Tissues undergo constant remodelling to maintain architecture during growth, in normal physiology and in response to disease. Interactions of the host with both commensals and pathogens, which include bacteria, viruses, fungi and parasites, may affect not only immune responses due to recognition of pathogen associated molecular patterns (PAMPS), but also tissue remodelling including for example through the generation of neo-epitopes and damage-associated molecular patterns (DAMPS). Roles for the microbiome, viriome, fungi, as well as pathogenic bacteria and parasites, in both homeostasis and in host-pathogen interactions, is a topic of considerable interest regarding effects relating to chronic disease, cancer, dysbiosis, the gut-brain axis, host metabolism, drug metabolism and zoonotic disease. This Research Topic sought to collect state-of-the-art primary research studies and review articles from international experts and diverse groups in the field to further current understanding of the contributions of both commensals and pathogens in tissue remodelling in physiological and pathophysiological processes of the host. The collection of articles presented here in this special topic is a small representation of research into host-pathogen/commensal interactions, highlighting the complexity of the interplay with the host in both health and disease. The co-evolution of pathogens and hosts must be considered, both in shaping the immune system throughout evolution, gut-brain axis communication, metabolism, chronic disease and cancers, as well as in relation to zoonotic and emerging diseases.