Organisms living on the seafloor are subject to encrustations by a wide variety of animal, plants, and microbes. Sea urchins, however, thwart this covering. Despite having a sophisticated immune system, there is no clear mechanism that allows sea urchins to remain clean. Here, by using CRISPR/Cas9, we test the hypothesis that pigmentation biosynthesis in sea urchin spines influences their interactions with microbes in vivo. We have three primary findings. First, the microbiome of sea urchin spines are species-specific and that much of this community is lost in captivity. Second, different color morphs associate with bacterial communities that are similar in composition and structure. Lastly, the gene activity of the pigmentation biosynthesis genes polyketide synthase and flavin-dependent mono-oxygenase induces a shift in which bacterial taxa colonize the tissues of sea urchin spines. We, therefore, find it plausible that host pigments are involved in host-microbe interactions and potentially in symbiotic homeostasis.