Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria

Bastian Seelbinder,Ruben Vazquez-Uribe,Kang Kang,Gianni Panagiotou,Siddharth Sridhar,Patrick Chiu-Yat Woo,Rakesh Santhaman,Morten Otto Alexander Sommer,Lejla Imamovic,Rex Pui-Kin Lam,Jiarui Chen,Ka-Fai Chan,Sascha Brunke,Chi-Ching Tsang,Daniel Loos,Bernhard Hube,Felipe Senne De Oliveira Lino,Anne-Christin Meyer

doi:10.1186/s40168-020-00899-6

Abstract

BackgroundAntibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear. Bacteria in the lumen of the gastrointestinal tract may limit fungal colonization and invasion. Antibiotic drugs targeting bacteria are therefore seen as an important risk factor for fungal infections and induced allergies. However, antibiotic effects on gut bacterial-fungal interactions, including disruption and resilience of fungal community compositions, were not investigated in humans. We analysed stool samples collected from 14 healthy human participants over 3 months following a 6-day antibiotic administration. We integrated data from shotgun metagenomics, metatranscriptomics, metabolomics, and fungal ITS2 sequencing.ResultsWhile the bacterial community recovered mostly over 3 months post treatment, the fungal community was shifted from mutualism at baseline to competition. Half of the bacterial-fungal interactions present before drug intervention had disappeared 3 months later. During treatment, fungal abundances were associated with the expression of bacterial genes with functions for cell growth and repair. By extending the metagenomic species approach, we revealed bacterial strains inhibiting the opportunistic fungal pathogen Candida albicans. We demonstrated in vitro how C. albicans pathogenicity and host cell damage might be controlled naturally in the human gut by bacterial metabolites such as propionate or 5-dodecenoate.ConclusionsWe demonstrated that antibacterial drugs have long-term influence on the human gut mycobiome. While bacterial communities recovered mostly 30-days post antibacterial treatment, the fungal community was shifted from mutualism towards competition.ACGvW8Xb2T7sNiinSps9YKVideo abstract.

Highlights

Antibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear
Antibiotic treatment led to a significant increase in species-level fungal alpha diversity during early post treatment compared to baseline (Fig. 1a; two-sided Wilcoxon rank-sum test, p = 0.016, q = 0.094)
We focused our study on C. albicans, testing in vitro if growth was affected by compounds produced by two bacterial species, B. eggerthii and O. splanchnicus

Summary

Introduction

Antibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear. Antibiotic drugs targeting bacteria are seen as an important risk factor for fungal infections and induced allergies. Antibiotic effects on gut bacterial-fungal interactions, including disruption and resilience of fungal community compositions, were not investigated in humans. The human gut microbiome is a complex ecosystem of bacteria, fungi, archaea, and phages [1]. The majority of research has focused on the bacterial part of the gut microbiome and their role in health and disease [2,3,4]. Fungal dysbiosis may increase symptoms of inflammation, especially in the gut lumen [5]. Fluconazole seems to substantially impact only certain types of fungi such as Candida, but not Aspergillus species [6]

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