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Abstract:
Background: Linear growth delay (stunting), as a result of chronic malnutrition, remains one of the most pressing global health concerns. While the underlying pathophysiological mechanisms remain poorly understood, a clear link with intestinal dysbiosis has recently been demonstrated. Bile acids, via regulation of fat absorption, immune and metabolic signaling, play a key role in intestinal homeostasis. Primary bile acids are produced by the host and subsequently transformed by the intestinal microbiota into secondary bile acids. If this mechanism of microbial detoxification is disturbed, inflammation and malabsorption arise. We hypothesized that the bile acid profile of stunted children is changed, contributing to the pathophysiology. Methods Gastric (n=138), duodenal (n=108) and fecal (n=696) samples from children aged 2-5 years suffering or not of stunting were collected in Bangui, Central African Republic and in Antananarivo, Madagascar (Afribiota project). 77 different bile acids and derivatives were extracted from lyophilized samples using acetonitrile and analyzed using UPLC-MRM/MS. Clinical metadata was gathered using anthropometric measurements and a standardized questionnaire. Statistical analysis was performed using Stata and R. Samples were normalized to dry weight as well as standardized to internal controls. Results As expected, there are clear differences in the relative abundance of primary and secondary bile acids along the gastrointestinal tract. Fecal bile acid profile is affected by age, country of origin, intestinal inflammation and, to a lesser extent, stunting. The relative abundance of fecal primary bile acids is higher in stunted chil-dren, especially at an early age (significant for 2-3 year old children). This trend is found in all age groups and conserved in both countries independently. Conclusion To the best of our knowledge, this is the first study to demonstrate fecal bile acid dysbiosis in stunted children. More detailed, multivariate analyses on specific bile acids and their association with given bile acid metaboliz-ing bacteria are currently being performed.
