Deciphering the role microbiomes may play in human health and disease

Piece by piece, scientists are trying to solve the puzzle of the ancient but evolutionary relationship between humans and their microbiomes, or the genetic world stemming from bacteria, viruses, fungi and other microbes inside or on the human body.

What's new: In the second part of a more than decade-long project to decode the genetic influence from these mysteriously important "bugs," the Integrative Human Microbiome Project (iHMP) published 3 studies Wednesday in Nature and Nature Medicine that look at how changes in the microbiome could be related to inflammatory bowel disease (IBD), prediabetes and preterm births.

The backdrop: Each person has a unique microbiome world in and on different parts of the body, including the nose, gut, vagina, amniotic fluid and mouth.

• It fluctuates depending on factors like age, environmental stressors, infections and seasonal nutrient availability.
• Microbes are suspected of playing a role in many aspects of human life, ranging from beneficial immune support to debilitating diseases.

Lita Proctor, former coordinator of the 10-year HMP who wrote a commentary, tells Axios that researchers need to better understand the basics of microbiomes, as scientists still can't really say what microbes do for human health.

The study on IBD, which affects 1.6 million Americans with Crohn’s disease or ulcerative colitis on a sporadic basis (but has seen a 400% increase in reports over the past 50 years), is published in Nature here and shows:

• What they did: Followed 132 people over 1 year, gathering 2,965 stool, biopsy and blood specimens. They developed a database based on these findings with what they called "the most comprehensive description to date of host and microbial activities" in IBD.
• What they found: "In numerous cases, the microbiome of a participant with IBD changed completely over the course of only weeks ... whereas such shifts were rare in individuals without IBD," per a related perspective in Nature.
• The authors point to at least 7 newly classified types of microbes — such as the Subdoligranulum species of bacteria — that tend to be disrupted when IBD flares up, but not always. Further study is needed on the role these may play, the authors say.
• What's next: "We're working to isolate and inspect each component of those systems to see if they can be targeted for new therapies ... [s]ee if they really do what they think might, and if so figure out which to increase (or decrease) in order to improve patient symptoms or prevent IBD flares in the first place," study author Curtis Huttenhower of Harvard University tells Axios.

The study on prediabetes, which 1 in 3 American adults have, is published in Nature here and reports:

• What they did: This study monitored the health of 106 people with and without prediabetes over 4 years to track microbiome activity via millions of molecular and microbial measurements in 51 lab tests.
• What they found: People who were at-risk of developing diabetes tended to have different microbes. And people whose cells are resistant to insulin (as are most prediabetics) showed different changes in their microbiome in response to viral infections or other infections.

• "[T]his study offers some new leads to define the biological underpinnings of [Type 2 Diabetes] in its earliest stages. These insights potentially point to high value targets for slowing or perhaps stopping the systemic changes that drive the transition from prediabetes to T2D," National Institutes of Health Director Francis Collins writes in his blog.

The study on preterm births, which follows up on previous research suggesting a link between vaginal microbiome and the risk of preterm birth, particularly in African Americans, is published in Nature Medicine here and states:

• What they did: The team tracked 45 preterm and 90 term births, 80% of whom were African American.
• What they found: There are differences in vaginal bacteria that may raise the risk of preterm birth among pregnant African American women, in particular the finding of lower levels of Lactobacillus crispatus in women who gave birth prematurely.
• "The findings suggest a link between the vaginal microbiome and preterm birth, and raise the possibility that a microbiome test, conducted early in pregnancy, might help to predict a woman’s risk for preterm birth. Even more exciting, this might suggest a possible way to modify the vaginal microbiome to reduce the risk of prematurity in susceptible individuals," Collins wrote.

The big picture: These 3 studies fall in a multitude of trials attempting to decipher the mysterious code, Proctor says. A multi-disciplinary approach including ecology and evolution is needed to truly grasp the interactions between individual humans and microbes, she says.

"We don't know how to really develop drugs or probiotics or prebiotics or cancer immunotherapy treatments ... unless we [first] understand how these networks work."