The physical biogeography of Fusobacterium nucleatum in health and disease.

Abstract

Fusobacterium nucleatum (Fn) is an oral commensal inhabiting the human gingival plaque that is rarely found in the gut. However, in colorectal cancer (CRC), Fn can be isolated from stool samples and detected in metagenomes. We hypothesized that ecological characteristics of the gut are altered by disease, enabling Fn to colonize. Multiple genomically distinct populations of Fn exist, but their ecological preferences are unstudied. We identified six well-separated populations in 133 Fn genomes and used simulated metagenomes to demonstrate sensitive detection of populations in human oral and gut metagenomes. In 9,560 samples from 11 studies, Fn population C2 animalis is elevated in gut metagenomes from CRC and Crohn's disease patients and is observed more frequently in CRC stool samples than in the gingiva. Polymorphum, the most prevalent gingival Fn population, is significantly increased in Crohn's stool samples; this effect was significantly stronger in male hosts than in female. We find polymorphum genomes are enriched for biosynthetic gene clusters and fluoride exporters, while C2 animalis are high in iron transporters. Fn populations thus associate with specific clinical and demographic phenotypes and harbor distinct functional features. Ecological differences in closely related groups of bacteria inform microbiome impacts on human health.

Importance: Fusobacterium nucleatum is a bacterium normally found in the gingiva. F. nucleatum generally does not colonize the healthy gut, but is observed in approximately a third of colorectal cancer (CRC) patient guts. F. nucleatum's presence in the gut during CRC has been linked to worse prognosis and increased tumor proliferation. Here, we describe the population structure of F. nucleatum in oral and gut microbiomes. We report substantial diversity in gene carriage among six distinct populations of F. nucleatum and identify population disease and body-site preferences. We find the C2 animalis population is more common in the CRC gut than in the gingiva and is enriched for iron transporters, which support gut colonization in known pathogens. We find that C2 animalis is also enriched in Crohn's disease and type 2 diabetes, suggesting ecological commonalities between the three diseases. Our work shows that closely related bacteria can have different associations with human physiology.