Article
Immunology
Nicola Laura Diny, Barbora Schonfeldova, Michael Shapiro, Matthew L. Winder, Sunita Varsani-Brown, Brigitta Stockinger
Summary: Intestinal eosinophils undergo substantial transcriptomic changes and adapt to their environment through the aryl hydrocarbon receptor (AHR). AHR-deficient eosinophils exhibit impairments in function and interactions within the intestine.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Aneta Vrzalova, Petra Pecinkova, Peter Illes, Sona Gurska, Petr Dzubak, Martin Szotkowski, Marian Hajduch, Sridhar Mani, Zdenek Dvorak
Summary: Aryl hydrocarbon receptor (AHR) plays important roles in intestinal physiology and is activated by microbial metabolites, with synergistic effects observed in combinations of low- or medium-efficacy agonists. High-efficacy agonists may show antagonist effects on AHR activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Karl Walter Bock
Summary: AHR is a ligand-modulated transcription factor and environmental sensor, but the explanation of its multiple agonistic and antagonistic ligands remains incomplete. The role of AHR in host-microbiome interaction is currently a fruitful area of research. Microbial products and virulence factors have been identified as AHR agonists, playing a role in maintaining intestinal barrier integrity. The activation of anti-microbial defense mechanisms by AHR contributes to ROS production and recruitment of immune cells.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Immunology
Paul J. Wisniewski, Mitzi Nagarkatti, Prakash S. Nagarkatti
Summary: Maintenance of intestinal homeostasis requires integration of immunological and molecular processes, environmental, diet, metabolic and microbial cues. The aryl hydrocarbon receptor (AhR) plays a critical role in regulating molecular pathways involved in epithelial cell renewal, contributing to ISC stemness and epithelial cell fate.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Karl Walter Bock
Summary: Aryl hydrocarbon receptor (AHR) is a multifunctional sensor and transcription factor that plays a role in regulating energy metabolism and inflammation. Challenges in AHR research include species differences and context dependence of its functions. The focus of the commentary is on AHR's integration between energy expenditure and inflammation.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Gastroenterology & Hepatology
Minyi Qian, Jun Liu, Danyang Zhao, Pengpeng Cai, Chuyue Pan, Wenxin Jia, Yingsheng Gao, Yufei Zhang, Nan Zhang, Yinan Zhang, Quan Zhang, Dalei Wu, Chengjie Shan, Meiling Zhang, Bernd Schnabl, Song Yang, Xu Shen, Lirui Wang
Summary: The intrinsic AHR in intestinal epithelial cells (IECs) plays a role in the development of alcohol-related liver disease (ALD) by modulating the intestinal microbiota and metabolite composition. AHR deficiency in IECs leads to the overgrowth of Helicobacter spp. in the gut, promoting their translocation to lymph nodes and liver and worsening liver injury. Isobutyric acid, an altered metabolite in Ahr(Delta IEC) mice, along with Helicobacter spp., exacerbates ethanol-induced liver injury. Activation of intestinal AHR with specific agonists protects mice from ALD development. Alcoholic patients have lower intestinal AHR expression and higher levels of Helicobacter spp.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Pharmacology & Pharmacy
Qing Liu, Limin Zhang, Erik L. Allman, Troy D. Hubbard, Iain A. Murray, Fuhua Hao, Yuan Tian, Wei Gui, Robert G. Nichols, Philip B. Smith, Mallappa Anitha, Gary H. Perdew, Andrew D. Patterson
Summary: Activation of Aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzofuran (TCDF) leads to hepatic ceramide accumulation, increased expression of ceramide biosynthetic genes, and elevated activity of their respective enzymes. AHR activation directly upregulates Sptlc2, resulting in ceramide accumulation, which promotes lipogenesis and hepatic lipid accumulation.
Article
Immunology
Santosh K. Panda, Vincent Peng, Raki Sudan, Susan Gilfillan, Marina Cella, Alina Ulezko, Blanda Di Luccia, Takahiro E. Ohara, Jose Luis Fachi, Gary E. Grajales-Reyes, Alina Natalia, Tihana Trsan, Susan Gilfilan, Marina Cella, Marco Colonna
Summary: This study demonstrates the vital role of AHRR in sustaining intestinal intraepithelial lymphocytes (IELs). AHRR deficiency leads to oxidative stress, lipid peroxidation, and ferroptosis in Ahrr-/- IELs, which can be rescued by dietary supplementation with selenium or vitamin E. Reduced expression of AHRR in inflammatory bowel disease patients may contribute to disease progression.
