Study finds three distinct stages in infant microbiome development

October 24, 2018, Baylor College of Medicine
Credit: CC0 Public Domain

In the largest clinical microbiome study in infants reported to date, a team led by researchers at Baylor College of Medicine explored the sequence of microbial colonization in the infant gut through age 4 and found distinct stages of development in the microbiome that were associated with early life exposures. Published in the journal Nature, their report and an accompanying report led by the Broad Institute are the result of extensive analysis of data collected from a cohort of participants involved in the TEDDY diabetes study.

The TEDDY study (The Environmental Determinants of Diabetes in the Young) study has been collecting data for 10 years with the goal of understanding what triggers type 1 diabetes in children at increased genetic risk for the disease. Researchers at six clinical centers in the U.S., Sweden, Finland, and Germany, as well as the Data Coordinating Center at the University of South Florida, have gathered monthly and data from more than 8,600 children who are genetically susceptible to type 1 diabetes. From this cohort, researchers at Baylor College of Medicine analyzed 12,005 stool samples that were collected from 903 children between three and 46 months of age to further understand what the looks like early in life.

"We know that the first few years of life are important for microbiome establishment. You are born with very few microbes, and microbial communities assemble on and in your body through those first years of your life," said Dr. Joseph Petrosino, director of the Alkek Center for Metagenomics and Microbiome Research and professor and interim chair of molecular virology and microbiology at Baylor. "In this study, we took a closer look in this amazing cohort at the establishment of the microbiome over the first few years of life and the early life exposures associated with that sequence of events."

Using state of the art sequencing of both RNA and DNA to uncover the complete genetic set up of all microbes, Petrosino and his team determined that the developing gut microbiome undergoes three distinct phases of microbiome progression:

  1. Developmental phase (3 to 14 months of age)
  2. Transitional phase (15 to 30 months of age) and
  3. Stable phase (31 to 46 months of age)

"This information is useful for any future microbiome studies looking at an infant cohort for scientific discovery and potential intervention purposes. The idea that we can stratify the development phases in this manner may give researchers additional resolution to reveal differences that could potentially be disease-associated," Petrosino said.

More insights into microbiome development

The study found an association between at least partial breastfeeding and having a higher abundance of Bifidobacterium breve and Bifidobacterium bifidum, two types of bacterial species with probiotic properties known to be prevalent early in life. In addition, the cessation of breastfeeding accelerated the maturation of the infant's microbiome, meaning it proceeded quickly through the other stages to the , which is hallmarked by higher amounts of the bacteria Firmicutes spp.

"Further research will help better understand the implications of having an accelerated rate of microbiome maturation," Petrosino said.

In those infants who were breastfed, the strains of Bifidobacterium that had the genetic capability of processing human milk were no longer detected once breastfeeding stopped.

"The presumption is that selective pressure for these organisms to be present during breastfeeding is removed once breastfeeding stops, and other strains of Bifidobacterium that do not process the metabolites in breast milk can then grow," Petrosino said. "This provides insight into how the early diet is impacting microbiome development."

The researchers also found an association between vaginal delivery and having a greater abundance of bacteria belonging to the Bacteroides genus. However, having more Bacteroides at birth was not exclusive to those infants who were delivered by this mode. Those who did have more Bacteroides at birth tended to have a greater diversity of microbes early in the first 40 months of life.

"Again, the implications are not yet clear. Having microbial diversity is typically thought of as beneficial, but we still don't fully understand which microbial signals early in life are important for development," Petrosino said.

Petrosino noted that these data already are being used, along with the extensive TEDDY metadata repository, to better understand how environmental exposures contribute to progression to type 1 diabetes. Additional provocative microbiome analyses, including the viral and fungal microbiome constituents, are underway and will also include human genomic, metabolomic and proteomic data, as well as dietary and infectious episode information.

