Socioeconomic and nutritional determinants outweigh gut microbiota influence on neurodevelopment in young children from Antananarivo, Madagascar.

Stunting was consistently associated with poorer neurodevelopmental outcomes across multiple developmental domains.

• Children were assessed using the Ages and Stages Questionnaire (ASQ-3) covering five developmental domains: communication, personal-social, problem-solving, fine and gross motor
• The study used a cross-sectional design from the Afribiota study in Madagascar with 2-5-year-old children
• Both bivariate and multivariate analyses as well as Structural Equation Modelling confirmed the association between stunting and neurodevelopmental delays
• Stunting was assessed in children aged 2-5 years from Antananarivo, Madagascar

Low socioeconomic status was consistently linked to poorer neurodevelopmental outcomes.

• Socioeconomic status was identified as a consistent determinant of neurodevelopment across multiple analytical approaches
• Classical bi- and multivariate analysis combined with Structural Equation Modelling were used to evaluate direct and indirect associations
• The study supports the hypothesis that neurodevelopment is primarily influenced by social factors alongside nutritional factors
• Socioeconomic factors outweighed gut microbiota influence on neurodevelopment

Low branched-chain amino acids and hemoglobin levels were associated with stunting.

• Branched-chain amino acids were identified as a nutritional factor linked to stunting status
• Hemoglobin levels were also associated with stunting, suggesting a nutritional/anemia pathway
• These nutritional markers represent indirect pathways through which nutrition may influence neurodevelopment via stunting
• The associations were identified through Structural Equation Modelling examining direct and indirect associations

Higher within-individual microbial diversity (alpha-diversity, specifically the Shannon index) was directly linked to improved neurodevelopment scores in one of the tested models.

• The Shannon index was the specific alpha-diversity metric associated with neurodevelopment
• The association with alpha-diversity was found in one of the tested models, indicating the finding was not uniformly robust across all analytical approaches
• Fecal samples were analyzed via 16S rRNA gene amplicon sequencing
• The association with Shannon diversity was described as a direct link to improved neurodevelopment scores

Gut microbiota variation between individuals (beta-diversity) was not associated with neurodevelopment.

• Beta-diversity, representing gut microbiota variation between individuals, showed no association with neurodevelopmental outcomes
• This contrasts with the limited positive association found for alpha-diversity (Shannon index)
• Fecal microbiota was characterized using 16S rRNA gene amplicon sequencing
• The null finding for beta-diversity supports the conclusion that microbiota composition differences between children do not drive neurodevelopmental variation in this population

The study concludes that nutritional and social factors primarily influence neurodevelopment, with a more limited role for microbiota diversity.

• The findings support the hypothesis that neurodevelopment is primarily influenced by nutritional and social factors
• The role of gut microbiota diversity in neurodevelopment was characterized as 'more limited'
• Structural Equation Modelling was used to evaluate both direct and indirect associations between clinical factors, microbiota, and neurodevelopment
• The study population comprised 2-5-year-old children from the Afribiota cross-sectional study in Antananarivo, Madagascar