The Integrative Human Microbiome Project (iHMP) is the second phase of the NIH Human Microbiome Project (HMP), which aims to study dynamic changes in the microbiome and host under three conditions: pregnancy and preterm birth, inflammatory bowel diseases, and stressors affecting individuals with prediabetes. The iHMP provides unique data resources and represents a paradigm for future multi-omic studies of the human microbiome. The HMP has been carried out over ten years and two phases, providing resources, methods, and discoveries that link interactions between humans and their microbiomes to health-related outcomes. The HMP has accelerated biological research, particularly in microbial communities and the human microbiome. Studies of the microbiome have grown from culture-based surveys to molecular profiles of microbial biochemistry in all ecological niches of the human body. Epidemiology and model systems have been used to identify associations between changes in the microbiome and conditions ranging from autism to cancer, and microbial and immunological mechanisms have been identified that affect drug efficacy and survival during graft-versus-host disease. The HMP has also been a source of basic biological and translational surprises, exposing novel findings and open questions. Every human appears to carry their own suite of microbial strains, which are acquired early in life, differ between environments and populations, and can persist for years or undergo rapid transitions. Microbial diversity manifests differently in different ecological niches of the body, and the microbiome can be perturbed by conditions such as inflammatory bowel disease and diabetes. The HMP1 found that the taxonomic composition of the microbiome alone was often not a good correlate with host phenotype, but prevalent microbial molecular function or personalized strain-specific makeup was better predictive. This finding served as the foundation for the development of the second phase of the HMP, the Integrative HMP (iHMP or HMP2), which aimed to explore host-microbiome interplay, including immunity, metabolism, and dynamic molecular activity, to gain a more holistic view of host-microbe interactions over time. The iHMP includes three studies: pregnancy and preterm birth (PTB), inflammatory bowel diseases (IBD), and stressors affecting individuals with prediabetes. These studies have now reached the first stage of completion and provide a wealth of information about microbial dynamics, associated human host responses, and microbial inter-relationships. The HMP2 has produced a total of 42 terabytes of multi-omic data, archived and curated by the DCC at http://ihmpdcc.org and in public and/or controlled-access repositories. The HMP2 has also revealed new biology within their respective areas of health and disease, with a surprising range of host-microbiome immune and ecological features common among them. The combination of shotgun metagenomics, untargeted metabolomics, and immunoprofiling was particularly effective in capturing interpretable host and microbial properties linked to disease. The HMPThe Integrative Human Microbiome Project (iHMP) is the second phase of the NIH Human Microbiome Project (HMP), which aims to study dynamic changes in the microbiome and host under three conditions: pregnancy and preterm birth, inflammatory bowel diseases, and stressors affecting individuals with prediabetes. The iHMP provides unique data resources and represents a paradigm for future multi-omic studies of the human microbiome. The HMP has been carried out over ten years and two phases, providing resources, methods, and discoveries that link interactions between humans and their microbiomes to health-related outcomes. The HMP has accelerated biological research, particularly in microbial communities and the human microbiome. Studies of the microbiome have grown from culture-based surveys to molecular profiles of microbial biochemistry in all ecological niches of the human body. Epidemiology and model systems have been used to identify associations between changes in the microbiome and conditions ranging from autism to cancer, and microbial and immunological mechanisms have been identified that affect drug efficacy and survival during graft-versus-host disease. The HMP has also been a source of basic biological and translational surprises, exposing novel findings and open questions. Every human appears to carry their own suite of microbial strains, which are acquired early in life, differ between environments and populations, and can persist for years or undergo rapid transitions. Microbial diversity manifests differently in different ecological niches of the body, and the microbiome can be perturbed by conditions such as inflammatory bowel disease and diabetes. The HMP1 found that the taxonomic composition of the microbiome alone was often not a good correlate with host phenotype, but prevalent microbial molecular function or personalized strain-specific makeup was better predictive. This finding served as the foundation for the development of the second phase of the HMP, the Integrative HMP (iHMP or HMP2), which aimed to explore host-microbiome interplay, including immunity, metabolism, and dynamic molecular activity, to gain a more holistic view of host-microbe interactions over time. The iHMP includes three studies: pregnancy and preterm birth (PTB), inflammatory bowel diseases (IBD), and stressors affecting individuals with prediabetes. These studies have now reached the first stage of completion and provide a wealth of information about microbial dynamics, associated human host responses, and microbial inter-relationships. The HMP2 has produced a total of 42 terabytes of multi-omic data, archived and curated by the DCC at http://ihmpdcc.org and in public and/or controlled-access repositories. The HMP2 has also revealed new biology within their respective areas of health and disease, with a surprising range of host-microbiome immune and ecological features common among them. The combination of shotgun metagenomics, untargeted metabolomics, and immunoprofiling was particularly effective in capturing interpretable host and microbial properties linked to disease. The HMP