Article
Microbiology
Hongtao Xu, Fang Fang, Kaizhang Wu, Jiangping Song, Yaqian Li, Xingyu Lu, Juncheng Liu, Liuyang Zhou, Wenqing Yu, Fei Yu, Jie Gao
Summary: FMT-dd transplantation reshaped the gut microbiota by increasing Faecalibaculum and Ruminococcaceae UCG-010, leading to elevated levels of CA, CDCA, and DCA, reduced bile acid synthesis, and increased cholesterol accumulation via the hepatic FXR-SHP axis in dyslipidemia mice. However, a high-fat diet impacted Muribaculum in humanized dyslipidemia mice, resulting in reduced HDCA, increased bile acid synthesis, and enhanced lipid absorption via the intestinal FXR-FGF19 axis.
Review
Medicine, Research & Experimental
Shuni Duan, Xiaojiaoyang Li, Guifang Fan, Runping Liu
Summary: Liver diseases and related complications are major causes of morbidity and mortality worldwide. Effective treatments are limited, highlighting the need for novel therapies. Bile acids (BAs) play important roles in regulating energy and immune homeostasis in various liver diseases, making them attractive therapeutic targets. This review summarizes recent progress in understanding the enterohepatic circulation of BAs, potential targets of BAs signaling, and the development of treatments. The protective effects, molecular mechanisms, and outcomes of clinical trials are discussed, along with future perspectives for the development of these candidates. In conclusion, pharmacological therapies targeting BAs signaling hold promise for the treatment of complex liver disorders.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Environmental Sciences
Yunhuan Liu, Weili Kang, Shuiping Liu, Jinyan Li, Jinyan Liu, Xingxiang Chen, Fang Gan, Kehe Huang
Summary: This study reveals a new mechanism of Cd-induced liver injury, in which Cd exposure leads to dysbiosis of gut microbiota, reduces fecal bile salt hydrolase activity, and increases the level of a certain substance in the intestine, thereby inhibiting intestinal FXR/FGF-15 signaling, increasing hepatic bile acid synthesis, and ultimately facilitating hepatic ductular proliferation, inflammation, and injury in mice.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Review
Gastroenterology & Hepatology
Yaoxuan Wang, Lei Zheng, Zhiyuan Zhou, Danhua Yao, Yuhua Huang, Bin Liu, Yantao Duan, Yousheng Li
Summary: The bile acid-gut microbiota axis is crucial in the pathogenesis of IFALD, serving as potential diagnostic markers and therapeutic targets. A multitarget, individualized therapy focused on the BA-GM axis may provide optimal clinical benefits and warrants further investigation.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Chao Yang, Min Wan, Dengfeng Xu, Da Pan, Hui Xia, Ligang Yang, Guiju Sun
Summary: The study found that flaxseed powder can prevent the development of NASH by regulating gut microbiomes and bile acids, activating two important pathways in the intestine, which has significant beneficial effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Gastroenterology & Hepatology
Benedikt Simbrunner, Michael Trauner, Thomas Reiberger
Summary: Bile acids play a crucial role in maintaining bile acid homeostasis and regulating the development of liver diseases through the gut-liver axis. The nuclear bile acid farnesoid X receptor (FXR) has emerged as a key therapeutic target in bile acid signalling pathways. Experimental evidence suggests that bile acid signalling can improve the intestinal barrier and protect against bacterial translocation in cirrhosis, showing efficacy in cholestatic and metabolic liver diseases. However, further research is needed to demonstrate similar effects in advanced liver disease, particularly in patients with decompensated cirrhosis.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Endocrinology & Metabolism
Xianjiao Liu, Jinyan Li, Mengdie Shi, Jun Fu, Yubo Wang, Weili Kang, Jinyan Liu, Fenxia Zhu, Kehe Huang, Xingxiang Chen, Yunhuan Liu
Summary: Melatonin (MT) improves hepatic injury and fibrosis in cholestatic liver disease mice by remodeling gut microbiota and activating intestinal farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF-15) axis-mediated inhibition of hepatic bile acid synthesis and promotion of bile acid excretion.
