Lab Activities

Laboratory for Intestinal Ecosystem

Research Activities

Hiroshi Ohno portrait

Team Director

Hiroshi Ohno

The human body is colonized by enormous numbers of commensal microorganisms on the skin and mucosal surfaces, which form interfaces with the external environment. The colon, in particular, harbors more than 40 trillion gut microbiota, a number exceeding that of human somatic cells, profoundly influencing host health and diseases. Our research focuses on elucidating host–gut microbiome interactions using integrated multi-omics approaches. 

The global rise in obesity and diabetes presents an urgent need for novel preventive and therapeutic strategies. While current interventions mainly target host metabolic pathways, modulating nutrient availability through the gut microbiota represents an alternative and promising approach. We recently demonstrated that acetylated cellulose (AceCel) reduces body weight gain in wild-type and obese mice by altering gut bacterial function. AceCel shifts host hepatic metabolism by limiting carbohydrate oxidation and promoting fatty acid oxidation. Mechanistically, AceCel-derived acetate enhances carbohydrate fermentation by colonic commensal Bacteroides species, thereby depleting host-accessible simple sugars in the gut. These findings establish AceCel as a novel prebiotic that coordinately regulates carbohydrate metabolism in both gut bacteria and the host, highlighting its therapeutic potential for obesity and diabetes. 

We also investigated the paradoxical effects of cigarette smoking on inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD). While smoking exacerbates CD, it is protective in UC, a phenomenon that has long remained unexplained. Metabolomic analyses revealed increased fecal aromatic compounds in UC smokers compared with ex-smokers, accompanied by an enrichment of oral bacteria in the colonic mucosa. Notably, germ-free mice monocolonized with Streptococcus mitis, an ectopically colonizing oral bacterium, showed enhanced Th1 cell induction. S. mitis attenuated inflammation in a UC mouse model but worsened disease in a CD model. These results provide mechanistic insight into smoking-dependent modulation of IBD and suggest novel therapeutic avenues for UC based on aromatic metabolites or Th1-inducing microbes.

Obesity-suppressing effect of acetylated cellulose (AceCel) via intestinal bacteria

Laboratory for Intestinal Ecosystem figure

Obesity-suppressing effect of acetylated cellulose (AceCel) via intestinal bacteria

Laboratory for Intestinal Ecosystem figure

Acetic acid released from AcxdCel in the colon promotes the proliferation and carbohydrate consumption of Bacteroides species (resulting in an increase in organic acids such as succinic acid, a product of bacterial carbohydrate metabolism). This reduces the carbohydrates available for absorption by the host, suppressing the host's carbohydrate utilization and shifting energy metabolism from carbohydrate to fatty acid breakdown, resulting in weight suppression and metabolic improvement (reproduced from a RIKEN press release introducing Takeuchi T et al. Cell Metab. 37: 1682-1697.e6, 2025).

Acetic acid released from AcxdCel in the colon promotes the proliferation and carbohydrate consumption of Bacteroides species (resulting in an increase in organic acids such as succinic acid, a product of bacterial carbohydrate metabolism). This reduces the carbohydrates available for absorption by the host, suppressing the host's carbohydrate utilization and shifting energy metabolism from carbohydrate to fatty acid breakdown, resulting in weight suppression and metabolic improvement (reproduced from a RIKEN press release introducing Takeuchi T et al. Cell Metab. 37: 1682-1697.e6, 2025).

Recent Major Publications

  1. Miyauchi E, Yamazaki K, Tsuboi Y, Nakajima T, Ono S, Mizuno K, Takahashi N, Imamura K, Morita H, Miura N, Okuda S, Kikuchi J, Sasaki N, Ohno H, Yamazaki K. Patients with periodontitis exhibit persistent dysbiosis of the gut microbiota and distinct serum metabolome. Journal of Oral Microbiology 17(1), 2499284 (2025)

  2. Takeuchi T, Miyauchi E, Nakanishi Y, Ito Y, Kato T, Yaguchi K, Kawasumi M, Tachibana N, Ito A, Shimamoto S, Matsuyama A, Sasaki N, Kimura I, Ohno H. Acetylated cellulose suppresses body mass gain through gut commensals consuming host-accessible carbohydrates. Cell Metab 37(8), 1682–1697.e6 (2025)

  3. Miyauchi E, Taida T, Uchiyama K, Nakanishi Y, Kato T, Koido S, Sasaki N, Ohkusa T, Sato N, Ohno H. Smoking affects gut immune system of patients with inflammatory bowel diseases by modulating metabolomic profiles and mucosal microbiota. Gut, (2025)

Invited Presentations

  • Ohno H. Neonatal gut microbial propionate prevents onset of later bronchial asthma. RIKEN BDR Symposium 2025 Towards Redesigning Lifecycles, Kobe, Japan, March 3–5 (2025)

  • Ohno H. Smoking and Gut Microbiota in Inflammatory Bowel Disease. 10th MICROBIOME R&D COLLABORATION AND BUSINESS CONGRESS ASIA, Singapore, Singapore, May 8–9 (2025)

  • Versalovic J, Ohno H, De Vos W. WMP and the Human Microbiome. One Health World Microbiome Partnership Summit – 20th June 2025, Paris, France, July 20 (2025)

  • Ohno H. Limosilactobacillus reuteri Possesses Host Autoantigen-Mimicry Peptide and Aggravates Neuroinflammation in a Mouse Model of Multiple Sclerosis. 15th Asian Conference on Lectic Acid Bacteria (ACLAB 15), Taipei, Taiwan, November 19–21 (2025)

  • Ohno H. Smoking and Gut Microbiota in Inflammatory Bowel Disease. The 54th Annual Meeting of the Japanese Society for Immunology, Himeji, Japan, December 10–12 (2025)

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