Research led by the University of Chicago shows an artificial intelligence (AI) driven “digital twin” modeling the infant microbiome can predict neurodevelopmental problems later in infancy.
Using data on very early gut microbiome composition from fecal samples from preterm babies the digital twin predicted later microbiome composition and associated neurodevelopmental deficits with a good degree of accuracy.
“You can only get so far by looking at snapshots of the microbiome and seeing the different levels of how many bacteria are there, because in a preterm infant, the microbiome is constantly changing and maturing,” said Ishanu Chattopadhyay, assistant professor of medicine at the University of Chicago and lead author of the Science Advances study, in a press statement.
“So, we developed a new approach using generative AI to build a digital twin of the system that models the interactions of the bacteria as they change.”
The research is still at an early stage, but if verified the team believes it could help predict which babies may need microbiome transplantation at an early stage to help improve their neurodevelopment.
“Increasing evidence suggests that microbial dysbiosis contributes to the development and progression of numerous diseases, ranging from facilitating essential digestive processes to regulating the central nervous system through the microbiota-gut-brain axis,” write the authors.
“While the microbiome’s role in brain development and the significance of microbial dysbiosis in neuroinflammation and neurodevelopmental disorders have been observed, including in preterm births, the specific mechanistic pathways operating along the gut-brain axis are yet to be fully understood.”
To try and improve knowledge of this area, Chattopadhyay and colleagues used 16S ribosomal RNA profiles extracted from 398 fecal samples taken from 88 preterm babies to inform and train the digital twin model. The data came from babies who went on to develop neurodevelopmental problems, as well as babies who developed normally, allowing the AI to learn to predict potential developmental issues in newborn babies.
The team found that the digital twin was able to predict risks for suboptimal development and poor head circumference growth with a 76% area under the receiver operator characteristic curve score. It had a 95% positive predictive value and 98% specificity at 30 weeks gestation.
The researchers calculated that early microbiome transplantation could potentially have helped around 45% of the cohort avoid developmental problems, but this would need to be validated in future work, particularly as incorrect supplementation could have adverse effects.
“You can’t just give probiotics and hope that the developmental risk is going to go down,” Chattopadhyay said. “What you are supplanting is important, and for many subjects, you also have to time it precisely.”
The researchers say the digital twin model has the potential to focus research on a smaller number of potential treatments or treatment targets in the gut microbiome. This could reduce the time for development of therapies significantly compared with current timelines.
Summary: Exposure to air pollution within the first 6 months of life alters a child’s microbiome, increasing the risk for allergies, diabetes, obesity, and influencing brain development.
Source: University of Colorado
Exposure to air pollution in the first six months of life impacts a child’s inner world of gut bacteria, or microbiome, in ways that could increase risk of allergies, obesity and diabetes, and even influence brain development, suggests new University of Colorado Boulder research.
The study, published this month in the journal Gut Microbes, is the first to show a link between inhaled pollutants—such as those from traffic, wildfires and industry—and changes in infant microbial health during this critical window of development.
Previous research by the same group found similar results in young adults.
“This study adds to the growing body of literature showing that air pollution exposure, even during infancy, may alter the gut microbiome, with important implications for growth and development,” said senior author Tanya Alderete, assistant professor of Integrative Physiology at CU Boulder.
At birth, an infant hosts little resident bacteria. Over the first two to three years of life, exposure to mother’s milk, solid food, antibiotics and other environmental influences shape which microorganisms take hold.
Those microbes, and the metabolites, or byproducts, they produce when they break down food or chemicals in the gut, influence a host of bodily systems that shape appetite, insulin sensitivity, immunity, mood and cognition.
While many are beneficial, some microbiome compositions have been associated with Chrohn’s disease, asthma, type 2 diabetes, and other chronic illnesses.
“The microbiome plays a role in nearly every physiological process in the body, and the environment that develops in those first few years of life sticks with you,” said first author Maximilian Bailey, who graduated in May with a master’s in Integrative Physiology and is now a medical student at Stanford University.
