Antibiotic treatment also affects the intestinal fungal microbiota

It is generally considered that following treatment with antibiotics, which reduces the bacterial population in the digestive tract, the fungal population present in the intestine will take advantage of these freed niches and proliferate... but our study proved the contrary!
Published in Microbiology
Antibiotic treatment also affects the intestinal fungal microbiota

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BioMed Central
BioMed Central BioMed Central

Antibiotic treatment using amoxicillin-clavulanic acid impairs gut mycobiota development through modification of the bacterial ecosystem - Microbiome

Background Effects of antibiotics on gut bacteria have been widely studied, but very little is known about the consequences of such treatments on the fungal microbiota (mycobiota). It is commonly believed that fungal load increases in the gastrointestinal tract following antibiotic treatment, but better characterization is clearly needed of how antibiotics directly or indirectly affect the mycobiota and thus the entire microbiota. Design We used samples from humans (infant cohort) and mice (conventional and human microbiota-associated mice) to study the consequences of antibiotic treatment (amoxicillin-clavulanic acid) on the intestinal microbiota. Bacterial and fungal communities were subjected to qPCR or 16S and ITS2 amplicon-based sequencing for microbiota analysis. In vitro assays further characterized bacterial-fungal interactions, with mixed cultures between specific bacteria and fungi. Results Amoxicillin-clavulanic acid treatment triggered a decrease in the total fungal population in mouse feces, while other antibiotics had opposite effects on the fungal load. This decrease is accompanied by a total remodelling of the fungal population with the enrichment in Aspergillus, Cladosporium, and Valsa genera. In the presence of amoxicillin-clavulanic acid, microbiota analysis showed a remodeling of bacterial microbiota with an increase in specific bacteria belonging to the Enterobacteriaceae. Using in vitro assays, we isolated different Enterobacteriaceae species and explored their effect on different fungal strains. We showed that Enterobacter hormaechei was able to reduce the fungal population in vitro and in vivo through yet unknown mechanisms. Conclusions Bacteria and fungi have strong interactions within the microbiota; hence, the perturbation initiated by an antibiotic treatment targeting the bacterial community can have complex consequences and can induce opposite alterations of the mycobiota. Interestingly, amoxicillin-clavulanic acid treatment has a deleterious effect on the fungal community, which may have been partially due to the overgrowth of specific bacterial strains with inhibiting or competing effects on fungi. This study provides new insights into the interactions between fungi and bacteria of the intestinal microbiota and might offer new strategies to modulate gut microbiota equilibrium. Video Abstract

In our study, we were surprised to find that treatment with amoxicillin and clavulanic acid (Augmentin), a treatment regularly prescribed by doctors, also reduced the fungal population in the intestine in an in vivo mouse model.

The study of the effect of these antibiotics on the fungal and bacterial intestinal microbiota allowed us to show that there was a massive modification of the bacterial microbiota and in particular an increase in amoxicillin-resistant populations, including enterobacteria. In vitro analyses of strains isolated from these microbiotas after treatment with this cocktail of antibiotics allowed us to identify a strain of bacteria partly responsible for the fall in the fungal population: Enterobacter hormaechei. Indeed, E. hormaechei is able in vitro in co-culture and in vivo after gavage in mice to decrease the amount of fungi. To date, the mechanisms explaining these effects are not completely understood. We have been able to show a slight competition effect around the nutrients useful to the fungi to grow but not strong enough to explain the observed effect. On the other hand, we have also demonstrated a clear physical interaction between the cells of the fungi and the bacteria after specific co-culture of this bacterium using scanning microscopy images.

This study allowed us to show that the effect of a treatment with antibiotics has different effects on the fungal population depending on the type of antibiotic. We have also identified a new bacterial strain capable of having a negative effect on the growth of fungi in a complex context of the intestinal microbiota. The continuation of our research work will allow us to elucidate the mechanisms of action of this bacterium on fungi and to progress in our understanding of the interaction between these 2 microbiotas.



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