Specific Gut Bacteria in Infants Linked to Future Anxiety

Deborah Brauser

February 21, 2020

Lower levels of a specific gut bacteria in infants are associated with the development of anxiety in toddlers, new research shows.

In one of the first human studies to compare the composition of a baby's gut bacteria with brain development, investigators found that levels of Prevotella in fecal samples at 12 months of age were linked to anxiety-like behaviors at age 2 years.

Interestingly, the biggest predictor of having decreased levels of Prevotella was recent exposure to antibiotic use.

"Growing evidence supports the idea that antibiotics, poor diet, and other factors in the modern world are leading to the loss of our traditional gut bacteria, and in turn, health problems," investigator Prof Peter Vuillermin, Deakin University, Geelong, Victoria, Australia, said in a press release.

Lead author Amy Loughman, PhD, from the Food and Mood Center at Deakin, added that the findings show that the microbiome plays an important role in brain development.

"This study and previous research suggest that the early-life gut microbiota may be important for health outcomes in later life," Loughman said.

The findings were published online February 18 in EBioMedicine.

Does Antibiotic Use Play a Role?

"Despite intense interest in the relationship between gut microbiota and brain development, longitudinal data from human studies are lacking," the investigators write.

For the current analysis, the researchers assessed data from 201 participants (52.7% boys) in the Barwon Infant Study, an Australian birth cohort study that included 1074 infants.

Stool samples were collected when the children were 1, 6, and 12 months of age, and 16S rRNA gene sequencing was performed.

The 99-item Child Behavior Checklist (CBCL) was completed by parents when their offspring were 2 years of age. The CBCL includes Internalizing, Externalizing, and Total Problems subscales.

Twenty-two participants were classified as "behavior cases" on the basis of CBCL scores. Among these 22, 14 had elevated scores (≥60) on the Externalizing subscale, nine had elevated scores on the Internalizing subscale, and 10 had elevated scores on the Total Problems subscale.

At 1 and 6 months, there were no significant associations between microbiota levels and subsequent behavioral outcomes. However, associations were found with stool samples collected at 12 months.

Prevotella was detected in only 4% of the case infants, vs 44% of the infants who had normal scores on the CBCL (P < .001).

After adjusting for a wide range of variables, including mode of birth, household pet ownership, breastfeeding at 4 weeks, and maternal depressive symptoms, the association between decreased Prevotella levels and subsequent behavioral problems persisted.

This association "was primarily related to the Internalizing subscale," the researchers report. This includes anxiety-like behaviors, such as sadness and shyness.

Unspecified Lachnospiraceae genera were detected in 91% of the case infants and in 69% of the non-case infants (P < .001). The association between increased levels of Lachnospiraceae and behavioral problems was attenuated, albeit still significant, after adjusting for the potential confounders (P = .002).

When evaluating the possibility of reverse causation, the investigators found no link between a child's temperament at the age of 1, 6, or 12 months and levels of either candidate bacteria.

Use of antibiotics between the ages of 9 and 12 months was significantly linked to reduced Prevotella levels (odds ratio, 0.37; P = .007) but not to reduced levels of Lachnospiraceae (P = .24). This use was not associated with behavior outcomes at age 2 years.

Early Warning Sign?

"The mechanisms by which Prevotella may influence brain development and behaviour are poorly characterised but may include stimulation of the vagus nerve, release of cytokines or enzymes, tryptophan metabolism, interaction with the peripheral immune system," and production of short-chain fatty acids, the investigators note.

Overall, the study "adds support to evidence that the human gut microbiota may have long-term neurodevelopmental consequences, conferring protection or vulnerability to behavioural and mental health outcomes in later life," they write.

In addition, there may be "a developmental window in late infancy in which increased Prevotella in the gut microbiota may predict a reduced risk of subsequent anxiety," the researchers write.

"One day we could get to the point where we can look at a child's poo at 12 months, and if they are showing levels of bacteria that put them into a high-risk category for anxiety, we can offer an early intervention," Loughman speculated.

"This might be a supplement of Prevotella or other bacteria, or it could be in the form of behavioral and family support to bolster their psychosocial environment. But we need to get more research behind us before we can reach that point," she added.

The study was funded by the National Health and Medical Research Council of Australia, the Murdoch Children's Research Institute, Barwon Health, Deakin University, Perpetual Trustees, and the Shepherd Foundation. Vuillermin and four other investigators report having a financial interest in Prevatax, a company that develops probiotic-based biotherapeutics for promoting a healthy microbiome. The original article has a full list of authors' disclosures.

EBioMedicine. Published online February 18, 2020. Full article

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