This prospective metagenomic study investigated the gut microbiome in individuals with Lynch syndrome compared with matched controls from the general population. Lynch syndrome was associated with a distinct gut microbiome composition and function, including increased microbial diversity and enrichment of specific bacterial taxa such as Blautia species and Actinobacteria. Unlike sporadic colorectal cancer, Fusobacterium nucleatum was not enriched. Microbiome features showed limited ability to detect advanced colorectal neoplasia, highlighting the need for longitudinal studies to clarify the microbiome's role in colorectal cancer development in Lynch syndrome.