Article
Chemistry, Multidisciplinary
Shuang Liu, Man Liu, Meng-lin Zhang, Cui-zhe Wang, Yin-liang Zhang, Yu-jie Zhang, Chun-yuan Du, Su-fang Sheng, Wei Wang, Ya-tong Fan, Jia-ni Song, Jin-can Huang, Yue-yao Feng, Wei Qiao, Jin-long Huang, Yu-hui Li, Lu Zhou, Jun Zhang, Yong-sheng Chang
Summary: This study investigates the regulatory mechanisms of bile acid (BA) in the intestine. It reveals that Krüppel-like factor 9 (Klf9) enhances BA absorption in the intestine by promoting the expression of apical sodium-dependent bile acid transporter (Asbt), thereby affecting BA levels in the gallbladder, faeces, and serum. Klf9 also regulates liver BA synthetic enzymes by regulating Fgf15 expression.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Agriculture, Multidisciplinary
Yuki Takashima, Kazuki Ishikawa, Rina Miyawaki, Mana Ogawa, Takeshi Ishii, Takumi Misaka, Shoko Kobayashi
Summary: In this study, the polyphenols theaflavin-3-gallate (TF2A) and theaflavin-3'-gallate (TF2B) were identified to significantly inhibit taurocholic acid (TC) uptake in Caco-2 cells by oxidizing their benzotropolone rings and covalently bonding with cysteine residues of ASBT. Their inhibitory effect was also found to be competitive through a substrate concentration-dependent TC uptake assay.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Food Science & Technology
Qiang Tang, Chen Wang, Ge Jin, Yun li, Huiqin Hou, Xianglu Wang, Qin Guo, Tianyu Liu, Sinan Wang, Xin Dai, Bangmao Wang, Hailong Cao
Summary: The prevalence of obesity is increasing rapidly worldwide, and it is closely related to diet and gut microbiota. Maternal emulsifier polysorbate 80 (P80) exposure in early life can lead to impaired intestinal development, barrier dysfunction, and increased low-grade inflammation in offspring, as well as gut dysbiosis. Offspring exposed to maternal P80 are more susceptible to gut dysbiosis and obesity after a high-fat diet, accompanied by alterations in bile acid composition and up-regulation of the FXR-FGF15 axis.
FOOD RESEARCH INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Mohammad Nazmul Hasan, Jianglei Chen, David Matye, Huaiwen Wang, Wenyi Luo, Lijie Gu, Yung Dai Clayton, Yanhong Du, Tiangang Li
Summary: This study investigates the enhanced therapeutic efficacy of combining the apical sodium-dependent bile acid transporter inhibitor GSK2330672 and fibroblast growth factor-15 (FGF15) over-expression in Cyp2c70 KO mice. The combined treatment was more effective in alleviating hepatobiliary injury in female Cyp2c70 KO mice, but ineffective in male mice. It reduced bile acid pool and improved gut barrier function.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Bhargavi Nallamothu, Kaushik Kuche, Rohan Ghadi, Dasharath Chaudhari, Sanyog Jain
Summary: This study examines the impact of charge and chain length of bile salts in bilosomes on the oral bioavailability of insulin and verifies the results by examining their uptake via ASBT. The results indicate that anionic bilosomes are more efficiently taken up by ASBT than cationic bilosomes, thereby improving the oral bioavailability of insulin in bilosomes. Additionally, the developed bilosomes are able to provide superior protection in biological fluids while maintaining the integrity of the loaded drug.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Multidisciplinary
Feiyang Deng, Kyoung Sub Kim, Jiyoung Moon, You Han Bae
Summary: Bile acid-modified nanoparticles can improve oral bioavailability of poorly permeable drugs by interacting with bile acid transporters. This study investigates the transport of glycocholic acid (GCA)-conjugated polystyrene nanoparticles (GCPNs) in Caco-2 cell models and identifies a new pathway correlated with both apical sodium-dependent bile acid transporter (ASBT) and chylomicron pathways. The study also reveals that the higher uptake of GCPNs does not result in higher transcytosis compared to unmodified nanoparticles (CPNs). Pharmacological and genomics analysis indicate that GCA conjugation alters endocytosis mechanisms and downregulates cellular response, leading to higher cellular retention of GCPNs.
