| Summary: | The health of mammals depends on a complex interplay with their microbial ecosystems. Compartments exposed to external environments such as the mucosal surfaces of the gastrointestinal tract accommodate the gut microbiota, composed by a wide range of bacteria. The gut microbiome confers benefits to the host, including expansion of metabolic potential and the development of an immune system that can robustly protect from external and internal insults. The cooperation between gut microbiome and host is enabled in part by the formation of partitioned niches that harbor diverse bacterial phyla. Bacterial secretion systems are commonly employed to manipulate the composition of these local environments. Here, we explore the roles of the bacterial type VI secretion system (T6SS), present in ~25% of gram-negative bacteria, including many symbionts, in the establishment and perturbation of bacterial commensalism, and symbiosis in host mucosal sites. This versatile apparatus drives bacterial competition, although in some cases can also interfere directly with host cells and facilitate nutrient acquisition. In addition, some bacterial pathogens cause disease when their T6SS leads to dysbiosis and subverts host immune responses in defined animal models. This review explores our knowledge of the T6SS in the context of the “host-microbiota-pathogen” triumvirate and examines contexts in which the importance of this secretion system may be underappreciated.
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