Correlation between gut microbiota composition, enteric infections and linear growth impairment: a case-control study in childhood stunting in Pidie, Aceh, Indonesia.

Abstract

Background: Gut microbiota is pivotal in maintaining children's health and well-being. The ingestion of enteric pathogens and dysbiosis lead to Environmental Enteric Dysfunction (EED), which is essential in stunting pathogenesis. The roles of gut microbiome and enteric infections have not been explored comprehensively in relation to childhood stunting in Indonesia. This study aimed to determine the correlation between gut microbiota composition, enteric infections, and growth biomarker, Insulin-like Growth Factor 1 (IGF-1), in stunted children from Pidie, Aceh, Indonesia.

Methods: This study was a case-control study involving 42 subjects aged 24 to 59 months, comprising 21 stunted children for the case and 21 normal children for the control group. The IGF-1 serum level was quantified using ELISA. The gut microbiome profiling was conducted using 16S rDNA amplicon sequencing. The expression of enteric pathogens virulence genes was determined using quantitative PCR (qPCR) assay. The correlations of observed variables were analysed using suitable statistical analyses.

Results: The result showed that the IGF-1 sera levels in stunted were lower than those in normal children (p ≤ 0.001). The abundance of Firmicutes (50%) was higher than Bacteroidetes (34%) in stunted children. The gut microbiome profile of stunted children showed enriched genera such as Blautia, Dorea, Collinsella, Streptococcus, Clostridium sensu stricto 13, Asteroleplasma and Anaerostipes. Meanwhile the depleted genera comprised Prevotella, Lactococcus, Butyrivibrio, Muribaculaceae, Alloprevotella, Akkermansia, Enterococcus, Terrisporobacter and Turicibacter. The abundance of water biological contaminants such as Aeromonas, Stappiaceae, and Synechococcus was also higher in stunted children compared to normal children. The virulence genes expression of Enteroaggregative Escherichia coli (aaiC), Enterotoxigenic E. coli (estA), Enteropathogenic E. coli (eaeA), Shigella/Enteroinvasive E. coli (ipaH3) and Salmonella enterica (ompC) in stunted was higher than in normal children (p ≤ 0.001), which negatively correlated to height and level of IGF-1.

Conclusion: The present study showed the distinctive gut microbiome profile of stunted and normal children from Pidie, Aceh, Indonesia. The gut microbiota of stunted children revealed dysbiosis, comprised several pro-inflammatory, metabolic abnormalities and high-fat/low-fiber diet-related taxa, and expressed virulence genes of enteric pathogens. These findings provide evidence that it is imperative to restore dysbiosis and preserve the balance of gut microbiota to support linear growth in children.