Review
Endocrinology & Metabolism
Monique D. Appelman, Suzanne W. van der Veen, Saskia W. C. van Mil
Summary: The FXR nuclear receptor is activated by bile acids and plays a crucial role in controlling gene expression related to bile acid, lipid, glucose, and amino acid metabolism. Post-translational modifications of FXR, such as phosphorylation, SUMOylation, and acetylation, have functional consequences on DNA binding, ligand binding, and transcription of target genes, and may be involved in cholestatic and metabolic disorders.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Integrative & Complementary Medicine
Jia-Cheng Shen, Qin Qi, Dong Han, Yuan Lu, Rong Huang, Yi Zhu, Lin-Shan Zhang, Xiu-Di Qin, Fang Zhang, Huan-Gan Wu, Hui-Rong Liu
Summary: This study explored the mechanism of moxibustion in regulating intestinal inflammation and barrier repair in Crohn's disease (CD) through bile acid (BA) enterohepatic circulation and intestinal farnesoid X receptor (FXR). The results showed that moxibustion improved CD symptoms, inhibited inflammation, and repaired mucosal damage in CD rats. Moxibustion also regulated the abnormal expression of BA, downregulated interferon-c expression, upregulated FXR mRNA expression, and inhibited TLR4 and MyD88 mRNA expression. Additionally, moxibustion upregulated FXR and mucin2 expression, inhibited TLR4 expression, and regulated the TLR4/MyD88 pathway. Overall, moxibustion improved CD by regulating BA circulation, activating FXR, inhibiting inflammation, and repairing the intestinal mucosal barrier.
JOURNAL OF INTEGRATIVE MEDICINE-JIM
(2023)
Article
Nutrition & Dietetics
Gianfranca Carta, Elisabetta Murru, Giovanna Trinchese, Gina Cavaliere, Claudia Manca, Maria Pina Mollica, Sebastiano Banni
Summary: This study investigated the effects of varying PUFA/SFA ratios in the diet on insulin resistance, fatty acid metabolism, NAE bioactive metabolite levels, and mitochondrial function. The results showed that reducing the dietary PUFA/SFA ratio positively influenced glucose and lipid metabolism in obese rats, possibly through an increase in OEA biosynthesis, improving metabolic flexibility.
Article
Pharmacology & Pharmacy
Rulin Wang, Tengteng Yuan, Jing Sun, Menghuan Yang, Yunna Chen, Lei Wang, Yanyan Wang, Weidong Chen, Daiyin Peng
Summary: Paeoniflorin alleviates estrogen-induced cholestasis by regulating bile acid transporters and synthesis enzymes, thereby maintaining bile acid homeostasis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Xiaowei Sun, Zhenhui Chen, Lu Yu, Weisen Zeng, Boyuan Sun, Hongying Fan, Yang Bai
Summary: This study found that Bacteroides dorei BDX-01 improved DSS-induced acute colitis by regulating intestinal BSH activity and the FXR-NLRP3 signaling pathway. These findings suggest that BDX-01 is a promising probiotic for improving the management of ulcerative colitis.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Nutrition & Dietetics
Claudia Balderas, Begona de Ancos, Concepcion Sanchez-Moreno
Summary: The intake of onion and apple can increase the abundance of beneficial bacteria, promote the production of short-chain fatty acids and decrease the excretion of certain bile acids. This finding is important for further research on the relationship between specific diseases and the microbiome, as well as the formation of fatty acids and bile acids.
Article
Pharmacology & Pharmacy
Yun Li, Huiqin Hou, Xianglu Wang, Xin Dai, Wanru Zhang, Qiang Tang, Yue Dong, Chen Yan, Bangmao Wang, Zhengxiang Li, Hailong Cao
Summary: DG treatment suppressed microbes associated with BSH activity, increased taurine-conjugated BAs, and inhibited ileal FXR-FGF15 signaling, leading to improvements in obesity-related metabolism. This demonstrates the potential for a novel approach in the treatment of obesity by targeting gut microbiota-conjugated BAs-FXR axis.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Ilenia Martinelli, Daniele Tomassoni, Proshanta Roy, Francesco Amenta, Seyed Khosrow Tayebati
Summary: The study revealed that obese Zucker rats exhibited abnormalities in cholinergic and synaptic markers in the frontal cortex and hippocampus, leading to cognitive dysfunction associated with obesity and aging.
