The composition of a newborn’s first poop can reveal whether they are likely to develop allergies within their first year of life, according to a new study, published in Cell Reports Medicine. The researchers discovered that babies who develop allergic sensitization – also known as atopy – by the age of one year, have a less diverse gut metabolome.
The “metabolome” includes a huge variety of small metabolites (typically < 1000 Da), which are produced by different cellular processes in the body. Metabolomics research belongs to the "omics" field that also includes genomics, proteomics and transcriptomics. Of these subdisciplines, it is regarded as the closest representation of the cellular phenotype.
Atopy is associated with an exaggerated immunoglobulin E immune response to particular allergens which can result in the development of allergic conditions including allergic rhinitis, asthma and eczema.
Why is the first poop so “special”?
Meconium is the scientific term to describe a baby’s first stool. It is dark green–black in color, has a thick and sticky consistency, and contains ingested amniotic fluid, skin cells, fine hairs (lanugo), pigments, enzymes and metabolites.
The meconium begins to form in the fetal gut at around 16 weeks of pregnancy and is therefore influenced by exposures from that point onwards. It also acts as the “starting material” for the developing fetus’ gut microbiota.
The study’s first author, Dr Charisse Petersen from The University of British Columbia, discusses the crosstalk between the microbiota and the immune system: “The bacteria that eventually make up our microbiota begin to colonize us as soon as we are born. For the first one to three years of life, our microbiota changes and diversifies a lot before reaching a mature, stable community around toddlerhood. It is a surprisingly short window of time.”
Interestingly, this timeframe coincides with the development of the baby’s immune system. According to Petersen, it is at this point that the body determines whether signals are harmless or harmful, emphasizing the value of this overlap.
Petersen continues, “The new microbes are tolerated and allowed to colonize us, and they in turn teach our immune cells not to overreact to benign signals. Unfortunately, we think that some babies are not being colonized with enough of these beneficial bacteria to train their immune cells.”
This results in allergic responses to – what should be – non-harmful signals as children get older.
Taking a closer look at meconium samples
As metabolites within the meconium can be further broken down and fermented by the microorganisms within the gut, the team set out to confirm if microbiota maturation and immune development were influenced by the meconium composition by interrogating the meconium’s metabolome.
Metabolic profiling was performed on meconium samples from 100 infants enrolled in the CHILD Cohort Study (CHILD), a prospective longitudinal birth cohort study.
Analysis revealed that babies who developed atopy by one year of age had a less-varied metabolic niche within their meconium at birth. “We found that the reduced diversity was mainly detected in the number of different amino acids, vitamins and plant compounds,” explains Petersen.
A large quantity of data was collected from the expectant mothers to enable the team to explore whether there was a link between mothers’ clinical characteristics and the infants’ likelihood of developing atopy. “For this study, we considered whether the mother or father had allergies, her exposure to antibiotics during pregnancy or while giving birth, how she chose to give birth, her history of smoking and her ethnicity. In the end, none of these could completely explain our findings,” reveals Petersen.
Other CHILD investigators are currently studying the mothers' reported diet; Petersen is excited to find out whether any associations are identified from their analysis.
A machine-learning approach was exploited to analyze the meconium, microbiological and clinical data to predict whether or not an infant would develop allergies.
The paper highlights one key limitation – while the microbiota stool analysis encompassed data from > 979 infants, the meconium metabolic profiling was limited to 100 of the infants. Petersen explains that while she “would love to reproduce these findings in a larger group and, particularly, from children in different parts of the world, it is logistically difficult to obtain meconium from newborns given all the other important considerations surrounding birth, that is one of the strengths of the CHILD study.” Researchers involved in the CHILD study actively follow the study participants over time as they grow and develop.
“The kids are eight years old now and the majority of them are still participating,” says Petersen.
Petersen elaborates on the additional research that she would like to see performed in this area: “I would like to see more mechanistic studies that try to understand precisely which metabolites are the most helpful for supporting the infant microbiota and immune system. This is the type of work that the Finlay Lab really excels in so I am excited to see what comes next. In a perfect world, we would eventually make sure that these were included in a healthy diet or vitamin supplement during pregnancy.”
Could early interventions be beneficial?
According to Petersen, the most effective means for combating allergies after a baby is born currently is through prevention, and a lot of these preventive strategies involve introducing beneficial microorganisms to the infants and then maintaining their balance. Petersen elaborates, “These [approaches] include supporting vaginal births and breastfeeding when possible, promoting antibiotic stewardship that reduces unnecessary antibiotic prescriptions, allowing babies to spend time in outdoor green spaces, and relaxing our cleaning standards a bit to reduce our disinfectant use.”
“As a new mother myself, I was initially hesitant to put any more pressure on pregnant women or moms (we worry about so much as it is!). But when it comes down to increasing the number of metabolites in a newborn’s meconium, many pregnant women are likely already doing this without realizing it,” concludes Petersen.
Reference: Petersen C, Dai DLY, Boutin RCT, et al. A rich meconium metabolome in human infants is associated with early-life gut microbiota composition and reduced allergic sensitization. Cell Rep. Med. 2021. doi: 10.1016/j.xcrm.2021.100260
Charisse Petersen was speaking with Laura Lansdowne, Managing Editor for Technology Networks.