Article
Agronomy
Zhenxin Wang, Chunyan Zhan, Yingying Zhang, Lin Zhang, Jiaolong Li, Tong Xing, Liang Zhao, Jianfei Wang, Feng Gao
Summary: This study investigated the effects of dietary corn-resistant starch on bile acid metabolism in broilers. The results showed that resistant starch supplementation reduced lipid levels and altered bile acid synthesis and reabsorption capacities in broilers.
Review
Gastroenterology & Hepatology
Junwei Xiang, Zhengyan Zhang, Hongyi Xie, Chengcheng Zhang, Yan Bai, Hua Cao, Qishi Che, Jiao Guo, Zhengquan Su
Summary: FXR, a nuclear receptor for bile acids, plays a key role in regulating metabolic pathways and improving various diseases. Bile acids link the intestine with the liver through the enterohepatic circulation, with different types of bile acids having diverse effects on the intestines, providing a foundation for new treatment methods.
Review
Biochemistry & Molecular Biology
Yulia Shulpekova, Elena Shirokova, Maria Zharkova, Pyotr Tkachenko, Igor Tikhonov, Alexander Stepanov, Alexandra Sinitsyna, Alexander Izotov, Tatyana Butkova, Nadezhda Shulpekova, Vladimir Nechaev, Igor Damulin, Alexey Okhlobystin, Vladimir Ivashkin
Summary: Bile acids play crucial physiological roles in the human body. They are essential for the absorption and excretion of nutrients and also act as sensors for intestinal contents, regulating their effects through processes such as intestinal absorption. Bile acids have significant impacts on liver function, cholesterol synthesis, and detoxification of xenobiotics. Their synthesis and regulation in different parts of the digestive tract are vital, as is their interaction with the intestinal microbiota.
Article
Biochemistry & Molecular Biology
Eun Young Kim, Jae Man Lee
Summary: The FXR receptor is essential for liver function, bile acid synthesis, glucose metabolism, and enzyme activity. Research shows that FXR in intestinal epithelial cells is directly linked to the Mg2+ channel Trpm6, potentially connecting bile acid signaling to Mg2+ homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Jing Zeng, Jiangao Fan, Huiping Zhou
Summary: Chronic cholestatic liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), gradually progress to liver fibrosis, cirrhosis, and failure. Disruption of bile acid metabolism and intrahepatic circulation plays a crucial role in accelerating the progression of cholestatic liver diseases. Bile acids not only act as detergents for nutrition absorption but also function as key signaling molecules that regulate hepatic metabolism and immune responses. This review focuses on the role of bile acid-mediated signaling in cholestatic liver disease.
CELL AND BIOSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Silvia Marchiano, Michele Biagioli, Rosalinda Roselli, Angela Zampella, Cristina Di Giorgio, Martina Bordoni, Rachele Bellini, Elva Morretta, Maria Chiara Monti, Eleonora Distrutti, Stefano Fiorucci
Summary: This study found that mice fed a high fat/high cholesterol diet are protected from developing a pro-atherogenic lipid profile due to their ability to dispose cholesterol through bile acids. This protective mechanism is mediated by the suppression of FXR signaling in the liver. In contrast, treatment with the FXR agonist obeticholic acid showed limited effectiveness in improving liver histopathology in patients with NAFLD, while treatment with the statin atorvastatin mitigated liver and vascular injury caused by the high fat/high cholesterol diet and increased bile acids synthesis and excretion.
Article
Gastroenterology & Hepatology
Pengcheng Cai, Xiaoyu Mao, Jieqiong Zhao, Li Nie, Yan Jiang, Qifen Yang, Rui Ni, Jianbo He, Lingfei Luo
Summary: This study found that FXR regulates BPPC-to-hepatocyte and BPPC-to-BEC redifferentiations through ERK1 and Notch, respectively. FXR agonists are being used in clinical trials for liver diseases, and this study proposes potential underlying mechanisms by characterizing the roles of FXR in the stimulation of dedifferentiation-redifferentiation transition and BPPC redifferentiation.