Article
Chemistry, Medicinal
Xiaojing Wang, Xuting Xie, Yanyang Li, Xueqian Xie, Shaowei Huang, Simin Pan, Yanling Zou, Zengfeng Pan, Qing Wang, Jinyan Chen, Lian Zhou, Xia Luo
Summary: The study discovered that quercetin has therapeutic effects on ulcerative colitis. Quercetin repairs the damaged intestinal barrier by activating AhR and enhancing the expression of tight junction proteins.
PHYTOTHERAPY RESEARCH
(2023)
Article
Immunology
Liyile Chen, Zeyu Huang, Qianhao Li, Changjun Chen, Yue Luo, Pengde Kang
Summary: This study evaluated the role of aryl hydrocarbon receptor (AhR) in the pathogenesis of osteoarthritis (OA) and its association with intestinal microbiome-related tryptophan metabolism. The severity of OA positively correlated with the expression of AhR and CyP1A1 in cartilage from patients. In a rat model of OA, antibiotic pretreatment led to lower expression of AhR and CyP1A1 and lower serum levels of lipopolysaccharide (LPS). Tryptophan supplementation activated intestinal microbiome-related tryptophan metabolism, exacerbating OA synovitis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Oncology
Chunting Peng, Chensi Wu, Xiaolan Xu, Liya Pan, Zhuoqi Lou, Yanhong Zhao, Haiyin Jiang, Zebao He, Bing Ruan
Summary: In DSS-induced colitis mice models, I3C exerts a protective effect by alleviating necroptosis and inflammation of intestinal epithelial cells through activating the aryl hydrocarbon receptor (AHR).
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Clinical Neurology
Roanna A. Debler, Caitlin A. Madison, Lauren Hillbrick, Paula Gallegos, Stephen Safe, Robert S. Chapkin, Shoshana Eitan
Summary: This study investigated the antidepressant-like effects of DHNA in obese female mice. The results demonstrated that DHNA protected against stress-induced depression-like behaviors, but did not improve spatial learning impairment.
JOURNAL OF AFFECTIVE DISORDERS
(2023)
Review
Pharmacology & Pharmacy
Ziyue Kou, Wei Dai
Summary: Aryl hydrocarbon receptor (AHR) is a cellular protein involved in detoxification of xenobiotic compounds. Research has shown that AHR plays important roles in normal development and homeostasis, and its deficiency can lead to various developmental abnormalities.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Microbiology
Zunji Shi, Hehua Lei, Gui Chen, Peihong Yuan, Zheng Cao, Hooi-Leng Ser, Xuehang Zhu, Fang Wu, Caixiang Liu, Manyuan Dong, Yuchen Song, Yangyang Guo, Chuan Chen, Kexin Hu, Yifan Zhu, Xin-an Zeng, Jinlin Zhou, Yujing Lu, Andrew D. Patterson, Limin Zhang
Summary: The consumption of saccharin/sucralose alters gut microbial community structure, leading to depletion of Akkermansia muciniphila and development of NAFLD in mice. Metformin or fructo-oligosaccharide supplementation can help restore gut microbiota balance and alleviate NAFLD. A new potential nutritional strategy involves using neohesperidin dihydrochalcone as a substitute for artificial sweeteners and free sugars.
Article
Pharmacology & Pharmacy
Josiane Fernandes da Silva, Juliana A. Bolsoni, Rafael M. da Costa, Juliano Alves, Alecsander F. M. Bressan, Luiz Eduardo Silva, Tiago J. Costa, Antonio E. R. Oliveira, Carla P. Manzato, Carlos A. Aguiar, Rubens Fazan, Fernando Q. Cunha, Helder Nakaya, Fernando S. Carneiro, Rita C. Tostes
Summary: The study suggests that AhR activation contributes to vascular dysfunction in obesity, but AhR deletion can alleviate dyslipidaemia and vascular dysfunction induced by a high-fat diet. Targeting AhRs may prevent obesity-associated vascular dysfunction.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Microbiology
Stephanie L. Collins, Jonathan C. Stine, Jordan E. Bisanz, C. Denise Okafor, Andrew D. Patterson
Summary: This Review discusses host-microbiota interactions and their impact on bile acid metabolism and composition. The gut microbiota plays a crucial role in bile acid metabolism, with diverse biological roles for bile acids being discovered. External factors such as antibiotics and diet also influence bile acid composition. Understanding the impact of bile acid signaling networks in different organs is increasingly important for the development of targeted therapeutics.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Medicine, Research & Experimental
Xiaoliang Zhou, Debopriya Chakraborty, Iain A. Murray, Denise Coslo, Zoe Kehs, Anitha Vijay, Carolyn Ton, Dhimant Desai, Shantu G. Amin, Andrew D. Patterson, Gary H. Perdew
Summary: Intestinal homeostasis is maintained through balanced cellular turnover, proliferation, differentiation, and self-renewal, but can be influenced by the aryl hydrocarbon receptor (AHR). The AHR plays a role in small intestinal gene expression and cellular repertoire remodeling, promoting intestinal resilience. Genetic ablation of Ahr impairs lineage commitment and differentiation, while exposure to AHR ligands reverses these effects.
