Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi
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RESEARCH
Open Access
Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria Bastian Seelbinder1†, Jiarui Chen1,2†, Sascha Brunke3, Ruben Vazquez-Uribe4, Rakesh Santhaman1, Anne-Christin Meyer3, Felipe Senne de Oliveira Lino4, Ka-Fai Chan5, Daniel Loos1, Lejla Imamovic4, Chi-Ching Tsang5, Rex Pui-kin Lam6, Siddharth Sridhar5,7,8, Kang Kang1, Bernhard Hube4, Patrick Chiu-yat Woo5,7,8, Morten Otto Alexander Sommer4* and Gianni Panagiotou1,2*
Abstract Background: Antibiotic 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. Results: While 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. Conclusions: We 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.
* Correspondence: [email protected]; [email protected] † Bastian Seelbinder and Jiarui Chen contributed equally to this work. 4 Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet 220, DK-2800 Lyngby, Denmark 1 Leibniz Institute for Natural Product Research and Infection Biology—Systems Biology and Bioinformatics, Hans Knöll Institute, Adolf-Reichwein-Straße 23, 07745 Jena, Germany Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appro
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