Article
Pharmacology & Pharmacy
Christopher Yip, Naomi C. Okada, Amber Howerton, Amei Amei, Ernesto Abel-Santos
Summary: The synthetic bile salt CamSA shows potential in preventing Clostridioides difficile infections, offering multi-day protection with a single dose in mice. Its pharmacokinetic properties suggest limited systemic absorption and a slow-release mechanism through cycling between the liver and intestines. This unique pattern of protection may be attributed to CamSA's stability in the gut of antibiotic-treated mice and degradation by the microbiota in non-antibiotic treated animals.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
T. M. Zaved Waise, Yu-Mi Lim, Zahra Danaei, Song-Yang Zhang, Tony K. T. Lam
Summary: The TCDCA-FXR axis in the upper small intestine and ileum plays a crucial role in regulating local nutrient sensing and glucose homeostasis in rats. Transplantation of healthy microbiota and FXR inhibition can improve the nutrient sensing dysfunction caused by high-fat diet.
MOLECULAR METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
Katrin Panzitt, Martin Wagner
Summary: The liver serves as a central metabolic hub that coordinates nutritional inputs and metabolic outputs. FXR in the liver and intestine plays a crucial role in regulating postprandial nutrient disposal. Aside from classical roles, FXR also has effects on amino acid, protein metabolism, autophagic turnover, and inflammation, which are less studied. Additionally, understanding of how FXR signaling is affected by posttranslational modifications and different isoforms is important for potential pharmaceutical targeting in clinical applications.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Dongqin Wei, Yizhou Li, Meng Che, Chaowei Li, Qiong Wu, Chao Sun
Summary: It has been reported that aging-induced changes in the gut microbiota may promote hepatic lipid dysmetabolism by shaping the pattern of secondary bile acids. Melatonin treatment reverses these effects and inhibits the expression of hepatic FXR, leading to a decrease in hepatic TMAO production and relief of hepatic lipid dysmetabolism.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Plant Sciences
Yu Fu, Han Feng, Xue Ding, Qing-Hai Meng, Shu-Rui Zhang, Jun Li, Ying Chao, Ting-Ting Ji, Yun-Hui Bi, Wei-Wei Zhang, Qi Chen, Yu-Han Zhang, You-Long Feng, Hui-Min Bian
Summary: AB23A may prevent postmenopausal atherosclerosis by regulating hepatic farnesoid X receptor, increasing bile acid and cholesterol excretion, and reducing plasma cholesterol levels, providing a potential therapeutic approach.
Article
Food Science & Technology
Andras Gregor, Sandra Auernigg-Haselmaier, Manuel Malleier, Stefan Bruckberger, Joana Seneca, Petra Pjevac, Marc Pignitter, Kalina Duszka
Summary: Previously, we found that caloric restriction (CR) led to increased levels of taurine and taurine-conjugated bile acids (BA) in the gut. In this study, we discovered that restrictive diets, such as intermittent fasting and fasting-mimicking diet, had a similar effect as CR. The type of cage bedding affected the levels of BAs and taurine, and removal of cage bedding reversed the CR phenotype. Microbiota transplant from CR mice increased BAs deconjugation. Inhibition of bile salt hydrolase (BSH) prevented the increase in free taurine while increasing taurine-conjugated BA levels. Consuming high fiber diets increased taurine conjugates without elevating BAs levels.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Review
Endocrinology & Metabolism
Roisin Ni Dhonnabhain, Qiao Xiao, Dervla O'Malley
Summary: Functional bowel disorders like IBS are multifactorial conditions that significantly impact individuals' quality of life. Gut-brain communication, bile acid modulation, and alterations in microbial profiles could be key factors in the pathophysiology of IBS symptoms.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Zi-Lin Ren, Chang-Xiang Li, Chong-Yang Ma, Dan Chen, Jia-Hui Chen, Wen-Xiu Xu, Cong-Ai Chen, Fa-Feng Cheng, Xue-Qian Wang
Summary: Non-alcoholic fatty liver disease (NAFLD) affects a significant population worldwide and has implications beyond the liver, including the brain. The bile acid signaling pathway plays a crucial role in the development of NAFLD and brain disorders. Bile acids can send messages to the brain through direct or indirect channels, potentially impacting brain health.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Ecology
Matthew S. Kelly, Catherine Plunkett, Yahe Yu, Jhoanna N. Aquino, Sweta M. Patel, Jillian H. Hurst, Rebecca R. Young, Marek Smieja, Andrew P. Steenhoff, Tonya Arscott-Mills, Kristen A. Feemster, Sefelani Boiditswe, Tirayaone Leburu, Tiny Mazhani, Mohamed Z. Patel, John F. Rawls, Jayanth Jawahar, Samir S. Shah, Christopher R. Polage, Coleen K. Cunningham, Patrick C. Seed
Summary: This study conducted in sub-Saharan Africa examined the nasopharyngeal microbiome of 179 mother-infant dyads to investigate the relationship between Corynebacterium abundance and Streptococcus pneumoniae colonization in infants. Results showed a negative correlation between Corynebacterium abundance and S. pneumoniae colonization, with in vitro experiments demonstrating growth inhibition of S. pneumoniae by secreted factors from Corynebacterium strains isolated from infants. Additionally, antibiotic exposure and seasonal variations were associated with changes in Corynebacterium abundance, suggesting potential implications for preventing pneumococcal infections.
