A research group led by Bio2Q Center Director Professor Kenya Honda has revealed how a low-protein diet induces energy-burning beige adipocytes via gut microbiota. The team identified four specific bacterial strains from humans that promote the “browning” of white adipose tissue. The study uncovered two key mechanisms: bile acid metabolism activating FXR and bacteria-derived ammonia triggering hepatic FGF21 expression. This evolutionary strategy for metabolic adaptation offers promising insights into treating obesity and type 2 diabetes through microbiome-based therapies. These groundbreaking findings were published in the journal Nature on March 4, 2026.

Affiliations:

Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan
Takeshi Tanoue, Manabu Nagayama, Ayumi J. A. Roochana, Satoshi Sasajima, Kozue Takeshita, Ashwin N. Skelly, Koji Atarashi & Kenya Honda

RIKEN Center for Integrative Medical Sciences, Yokohama, JapanTakeshi Tanoue, Manabu Nagayama, Nicola Hetherington, Nobuyuki Okahashi, Masahiro Ueda, Aki Minoda, Makoto Arita, Wataru Suda, Koji Atarashi & Kenya Honda

City of Hope National Medical Center, Duarte, CA, USA
Takeshi Tanoue, Koji Atarashi & Kenya Honda

Division of Gastroenterology, Department of Medicine, Jichi Medical University, Tochigi, Japan
Manabu Nagayama, Hironori Yamamoto, Shunji Watanabe & Kouichi Miura

Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Samuel Zimmerman, Damian R. Plichta & Ramnik J. Xavier

Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Orr Ashenberg, Tanvi Jain & Ramnik J. Xavier

Department of Integrated Medicine and Biochemistry, Keio University School of Medicine, Tokyo, Japan
Ryo Igarashi & Toshiro Sato

Department of Human Biology, Radboud Institute for Molecular Life Sciences, Faculty of Science, University of Radboud, Nijmegen, The Netherlands
Nicola Hetherington & Aki Minoda

JSR-Keio University Medical and Chemical Innovation Center, Keio University School of Medicine, Tokyo, Japan
Masahiro Ueda

Laboratory of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan
Morichika Konishi & Yoshiaki Nakayama

Division of Endocrinology and Metabolism, National Institute for Physiological Sciences, Okazaki, Japan
Yasuhiko Minokoshi

Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Nicholas Pucci & Daniel R. Mende

Human Biology Microbiome Quantum Research Center (WPI-Bio2Q), Keio University, Tokyo, Japan
Daniel R. Mende, Makoto Arita, Scott W. Behie, Toshiro Sato & Koji Atarashi

Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan
Makoto Arita & Kenya Honda

Department of Nutrition, School of Nursing and Nutrition, Tenshi College, Sapporo, Japan
Mami Matsushita

Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
Shingo Kajimura