Journal Article10.1016/j.celrep.2023.113005
The gut microbiota-induced kynurenic acid recruits GPR35-positive macrophages to promote experimental encephalitis.
Kentaro Miyamoto,Tomohisa Sujino,Yosuke Harada,Hiroshi Ashida,Yusuke Yoshimatsu,Yuki Yonemoto,Yasuhiro Nemoto,Michio Tomura,Hassan Melhem,Jan Hendrik Niess,Toshihiko Suzuki,Toru Suzuki,S. Suzuki,Yuzo Koda,Ryuichi Okamoto,Yohei Mikami,Toshiaki Teratani,Kenji Tanaka,Akihiko Yoshimura,Toshiro Sato,Takanori Kanai +20 more
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TL;DR: Modulating the KYNA-mediated GPR35 signaling in Cx3cr1+ macrophages leads to a remarkable amelioration of EAE, shedding light on the crucial role of microbial-derived tryptophan metabolites in regulating immune responses within extraintestinal tissues.
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Abstract: The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities between CD4+ T cells in the spinal cord and their counterparts in the small intestine. Furthermore, we unveil a synergistic relationship between the microbiota, particularly enriched with the tryptophan metabolism gene EC:1.13.11.11, and intestinal cells. This symbiotic collaboration results in the biosynthesis of kynurenic acid (KYNA), which modulates the recruitment and aggregation of GPR35-positive macrophages. Subsequently, a robust T helper 17 (Th17) immune response is activated, ultimately triggering the onset of EAE. Conversely, modulating the KYNA-mediated GPR35 signaling in Cx3cr1+ macrophages leads to a remarkable amelioration of EAE. These findings shed light on the crucial role of microbial-derived tryptophan metabolites in regulating immune responses within extraintestinal tissues.
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Citations
Interaction of the Gut Microbiome and Immunity in Multiple Sclerosis: Impact of Diet and Immune Therapy
Sudhir Kumar Yadav,Kouichi Ito,Suhayl Dhib-Jalbut +2 more
TL;DR: The role of gut immunity and its modulation by diet and DMTs via gut microbiota during MS pathophysiology is addressed.
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GPR35 acts a dual role and therapeutic target in inflammation
Yetian Wu,Pei Zhang,Hongjie Fan,Caiying Zhang,Pengfei Yu,Xinmiao Liang +5 more
TL;DR: The purpose of this review is to concurrently investigate the pro-inflammatory and anti-inflammatory roles of GPR35, thus illuminating both facets of this complex issue.
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The tryptophan metabolic pathway of the microbiome and host cells in health and disease
Kentaro Miyamoto,Tomohisa Sujino,Takanori Kanai +2 more
TL;DR: The intricate tryptophan metabolic pathway in the microbiome and host cells plays a significant role in maintaining health and disease. It involves complex interactions between host cellular and bacterial processes, producing bioactive compounds and influencing immune responses.
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Integrated metabolomics and serum-feces pharmacochemistry-based network pharmacology to reveal the mechanisms of an herbal prescription against ulcerative colitis
Ka Wing Cheng,Jingchun Shi,Chunhua Huang,Hor Yue Tan,Ziwan Ning,Cheng Liu,Yi Xu,Henry Mok,Lixiang Zhai,Xiang Li,Hongjiu Qin,Chengyuan Lin,Lin Zhu,Zhaoxiang Bian +13 more
Abstract: BACKGROUND
CDD-2103 is an herbal prescription used to treat ulcerative colitis (UC). This study aimed to uncover its mechanism by integrating metabolomics and serum-feces pharmacochemistry-based network pharmacology.
METHODS
A DSS-induced chronic colitis mice model was used to evaluate the anti-colitis effect of CDD-2103. Serum and feces metabolomics were conducted to identify differential metabolites and pathways. In the serum-feces pharmacochemistry study, biological samples were collected from rats treated with CDD-2103. Then, network pharmacology was utilized to predict the targets of the identified compounds. Critical genes were extracted through the above-integrated analysis. The interactions between targets, CDD-2103, and its compounds were validated through molecular docking, immunoblotting, and enzyme activity assays.