Article
Immunology
Shan Cao, Xinyu Meng, Yixuan Li, Li Sun, Lindi Jiang, Hanqing Xuan, Xiaoxiang Chen
Summary: This study revealed that bile acids, especially CDCA, may dampen inflammation via FXR-mediated downregulation of IL-6 in mononuclear cells, providing a protective mechanism for CP patients. The altered bile acid spectrum and signaling pathway enrichment analysis suggest a potential therapeutic target for CP in FXR agonists.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Zeid J. Khitan, Imran Khawaja, Maurice A. Mufson, Juan R. Sanabria, Nader G. Abraham, Stephen J. Peterson, Uma Sundaram, Joseph I. Shapiro
MEDICAL HYPOTHESES
(2020)
Article
Nutrition & Dietetics
Balasubramanian Palaniappan, Shanmuga Sundaram, Subha Arthur, Sheuli Afroz, Uma Sundaram
Article
Medical Informatics
Alfred A. Cecchetti, Niharika Bhardwaj, Usha Murughiyan, Gouthami Kothakapu, Uma Sundaram
JMIR MEDICAL INFORMATICS
(2020)
Article
Biochemistry & Molecular Biology
M. Motiur Rahman, Alip Borthakur, Sheuli Afroz, Subha Arthur, Uma Sundaram
Summary: Inflammatory bowel disease (IBD) causes diarrhea due to electrolyte (NaCl) and fluid malabsorption, with arachidonic acid metabolites (AAMs) formed via the COX pathway potentially contributing to this effect.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
M. Motiur Rahman, Sheuli Afroz, Subha Arthur, Uma Sundaram
Summary: This study demonstrates that mast cell mediators likely inhibit Cl:HCO3 exchange in Inflammatory Bowel Disease (IBD), leading to electrolyte malabsorption and diarrhea. Treatment with a mast cell stabilizer, ketotifen, restores Cl:HCO3 exchange activity in SAMP1 mice, alleviating the symptoms of IBD.
Article
Cell Biology
Niraj Nepal, Subha Arthur, Jennifer Haynes, Balasubramanian Palaniappan, Uma Sundaram
Summary: PGE2 inhibits the activity of Na-K-ATPase in villus cells by activating the PKA pathway, leading to a transcriptional reduction in the alpha 1 and beta 1 subunit genes of Na-K-ATPase.
Article
Gastroenterology & Hepatology
Subha Arthur, Balasubramanian Palaniappan, Sheuli Afroz, Uma Sundaram
Summary: The study found that inducible nitric oxide inhibits coupled NaCl absorption by regulating the phosphorylation of the Cl:HCO3 exchanger DRA in mice with chronic inflammatory bowel disease. This effect can be reversed by L-NIL treatment.
INFLAMMATORY BOWEL DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Niraj Nepal, Subha Arthur, Molly R. Butts, Soudamani Singh, Balasubramanian Palaniappan, Uma Sundaram
Summary: Na-K-ATPase is crucial in providing the necessary transcellular Na gradient for the functioning of Na-dependent nutrient transporters in intestinal epithelial cells. LTD4, acting through the Ca-activated PKC pathway, stimulates Na-K-ATPase activity in intestinal crypt cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Chelsea Thompson, M. Motiur Rahman, Soudamani Singh, Subha Arthur, Cecilia Sierra-Bakhshi, Rebecca Russell, Krista Denning, Uma Sundaram, Travis Salisbury
Summary: Obesity increases the risk of postmenopausal breast cancer through changes in the adipose-derived secretome that mediate the activity of LAT1 and mTOR in breast cancer cells. LAT1 supports mTOR hyperactivation in obese-ADS induced breast cancer cells, which may contribute to breast cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Vivian Naa Amua Wellington, Vijaya Lakshmi Sundaram, Soudamani Singh, Uma Sundaram
Summary: The gut microbiome plays a significant role in gastrointestinal health and can be affected by dietary choices. Dietary supplementation with anti-inflammatory supplements may help restore gut microbiota homeostasis and reduce intestinal inflammation in inflammatory bowel disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nutrition & Dietetics
Maafi R. Islam, Subha Arthur, Jennifer Haynes, Molly R. Butts, Niraj Nepal, Uma Sundaram
Summary: The gut microbiota has been receiving attention due to its association with various human diseases. Disruption of the gut microbiota, caused by obesity, has been linked to the development of inflammatory bowel disease and colorectal cancer. This review focuses on the mechanisms by which obesity-induced dysbiosis leads to these diseases, particularly the altered absorption of short-chain fatty acids.
Article
Medical Laboratory Technology
Jennifer Haynes, Balasubramanian Palaniappan, Eliane Tsopmegha, Uma Sundaram
Summary: Recent studies have shown that human intestinal organoid-derived monolayer cultures can physiologically regulate the apical nutrient and electrolyte transporter function in intestinal cells, similar to observations in in vivo and in vitro animal models. Therefore, this culture model is of great importance for a better understanding of intestinal nutrient absorption regulation.
TRANSLATIONAL RESEARCH
(2022)