Below you can find summaries of previous and ongoing research projects with links to publications and media coverage.
Horizontal gene transfer events between maternal and infant gut microbiomes
  • Mobile genetic elements from maternal bacteria shape offspring gut microbiomes
  • Microbiome and metabolome shifts in pregnancy may impact maternal metabolic health
  • The infant gut harbors unique metabolites and species-metabolite relationships
  • Diet modulates metabolomic profiles and immune system maturation in infants

We explored how the microbiomes of the mother and baby change during pregnancy and the first year of life, and discovered that some bacteria in the mother’s gut donate hundreds of genes to bacteria in the baby’s gut. These genes are involved in the development of the immune and cognitive systems and help the baby to digest a changing diet as it grows. This was the first  study to uncover large-scale horizontal gene transfer events between different species of maternal and infant gut bacteria. The research also revealed a wide range of chemicals produced by the bacteria, or metabolites, that are unique to the baby. Together, the findings add to a growing appreciation for the complex physiological connection between mother and infant during early life. Read more details from a Broad Institute and Quanta news stories and a tweetorial by Simona Cristea or from the article below.

A distinct clade of Bifidobacterium longum in the gut of Bangladeshi children thrives during weaning
  • Gut microbiomes of infants from Bangladesh harbored three Bifidobacterium longum clades
  • Transitional B. longum clade carried enzymes to utilize breast milk and food substrates in weaning
  • B. longum clades and associated metabolites were implicated in diarrhea and growth

We investigated gut microbiomes and metabolomes in 222 young children in Dhaka, Bangladesh during two first years of life and found that they harbord three successive clades of B. longum. In addition to two well-known subspecies clades – B. longum subsp. infantis and B. longum subsp. longum – we observed a third clade that peaked during weaning. We named this clade Transitional B. longum.

Transitional B. longum carried enzymes to utilize both breast milk and solid food substrates in weaning, suggesting that the clade has adapted to thrive when both breastmilk sugars and solid food substrates are available. We identified a group of metabolites, including pipecolic acid, that correlated with the previously Transitional B. longum, providing further cues on the role of this organism in the gut ecosystem and host development. B. longum clades and associated metabolites were implicated in childhood diarrhea and early growth, including positive associations between growth measures and B. longum subsp. infantis, indolelactate and N-acetylglutamate. These data demonstrate geographic, cultural, seasonal, and ecological heterogeneity that should be accounted for when identifying microbiome factors implicated in and potentially benefiting infant development.

Gut Microbiome in type 1 diabetes and autoimmunity
  • Changes in gut  microbiome  taxa and functional capacity prior to onset of type 1 diabetes
  • Differences in lipopolysaccharide immunogenicity are implicated in immune maturation and type 1 diabets 
  • Certain bacteria, such as B. longum subsp. Infantis, may confer protective effects against early-onset autoimmunity

The DIABIMMUNE study followed nearly 300 children from Finland, Estonia and Russian Karelia who had an increased genetic risk of developing type 1 diabetes; monthly stool samples were taken from birth until three years of age. We used 785 stool samples profiled using metagenomic sequencing to test the hygiene hypothesis, which postulates that differences in early microbial exposure lead to altered immune maturation. In this collaborative study, we established a mechanistic connection between the infant gut microbiome, immune system development and diabetes by demonstrating how differences in microbiota-derived lipopolysaccharides affect human immune cell responses cells and diabetes development in a mouse model. Results were published in the journal Cell. The article has received more than 1,000 citations and the findings were highlighted in the media (e.g. New York Times and Scientific American). 

The TEDDY (The Environmental Determinants of Diabetes in the Young) study followed more than 1,000 children from three European countries and three states in the USA with increased genetic risk to type 1 diabetes (similar to the DIABIMMUNE participants above). In TEDDY, we generated and analyzed over 10,000 metagenomes from the stool samples of 783 children; samples were collected monthly from birth until five years of age and found that the early administration of probiotics and bacterial short-chain fatty-acid biosynthesis provided protection from islet autoimmunity and early onset type 1 diabetes. The results were published in the journal Nature and the article was featured as a cover story of the issue.

Bifidobacterium longum subsp. infantis (B. infantis) is a bacterial species highly specialized in human milk metabolism and common in babies from many non-Western populations. Oyur follow up research in DIABIMMUNE and TEDDY cohorts found that that B. infantis appears to be disappearing from many Western populations, with less than 20% of the babies harboring B. infantis during breastfeeding in these populations. Based on the results from DIABIMMUNE (where Bacteroides species had largely replaced Bifidobacterium in Finnish and Estonian babies) and TEDDY suggesting that early probiotic administration may be protective from islet autoimmunity, we further hypothesized that early B. infantis supplementation may protect genetically predisposed babies from developing autoimmunity. This analysis was recently published in the journal Nature Microbiology. This hypothesis (also supported by data from other labs) is currently being tested in a large, multi-center randomized placebo-controlled GPPAD-SINT1A trial. Our role in this line of research was featured in an article in Drug Discovery News titled Can a probiotic prevent type 1 diabetes in children?

Gene expression shift in gut bacteria following mother-to-infant transmission

It is essential to measure bacterial transcription to fully appreciate microbiome activities in changing environments.

We co-led an international collaboration which generated and pioneered the use of metatranscriptomic (community gene expression) data from stool samples in the multi-center (UK, Singapore, New Zealand) NiPPeR infant nutritional trial. We developed a new computational analysis method and found that maternally-derived bacterial strains exhibited large scale gene expression shifts following vertical transmission to the infant gut. These included changes in transferase expression, carbohydrate metabolism and bacteriophage activity. These environment-dependent, strain-specific shifts in gut bacterial functions convinced me of the importance of metatranscriptomic data and computational analysis methods for future microbiome investigations. 

Prophylactic dextrose gel does not alter neonatal gut microbiome

Sugar gel given orally to newborn babies for preventing low blood sugar levels does not alter their gut microbiomes soon after or several weeks later.

Oral dextrose gel is effective for treating and preventing neonatal hypoglycaemia (low blood sugar levels), but concerns have been expressed that administration of dextrose gel may alter the neonatal gut microbiome. To address these concerns, we obtained funding to evaluate neonatal gut microbiome in a nested case-control cohort within the hPOD prophylactic dextrose gel trial. We found no differences in neonatal gut microbiomes in infants given prophylactic dextrose gel, placebo or no gel. Clinicians and consumers can be reassured that dextrose gel used for prophylaxis or treatment of neonatal hypoglycaemia does not alter the neonatal gut microbiome.