New research has uncovered millions of previously unknown genes from microbial communities in the human gut, skin, mouth, and vaginal microbiome, allowing for new insights into the role these microbes play in human health and disease.
The microbiome—the encompassing term for the trillions of microbial organisms that live on and within our bodies—has been the focus of intensive research by members of the Human Microbiome Project (HMP), an NIH initiative launched in 2008.
Seemingly every other week new data is published underscoring the importance the microbiome has on human well-being and disease.
Now, new data from HMP members at the University of Maryland School of Medicine (UM SOM), Harvard T.H. Chan School of Public Health, the Broad Institute of MIT and Harvard, and the University of California San Diego has uncovered millions of previously unknown genes from microbial communities in the human gut, skin, mouth, and vaginal microbiome, allowing for new insights into the role these microbes play in human health and disease.
Findings from the new study—published recently in Nature in an article entitled “Strains, Functions, and Dynamics in the Expanded Human Microbiome Project”—triple the amount of data previously analyzed in this project, and is the largest human microbiome study ever. The results are a significant jump in the amount of information available to scientists and should provide new insight into the changes in our microbiome over time—leading to a greater understanding of the genetic differences that are unique to an individual’s microbes.
Human survival depends on the trillions of microbes that that inhabit our bodies. In a healthy person, those bacteria, fungi and viruses – the human microbiota – are well balanced. But shifts in the makeup and function of those populations can lead to diseases.
“This new data really expands our appreciation for the fingerprint created by microorganisms that make up each human’s microbiome,” noted co-senior study investigator Owen White, Ph.D., professor of epidemiology and public health and associate director at the Institute for Genome Sciences (IGS) at UM SOM. “These organisms play a crucial role in many key aspects of our health. The more we know about them and their role, the more likely it is that we will be able to manipulate them to improve our health.”
HMP set out to identify and characterize human microbes, explore microbes’ relationship to health and disease, and develop computational tools to analyze the microbes. The microbiome has been linked to various aspects of human health, including the robustness of our immune system and our susceptibility to chronic illnesses such as Crohn’s disease and cancer. The current study is a continuation of work published in Nature in 2012.
“Here we introduce a second wave of data from the study, comprising 1,631 new metagenomes (2,355 total) targeting diverse body sites with multiple time points in 265 individuals,” the authors wrote.
“We applied updated profiling and assembly methods to provide new characterizations of microbiome personalization. Strain identification revealed subspecies clades specific to body sites; it also quantified species with phylogenetic diversity under-represented in isolate genomes. Body-wide functional profiling classified pathways into universal, human-enriched, and body site-enriched subsets. Finally, temporal analysis decomposed microbial variation into rapidly variable, moderately variable, and stable subsets.”
The research team used DNA sequence analysis tools to identify which organisms are present in various body sites, determine whether they change or stay relatively stable over time, and explore their function. This study also provides one of the largest profiles of nonbacterial members—viruses and fungi—of the microbiome. In addition, it unraveled some of the biochemical activity that allows microbes to play a role in human health.
a–d, Tukey boxplots of total assembly size, maximum and average contig lengths, and gene counts for single and co-assemblies (sample sizes in Supplementary Table 1). e, Rarefaction curves of gene families (open reading frame (ORF) clust…
“These communities of organisms are tremendously complex. In one sense, this study is a great advancement for the research community,” explained Anup Mahurkar, executive director of software engineering & information technology at IGS. Mr. Mahurkar was responsible for the months of intensive computations required to process the data. However, he was also cautious, saying “On the other hand, it still just moves the needle. There will always be more we can learn.”
“The microbiome is one of the great undiscovered areas in medicine today, with links to many common and problematic chronic diseases,” said UM SOM Dean E. Albert Reece, M.D., Ph.D., who is also the vice president for medical affairs at the University of Maryland. “This pathbreaking research will open the door for a wide range of clinically relevant research in the years to come.”
“This study furthers our knowledge of baseline human microbial diversity and enables an understanding of personalized microbiome function and dynamics,” the authors concluded.