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New findings on intestinal flora development in infants

In the so far largest clinical study of the development of microbiomes, i.e. intestinal flora, in infants, researchers at the Baylor College of Medicine, USA, have found that development takes place in different phases that can be associated with lifestyle changes during the early stages in life. The findings are based on samples from the TEDDY study and are published in two articles in the scientific journal Nature.

The first years of life are important for the development of microbiomes. We are born with very few microorganisms and, during our first few years, microbial communities form on and inside the body.
In the present study, the researchers studied the establishment of microbiomes in children who are part of the TEDDY study* and the events associated with the first years of life.
More than 12 000 stool samples collected from 903 children between 3 and 46 months old with an increased hereditary risk of developing type 1 diabetes were analysed by researchers at the Baylor College of Medicine and the Broad Institute of the Massachusetts Institute of Technology and Harvard University.

The three development phases of the intestinal flora:
Through gene sequencing and metagenome sequencing (for analysing all genes that exist in an organism, i.e. also in bacteria, fungi, viruses, etc.), the researchers were able to determine that the development of the intestinal flora takes place in three distinct phases:
1.    Developmental phase (3–14 months)
2.    Transitional phase (15–30 months)
3.     Stable phase (31–46 months)

“Being able to organise the development phases in this way can allow us to reveal differences that may explain why children develop autoantibodies that subsequently involve an increased risk of type 1 diabetes”, says Professor Åke Lernmark, Lund University, who is responsible for the Swedish part of the TEDDY study and co-author of both articles. In total, the Swedish TEDDY children account for 30 per cent of the results.

Connection between breastfeeding and probiotic bacteria

The researchers discovered a link between breastfeeding and increased presence of Bifidobacterium breve and Bifidobacterium bifidum, two types of beneficial bacterial species with probiotic properties. Furthermore, the maturation of the child’s microbiome accelerated after the end of breastfeeding.

“This gives us insight into the effects of early diet on microbiological development”, says Joseph Petrosino, professor and director of the Alkek Center for Metagenomics and Microbiome Research at the Baylor College of Medicine, Houston, USA, who led the study.

Several epidemiological studies have shown a link between breastfeeding and a lower risk of several diseases later in life, such as allergies and obesity. Focusing on nutrients in breast milk that promote healthy intestinal bacteria, or prescribing probiotics containing bifidobacteria, is an important way forward in future research aimed at recreating or replacing the beneficial properties of breast milk when breastfeeding is not possible.

Vaginal delivery involves more bacteria

There was also a connection between vaginal birth and a larger amount of bacteria of the Bacteroides genus. However, more bacteria at birth was not limited to infants delivered vaginally. Those who had more bacteria at birth tended to have a larger variety of microbes during their first 40 months of life.

“Again, the implications of this are not yet clear. Microbial diversity is typically regarded as beneficial, but we still do not fully understand which microbial signs during early stages in life are important for development”, says Petrosino.

Autoimmunity and fewer bacteria

The study also showed that children who developed autoimmunity to the beta cells in the pancreas and therefore developed type 1 diabetes had fewer bacteria that can form and assimilate short-chain fatty acids.

“The research was made possible thanks to the TEDDY children’s parents sending in stool samples every month starting at 4 months. We hope that it can provide an increased understanding of the factors that affect the risk of developing autoantibodies to beta cells and type 1 diabetes”, says Helena Elding Larsson, researcher at Lund University and medical director of the TEDDY study in Sweden.

 

Publications in Nature:
The human gut microbiome of early onset type 1 diabetes in the TEDDY study
Nature, 24 oktober 2018, DOI: https://doi.org/10.1038/s41586-018-0620-2
 

Temporal development of the gut microbiome in early childhood from the TEDDY study
Nature, 24 oktober 2018 DOI, https://doi.org/10.1038/s41586-018-0617-x

*TEDDY

TEDDY logga

The TEDDY study has collected samples and data for over ten years with the goal of understanding what causes a child, with an increased hereditary risk of developing type 1 diabetes, to actually develop the disease. Researchers at six clinical centres, in Sweden among other countries, together with the University of South Florida, USA, which coordinates the data collection, have collected data and samples from more than 8 600 children with an increased hereditary risk of type 1 diabetes, including a small group (10%) in which at least one parent or sibling has the disease.
The TEDDY study is funded by the National Institutes of Health (NIH) in the United States.
Read more: www.med.lu.se/teddy

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