Comprehensive insight into the alterations in the gut microbiome and the intestinal barrier as a consequence of iron deficiency anaemia.

ABSTRACT

BACKGROUND: Iron deficiency is the top leading cause of anaemia, whose treatment has been shown to deteriorate gut health. However, a comprehensive analysis of the intestinal barrier and the gut microbiome during IDA have not been performed to date. This study aims to delve further into the analysis of these two aspects, which will mean a step forward minimising the negative impact of iron supplements on intestinal health. METHODS: IDA was experimentally induced in an animal model. Shotgun sequencing was used to analyse the gut microbiome in the colonic region, while the intestinal barrier was studied through histological analyses, mRNA sequencing (RNA-Seq), qPCR and immunofluorescence. Determinations of lipopolysaccharide (LPS) and bacteria-specific immunoglobulins were performed to assess microbial translocation. RESULTS: Microbial metabolism in the colon shifted towards an increased production of certain amino acids, short chain fatty acids and nucleotides, with Clostridium species being enriched during IDA. Structural alterations of the colonic epithelium were shown by histological analysis. RNA-Seq revealed a downregulation of extracellular matrix-associated genes and proteins and an overall underdeveloped epithelium. Increased levels of serum LPS and an increased immune response against dysbiotic bacteria support an impairment in the integrity of the gut barrier during IDA. CONCLUSIONS: IDA negatively impacts the gut microbiome and the intestinal barrier, triggering an increased microbial translocation. This study emphasizes the deterioration of gut health during IDA and the fact that it should be addressed when treating the disease.