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

Abstract

Background Iron is an essential micronutrient for all living organisms, and as such, iron deficiency is the top leading cause of anaemia. Iron supplements have been shown to be detrimental to the gut microbiome and the intestinal epithelium, triggering dysbiosis and an impaired gut barrier. However, a comprehensive analysis of these two aspects have not been performed during IDA. This study aims to delve further into the analysis of the gut microbiome in an animal model of IDA and to relate microbial changes to the biological processes occurring in the colonic epithelium, with a special focus on the gut barrier. This in-depth analysis might mean a step forward minimising the negative impact of iron supplements on intestinal health during IDA. Methods IDA was experimentally induced in an animal model through the use of an iron deficient diet. Shotgun sequencing was used to gain insight into alterations of the gut microbiome in the most affected intestinal region during IDA, the colon. Histological analyses, mRNA sequencing (RNA-Seq), qPCR and immunofluorescence were used to study transcriptionally deregulated processes in the colonic epithelium. Determinations of lipopolysaccharide 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 in the anaemic animals and an increased immune response against IDA dysbiotic bacteria support an impairment in the integrity of the gut barrier. 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.

Fermented Goat’s Milk Contributes to the Recovery of Iron Deficiency Anemia via Modulation of the Gut Microbiome

“…As reported by Soriano-Lerma et al, (2023), the gut barrier function is impaired in the colonic region during IDA, leading to an increased LPS translocation. To globally assess whether the inflammatory state was corrected after treatment with both diets, histological analyses were performed as described by Soriano-Lerma et al, (2023) and Fachi et al, (2019) .…”

“…Since intestinal dysbiosis is developed as a consequence of IDA, , a more efficient recovery of IDA would result in a more efficient restoration of IDA-derived dysbiosis.…”

“…In the case of the small intestine, no clustering could be observed neither between the AG-CG groups (Figure A) nor between the AS-CS groups (Figure B), suggesting dysbiosis had been restored by both diets in the small intestine. Since the colon was the region showing the greatest dysbiosis during IDA, , PCoA was performed on colonic content samples, revealing almost no clustering between the AG-CG groups (Figure A). However, samples belonging to the AS-CS groups did cluster separately (Figure B).…”

“…Ten animals from each experimental group were then sacrificed. Feces, intestinal content samples, and serum and colonic mucous samples were collected to evaluate the intestinal barrier functionality, microbial translocation, and changes in the gut microbiome and gut metabolites during IDA. , …”

“…Such is the case of iron deficiency anemia (IDA), the most common cause of anemia . A severe dysbiosis can be found in the large intestine of patients suffering from IDA, − as well as in animal models. − Moreover, the intestinal barrier functionality is impaired during IDA, leading to increased gut permeability and lipopolysaccharide (LPS) translocation. , These effects are aggravated during IDA treatment, since iron supplements have been described to trigger intestinal dysbiosis and to exert additional damage to enterocytes . Hence, there is a crucial need to explore gut protective approaches when treating the disease.…”