JOURNAL OF PINEAL RESEARCH
(2023)
Article
Food Science & Technology
Yunhuan Liu, Jinyan Li, Weili Kang, Shuiping Liu, Jinyan Liu, Mengdie Shi, Yubo Wang, Xianjiao Liu, Xingxiang Chen, Kehe Huang
Summary: This study investigated the mechanism of AFB1-induced liver injury. It was found that AFB1 exposure caused bile duct proliferation, oxidative stress, inflammation, and liver injury in mice. AFB1 exposure also led to gut microbiota dysbiosis and reduced fecal bile salt hydrolase activity. Furthermore, AFB1 exposure altered intestinal bile acid metabolism and inhibited intestinal FXR/FGF-15 signaling. The study suggests that modifying the gut microbiota, altering intestinal bile acid metabolism, and activating intestinal FXR/FGF-15 signaling may be potential treatment strategies for AFB1-induced liver disease.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Gastroenterology & Hepatology
Kyounghwa Jung, Minwook Kim, Juhoon So, Seung-Hoon Lee, Sungjin Ko, Donghun Shin
Summary: This study identifies that activation of farnesoid X receptor (FXR) impairs biliary epithelial cell (BEC)-driven liver regeneration by enhancing PTEN activity. FXR activation reduces hepatic progenitor cell proliferation and increases cell death by inhibiting the PI3K-AKT-mTOR signaling pathway.
Article
Gastroenterology & Hepatology
Yankai Wen, Christoph Emontzpohl, Long Xu, Constance L. Atkins, Jong-Min Jeong, Yang Yang, Kangho Kim, Chuan Wu, Shizuo Akira, Cynthia Ju
Summary: IL-33 has been found to promote liver regeneration through the IL-33/ST2-induced release of serotonin from enterochromaffin cells into portal blood and subsequent activation of HTR2A/p70S6K in hepatocytes.
Article
Cell Biology
Kun Zuo, Chen Fang, Yuanfeng Gao, Yuan Fu, Hongjiang Wang, Jing Li, Jiuchang Zhong, Xinchun Yang, Li Xu
Summary: This study investigates the role of the gut microbiota-bile acid-fibroblast growth factor 19 axis in patients with atrial fibrillation. The study found dysregulated gut microbial biotransformation of bile acids in AF patients, as well as a decrease in secondary bile acids in the faeces of AF patients. Additionally, reduced levels of circulating FGF19 were observed in AF patients. In vitro cell experiments demonstrated the protective role of FGF19 against lipid accumulation in atrial cardiomyocytes. Overall, the study suggests that decreased levels of secondary bile acids and circulating FGF19 contribute to impaired protective function in AF patients.
CELL PROLIFERATION
(2023)
Review
Cell Biology
Herbert Tilg, Timon E. Adolph, Michael Trauner
Summary: Bidirectional crosstalk between the gut and liver plays a crucial role in regulating gastrointestinal health and disease. Nutrients, microbial antigens, metabolites, and bile acids regulate metabolism and immune responses in the gut and liver, which reciprocally shape the structure and function of the microbial community. Perturbation of this host-microbe interaction is observed in various liver diseases and is exacerbated by impaired intestinal barrier, contributing to hepatic inflammation and disease progression.
Review
Nutrition & Dietetics
Andreas Blesl, Vanessa Stadlbauer
Summary: The gut-liver axis is a crucial physiological interplay between the gut and liver, with disruptions playing a key role in the evolution and progression of chronic cholestatic liver diseases. Key features of this cycle include the gut microbiome, gut barrier, bacterial translocation, and bile acid metabolism. Understanding of the alterations in the gut-liver axis has significantly increased, influencing the pathogenesis and outcome of these diseases. Therapeutic implications and future scientific objectives are also outlined in this review.
Review
Microbiology
Cynthia L. Hsu, Bernd Schnabl
Summary: The trillions of microorganisms in the human intestine play a crucial role in maintaining health, and disruptions in the gut microbial communities can lead to diseases. The gut microbiota has a symbiotic relationship with the gut, liver, and immune system. Environmental factors such as high-fat diets and alcohol consumption can disrupt and alter the microbial communities, resulting in dysfunction of the intestinal barrier, translocation of microbial components to the liver, and the development or progression of liver disease.
NATURE REVIEWS MICROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Paola Brescia, Maria Rescigno
Summary: The intestinal barrier is crucial for protecting the body from external insults, and a breach in this barrier can lead to systemic microbial dissemination and various diseases. Imbalance in gut microbiota has been associated with intestinal vascular barrier leakage, contributing to the development of a range of disorders.
