. This study investigated the effects of colonizing germ-free mice with CD microbiota and healthy control microbiota. It was found that CD proteolytic microbiota increased colitis severity through a PAR2 pathway. These findings highlight the proinflammatory nature of CD proteolytic microbiota and its role in exacerbating colitis.
Article
Gastroenterology & Hepatology
Yvonne L. L. Latour, Margaret M. M. Allaman, Daniel P. P. Barry, Thaddeus M. M. Smith, Kamery J. J. Williams, Kara M. M. McNamara, Justin Jacobse, Jeremy A. A. Goettel, Alberto G. G. Delgado, M. Blanca Piazuelo, Shilin Zhao, Alain P. P. Gobert, Keith T. T. Wilson
Summary: Lack of talin-1 in intestinal epithelial cells increases susceptibility to colonic disease caused by pathogenic Escherichia coli, leading to decreased survival, increased colonization, colon weight, and histologic colitis. Loss of talin-1 in colonic epithelial cells impairs recruitment and activation of T cells, exacerbating colonic mucosal hyperplasia and cell crowding in the glands.
Review
Gastroenterology & Hepatology
Natalia Szostak, Marek Figlerowicz, Anna Philips
Summary: In recent years, the role of gut microbiota in human health and disease has gained increasing attention. However, most studies on the gut microbiome primarily focus on bacteria and neglect the fungi that exist in the human intestines. This review highlights the importance of the gut mycobiome in liver homeostasis and its perturbations, emphasizing the compositional changes of fungi in liver diseases and providing new insights for liver research and potential therapeutic targets.
Article
Gastroenterology & Hepatology
Kyoung Su Kim, Eunike Tiffany, Ji-Young Lee, Ara Oh, Hyeon-Su Jin, Ji-Sun Kim, Jung-Sook Lee, Myung Hee Nam, Soo-Jong Hong, Sowon Park, Hong Koh, Bong-Soo Kim, Yun Kyung Lee, Dong-Woo Lee
Summary: In this study, the functional modules of mucin catabolism were assessed through bioinformatics-aided functional annotation. The metabolic pathways of A. muciniphila and R. gnavus were identified and their distinct metabolic features were found to influence the host immune response and gut ecosystem.
