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.

Profiling of the intestinal microbiota of stunted children in Semarang, Indonesia

“…Meanwhile, for health, it was 26.05. The high F/B ratio was also reported in stunted children in Aceh (Rinanda et al 2023) At the species level, 52,836 OTUs were recorded in the gut microbiota of healthy children, which were grouped into 65 species. Moreover, 26 species of bacteria are only found in the intestines of healthy children, and 23 species are only found in the intestines of stunted children.…”

Gut microbiota differences in stunted and normal-lenght children aged 36–45 months in East Nusa Tenggara, Indonesia

“…All taxa currently at most correlate to being stunted; no cause and effect relationship has been established. Also, as is clear from our own two studies in Indonesia (on Java and ENT), as well as the study by Rinanda et al [47] on Sumatra, the composition of the gut microbiota, even within one country, is geography specific, which is corroborated by the studies in Zimbabwe, India and Peru [47][48][49][50][51]. Hence no general conclusions can be drawn.…”

“…In another region in Indonesia, on the northern tip of Sumatra, the gut microbiome profle of stunted children (n = 21) showed enriched genera such as Blautia, Dorea, Collinsella, Streptococcus, Clostridium sensu stricto 13, Asteroleplasma and Anaerostipes. Meanwhile, compared to the normal children (n = 21), there was a depletion of Prevotella, Lactococcus, Butyrivibrio, Muribaculaceae, Alloprevotella, Akkermansia, Enterococcus, Terrisporobacter and Turicibacter [47]. In a small longitudinal analysis of the gut microbiota in persistently stunted young children in South India (n = 10 children in each group), the RA of the Bacteroidetes phylum was higher in stunted children compared to that of control children at 12 months of age but otherwise did not find significant differences in diversity indices between cases and…”

“…How this relates to stunting remains to be seen, as it was not correlated to being stunted or not (q = 0.26). Rinanda et al [47] noticed that water contaminants such as Aeromonas, Stappiaceae, and Synechococcus were higher in stunted children compared to normal children. In our study, an overall increase in the Escherichia/Shigella taxon, usually correlated with hygiene, was observed (not specifically in stunted children), as well as a specific increase in stunted PLOS ONE children in the phylum Cyanobacteria, of which the natural habitat is considered to be water environments.…”

“…The strength of this study is the inclusion of 100 children in each group. Most previous studies have only looked at a limited numbers of stunted children [47][48][49][50][51]. However, the study also has limitations.…”