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Time-dependent modulation of gut microbiome in response to systemic antifungal agents

View ORCID ProfileNadeeka S. Udawatte, Kang S. Wook, Yue Wang, Silvia Manzanero, Thiruma V. Arumugam, Chaminda J. Seneviratne
doi: https://doi.org/10.1101/2020.10.05.315184
Nadeeka S. Udawatte
1National Dental Research Institute Singapore (NDRIS), National Dental Centre Singapore, Oral Health ACP, Duke-NUS, Singapore
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  • ORCID record for Nadeeka S. Udawatte
Kang S. Wook
2Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Yue Wang
3Institute of Molecular and Cell Biology, A*STAR, Singapore
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Silvia Manzanero
4Jamieson Trauma Institute, Royal Brisbane and Women’s Hospital, Metro North Hospital and Health Service, Brisbane, Queensland, Australia
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Thiruma V. Arumugam
5Department of Physiology, Anatomy & Microbiology, School of Life Sciences, La Trobe University, Australia
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  • For correspondence: jaya.seneviratne@ndcs.com.sg G.Arumugam@latrobe.edu.au
Chaminda J. Seneviratne
1National Dental Research Institute Singapore (NDRIS), National Dental Centre Singapore, Oral Health ACP, Duke-NUS, Singapore
6Oral Health ACP, Duke-NUS Medical School, Singapore
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  • For correspondence: jaya.seneviratne@ndcs.com.sg G.Arumugam@latrobe.edu.au
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Abstract

The effects of antifungal agents on the human microbiome can be challenging to study due to confounding factors such as the underlying disease states and concomitant use of antibiotics and other therapies. We elucidated longitudinal modification of gut microbiome in response to a short course (5 days) of antifungal treatment in healthy male Sprague-Dawley (SD) rats by sequencing 16S rRNA V1–V3 and ITS2 hypervariable regions. SD rats were randomized into a control group and three antifungal treated (AT) groups including Amphotericin B (AmB), voriconazole and, our novel antifungal drug candidate SM21 once per day for 5 consecutive days. Fecal samples were collected at three different time points (day 0, day 1 and day 5). Microbial communities of both bacteria and fungi were compared between conditions. In silico analysis of differential microbial abundance and the predictive functional domains of microbial communities was further done by inferring metabarcoding profiles from 16S data. AT animals exhibited significant change in bacteriome alphadiversity although no divergence in community structure (beta-diversity) was observed compared with respective control groups (day 0). Specific bacterial clades and taxa were longitudinally and significantly modified in the AT animals. The AT bacterium of AmB and SM21 was particularly enriched in probiotic Lactobacillus strains including L. reuteri. The key pathways overrepresented in the bacteriome under AT animals were linked to cellular processes, environment information processing and metabolism. Moreover, AT treated mycobiome diversity decreased longitudinally with insignificant variations along the time course; different fungal taxa dominating at different timepoints in a wave-like fashion. However, acute antifungal treatments could not alter healthy gut microbial community structure. Hence, the healthy gut microbiome is capable of resisting a major dysbiotic shift during a short course of antifungal treatment.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 06, 2020.
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Time-dependent modulation of gut microbiome in response to systemic antifungal agents
Nadeeka S. Udawatte, Kang S. Wook, Yue Wang, Silvia Manzanero, Thiruma V. Arumugam, Chaminda J. Seneviratne
bioRxiv 2020.10.05.315184; doi: https://doi.org/10.1101/2020.10.05.315184
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Time-dependent modulation of gut microbiome in response to systemic antifungal agents
Nadeeka S. Udawatte, Kang S. Wook, Yue Wang, Silvia Manzanero, Thiruma V. Arumugam, Chaminda J. Seneviratne
bioRxiv 2020.10.05.315184; doi: https://doi.org/10.1101/2020.10.05.315184

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