Main text The mammalian gut microbiome is intimately involved in supporting host homeostasis and can be a major driver of disease. Many microbiome studies focus on identifying taxonomic or functional gene signatures of disease, as inferred from relative read counts.2 However, these signatures can vary greatly depending on context, including lifestyle, diet, pharmaceutical use, genetics, batch effects, and other unmeasured (latent) factors.3 Here, Ruple et al.