Oral iron supplementation after antibiotic exposure induces a deleterious recovery of the gut microbiota

Annie Calvé,Manuela M. Santos,Gabriela Fragoso,Thibault Cuisiniere,Roy Hajjar,Emmanuel Gonzalez,Manon Oliero

doi:10.1186/s12866-021-02320-0

Abstract

BackgroundOral iron supplementation is commonly prescribed for anemia and may play an important role in the gut microbiota recovery of anemic individuals who received antibiotic treatment. This study aims to investigate the effects of iron supplementation on gut microbiota recovery after antibiotics exposure.ResultsMice were subjected to oral antibiotic treatment with neomycin and metronidazole and were fed diets with different concentrations of iron. The composition of the gut microbiota was followed throughout treatment by 16S rRNA sequencing of DNA extracted from fecal samples. Gut microbiota functions were inferred using PICRUSt2, and short-chain fatty acid concentration in fecal samples was assessed by liquid-chromatography mass spectrometry. Iron supplementation after antibiotic exposure shifted the gut microbiota composition towards a Bacteroidetes phylum-dominant composition. At the genus level, the iron-supplemented diet induced an increase in the abundance of Parasutterella and Bacteroides, and a decrease of Bilophila and Akkermansia. Parasutterella excrementihominis, Bacteroides vulgatus, and Alistipes finegoldii, were more abundant with the iron excess diet. Iron-induced shifts in microbiota composition were accompanied by functional modifications, including an enhancement of the biosynthesis of primary bile acids, nitrogen metabolism, cyanoamino acid metabolism and pentose phosphate pathways. Recovery after antibiotic treatment increased propionate levels independent of luminal iron levels, whereas butyrate levels were diminished by excess iron.ConclusionsOral iron supplementation after antibiotic therapy in mice may lead to deleterious changes in the recovery of the gut microbiota. Our results have implications on the use of oral iron supplementation after antibiotic exposure and justify further studies on alternative treatments for anemia in these settings.

Highlights

Oral iron supplementation is commonly prescribed for anemia and may play an important role in the gut microbiota recovery of anemic individuals who received antibiotic treatment
The structure of gut microbiota communities is affected by dietary iron supplementation after antibiotic exposure To assess gut microbiota recovery from antibiotic treatment in the presence or absence of oral iron supplementation, mice were first treated with metronidazole and neomycin for one week while fed an iron-sufficient diet
Mice were divided into two groups: one continued to be fed the iron-sufficient diet while the other was switched to an iron-supplemented diet (Fig. 1A)

Summary

Introduction

Oral iron supplementation is commonly prescribed for anemia and may play an important role in the gut microbiota recovery of anemic individuals who received antibiotic treatment. Antibiotic-induced dysbiosis leads to a marked reduction in alpha-diversity [5, 6] and beneficial bacteria [6], a decrease in the levels of beneficial short-chain fatty acids (SCFAs) [7], a weakening of the gut barrier function, and inflammasome activation [7, 8]. Once antibiotic treatments are stopped, the gut microbiota can return to its initial composition [10]. This return to baseline or recovery may be impaired by several exogenous factors such as nutrient availability in the gastrointestinal tract [11]

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