Boosting inflammation
For the study, the researchers obtained fecal samples from 103 healthy, primarily breast-fed Latino infants enrolled in the Southern California Mother’s Milk Study and used genetic sequencing to analyze them.
Using their street addresses and data from the U.S. Environmental Protection Agency’s Air Quality System, which records hourly data from monitoring systems, they estimated exposure to PM2.5 and PM10 (fine inhalable particles from things like factories, wildfires and construction sites) and Nitrogen Dioxide (NO2), a gas largely emitted from cars.
“Overall, we saw that ambient air pollution exposure was associated with a more inflammatory gut-microbial profile, which may contribute to a whole host of future adverse health outcomes,” said Alderete.
For instance, infants with the highest exposure to PM2.5 had 60% less Phascolarctobacterium, a beneficial bacterium known to decrease inflammation, support gastrointestinal health and aid in neurodevelopment. Those with the highest exposure to PM10 had 85% more of the microorganism Dialister, which is associated with inflammation.
Disadvantaged communities at higher risk
In a previous study, Alderete found that pregnant Latino women exposed to higher levels of air pollution during pregnancy have babies who grow unusually fast in the first month after birth, putting them at risk for obesity and related diseases later in life.
Infants are particularly vulnerable to the health hazards of air pollution because they breathe faster and their gut microbiome is just taking shape.
“This makes early life a critical window where exposure to air pollution may have disproportionately deleterious health effects,” they write.
Racial minorities and low-income communities, who tend to work, live and attend school in regions closer to busy highways or factories, are at even greater risk. One 2018 Environmental Protection Agency study found that communities of color are exposed to as much as 1.5 times more airborne pollutants than their white counterparts.
At birth, an infant hosts little resident bacteria.
“Our findings highlight the importance of addressing the impact of pollution on disadvantaged communities and point to additional steps all families can take to protect their health,” said Alderete, who hopes her research will influence policymakers to move schools and affordable housing projects away from pollution sources.
The authors caution that more research is needed to determine whether changes in the gut in infancy have lasting impacts, and just what those are. More studies are underway.
Meantime, Alderete advises everyone to take these steps to reduce their exposure to both indoor and outdoor pollutants:
Avoid walking outdoors in high traffic zones
Consider a low-cost air-filtration system, particularly for rooms children spend a lot of time in
If you are cooking, open the windows
And for new moms, breastfeed for as long as possible
“Breast milk is a fantastic way to develop a healthy microbiome and may help offset some of the adverse effects from environmental exposures,” Alderete said.
Abstract
Postnatal exposure to ambient air pollutants is associated with the composition of the infant gut microbiota at 6-months of age
Epidemiological studies in adults have shown that exposure to ambient air pollution (AAP) is associated with the composition of the adult gut microbiome, but these relationships have not been examined in infancy.
We aimed to determine if 6-month postnatal AAP exposure was associated with the infant gut microbiota at 6 months of age in a cohort of Latino mother-infant dyads from the Southern California Mother’s Milk Study (n = 103).
We estimated particulate matter (PM2.5 and PM10) and nitrogen dioxide (NO2) exposure from birth to 6-months based on residential address histories. We characterized the infant gut microbiota using 16S rRNA amplicon sequencing at 6-months of age. At 6-months, the gut microbiota was dominated by the phyla Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria.
Our results show that, after adjusting for important confounders, postnatal AAP exposure was associated with the composition of the gut microbiota. As an example, PM10 exposure was positively associated with Dialister, Dorea, Acinetobacter, and Campylobacter while PM2.5 was positively associated with Actinomyces.
Further, exposure to PM10 and PM2.5 was inversely associated with Alistipes and NO2 exposure was positively associated with Actinomyces, Enterococcus, Clostridium, and Eubacterium. Several of these taxa have previously been linked with systemic inflammation, including the genera Dialister and Dorea.
This study provides the first evidence of significant associations between exposure to AAP and the composition of the infant gut microbiota, which may have important implications for future infant health and development.
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