RESULTS
CDD-2103 alleviated ulcerous symptoms and colonic injuries in colitis mice. Metabolomics study identified differential metabolites associated with tryptophan, glycerophospholipid, and linoleic acid metabolisms. The serum-feces pharmacochemistry study revealed twenty-three compounds, which were subjected to network pharmacology analysis. Integration of these results identified three key targets (AHR, PLA2, and PTGS2). Molecular docking showed strong affinities between the compounds and targets. PTGS2 was identified as a hub gene targeted by most CDD-2103 compounds. Immunoblotting and enzyme activity assays provided further evidence that CDD-2103 alleviates UC, potentially through its inhibitory effect on cyclooxygenase-2 (COX-2, encoded by PTGS2), with alkaloids and curcuminoids speculated as crucial anti-inflammatory compounds.
CONCLUSION
This integrated strategy reveals the mechanism of CDD-2103 and provides insights for developing herbal medicine-based therapies for UC.
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The toxic effects of tetracycline exposure on the physiological homeostasis of the gut-liver axis in grouper
Yafei Duan,Yukai Yang,Hua Li,Zhe Zhang,Xiaoying Chen,Meng Xiao,Yuxiu Nan +6 more
TL;DR: Tetracycline exposure disrupts the gut-liver axis in grouper, leading to histopathology, lipid accumulation, and metabolic changes.
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Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2
Evan Bolyen,Jai Ram Rideout,Matthew R. Dillon,Nicholas A. Bokulich,Christian C. Abnet,Gabriel A. Al-Ghalith,Harriet Alexander,Harriet Alexander,Eric J. Alm,Manimozhiyan Arumugam,Francesco Asnicar,Yang Bai,Jordan E. Bisanz,Kyle Bittinger,Asker Daniel Brejnrod,Colin J. Brislawn,C. Titus Brown,Benjamin J. Callahan,Andrés Mauricio Caraballo-Rodríguez,John Chase,Emily K. Cope,Ricardo Silva,Christian Diener,Pieter C. Dorrestein,Gavin M. Douglas,Daniel M. Durall,Claire Duvallet,Christian F. Edwardson,Madeleine Ernst,Madeleine Ernst,Mehrbod Estaki,Jennifer Fouquier,Julia M. Gauglitz,Sean M. Gibbons,Sean M. Gibbons,Deanna L. Gibson,Antonio Gonzalez,Kestrel Gorlick,Jiarong Guo,Benjamin Hillmann,Susan Holmes,Hannes Holste,Curtis Huttenhower,Curtis Huttenhower,Gavin A. Huttley,Stefan Janssen,Alan K. Jarmusch,Lingjing Jiang,Benjamin D. Kaehler,Benjamin D. Kaehler,Kyo Bin Kang,Kyo Bin Kang,Christopher R. Keefe,Paul Keim,Scott T. Kelley,Dan Knights,Irina Koester,Tomasz Kosciolek,Jorden Kreps,Morgan G. I. Langille,Joslynn S. Lee,Ruth E. Ley,Ruth E. Ley,Yong-Xin Liu,Erikka Loftfield,Catherine A. Lozupone,Massoud Maher,Clarisse Marotz,Bryan D Martin,Daniel McDonald,Lauren J. McIver,Lauren J. McIver,Alexey V. Melnik,Jessica L. Metcalf,Sydney C. Morgan,Jamie Morton,Ahmad Turan Naimey,Jose A. Navas-Molina,Jose A. Navas-Molina,Louis-Félix Nothias,Stephanie B. Orchanian,Talima Pearson,Samuel L. Peoples,Samuel L. Peoples,Daniel Petras,Mary L. Preuss,Elmar Pruesse,Lasse Buur Rasmussen,Adam R. Rivers,Michael S. Robeson,Patrick Rosenthal,Nicola Segata,Michael Shaffer,Arron Shiffer,Rashmi Sinha,Se Jin Song,John R. Spear,Austin D. Swafford,Luke R. Thompson,Luke R. Thompson,Pedro J. Torres,Pauline Trinh,Anupriya Tripathi,Peter J. Turnbaugh,Sabah Ul-Hasan,Justin J. J. van der Hooft,Fernando Vargas,Yoshiki Vázquez-Baeza,Emily Vogtmann,Max von Hippel,William A. Walters,Yunhu Wan,Mingxun Wang,Jonathan Warren,Kyle C. Weber,Kyle C. Weber,Charles H. D. Williamson,Amy D. Willis,Zhenjiang Zech Xu,Jesse R. Zaneveld,Yilong Zhang,Qiyun Zhu,Rob Knight,J. Gregory Caporaso +123 more
TL;DR: QIIME 2 development was primarily funded by NSF Awards 1565100 to J.G.C. and R.K.P. and partial support was also provided by the following: grants NIH U54CA143925 and U54MD012388.