TRENDS IN MOLECULAR MEDICINE
(2021)
Review
Oncology
Roberta Zerlotin, Maria Arconzo, Elena Piccinin, Antonio Moschetta
Summary: LRH-1, a nuclear receptor highly expressed in stem cells of the crypts, plays a key role in regulating intestinal epithelium and is associated with colorectal cancer.
Review
Gastroenterology & Hepatology
Marica Cariello, Elena Piccinin, Antonio Moschetta
Summary: Nonalcoholic fatty liver disease encompasses a spectrum of liver injuries, from simple steatosis to steatohepatitis and cirrhosis. Nonalcoholic steatohepatitis (NASH) is characterized by liver steatosis, inflammation, hepatocyte damage, and fibrosis. Genetic predisposition and environmental factors such as dietary habits and obesity may contribute to the progression of NASH. The role of lipid-sensing nuclear receptors in the pathogenesis and treatment of NASH, including peroxisome proliferator-activated receptors, farnesoid X receptor, and liver X receptors, is discussed in this study.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Elena Piccinin, Marica Cariello, Antonio Moschetta
Summary: Colorectal cancer is a common cancer worldwide, with cellular metabolism reprogramming recognized as a key step in carcinogenesis. Aberrant activation of lipid metabolism in intestinal tumor cells leads to increased lipid uptake or endogenous synthesis to support proliferation. Strategies to limit lipid accumulation are being developed, with a focus on two major players - Liver X Receptor and Stearoyl-CoA Desaturase 1 - in lipid metabolism contributing to CRC development. Further investigations are needed to develop specific therapies targeting intestinal cancer cell proliferation and CRC progression.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Marica Cariello, Roberto Salvia, Jennifer Hardfeldt, Marilidia Piglionica, David Rutigliano, Pasquale Caldarola, Alice Ossoli, Michele Vacca, Giusi Graziano, Stefano Battaglia, Roberta Zerlotin, Maria Arconzo, Lucilla Crudele, Carlo Sabba, Laura Calabresi, Antonio Moschetta
Summary: The study observed differences in cholesterol acceptability and efflux capacity in serum and monocytes of NSTEMI patients, indicating potential mechanisms for post-infarction treatment. The activation of LXR-driven cholesterol efflux capacity in intracoronary monocytes post-infarction may help overcome reduced serum cholesterol acceptance and inhibit local inflammation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Review
Gastroenterology & Hepatology
Raffaella Maria Gadaleta, Antonio Moschetta
Summary: FGFR4 and its ligand FGF19 play crucial roles in cellular processes, including the development of liver tumors. FGFR4 inhibitors are a promising treatment option for HCC, while using FGF19 analogues to activate FGFR4-KLOTHO represents a novel therapeutic strategy for other liver diseases.
JOURNAL OF HEPATOLOGY
(2021)
Article
Oncology
Marica Cariello, Elena Piccinin, Roberta Zerlotin, Marilidia Piglionica, Claudia Peres, Chiara Divella, Anna Signorile, Gaetano Villani, Giuseppe Ingravallo, Carlo Sabba, Antonio Moschetta
Summary: Platelets play a crucial role in inflammation and tumor development through direct interactions with other cell types, especially through their association with P-selectin. Removing P-selectin from platelets has been shown to reduce tumor growth and inhibit colon cancer progression. This suggests that inhibiting platelets' adhesion to tumor cells could be a novel therapeutic approach for treating colon cancer.
Article
Nutrition & Dietetics
Carlo De Matteis, Lucilla Crudele, Marica Cariello, Stefano Battaglia, Giuseppina Piazzolla, Patrizia Suppressa, Carlo Sabba, Elena Piccinin, Antonio Moschetta
Summary: This study investigated the association between vitamin D levels and inflammatory status in a population of adults. The results showed an inverse relationship between vitamin D levels and the monocytes-to-high density lipoprotein ratio (MHR). When stratified by gender and body composition, men showed a significant relationship only in cases of central obesity, while women exhibited a lifelong negative correlation between circulating vitamin D levels and MHR, regardless of metabolic status.
