Fusobacterium species are distinctly associated with patients with Lynch syndrome colorectal cancer

Highlights•Lynch Syndrome (LS) subjects gut microbiota has lower diversity compared to non-LS•Distinct enrichment of F. nucleatum and fap2 in LS CRC subjects•LS CRC gut microbiota exhibits increased lysine and arginine metabolism•Distinct fecal metabolites with minimal dysbiosis in LS subjects with no adenomaSummaryAccumulating evidence demonstrates clear correlation between the gut microbiota and sporadic colorectal cancer (CRC). Despite this, there is limited understanding of the association between the gut microbiota and CRC in Lynch Syndrome (LS), a hereditary type of CRC. Here, we analyzed fecal shotgun metagenomic and targeted metabolomic of 71 Japanese LS subjects. A previously published Japanese sporadic CRC cohort, which includes non-LS controls, was utilized as a non-LS cohort (n = 437). LS subjects exhibited reduced microbial diversity and low-Faecalibacterium enterotypes compared to non-LS. Patients with LS-CRC had higher levels of Fusobacterium nucleatum and fap2. Differential fecal metabolites and functional genes suggest heightened degradation of lysine and arginine in LS-CRC. A comparison between LS and non-LS subjects prior to adenoma formation revealed distinct fecal metabolites of LS subjects. These findings suggest that the gut microbiota plays a more responsive role in CRC tumorigenesis in patients with LS than those without LS.Graphical abstract