The human gut microbiome composition is generally in a stable dynamic equilibrium, but it can deteriorate into dysbiotic states detrimental to host health. To disentangle the inherent complexity and capture the ecological spectrum of microbiome variability, we used 5,230 gut metagenomes to characterize signatures of bacteria commonly co-occurring, termed enterosignatures (ESs). We find five generalizable ESs dominated by either Bacteroides, Firmicutes, Prevotella, Bifidobacterium, or Escherichia. This model confirms key ecological characteristics known from previous enterotype concepts, while enabling the detection of gradual shifts in community structures. Temporal analysis implies that the Bacteroides-associated ES is “core” in the resilience of westernized gut microbiomes, while combinations with other ESs often complement the functional spectrum. The model reliably detects atypical gut microbiomes correlated with adverse host health conditions and/or the presence of pathobionts. ESs provide an interpretable and generic model that enables an intuitive characterization of gut microbiome composition in health and disease. Display omitted •The human gut microbiome is described as combinations of five enterosignatures•Enterosignatures represent microbial guilds, complementary in their metabolism•Enterosignature composition is dynamic and changes with host’s age•Gut microbiomes deviating from this model could indicate dysbiotic states Frioux et al. introduce enterosignatures as microbial guilds whose assemblies are accurate descriptors of the human gut microbiome composition. Enterosignature composition relates to changes and perturbations in the microbiome over a lifetime. The model generalizes to diverse human populations and can be used to detect anomalies in the gut microbiome.