Children have 2.5 years to establish healthy gut bacteria

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A child has until the age of two-and-a-half to establish healthy gut bacteria – with little change after this point, research has revealed. The study also reinforced the important role breastfeeding plays in providing good gut bacteria to babies during the early stages of their life.

The team, involving Newcastle University, UK, identified that the bacterium, Bifidobacterium, was abundant in breast milk and declined rapidly after breastfeeding stopped. The research is one of the largest clinical microbiome studies in babies to date.

Dr Christopher Stewart, from Newcastle University’s Institute of Cellular Medicine, co-led the research, which used a cohort of patients involved in the pioneering TEDDY (The Environmental Determinants of Diabetes in the Young) study.

Bifidobacterium is regarded as beneficial and is one of the main bacteria used in probiotics, owing to its potential therapeutic properties. It is hoped that this research will enable a greater understanding into what can be done to produce the same benefits of breastfeeding when breast milk is not available.

Stewart said: “Breastfeeding has long been understood to be good for infants and epidemiological evidence shows being breastfed early in life is associated with lower risk of many later life diseases, such as allergy and obesity.

“Targeting the nutrients in breast milk that encourage the growth of healthy bacteria in the infant gut, or providing probiotic containing Bifidobacterium, represent important avenues for future research aimed at restoring the beneficial properties of being breastfed when breast milk is not available.”

The research revealed that once infants were weaned there was a rapid turnover in the bacterial community and a loss of most of the Bifidobacterium, replaced by bacteria within the Firmicutes phyla. Firmicutes are typical of an adult microbiome and the appearance of these bacteria once breastfeeding was stopped occurred much quicker than experts expected.

Stewart said: “Because a diet without breast milk delivers different nutrients to the gut, this rapid turnover in the bacterial community is likely to be in response to the new food sources promoting the growth of a different community.

“Remarkably, from this point on, the microbiome progressed quickly towards being stable, where the bacteria in the gut will potentially remain for the rest of that individual’s life.”

Scientists used sequencing-based approaches to analyse 12,500 stool samples from 903 children in the TEDDY study, collected monthly from children aged three to 46 months old. Microbiome composition and diversity changed over time in three distinct phases: the developmental phase (3-14 months), transitional phase (15-30 months) and stable phase (31 months onwards).

Vaginal birth was associated with a temporary increase in Bacteroides bacteria. Siblings, exposure to pets, and geographical location were also factors in the differences between microbiome profiles.

Dr Joseph Petrosino, director of the Alkek Centre for Metagenomics and Microbiome Research at Baylor College of Medicine, Texas, was group leader of the microbiome study. He said: “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.

“In this study, we took a closer look at the establishment of the microbiome over the first few years of life, and the early life exposures associated with that sequence of events, in this amazing cohort.”

In a sister paper in the same journal, experts from the Broad Institute analysed nearly 11,000 stool samples from 783 infants in the TEDDY study to characterise the early gut microbiome in children progressing to type 1 diabetes. They report that the microbiomes of infants without type 1 diabetes harbour more genes related to fermentation and short-chain fatty-acid synthesis that, in combination with previous evidence, are associated with a protective effect.

Abstract
The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial–immune crosstalk during this time thought to be involved in the pathobiology of later life diseases1,2,3,4,5,6,7,8,9 such as persistent islet autoimmunity and type 1 diabetes10,11,12. However, to our knowledge, no studies have performed extensive characterization of the microbiome in early life in a large, multi-centre population. Here we analyse longitudinal stool samples from 903 children between 3 and 46 months of age by 16S rRNA gene sequencing (n = 12,005) and metagenomic sequencing (n = 10,867), as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We show that the developing gut microbiome undergoes three distinct phases of microbiome progression: a developmental phase (months 3–14), a transitional phase (months 15–30), and a stable phase (months 31–46). Receipt of breast milk, either exclusive or partial, was the most significant factor associated with the microbiome structure. Breastfeeding was associated with higher levels of Bifidobacterium species (B. breve and B. bifidum), and the cessation of breast milk resulted in faster maturation of the gut microbiome, as marked by the phylum Firmicutes. Birth mode was also significantly associated with the microbiome during the developmental phase, driven by higher levels of Bacteroides species (particularly B. fragilis) in infants delivered vaginally. Bacteroides was also associated with increased gut diversity and faster maturation, regardless of the birth mode. Environmental factors including geographical location and household exposures (such as siblings and furry pets) also represented important covariates. A nested case–control analysis revealed subtle associations between microbial taxonomy and the development of islet autoimmunity or type 1 diabetes. These data determine the structural and functional assembly of the microbiome in early life and provide a foundation for targeted mechanistic investigation into the consequences of microbial–immune crosstalk for long-term health.

Authors
Christopher J Stewart, Nadim J Ajami, Jacqueline L O’Brien, Diane S Hutchinson, Daniel P Smith, Matthew C Wong, Matthew C Ross, Richard E Lloyd, Harsha Vardhan Doddapaneni, Ginger A Metcalf, Donna Muzny, Richard A Gibbs, Tommi Vatanen, Curtis Huttenhower, Ramnik J Xavier, Marian Rewers, William Hagopian, Jorma Toppari, Anette-G Ziegler, Jin-Xiong She, Beena Akolkar, Ake Lernmark, Heikki Hyoty, Kendra Vehik, Jeffrey P Krischer, Joseph F Petrosin

Newcastle University material
Nature abstract


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