LABORATORY INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Sougat Misra, Tai-Jung Lee, Aswathy Sebastian, John McGuigan, Chang Liao, Imhoi Koo, Andrew D. Patterson, Randall M. Rossi, Molly A. Hall, Istvan Albert, K. Sandeep Prabhu
Summary: Macrophages play a crucial role in inflammation and its resolution. Selenium and selenoproteins, which contain the amino acid selenocysteine, are essential for the functions of macrophages. In this study, the researchers investigated the role of SELENOW, a highly expressed selenoprotein, in inflammation using Selenow knock-out macrophages. The results suggest that SELENOW is involved in redox processes and bioenergetics during inflammation and its resolution.
Article
Biochemistry & Molecular Biology
Jonathan A. A. Young, Silvana Duran-Ortiz, Stephen Bell, Kevin Funk, Yuan Tian, Qing Liu, Andrew D. D. Patterson, Edward O. O. List, Darlene E. E. Berryman, John J. J. Kopchick
Summary: Growth hormone (GH) affects protein metabolism and alters circulating levels of glycine and hydroxyproline. GH abnormality, such as increased GH action or GH resistance, leads to changes in amino acid concentrations in plasma and feces. Acute GH treatment decreases liver gene expression of glycine metabolism genes and serum glycine in mice.
Article
Biochemistry & Molecular Biology
Fangcong Dong, Iain A. Murray, Andrew Annalora, Denise M. Coslo, Dhimant Desai, Krishne Gowda, Jian Yang, Dingbowen Wang, Imhoi Koo, Fuhua Hao, Shantu G. Amin, Andrew D. Patterson, Craig Marcus, Gary H. Perdew
Summary: A certain diet can enhance the activity of the aryl hydrocarbon receptor (AHR) in the intestinal tract, which is responsible for maintaining intestinal barrier homeostasis. This is possibly achieved through the role of certain dietary substrates as CYP1A1/1B1 substrates, which increase the half-life of potent AHR ligands. The gut bacterial metabolite urolithin A (UroA) has been identified as one of these substrates, and its intake can lead to increased AHR activity in key barrier tissues.
Article
Multidisciplinary Sciences
Dari Shalon, Rebecca Neal Culver, Jessica A. Grembi, Jacob Folz, Peter V. Treit, Handuo Shi, Florian A. Rosenberger, Les Dethlefsen, Xiandong Meng, Eitan Yaffe, Andres Aranda-Diaz, Philipp E. Geyer, Johannes B. Mueller-Reif, Sean Spencer, Andrew D. Patterson, George Triadafilopoulos, Susan P. Holmes, Matthias Mann, Oliver Fiehn, David A. Relman, Kerwyn Casey Huang
Summary: This study developed an ingestible device that can collect samples from multiple regions of the human intestinal tract during normal digestion. Multi-omics analysis of the collected samples revealed significant differences in bacteria, phages, host proteins, and metabolites between the intestines and stool. The study provides insights into the roles of the gut microbiome and metabolome in human physiology and disease through non-invasive longitudinal profiling of microorganisms, proteins, and bile acids along the intestinal tract.
Article
Toxicology
Anitha Vijay, Nina R. Boyle, Supriya M. Kumar, Gary H. Perdew, Shanthi Srinivasan, Andrew D. Patterson
Summary: This study investigates the effects of a persistent organic pollutant on the enteric nervous system, finding that it leads to delayed intestinal motility and neuronal damage, thereby affecting gastrointestinal function.
TOXICOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Lulu Sun, Yi Zhang, Jie Cai, Bipin Rimal, Edson R. Rocha, James P. Coleman, Chenran Zhang, Robert G. Nichols, Yuhong Luo, Bora Kim, Yaozong Chen, Kristopher W. Krausz, Curtis C. Harris, Andrew D. Patterson, Zhipeng Zhang, Shogo Takahashi, Frank J. Gonzalez
Summary: Bile salt hydrolase (BSH) in Bacteroides is associated with the development of colorectal cancer (CRC) by activating the beta-catenin/CCL28 pathway and promoting the generation of immunosuppressive T-reg cells. Inhibition of BSH activity could slow down CRC progression and serve as a potential target for CRC prevention and treatment.