"These initial analyses have reinforced previous infant studies and also have revealed additional important microbiome associations during this critical time in life. Future discoveries from this cohort will pave the way for focused mechanistic work to elucidate how the microbiome influences health and disease, particularly type 1 diabetes," said Dr. Christopher Stewart, co-first author of the study, formerly a postdoctoral researcher at the Petrosino lab at Baylor and now a research fellow at Newcastle University.

"It is cohorts such as this, where we can integrate clinical data with patient-specific exposure, genomic and microbiome analyses, that will lead to precision medicine-based diagnostics and therapeutics for type 1 diabetes and many other diseases," Petrosino concluded.

Explore further: Researchers connect lower antibiotic resistance with higher levels of bifidobacteria in infant gut

More information: Christopher J. Stewart et al, Temporal development of the gut microbiome in early childhood from the TEDDY study, Nature (2018). DOI: 10.1038/s41586-018-0617-x

Related Stories

Researchers connect lower antibiotic resistance with higher levels of bifidobacteria in infant gut

September 26, 2018
A study published this week in mSphere suggests that infants, who are vulnerable to an array of infectious diseases, may have a microbial ally in keeping antibiotic-resistant infections at bay. Researchers found that children ...

What you eat while pregnant may affect your baby's gut

July 4, 2018
A mother's diet during pregnancy may have an effect on the composition of her baby's gut microbiome—the community of bacteria living in the gut—and the effect may vary by delivery mode, according to study published in ...

First gut bacteria may have lasting effect on ability to fight chronic diseases

September 18, 2018
New research showing that the first bacteria introduced into the gut have a lasting impact may one day allow science to adjust microbiomes—the one-of-a-kind microbial communities that live in our gastrointestinal tracts—to ...

Study looks at association of infant gut microbiome, delivery mode and feeding

January 11, 2016
The composition of the gut microbiome in infants at six weeks of age appears to be associated with the delivery method by which they were born and how they were fed, according to an article published online by JAMA Pediatrics.

Microbiome profiling reveals associations with ulcerative colitis severity, treatment

October 11, 2018
A study of gut microbes from more than 400 children points to how the microbiome behaves in this inflammatory bowel disease.

Study looks at how changes in maternal diet impact human milk oligosaccharides and milk microbiome

January 23, 2017
In a study to be presented Thursday, Jan. 26, in the oral plenary session, at the Society for Maternal-Fetal Medicine's annual meeting, The Pregnancy Meeting, researchers with Baylor College of Medicine, Houston, Texas and ...

Recommended for you

New inflammation inhibitor discovered

November 16, 2018
A multidisciplinary team of researchers led from Karolinska Institutet in Sweden have developed an anti-inflammatory drug molecule with a new mechanism of action. By inhibiting a certain protein, the researchers were able ...

Gut hormone and brown fat interact to tell the brain it's time to stop eating

November 15, 2018
Researchers from Germany and Finland have shown that so-called "brown fat" interacts with the gut hormone secretin in mice to relay nutritional signals about fullness to the brain during a meal. The study, appearing November ...

Brain, muscle cells found lurking in kidney organoids grown in lab

November 15, 2018
Scientists hoping to develop better treatments for kidney disease have turned their attention to growing clusters of kidney cells in the lab. One day, so-called organoids—grown from human stem cells—may help repair damaged ...

How the Tasmanian devil inspired researchers to create 'safe cell' therapies

November 15, 2018
A contagious facial cancer that has ravaged Tasmanian devils in southern Australia isn't the first place one would look to find the key to advancing cell therapies in humans.

Researchers discover important connection between cells in the liver

November 15, 2018
University of Minnesota Medical School researchers have made a discovery which could lead to a new way of thinking about how disease pathogenesis in the liver is regulated, which is important for understanding the condition ...

Precision neuroengineering enables reproduction of complex brain-like functions in vitro

November 14, 2018
One of the most important and surprising traits of the brain is its ability to dynamically reconfigure the connections to process and respond properly to stimuli. Researchers from Tohoku University (Sendai, Japan) and the ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.