Sawako Tomioka, Natsumi Seki, Yuki Sugiura, Masahiro Akiyama, Jun Uchiyama, Genki Yamaguchi, Kyosuke Yakabe, Ryuta Ejima, Kouya Hattori, Tatsuki Kimizuka, Yumiko Fujimura, Hiroki Sato, Monica Gondo, Satoru Ozaki, Yoshiko Honme, Makoto Suematsu, Ikuo Kimura, Naohiro Inohara, Gabriel Núñez, Koji Hase, and Yun-Gi Kim
Microbiota-accessible carbohydrates (MACs) exert health-promoting effects, but how each MAC impacts gut microbiota and regulates host physiology remains unclear. Here, we show that l-arabinose and sucrose cooperatively act on gut microbiota and exert anti-obesogenic effects. Specifically, l-arabinose, a monosaccharide that is poorly absorbed in the gut and inhibits intestinal sucrase, suppresses diet-induced obesity in mice in the presence of sucrose. Additionally, the suppressive effect of l-arabinose on adiposity is abrogated in mice lacking the short-chain fatty acid (SCFA) receptors GPR43 and GPR41. Mechanistically, l-arabinose increases the relative abundance of acetate and propionate producers (e.g., Bacteroides), while sucrose enhances SCFA production. Furthermore, l-arabinose and sucrose activate the glycolytic and pentose phosphate pathways of Bacteroides, respectively, indicating that they synergistically promote acetate production through distinct pathways. These findings suggest that each MAC has a unique property and thus may serve as a precision gut-microbiota modulator to promote host homeostasis.