NATURE COMMUNICATIONS
(2023)
Article
Food Science & Technology
Xiaoling Chen, Andrew D. Patterson, Gary H. Perdew, Iain A. Murray, Joshua J. Kellogg
Summary: A novel AHR modulator, 2-amino-4-methyl-benzothiazole, was predicted, identified, and characterized in white button mushrooms using a molecular networking approach. Cell-based assays showed that this compound has agonistic activity and upregulates CYP1A1 expression. These findings demonstrate the potential of molecular networking in identifying novel receptor modulators from natural products.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Article
Biochemistry & Molecular Biology
Xiaoyang Zhu, Qing Liu, Andrew D. Patterson, Arun K. Sharma, Shantu G. Amin, Samuel M. Cohen, Frank J. Gonzalez, Jeffrey M. Peters
Summary: Long-term ligand activation of PPARa in mice causes hepatocarcinogenesis, while hepatocarcinogenesis is diminished in Ppara-null and PPARA-humanized mice. Lipidomic analyses showed elevated levels of hepatic linoleic acid and overall fatty liver in Ppara-null and PPARA-humanized mice. The accumulation of linoleic acid and loss of CD4+ T cells suggest a new role for PPARa in age-associated hepatocarcinogenesis.
Article
Oncology
Sangshan Tian, Devendra Paudel, Fuhua Hao, Rabin Neupane, Rita Castro, Andrew D. Patterson, Amit K. Tiwari, K. Sandeep Prabhu, Vishal Singh
Summary: This study reveals that supplementation of diet with refined inulin leads to abnormal succinate accumulation in the intestinal lumen, which contributes to promoting colon inflammation and tumorigenesis.
Article
Cell Biology
Beng San Yeoh, Rachel M. Golonka, Piu Saha, Mrunmayee R. Kandalgaonkar, Yuan Tian, Islam Osman, Andrew D. Patterson, Andrew T. Gewirtz, Bina Joe, Matam Vijay-Kumar
Summary: Congenital portosystemic shunt (PSS) occurs sporadically in C57BL/6 J mice, leading to abnormal serologic, metabolic, and physiologic parameters. To reliably and efficiently identify PSS mice, we explored simple, inexpensive, and noninvasive urine-based screening tests. Metabolome profiling revealed elevated levels of Krebs cycle intermediates in the urine of PSS mice, which we utilized to develop three colorimetric assays: urinary iron-chelation, pH strip, and phenol red assays. These assays provide a feasible and noninvasive method for diagnosing PSS in mice, aiding biomedical research by stratifying PSS mice and minimizing confounding factors.
Article
Neurosciences
Fangcong Dong, Andrew J. Annalora, Iain A. Murray, Yuan Tian, Craig B. Marcus, Andrew D. Patterson, Gary H. Perdew
Summary: The aryl hydrocarbon receptor (AHR) plays important roles in xenobiotic metabolism, immune function, and tissue homeostasis. The regulation of AHR activity by endogenous ligands is still poorly understood. In this study, we identified and quantified 6 tryptophan metabolites that individually activate AHR in mouse and human serum. These metabolites are not significantly metabolized by CYP1A1/1B1, unlike the potent endogenous AHR ligand 6-formylindolo[3,2b]carbazole. Our results suggest that these tryptophan metabolites may contribute to constitutive but low level systemic AHR activity in humans.
INTERNATIONAL JOURNAL OF TRYPTOPHAN RESEARCH
(2023)
Article
Neurosciences
Ethan W. Morgan, Fangcong Dong, Andrew J. Annalora, Iain A. Murray, Trenton Wolfe, Reece Erickson, Krishne Gowda, Shantu G. Amin, Kristina S. Petersen, Penny M. Kris-Etherton, Craig B. Marcus, Seth T. Walk, Andrew D. Patterson, Gary H. Perdew
Summary: The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that regulates various cellular functions. Tryptophan metabolites derived from host and bacterial metabolism act as AHR activators. This study investigates the presence and metabolic source of these metabolites and examines the biological relevance of circulating tryptophan metabolites. The results improve our understanding of homeostatic AHR activity and related diseases.
INTERNATIONAL JOURNAL OF TRYPTOPHAN RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Gary H. Perdew, Charlotte Esser, Megan Snyder, David H. Sherr, Ellen H. van den Bogaard, Karen McGovern, Pedro M. Fernandez-Salguero, Xavier Coumoul, Andrew D. Patterson
Summary: The aryl hydrocarbon receptor (AHR) senses low-molecular-weight molecule signals from environmental exposures, the microbiome, and host metabolism. It plays important roles in host homeostasis, chronic disease development, and responses to toxic insults. Recent research has shown that AHR is a promising target for cancer, metabolic diseases, skin conditions, and autoimmune disease. This meeting aimed to explore the potential therapeutic applications based on our understanding of this receptor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
