【Related Papers】Summary of Gut Microbiota and FMT Research (October 21, 2026)

Table of Contents

・Gut bacterial toxins implicated in about half of colorectal cancer cases in Japanese people, and 70% of cases in patients aged 40 or younger, according to Whole-Genome Analysis of 200 patients by the University of Tokyo and Osaka University.

・The gut bacterial metabolite imidazole propionate (ImP) may exacerbate Alzheimer’s disease pathology by impairing the brain endothelial barrier and promoting tau hyperphosphorylation. Targeting ImP may offer a novel strategy for the prevention and treatment of Alzheimer’s disease.

Gut bacterial toxins implicated in about half of colorectal cancer cases in Japanese people, and 70% of cases in patients aged 40 or younger, according to Whole-Genome Analysis of 200 patients by the University of Tokyo and Osaka University.

(Title) Prevalence and chronology of colibactin-associated mutational processes and their microbiome spectra in Japanese colorectal cancer.

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(Abstract) The incidence of colorectal cancer (CRC) has risen in recent decades, with a disproportionate increase observed among younger individuals in Japan and other countries. The etiological contribution of the gut microbiota to CRC pathogenesis is recognized, yet the mechanisms involved remain to be fully clarified. Here we integrated whole-genome sequencing (WGS) and transcriptome profiling of CRC with whole-genome metagenomic sequencing of fecal samples to interrogate host–microbiome interactions at high resolution. Application of interpretable artificial intelligence enabled the stratification of CRC into four distinct microbiome-informed subtypes. WGS analysis identified mutational signatures SBS88 and ID18, linked to colibactin exposure, as early clonal events detected in 44.8% of non-hypermutated patients. Notably, these signatures were significantly more frequent among patients born after the 1960s. Microbiome-based subclassification revealed subtype-specific clinical and molecular features. Collectively, our findings indicate that colibactin exposure constitutes a prevalent and potentially modifiable risk factor for CRC in the Japanese population.

(Authors) Satoshi Shiba, Shinichi Yachida, Sayaka Mizutani, et al.

(Affiliations) Department of Cancer Genome Informatics, Graduate School of Medicine, The University of Osaka, Osaka, Japan. School of Life Science and Technology, Institute of Science Tokyo, Tokyo, Japan. and numerous other research institutions.

(Journal Title) Nature Genetics volume 58, pages2211–2225 (2026).

(Date of Publication) August 10, 2026

DOI: https://doi.org/10.1038/s41588-026-02692-x

URL: https://www.nature.com/articles/s41588-026-02692-x

The gut bacterial metabolite imidazole propionate (ImP) may exacerbate Alzheimer’s disease pathology by impairing the brain endothelial barrier and promoting tau hyperphosphorylation. Targeting ImP may offer a novel strategy for the prevention and treatment of Alzheimer’s disease.

(Title) Gut bacterial metabolite imidazole propionate potentiates Alzheimer’s disease pathology.

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(Abstract) The gut microbiome modulates metabolic and neurovascular processes implicated in Alzheimer’s disease and related dementias (ADRD), but the underlying mechanisms remain unclear. Here, we identify the bacterial metabolite imidazole propionate (ImP) as a modifier of ADRD pathology. In a cohort of 1196 cognitively unimpaired adults, higher plasma ImP levels were associated with lower preclinical cognitive scores and biomarkers of ADRD, both cross-sectionally and longitudinally. Fecal metagenomic analysis linked putative ImP producers to ADRD phenotypes. Genome-wide integrative analysis revealed a locus on chromosome 12 associated with both plasma ImP levels and AD risk in humans, supporting a host genetic contribution to ImP regulation and a causal role of this metabolite in AD. In mice, chronic ImP administration exacerbated AD-like pathology. ImP impaired brain endothelial barrier and promoted tau hyperphosphorylation in primary neurons, an effect blocked by glycogen synthase kinase-3β inhibition. Together, this study links ImP to hallmarks of neurodegeneration and suggests that targeting ImP may represent a potential strategy to modify ADRD risk.

(Authors) Vemuganti, V., Kang, J.W., Zhang, Q. et al.

(Affiliations) Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA. Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA. and numerous other research institutions. and numerous other research institutions.

(Journal Title) Nature Communications volume 17, Article number: 8017 (2026).

(Date of Publication) 26 June 2026

DOI: https://doi.org/10.1038/s41467-026-74744-z

URL: https://www.nature.com/articles/s41467-026-74744-z