1: Gut pathobionts underlie intestinal barrier dysfunction and liver Th17 immune responses in primary sclerosing cholangitis.
Science of the Month - May 2019
Nature Microbiology
Nobuhiro Nakamoto, Nobuo Sasaki, Ryo Aoki, Kentaro Miyamoto, Wataru Suda, Toshiaki Teratani, Takahiro Suzuki, Yuzo Koda, Hakusyo Cho, Nobuhito Taniki, Akihiro Yamaguchi, Mitsuhiro Kanamori, Nobuhiko Kamada, Masahira Hattori, Hiroshi Ashida, Michiie Sakamoto, Koji Atarashi, Seiko Narushima, Akihiko Yoshimura, Kenya Honda, Toshiro Sato, Takanori Kanai
Primary sclerosing cholangitis (PSC) is an intractable disease characterized by inflammation of the bile ducts inside and outside the liver, leading to cirrhosis over several years to decades, with no effective treatment other than liver transplantation. The high rate of inflammatory bowel disease comorbidity in PSC has suggested the involvement of intestinal inflammation and gut microbiota in its pathogenesis, but the details have remained unclear. To clarify the direct link between gut microbiota and the disease's pathology, our group conducted research using "humanized gnotobiotic mice," which replicate a patient's gut environment by administering fecal microbial samples from patients to germ-free mice. As a result, we discovered that three types of intestinal bacteria that trigger the activation of TH17 cells in the liver are present at a high frequency in the feces of PSC patients. We successfully demonstrated that one of these, *Klebsiella pneumoniae*, breaches the colonic epithelium, disrupts the intestinal barrier, migrates to lymph nodes outside the intestinal tract, and induces an immune response in the liver. Furthermore, we showed that eliminating *K. pneumoniae* with antibiotics markedly reduced the TH17 cells induced in the liver. These findings indicate that specific intestinal bacteria may be a cause of liver inflammation and clarify the mechanism, and are expected to lead to the development of new therapeutic and diagnostic agents for PSC (Fig. 1).
(Nobuhiro Nakamoto, Department of Gastroenterology and Hepatology, 77th class)
2: A serum microRNA classifier for the diagnosis of sarcomas of various histological subtypes.
Nature Communications.
2019 Mar 21;10(1):1299. doi: 10.1038/s41467-019-09143-8.
Naofumi Asano, Juntaro Matsuzaki, Makiko Ichikawa, Junpei Kawauchi, Satoko Takizawa, Yoshiaki Aoki, Hiromi Sakamoto, Akihiko Yoshida, Eisuke Kobayashi, Yoshikazu Tanzawa, Robert Nakayama, Hideo Morioka, Morio Matsumoto, Masaya Nakamura, Tadashi Kondo, Ken Kato, Naoto Tsuchiya, Akira Kawai & Takahiro Ochiya
This research was conducted with support from the Japan Agency for Medical Research and Development (AMED) under the Project for Developing Fundamental Technologies for Drug Discovery to Realize Next-Generation Treatment and Diagnosis, "Project for Developing Fundamental Technologies for Measuring microRNA in Body Fluids." In this study, we comprehensively analyzed serum microRNAs (DNA chip, 3D-Gene, 2,565 types of microRNA) from an unprecedented 897 cases of bone and soft tissue tumor patients (malignant: 414 cases, intermediate: 144 cases, benign: 339 cases) and found that the expression patterns of serum microRNAs differ significantly between malignant and benign tumors. Furthermore, we identified a diagnostic index combining seven microRNAs that are highly expressed in patients with malignant bone and soft tissue tumors, and confirmed that it can distinguish between benign and malignant tumors with extremely high accuracy, with a sensitivity of 90% and a specificity of 95% for malignancy. We believe these research findings are highly significant as they indicate the potential for improving the diagnostic accuracy of bone and soft tissue tumors, which are rare cancers that are difficult to diagnose, and for enabling early diagnosis of recurrence through a minute blood test. We hope that with further validation, this will become a useful biomarker in actual clinical practice.
(Naofumi Asano, Department of Orthopaedic Surgery, equivalent to the 83rd class; Juntaro Matsuzaki, Department of Gastroenterology and Hepatology, 84th class)
Other Published Papers
1: Toward a new generation of smart skins
2: F-18-Fluoride Positron Emission Tomographic Imaging of Penile Arteries and Erectile Dysfunction
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY,
APR 2 2019, 73 (12):1386-1394;10.1016
Nakahara, T; Narula, J; Tijssen, JGP; Agarwal, S; Chowdhury, MM; Coughlin, PA; Dweck, MR; Rudd, JHF; Jinzaki, M; Mulhall, J; Strauss, HW