Gut Microbiome Tied to Nonsocial Fear Response in Infants

By Marilynn Larkin

June 18, 2021

NEW YORK (Reuters Health) - The composition of the gut microbiome is associated with how infants experience non-social fear - e.g., fear in response to someone wearing a mask compared to someone who isn't, researchers suggest.

"The findings surprised us," Dr. Rebecca Knickmeyer of Michigan State University in East Lansing told Reuters Health by email. "We hypothesized that features of the gut microbiome would be associated with fear reactivity in both social and non-social contexts."

"However," she noted, "we only observed associations with non-social fear, which was operationalized as behavioral responses such as vocal distress and escape behavior when viewing a research assistant wearing a Halloween mask."

"We didn't observe any associations between the gut microbiome and social wariness when approached by a research assistant without a mask," she said. "We think the mask task may be tapping into an evolutionarily older neural circuit for responding to immediate threats, such as predators."

As reported in Nature Communications, previous studies identified factors that influence the bacterial mix of an infant's microbiome - e.g., whether the infant is breast or formula-fed, mode of delivery, maternal BMI, presence of older siblings in the home, furry pets, geographical location, and exposure to antibiotics.

"We tried to control for many of these factors by only enrolling infants that were vaginally delivered and exclusively breast-fed and antibiotic naive until the first MRI visit, which occurred around one month of age," Dr. Knickmeyer explained.

"Interestingly," she added, "none of the factors (we controlled for) explain more than about 12% of the variation in infant microbiomes, suggesting there is still much to learn about the factors shaping microbiome development."

The pilot study of 34 infants showed in stool analyses that a specific gut microbiome composition at one year - i.e., negative weighted Unifrac values; lower abundance of Bacteroides; increased abundance of Veillonella, Dialister, and Clostridiales - is significantly associated with increased non-social fear behavior.

Infants with increased richness of micro-organisms and reduced evenness of the one-month microbiome also displayed increased non-social fear.

However, as Dr. Knickmeyer noted, no connection was seen between the gut microbiome and social fear (i.e., how infants responded to maskless strangers).

The authors conclude, "With further research, the gut microbiome may emerge as a key modulator of fear development and as such may become a means to prevent or ameliorate psychiatric disorders and behavioral problems characterized by abnormal fear reactivity."

Dr. Knickmeyer added, "There are many potential ways to manipulate the microbiome, including dietary interventions, administering probiotics, and performing fecal transplants. Furthermore, microbial metabolites may hold promise as therapeutics or therapeutic targets."

"Although we did not directly examine relationships between the infant microbiome and later behavioral problems," she said, "our findings suggest that the composition of the microbiome is an early risk/protective factor which could potentially be manipulated to improve long-term mental health."

Dr. Jennifer Kurtz, chief of neonatal medicine at Long Island Jewish Forest Hills in New York City, commented in an email to Reuters Health, "These findings are really interesting...There have been several studies in animals that have similar results, so I'm not entirely surprised by the findings."

Nonetheless, she said, "a much larger, and likely more diverse, study needs to be done next."

"Aside from being exclusively breast fed, vaginally delivered, and receiving no antibiotics the first month of life, we are given little other information on the subjects," she said. "Some questions I have are at what gestational age were they born, what is their ethnic background, and did they receive antibiotics after one month of age? Were they all breast fed for the entirety of the year? These are all possible confounding variables."

"Additionally," she said, "we should follow up with the subjects later in life to see if their social fears or anxieties have evolved over time."

"This is a fascinating study, and I believe it will lead to numerous other studies in the future," Dr. Kurtz concluded.

SOURCE: Nature Communications, online June 2, 2021.