Systemic anti-commensal response to fungi analyzed by flow cytometry is related to gut mycobiome ecology
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METHODOLOGY
Open Access
Systemic anti-commensal response to fungi analyzed by flow cytometry is related to gut mycobiome ecology Alicia Moreno-Sabater1,2* , Gaelle Autaa1, Delphine Sterlin1,3,4, Amenie Jerbi3, Remy Villette1, Johanna B. Holm5, Christophe Parizot3, Sameh Selim6, Yaye Senghor2, Pascale Ghillani-Dalbin3, Claude Bachmeyer7, Christophe Hennequin2,8, Guy Gorochov1,3 and Martin Larsen1
Abstract Background: Interest for the study of gut mycobiota in relation with human health and immune homeostasis has increased in the last years. From this perspective, new tools to study the immune/fungal interface are warranted. Systemic humoral immune responses could reflect the dynamic relationships between gut mycobiota and immunity. Using a novel flow cytometry technology (Fungi-Flow) to determine immunoglobulin (Ig) responses to fungi, we studied the relationships between gut mycobiota and systemic humoral anti-commensal immunity. Results: The Fungi-Flow method allows a sensitive and specific measurement of systemic IgG responses against 17 commensal and environmental fungi from the two main divisions; Ascomycota and Basidiomycota. IgG responses exhibited a high inter-individual variability. Anti-commensal IgG responses were contrasted with the relative abundance, alpha-diversity, and intra-genus richness of fungal species in gut mycobiota of twenty healthy donors. Categorization of gut mycobiota composition revealed two differentiated fungal ecosystems. Significant difference of anti-Saccharomyces systemic IgG responses were observed in healthy donors stratified according to the fungal ecosystem colonizing their gut. A positive and significant correlation was observed between the variety of IgG responses against fungal commensals and intestinal alpha-diversity. At the level of intra-genus species richness, intense IgG responses were associated with a low intra-genus richness for known pathobionts, but not commensals. Conclusions: Fungi-Flow allows an easy and reliable measure of personalized humoral responses against commensal fungi. Combining sequencing technology with our novel Fungi-Flow immunological method, we propose that there are at least two defined ecosystems in the human gut mycobiome associated with systemic humoral responses. Fungi-Flow opens new opportunities to improve our knowledge about the impact of mycobiota in humoral anti-commensal immunity and homeostasis. Keywords: Mycobiota, Flow cytometry, Systemic anti-commensal responses, Humoral immunity, Immunoglobulin G, ITS rRNA gene sequencing
* Correspondence: [email protected] 1 Sorbonne Université, Inserm U1135, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), 75013 Paris, France 2 Service de Parasitologie-Mycologie AP-HP, Hôpital Saint-Antoine, 75012 Paris, France 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, distrib
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