Article
Pediatrics
Lilianna Suarez, Asheley C. Skinner, Tracy Truong, Jessica R. McCann, John F. Rawls, Patrick C. Seed, Sarah C. Armstrong
Summary: In a specialized healthcare setting, a significant number of adolescents opt for new and advanced obesity treatments, particularly those at higher risk for developing diabetes.
Article
Biotechnology & Applied Microbiology
Jayanth Jawahar, Alexander W. McCumber, Colin R. Lickwar, Caroline R. Amoroso, Sol Gomez de la Torre Canny, Sandi Wong, Margaret Morash, James H. Thierer, Steven A. Farber, Brendan J. M. Bohannan, Karen Guillemin, John F. Rawls
Summary: This study reveals the effects of long-term starvation and refeeding on the intestinal transcriptome and microbiome in zebrafish. Starvation leads to changes in intestinal microbiome composition and host gene expression, which are rapidly reversed after refeeding.
Article
Immunology
Jillian H. Hurst, Alexander W. McCumber, Jhoanna N. Aquino, Javier Rodriguez, Sarah M. Heston, Debra J. Lugo, Alexandre T. Rotta, Nicholas A. Turner, Trevor S. Pfeiffer, Thaddeus C. Gurley, M. Anthony Moody, Thomas N. Denny, John F. Rawls, James S. Clark, Christopher W. Woods, Matthew S. Kelly
Summary: The upper respiratory microbiome features are associated with SARS-CoV-2 infection susceptibility and symptoms among children, adolescents, and young adults, and the relationship is influenced by age.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Filipe M. Cerqueira, Amanda L. Photenhauer, Heidi L. Doden, Aric N. Brown, Ahmed M. Abdel-Hamid, Sarah Morais, Edward A. Bayer, Zdzislaw Wawrzak, Isaac Cann, Jason M. Ridlon, Jesse B. Hopkins, Nicole M. Koropatkin
Summary: Researchers performed a structure-function analysis of Sas20 and found that it has two distinct starch-binding domains that facilitate the degradation of resistant starch in the human gut by Ruminococcus bromii.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Gastroenterology & Hepatology
Colin R. Lickwar, James M. Davison, Cecelia Kelly, Gilberto Padilla Mercado, Jia Wen, Briana R. Davis, Matthew C. Tillman, Ivana Semova, Sarah F. Andres, Goncalo Vale, Jeffrey G. McDonald, John F. Rawls
Summary: This study reveals that the combination of microbiota and high-fat diet may suppress the expression of hepatocyte nuclear factor 4 alpha, leading to the preferential activation of intestinal epithelial cell proliferation programs, which in turn affects intestinal lipid absorption, epithelial cell renewal, and systemic energy balance.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Ismael Gomez-Martinez, R. Jarrett Bliton, Keith A. Breau, Michael J. Czerwinski, Ian A. Williamson, Jia Wen, John F. Rawls, Scott T. Magness
Summary: Through single-cell RNA sequencing, it was found that the expression of lipid-handling genes increases as absorptive enterocytes mature. Culture conditions promote differentiation of intestinal stem cells into dense absorptive enterocyte monolayers. Fatty acid oxidation modulation affects fatty acid export, while short-chain fatty acids are unaffected.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Review
Immunology
Jean-Pierre Levraud, John F. Rawls, Anne E. Clatworthy
Summary: Animals rely on their nervous and immune systems to perceive and adapt to their environment, with microorganisms playing a significant role. The zebrafish serves as a model organism for studying the interactions between the immune and nervous systems, the nervous system and the microbiota, and the microbiota and immune system.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Gastroenterology & Hepatology
Genta Kakiyama, Kei Minowa, Daniel Rodriguez-Agudo, Rebecca Martin, Hajime Takei, Kuniko Mitamura, Shigeo Ikegawa, Mitsuyoshi Suzuki, Hiroshi Nittono, Michael Fuchs, Douglas M. Heuman, Huiping Zhou, William M. Pandak
