Determinants of the healthy gut microbiome: core features, modifying factors and normal functions.

Abstract

The human gut microbiome represents a complex and dynamic ecosystem that is central to maintaining health and preventing disease. Defining a "normal" gut microbiome remains challenging, given the significant variability arising from host physiology, lifestyle, genetics, geography and environmental exposures. This review synthesizes current evidence regarding the composition and functions of the gut microbiota in healthy individuals from diverse populations. At the taxonomic level, healthy gut microbial communities are typically dominated by the phyla Firmicutes and Bacteroidetes, with additional contributions from Actinobacteria and Proteobacteria. However, substantial inter-individual and regional differences are observed, such as a higher prevalence of Prevotella in populations consuming fiber-rich Eastern diets, and greater Bacteroides abundance in Western cohorts. Anatomical location and health status also influence alpha-diversity, underscoring the need to interpret diversity metrics within context. Furthermore, the gut microbiome performs essential functional roles across multiple organ systems, including fermentation of dietary fibers into short-chain fatty acids, regulation of immune responses, modulation of the gut-brain axis, maintenance of intestinal barrier integrity, and support of cardiovascular and hepatic functions. These findings support the conceptualization of the microbiome as a multifunctional organ system that integrates host and environmental signals. In summary, a healthy gut microbiome is best understood as a dynamic equilibrium, characterized by functional resilience and adaptability, rather than a fixed microbial profile. Interpreting this variability is crucial for developing targeted interventions to prevent disease.