Neurodevelopment correlates with gut microbiota in a cross-sectional analysis of children at 3\xa0years of age in rural China

Sarah E Rothenberg,Fengxiu Ouyang,Eva P Trinh,Yunfeng Zou,Fred J Biasini,Jian Shen,Hua Nong,Xiaoyun Zeng,Yanfen Nong,Susan A Korrick,Qiurong Chen,Jihong Liu

doi:10.1038/s41598-021-86761-7

Abstract

We investigated cross-sectional associations between children’s neurodevelopment and their gut microbiota composition. Study children (36 months of age) lived in rural China (n = 46). Neurodevelopment was assessed using the Bayley Scales of Infant Development, 2nd Edition, yielding the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI). Children's gut microbiota was assessed using 16S rRNA gene profiling. Microbial diversity was characterized using alpha diversity patterns. Additionally, 3 coabundance factors were determined for the 25 most abundant taxa. Multivariable linear regression models were constructed to examine the relationships between Bayley scores (MDI and PDI) and children's gut microbiota. In adjusted models, MDI and PDI scores were not associated with alpha diversity indices. However, in adjusted models, MDI and PDI scores were positively associated with the first coabundance factor, which captured positive loadings for the genera Faecalibacterium, Sutterella, and Clostridium cluster XIVa. For an interquartile range increase in the first coabundance factor, MDI scores increased by 3.9 points [95% confidence interval (CI): 0, 7.7], while PDI scores increased by 8.6 points (95% CI 3.1, 14). Our results highlight the potential for gut microbial compositional characteristics to be important correlates of children's Bayley Scales performance at 36 months of age.

Highlights

Increasing evidence supports a central role for the gut microbiome in neurodevelopment, with communication along the gut-brain axis postulated as one plausible mechanism[1,2]
Of 398 mother-infant pairs enrolled in our study, 196 participants (49%) returned at 36 months and completed BSID-II assessments, including 46 participants (23%), who collected their child’s stool sample (Table 1)
Mean (± 1 SD) standardized Mental Developmental Index (MDI) and Psychomotor Developmental Scores (PDI) scores were 90 ± 9.0 and 95 ± 13, respectively, which were slightly lower than the U.S English-speaking standardization population[12]

Summary

Introduction

Increasing evidence supports a central role for the gut microbiome in neurodevelopment, with communication along the gut-brain axis postulated as one plausible mechanism[1,2] This association may be especially important during the first 3 years of life, when children’s brains are rapidly d eveloping[3], and when their gut microbiomes are changing, as their diets become e stablished[4,5]. Since 2013, we have investigated associations between prenatal methylmercury exposure through maternal rice ingestion and children’s subsequent neurodevelopment, among participants in a birth cohort study in rural China[9,10,11]. For the current cross-sectional analysis in a subset of the cohort, we investigated whether children’s gut microbiota was associated with neurodevelopmental outcomes at 36 months of age, assessed using the Bayley Scales of Infant Development, 2nd edition (BSID-II)[12]

Methods

Results

Conclusion