Summary: This study demonstrated that dietary coffee can prevent the accumulation of hepatic oxysterols by maintaining the expression of Cyp7b1/Sult2b1 genes in a diet-induced NAFLD mice model. Lowering liver oxysterols markedly reduced inflammation in the coffee-ingested mice. Caffeine is not fundamental to this effect. In addition, this study showed that the responses of Cyp7b1/Sult2b1 genes to insulin signaling can be mediated through a transcriptional factor, HNF4 alpha. The insulin-HNF4 alpha-Cyp7b1/Sult2b1 signaling pathway, which directly correlates to the onset of NASH triggered by insulin resistance, offers insight into approaches for NAFLD treatment.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wenxin Tong, Sarah A. Hannou, You Wang, Inna Astapova, Ashot Sargsyan, Ruby Monn, Venkataramana Thiriveedi, Diana Li, Jessica R. McCann, John F. Rawls, Jatin Roper, Guo-fang Zhang, Mark A. Herman
Summary: The tricarboxylic acid (TCA) cycle plays a crucial role in cellular aerobic metabolism, producing energy and precursor molecules while also acting as a signaling pathway. Research shows that the gut is a major contributor to circulating TCA cycle metabolites, with endogenous succinate production being a key physiological source.
Article
Genetics & Heredity
Jennifer K. Heppert, Colin R. Lickwar, Matthew C. Tillman, Briana R. Davis, James M. Davison, Hsiu-Yi Lu, Wei Chen, Elisabeth M. Busch-Nentwich, David L. Corcoran, John F. Rawls
Summary: Transcription factors hnf4a and hnf4g play important roles in the development and function of the intestinal epithelium, showing partial genetic redundancy.
Article
Biochemistry & Molecular Biology
Yamato Muto, Mitsuyoshi Suzuki, Genta Kakiyama, Takahiro Sasaki, Tsuyoshi Murai, Hajime Takei, Hiroshi Nittono
Summary: In this study, we investigated the age-related changes in urinary excretion of glucuronidated bile acids, finding that the secretion of 3-glucuronides of secondary bile acids coincided with the establishment of gut bacterial flora in infants. Furthermore, the hepatic enzyme activity varied with age, with higher glucuronidation activity towards nonamidated bile acids.
Review
Cell Biology
Genta Kakiyama, Daniel Rodriguez-Agudo, William M. Pandak
Summary: The rising prevalence of NAFLD-related cirrhosis emphasizes the importance of understanding the molecular mechanisms involved in the progression from hepatic steatosis to steatohepatitis and fibrosis/cirrhosis. Insulin resistance is a known factor in early NAFLD, but the link between aberrant insulin signaling and hepatocyte inflammation has been unclear. Recent research has shown that hepatocyte toxicity caused by hepatic free cholesterol and its metabolites is fundamental to the development of NASH. Specifically, abnormal hepatocyte insulin signaling leads to dysregulation in bile acid biosynthetic pathways and the accumulation of toxic cholesterol metabolites, driving hepatocyte toxicity. This two-hit model highlights the importance of both abnormal insulin signaling and the accumulation of toxic cholesterol metabolites in NAFL progression.
Article
Microbiology
Cecelia Kelly, Jayanth Jawahar, Lauren Davey, Jeffrey I. Everitt, Joseph A. Galanko, Chelsea Anderson, Jonathan E. Avendano, Jessica R. McCann, R. Balfour Sartor, Raphael H. Valdivia, John F. Rawls
Summary: This study explores the subclinical stages of inflammatory bowel diseases (IBD) in mice lacking the IBD-associated transcription factor HNF4A in the intestinal epithelium. The results suggest that interactions between host genotype and microbiota can drive early subclinical pathologies that precede the overt onset of IBD.