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Contribution of fungal microbiome to intestinal physiology, early-life immune development and mucosal inflammation in mice

View ORCID ProfileErik van Tilburg Bernardes, Veronika Kuchařová Pettersen, Mackenzie W. Gutierrez, View ORCID ProfileIsabelle Laforest-Lapointe, View ORCID ProfileNicholas G. Jendzjowsky, View ORCID ProfileJean-Baptiste Cavin, Fernando A. Vicentini, Catherine M. Keenan, Hena R. Ramay, Jumana Samara, View ORCID ProfileWallace K. MacNaughton, Richard J. A. Wilson, Margaret M. Kelly, View ORCID ProfileKathy D. McCoy, View ORCID ProfileKeith A. Sharkey, View ORCID ProfileMarie-Claire Arrieta
doi: https://doi.org/10.1101/819979
Erik van Tilburg Bernardes
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
2Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
3International Microbiome Centre, University of Calgary, Calgary, AB, Canada
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
5Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
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  • ORCID record for Erik van Tilburg Bernardes
Veronika Kuchařová Pettersen
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
2Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
3International Microbiome Centre, University of Calgary, Calgary, AB, Canada
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
5Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
6Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
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Mackenzie W. Gutierrez
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
2Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
3International Microbiome Centre, University of Calgary, Calgary, AB, Canada
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
5Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
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Isabelle Laforest-Lapointe
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
2Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
3International Microbiome Centre, University of Calgary, Calgary, AB, Canada
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
5Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
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  • ORCID record for Isabelle Laforest-Lapointe
Nicholas G. Jendzjowsky
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
5Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
7Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
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Jean-Baptiste Cavin
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
7Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
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Fernando A. Vicentini
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
7Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
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Catherine M. Keenan
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
7Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
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Hena R. Ramay
3International Microbiome Centre, University of Calgary, Calgary, AB, Canada
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
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Jumana Samara
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
2Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
3International Microbiome Centre, University of Calgary, Calgary, AB, Canada
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
5Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
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Wallace K. MacNaughton
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
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  • ORCID record for Wallace K. MacNaughton
Richard J. A. Wilson
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
5Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
7Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
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Margaret M. Kelly
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
8Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
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Kathy D. McCoy
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
3International Microbiome Centre, University of Calgary, Calgary, AB, Canada
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
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Keith A. Sharkey
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
7Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
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Marie-Claire Arrieta
1Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
2Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
3International Microbiome Centre, University of Calgary, Calgary, AB, Canada
4Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
5Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
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  • For correspondence: marie.arrieta@ucalgary.ca
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Abstract

Gut microbiomes make major contributions to the physiological and immunological development of the host, but the relative importance of their bacterial and fungal components, and how they interact, remain largely unknown. We applied carefully controlled experiments in gnotobiotic mice colonized with defined communities of bacteria, fungi, or both to differentiate the direct role of fungi on microbiome assembly, host development, and susceptibility to colitis and airway inflammation. Our results revealed that fungal colonization alone was insufficient to promote the intestinal anatomic and physiological changes seen in mice colonized by bacteria, and had limited impact on the fecal metabolome. However, fungal colonization promoted major shifts in bacterial microbiome ecology, and had an independent effect on the innate and adaptive immune development in young mice. Fungi further exacerbated some aspects of the inflammatory effects of the bacterial community during OVA-induced airway inflammation by promoting macrophage infiltration in the airway. Our results demonstrate a dominant ecological and physiological role of bacteria in gut microbiomes, but highlight fungi as an ecological factor shaping the assembly of the bacterial community and a direct capacity to impact immune system and modulate disease susceptibility. These findings demonstrate that studies focused on bacteria alone provide an incomplete portrayal on microbiome ecology and functionality, and prompt for the inclusion of fungi in human microbiome studies.

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Posted October 25, 2019.
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Contribution of fungal microbiome to intestinal physiology, early-life immune development and mucosal inflammation in mice
Erik van Tilburg Bernardes, Veronika Kuchařová Pettersen, Mackenzie W. Gutierrez, Isabelle Laforest-Lapointe, Nicholas G. Jendzjowsky, Jean-Baptiste Cavin, Fernando A. Vicentini, Catherine M. Keenan, Hena R. Ramay, Jumana Samara, Wallace K. MacNaughton, Richard J. A. Wilson, Margaret M. Kelly, Kathy D. McCoy, Keith A. Sharkey, Marie-Claire Arrieta
bioRxiv 819979; doi: https://doi.org/10.1101/819979
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Contribution of fungal microbiome to intestinal physiology, early-life immune development and mucosal inflammation in mice
Erik van Tilburg Bernardes, Veronika Kuchařová Pettersen, Mackenzie W. Gutierrez, Isabelle Laforest-Lapointe, Nicholas G. Jendzjowsky, Jean-Baptiste Cavin, Fernando A. Vicentini, Catherine M. Keenan, Hena R. Ramay, Jumana Samara, Wallace K. MacNaughton, Richard J. A. Wilson, Margaret M. Kelly, Kathy D. McCoy, Keith A. Sharkey, Marie-Claire Arrieta
bioRxiv 819979; doi: https://doi.org/10.1101/819979

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