Article
Biochemistry & Molecular Biology
Gabriele Mocciaro, Simona D'Amore, Benjamin Jenkins, Richard Kay, Antonio Murgia, Luis Vicente Herrera-Marcos, Stefanie Neun, Alice P. Sowton, Zoe Hall, Susana Alejandra Palma-Duran, Giuseppe Palasciano, Frank Reimann, Andrew Murray, Patrizia Suppressa, Carlo Sabba, Antonio Moschetta, Albert Koulman, Julian L. Griffin, Michele Vacca
Summary: Metabolic syndrome (MetS) is characterized by cardiovascular risk factors such as central obesity and atherogenic dyslipidemia. This study used an integrated omics approach to study lipoprotein remodeling and HDL composition in subjects with MetS. The results showed abnormal lipid levels and impaired phospholipid metabolism in HDL, which may be related to the decreased activity of lecithin cholesterol acyltransferase (LCAT).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Nutrition & Dietetics
Raffaella Maria Gadaleta, Marica Cariello, Lucilla Crudele, Antonio Moschetta
Summary: Bile acid species and gut microbiota are crucial for intestinal mucosa homeostasis, shaping and affecting each other. High levels of secondary bile acids are detrimental, and a lack of BSH-active bacteria can lead to intestinal inflammation.
Article
Oncology
Marica Cariello, Roberta Zerlotin, Emanuela Pasculli, Elena Piccinin, Claudia Peres, Emanuele Porru, Aldo Roda, Raffaella Maria Gadaleta, Antonio Moschetta
Summary: The activation of intestinal FXR can prevent both inflammation- and genetically-driven colorectal tumorigenesis by modulating the size and composition of bile acid pool, providing new possibilities for the therapeutic management of intestinal inflammation and tumorigenesis.
Article
Medicine, General & Internal
Lucilla Crudele, Fabio Novielli, Stefano Petruzzelli, Stefano Battaglia, Antonio Francesco Maria Giuliano, Rosa Melodia, Chiara Maria Morano, Paola Dell'Aquila, Renata Moretti, Luigi Castorani, Roberto Salvia, Gianfranco Inglese, Nicola Susca, Lucrezia Dell'Olio, Francesca Falcone, Mariapaola Castaldo, Carlo De Matteis, Carlo Sabba, Antonio Moschetta
Summary: This study aimed to determine if parameters assessing metabolic status can predict prognosis and mortality risk in COVID-19 patients. The results showed that liver fibrosis scores have strong predictive power for in-hospital mortality, length of hospitalization, and admission to ICU.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Nutrition & Dietetics
Carlo De Matteis, Lucilla Crudele, Stefano Battaglia, Tiziana Loconte, Arianna Rotondo, Roberta Ferrulli, Raffaella Maria Gadaleta, Giuseppina Piazzolla, Patrizia Suppressa, Carlo Sabba, Marica Cariello, Antonio Moschetta
Summary: Adherence to the Mediterranean diet is associated with reduced mortality, particularly in individuals with cardiovascular disease, obesity, and diabetes. Existing validated Mediterranean diet scores did not show a significant association with adiposity, leading to the proposal of a new questionnaire, the Chrono Med-Diet score (CMDS), which focuses on dietary chronobiology and physical activity. CMDS was found to be linked to increased waist circumference, dysmetabolic conditions, cardiovascular risk, and Fatty Liver Index.
Article
Infectious Diseases
Davide Fiore Bavaro, Nicolo De Gennaro, Alessandra Belati, Lucia Diella, Roberta Papagni, Luisa Frallonardo, Michele Camporeale, Giacomo Guido, Carmen Pellegrino, Maricla Marrone, Alessandro Dell'Erba, Loreto Gesualdo, Nicola Brienza, Salvatore Grasso, Giuseppe Columbo, Antonio Moschetta, Giovanna Elisiana Carpagnano, Antonio Daleno, Anna Maria Minicucci, Giovanni Migliore, Annalisa Saracino
Summary: The introduction of a pro-active Infectious Disease (ID) consultation in a COVID-19 hospital can reduce the mortality risk of patients with MDROs infections by optimizing treatment and diagnostic strategies to improve patient outcomes.
Letter
Gastroenterology & Hepatology
Lucilla Crudele, Carlo De Matteis, Antonio Moschetta
Review
Medicine, General & Internal
Lucilla Crudele, Raffaella Maria Gadaleta, Marica Cariello, Antonio Moschetta
Summary: The gut-liver axis plays a significant role in the development and treatment of diabetes, and the gut microbiota is a key factor. There are ongoing studies evaluating the therapeutic efficacy of probiotics in diabetes and its complications.
