Competition, Mutualism, and Host Immune Control in a Cancer Microbiome

Abstract The microbiome functions as an ecological community, where diverse microbes engage in metabolically mediated interactions such as mutualism and competition. Host immune response can regulate microbial community richness and abundance, which in turn can shape the prevalence of different ecological interactions within the microbiome. Theory predicts that host immune states shift dominant interaction modes among microbes: inflammation favors competition, while immunosuppression favors mutualism. We test these theoretical predictions using the stomach cancer microbiome data through integrated genomic and metabolic analyses. We observe that tumors with high-richness and high-abundance microbiomes were associated with increased mutualistic interactions, whereas tumors with low-richness and low-abundance microbiomes had fewer mutualistic interactions. Host immune gene expression in the high-richness and abundance group was suggestive of a dysregulated or immunosuppressed tumor microenvironment, whereas in the low-richness and abundance group immune signatures were indicative of intact immune function. Notably, competitive interactions remained relatively consistent between groups, whereas mutualism varied markedly, highlighting its sensitivity to shifts in immune state. Finally, the microbiome and host immune states were linked to patient clinical outcomes, with high-richness and abundance microbiomes associated with poorer survival and elevated expression of immune markers linked to adverse prognosis. These results reveal how host immune control can covary with ecological interactions within the microbiome, and the potential consequences of these interactions for host health.