Microbes living in and on the human body number in the tens of trillions, where they set up camp in locations as diverse as the depths of the large intestine, inside the mouth, within the urogenital tract, and even behind the ears. By the early 2000s, scientists had primarily studied the harmful effects of microbes, but less was known about humans’ commensal microbes. Inspired by the success of the Human Genome Project, the National Institutes of Health (NIH) launched the Human Microbiome Project, which ran from 2007 to 2016. The project aimed to sequence the human microbiome from multiple body sites of healthy people as well as those with certain diseases over time, build computational tools to analyze that data, evaluate ethical issues that might arise in human microbiome research, and ultimately build datasets that could serve as a resource for researchers for years to come. In celebration of The Scientist’s 40th Anniversary, take a look back at our coverage of this microbial milestone.
2012: The Most Extensive Measure of the Human Microbial Menagerie
In 2012, researchers published the most extensive population-level analysis of Human Microbiome Project data to date in a pair of papers in Nature as well as 15 other papers published simultaneously in various journals. In one of the Nature papers, researchers sequenced microbes collected from 242 healthy volunteers from 18 different body parts in women and 15 in men. To their surprise, the team found that while some of the same microbes inhabited the same body parts in many people, there was no one species shared by every person. Furthermore, even if the species were the same, different people carried diverse strains of these bacteria. The team also found that people’s microbiomes tended to stay the same over time. One researcher not involved in the study called the dataset “a real treasure trove” of information.
2014: Microbiome Associations with Gender, Education Level, and Breastfeeding Discovered
Analyzing Human Microbiome Project data from 300 healthy people from 18 different body sites, scientists discovered that a person’s gender, whether they were breastfed as an infant, and their education level influenced their adult microbiome composition. The researchers stressed that these findings were correlations and added that other factors such as wealth and social status, which can affect education level for example, could also contribute to a person’s microbial population. The team also found that the microbiome of some body sites, such as the mouth, changed more often than other sites, such as the vagina and the gut.
2014: Cataloging Bacterial Genes in Additional Human Microbiomes
Researchers integrated data from multiple human microbiome datasets to extend the list of known bacterial genes to almost 9.8 billion. The team used data from the Human Microbiome Project, human microbiome data collected as a part of the European Commission’s project METAgenomics of the Human Intestinal Tract, samples from a Chinese diabetes study, 500 gut microbial genomes, and 249 fecal samples from adults in Denmark and Spain. They identified country-specific differences in gut microbes, with Danish and Chinese adults’ microbes having different metabolic activities and different frequencies of genes involved in different kinds of antibiotic resistance.
2015: The Unique Fingerprints of the Human Microbiome
Like DNA left at a crime scene, a person’s microbiome can also help identify them. Using data from the Human Microbiome Project, researchers found that people have a unique microbial fingerprint. They developed an algorithm that scanned the genetic sequences of individuals’ microbiomes and trained it on microbiome data from people in the Human Microbiome Project who had been sampled multiple times. While they found that the algorithm was accurate more than 80 percent of the time when identifying a person based on their gut microbiome, the accuracy dropped considerably when mouth, skin, or vaginal microbiome samples were used. The discovery, while exciting, also led to questions about how to protect the privacy of people who submit their microbial samples for research.
2016: What About Fungi? Don’t Leave Out the Mycobiome
In this opinion piece, mycologist Mahmoud Ghannoum from Case Western Reserve University argued that the Human Microbiome Project should include not just the bacteria present in the human microbiome, but other major microbial commensals too, such as fungi. The fungi associated with the human body—called the mycobiome—play an important role in maintaining human health. Researchers have found fungi in multiple body sites including the mouth, skin, and even the lungs. Disruptions in the mycobiome are associated with different diseases from inflammatory bowel disease (IBD) to graft versus host disease.
2017: Mining Thousands of Samples for Microbial Insights
With more than two thousand samples collected over the course of the Human Microbiome Project, researchers published new findings about both the identities of microbes in various body sites and information on their biochemical and molecular activities there. The scientists also added human commensal viruses and fungi to their analysis. The researchers found that both the gut and vaginal microbiomes were very personal to the individual. However, the skin and oral microbiomes were less personalized, and these microbial communities were more variable as well, echoing findings from prior Human Microbiome Project studies.
2019: How is the Human Microbiome Connected to Disease?
While the first phase of the Human Microbiome Project focused on sample collection and creating databases of microbial genomic sequences, the second phase—named the integrative Human Microbiome Project—zeroed in on evaluating the human microbiome over time and in the context of disease. In three separate studies, researchers studied the association between the human microbiome and pregnancy, IBD, and type 2 diabetes, respectively. Overall, the researchers found that the microbiome is intricately connected to human health. “Everything changes at once, and when the bugs change, you can see the human respond, and vice versa,” said Harvard University computational biologist Curtis Huttenhower, a coauthor of the IBD study.
2026: At-Home Microbiome Tests Face Regulatory Hurdles
As multiple studies have linked the human microbiome to conditions including obesity and mental health, the popularity of and desire for direct-to-consumer microbiome tests has risen. The companies that manufacture and market these tests ask consumers to send them a stool sample, which they analyze and then send information about the individual’s gut microbiome back to the sender. These tests, with their diverse sampling protocols and analysis pipelines, often show inconsistent results. Additionally, with their status as “wellness tests” rather than “in vitro diagnostic devices,” the FDA does not regulate them. While scientists and the public are excited by the potential of these tests, they want to see more standardized methods, increased workflow transparency, and clear communication about what these tests can actually tell people about their health.
