Profiling the gut microbes passed from mother to baby
How an infant is born (by vaginal or cesarean delivery) and what she eats after birth (breast milk or formula) influence the growth of her gut microbiome — the community of bacteria that live in the GI tract. Precisely how infants acquire their microbiome is still largely a mystery. A mother's gut microbes contribute to her baby's microbiome, but only certain microbial species make the jump from mom to child, with some colonizing more effectively than others.
To find out why, a team of researchers co-led by Ramnik Xavier, core institute member and co-director of the Infectious Disease and Microbiome Program at the Broad Institute of MIT and Harvard, and Mikael Knip at the University of Helsinki, surveyed the gut microbiomes of 44 infants and their mothers in Finland, during the first three months of the infants’ lives. Their findings, published in Cell Host and Microbe, both confirmed microbiome transmission from mother to child and provided snapshots of how gut microbial communities develop during a baby's early days.
To track differences and similarities between microbiomes down to the level of bacterial strains, the researchers turned to whole-genome metagenomic sequencing, a technique that aims to sequence DNA from every bacteria present in the gut. Two bacteria of the same species can differ at the strain level, somewhat like two different editions of the same book.
The team's analysis provided a highly comprehensive view of both maternal and infant gut communities. While in most cases the mother’s dominant strain was transmitted to the child, the researchers found some instances in which the mother's secondary strain was transmitted instead. It’s still not totally clear why. The team also noted strain-specific factors, such as the presence or absence of certain metabolic genes, that may influence the balance of strains.
The Broadminded Blog talked to the paper's two co-first authors, Moran Yassour, a postdoctoral researcher in the labs of Xavier and Eric Lander; and Larson Hogstrom, a computational scientist in the Lander lab. They shared what excites them about studying the infant gut microbiome, and how next-generation computational and sequencing tools are providing a much more granular view of the microbial ecology of the human gut.
What got you interested in studying the infant gut microbiome?
Moran Yassour: We are learning more and more, every day, about the human gut microbiome and how it may influence health and disease. We want to fully comprehend why the microbiome of infants born by C-section differs from those delivered by natural birth. We want to know where the first bacteria in their gut comes from and how they establish a full community. By the age two or three, kids start to have adult-like microbial communities in their guts. That is why we want to dig deeper into those initial years, even months, of a child’s life.
Larson Hogstrom: The other big motivation for this field is to understand the link between the human gut and the infant immune system. Bacteria play a prominent role in activating our immune system. Understanding how these microbial communities form will be the first step toward learning how changes in those communities may affect our immunity.
Can you give an overview of this study?
Yassour: We collected and analyzed stool samples from 44 infants, all of whom were breastfed, at five time points: at birth, two weeks, one month, two months, and three months after birth. We collected three sets of samples from their mothers, two months prior to delivery, at delivery, and three months after. This is one aspect that is unique to this cohort; not only do we have samples from both mother and child, but these samples represent various time points. The idea here was to look at the microbial communities as they develop within the child and also observe how they change over time in the mother during pregnancy.
Most importantly, we were able to compare mother and child’s microbiome and ask whether specific species were potentially transmitted from the mother to the child, down to the level of strains and genes.
Hogstrom: We first ranked the list of species that were most commonly found in both mother and child. For those mother-child pairs where we saw a common shared species, we delved in and looked at fine-grained genetic variants within the two different samples (from mother and child) of that specific bacterial species. We then asked whether these variants or patterns suggested shared strains between mother and child.
What were the most significant findings from this study?
Yassour: One fascinating finding is that we were able to get snapshots of how the infant’s gut microbiome is developing. However, the paper's most substantial contribution to the field revolves around transmission. Using a new computational approach, we were able to characterize the different strains, literally looking at individual nucleotide positions within different genomes, and could confirm which strains were shared between mother and child. In many cases the mother’s dominant strain is identical to the child’s, suggesting a transmission event.
The other interesting aspect about transmission, which we found in this study, was that in some cases it is not the mother’s dominant strain that is transmitted to the child, but rather one of her secondary strains. It still unclear what the selective pressures are that may be driving this, but one obvious factor can be the difference in diet. Infants who are breastfed get human milk oligosaccharides [a type of carbohydrate] from their mother's milk, and while these cannot be digested by the child, they serve as food for their gut bacteria. So it would seem reasonable, for example, that some secondary strains that do not grow preferentially in the mother would have a fitness advantage in the child’s gut if they can utilize these sugars.
Hogstrom: I think that gaining this new view of strain mixtures in early life is an important contribution to the field. First, we came up with a computational method that allowed us to better profile secondary strains. Second, that then led us to find that a mother’s secondary strains, and not dominant ones, were in some cases colonizing the child’s gut. Third, we were able to suggest functional differences which led to certain strains of bacteria better thriving in the child’s gut versus the mother’s.
What will be the future directions for this study?
Yassour: The next step would involve looking at other interventions that may affect the microbiome transmission from mother to the child. For example, if a mother takes antibiotics before delivery, does that change her infant's gut microbe profile?
Hogstrom: The delivery mode of an infant is known to be a driving factor in differences we may observe later on in their microbiome. This study only looked at infants born via vaginal delivery. We want to investigate further how dominant and secondary strain transmission may differ after C-section.
Yassour: Several other factors, which we have not looked at, such as hygiene, nutrition, and environment, also play significant roles in altering the microbiome. Is the family living in the city or countryside? Do they have a pet in the house? Do they consume more or fewer probiotics? These are the kind of questions we can ask in future studies.
Hogstrom: We know that in adults, the most significant difference in the microbiome arise from the food they eat. Even in children, breast milk versus formula will make a difference. In this study, the infants were breastfed, but in future studies, we will need to compare and observe diets across many mothers and their infants.