H2020Individual fellowship2015–2017

INFANT MICROBIOTA · Elucidating how Bifidobacteria shapes the microbiota in response to infant diet.

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2015-07-01 → 2017-06-30
EU contribution
€183,455
Participants
2
Scheme
MSCA-IF-EF-ST

Lines connect the coordinator with its partners.

Results in brief

Elucidating how Bifidobacteria shapes the microbiota in response to infant diet.

After birth our body surfaces are rapidly colonised by microbial communities, collectively termed the microbiota. Within our body, our gut microbiota is the largest and most diverse bacterial community, with upwards of trillions bacteria per gram of content. These resident microbes form an intricately balanced mutualistic relationship in early life with the host, which is maintained throughout life and promotes long-term host health. The infant microbiota is established by vertical transmission through the birth canal, skin-to-skin contact and breast-feeding. Pioneer bacteria, like Bifidobacterium are one of the first bacteria to colonise and in time, reach upwards of 80% of the total population density. In contrast, Bifidobacteria represent about 5% of the gut microbiota in formula-fed infants. The predominance of Bifidobacteria in the infant microbiota is proposed to be critical for establishing a ‘healthy’ microbiota and promoting paediatric wellbeing. However, the mechanism by which this Bifidobacterium-rich ‘state’ occurs remains largely unknown. Several studies indicate that an infant’s diet (breast-milk vs. formula) plays a central role in driving intestinal microbial composition and diversity. Crucially, enhanced infant well-being, such as robust mucosal immunity and reduced inflammatory diseases, can be attributed to breast-feeding and improved microbiota development in early life. Despite the significant health benefits associated with maternal milk, the rate of infants solely breast-fed in the UK is only 45% by one-week of age, and 7% at four months; this rate is lower than that observed in neighbouring European countries such as France and Germany (Renfrew, M.J. et al., 2012, UNICEF UK). However, key questions remain to be answered as to why Bifidobacteria populations are dramatically altered in breast- and formula-fed infants. It is imperative to understand the mechanisms driving beneficial bacterial colonisation, whilst excluding potentially harmful bacteria, during infant microbiota development in response to diet. The ultimate future aim is to develop improved infant formula(s) that more closely replicate the microbial community dynamic benefits derived from breast milk. Our research objectives were to investigate the mechanisms that enhance Bifidobacteria colonisation in the gut of breast fed infants, and not in infants fed with formula. In addition, we sought to identify how Bifidobacteria modulates the wider infant gut community; establishing and shaping these communities over time. Through our experimental set-ups we have been able to identify key factors in breast-milk that promote Bifidobacteria growth at high levels and prolonged survival in the host. This research will provide insights into the function and mechanisms of how infant diet impacts Bifidobacteria colonisation in the infant gut, with the potential to identify key components that could be incorporated in new infant formula(s) to promote ‘healthy’ infant microbiota development, thus positively impacting infant wellbeing.

Data: CORDIS, © European Union

Project objective

After birth we are colonized by a consortium of bacteria that are critical for health. Bifidobacteria represent pioneer members, and reach high levels within the gut microbiota of breast-fed infants. These bacteria are proposed to be critical for establishing ‘healthy’ microbiota development and immune defense; however the mechanisms remain unknown. We hypothesize that breast-milk metabolism by Bifidobacteria provides microbial-derived metabolic products key to promoting stable colonisation of other members in the microbiota, suggesting a mechanism as to why formula-fed infants have an altered microbiota and associated increased risk to a variety of diseases. This MCSA seeks to elucidate the function of Bifidobacteria with host diet, by developing a model colon ecosystem colonised with defined infant bacterial isolates to identify key bifidobacterial-derived metabolic byproducts that differ between breast milk and formula metabolism using cutting-edge metabolic tracer experiments and [13C]-Bifidobacteria pseudocatenulatum. Aim 2 will determine the genomic and regulatory elements in B. pseudocatenulatum required for adaption/metabolism of breast-milk or infant formula in the model colon via construction of a genome-wide mutant library generated by high through-put transposon mutagenesis. Metabolites identified in aim 1 will be linked to specific bifidobacterial gene function, based on the identity of essential mutants unable to grow in the presence of breast-milk (aim 2). We will also determine how host diet impacts microbiota composition in the model ecosystem, by monitoring microbial diversity by 16S rRNA analysis. Finally, to promote a ‘healthy’ microbiota, identified breast-milk metabolites will be used to supplement the formula fed model. This research will provide critical insight into the function and mechanism of how infant diet impacts bifidobacteria colonisation, with the potential to identify key bifidobacterial-metabolites that promote life-long health.

Original text from CORDIS.

Participants

Links

Data: CORDIS, © European Union