1. A Clinical Study Provides the First Direct Evidence That Interindividual Variations in Fecal β-Lactamase Activity Affect the Gut Mycobiota Dynamics in Response to β-Lactam Antibiotics
- Author
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Delavy, Margot, Burdet, Charles, Sertour, Natacha, Devente, Savannah, Docquier, Jean-Denis, Grall, Nathalie, Volant, Stevenn, Ghozlane, Amine, Duval, Xavier, Mentré, France, D’enfert, Christophe, Bougnoux, Marie-Elisabeth, Study Group, Predires, Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity (BPF), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli Studi di Siena = University of Siena (UNISI), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], This work was supported by grants from Agence Nationale de la Recherche (FunComPath ANR-14-IFEC-0004 and PrediRes ANR-16-CE15-0022), the French Government’s Investissement d’Avenir program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases [ANR10-LABX-62-IBEID]), the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie action, Innovative Training Network (FunHoMic, Grant No. 812969) and Assistance Publique – Hôpitaux de Paris (CEREMI CRC13-179)., For the PrediRes study group: Charles Burdet (INSERM, Université de Paris APHP-Bichat Hospital), Erick Denamur (INSERM, Université de Paris), Xavier Duval (INSERM, Université de Paris, APHP-Bichat Hospital), Dusko Ehrlich (INRA Metagenopolis), France Mentré (INSERM, Université de Paris, APHP-Bichat Hospital), Eduardo P. C. Rocha (Institut Pasteur), Laurie Alla (INRA Metagenopolis), Emmanuelle Lechatelier (INRA Metagenopolis), Florence Levenez (INRA Metagenopolis), Nicolas Pons (INRA Metagenopolis), Benoît Quinquis (INRA Metagenopolis), Khadija Bourabha (INSERM), Antoine Bridier Nahmias (INSERM, Université de Paris), Olivier Clermont (INSERM, Université de Paris), Mélanie Magnan (INSERM, Université de Paris), Olivier Tenaillon (INSERM, Université de Paris), Camille d’Humières (INSERM, Université de Paris, APHP-Bichat Hospital, Institut Pasteur), Amandine Perrin (Institut Pasteur), Marie Touchon (Institut Pasteur), Dominique Rainteau (INSERM, Université Pierre et Marie Curie, APHP – Saint Antoine Hospital), Farid Ichou (ICAN), Philippe Lesnik (ICAN), Jimmy Mullaert (INSERM, Université de Paris, APHP – Bichat Hospital), Thu Thuy Nguyen (INSERM)., ANR-14-IFEC-0004,FunComPath,From fungal commensalism to pathogenicity:dissection of the colonization-to-infection shift of Candida albicans(2014), ANR-16-CE15-0022,PREDIRES,PREDIction de l'émergence de la RESistance bactérienne dans le microbiote intestinal humain lors d'un traitement antibiotique(2016), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and European Project: 812969,H2020-MSCA-ITN-2018,FunHoMic(2019)
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beta-lactamases ,healthy individuals ,Virology ,[SDV]Life Sciences [q-bio] ,Candida albicans ,gut mycobiota ,Microbiology ,antibiotics - Abstract
International audience; Antibiotics disturb the intestinal bacterial microbiota, leading to gut dysbiosis and an increased risk for the overgrowth of opportunistic pathogens. It is not fully understood to what extent antibiotics affect the fungal fraction of the intestinal microbiota, the mycobiota. There is no report of the direct role of antibiotics in the overgrowth in healthy humans of the opportunistic pathogenic yeast Candida albicans. Here, we have explored the gut mycobiota of 22 healthy subjects before, during, and up to 6 months after a 3-day regimen of third-generation cephalosporins (3GCs). Using ITS1-targeted metagenomics, we highlighted the strong intra- and interindividual diversity of the healthy gut mycobiota. With a specific quantitative approach, we showed that C. albicans prevalence was much higher than previously reported, with all subjects but one being carriers of C. albicans, although with highly variable burdens. 3GCs significantly altered the mycobiota composition and the fungal load was increased both at short and long term. Both C. albicans relative and absolute abundances were increased but 3GCs did not reduce intersubject variability. Variations in C. albicans burden in response to 3GC treatment could be partly explained by changes in the levels of endogenous fecal β-lactamase activity, with subjects characterized by a high increase of β-lactamase activity displaying a lower increase of C. albicans levels. A same antibiotic treatment might thus affect differentially the gut mycobiota and C. albicans carriage, depending on the treated subject, suggesting a need to adjust the current risk factors for C. albicans overgrowth after a β-lactam treatment.IMPORTANCE Fungal infections are redoubtable healthcare-associated complications in immunocompromised patients. Particularly, the commensal intestinal yeast Candida albicans causes invasive infections in intensive care patients and is, therefore, associated with high mortality. These infections are preceded by an intestinal expansion of C. albicans before its translocation into the bloodstream. Antibiotics are a well-known risk factor for C. albicans overgrowth but the impact of antibiotic-induced dysbiosis on the human gut mycobiota—the fungal microbiota—and the understanding of the mechanisms involved in C. albicans overgrowth in humans are very limited. Our study shows that antibiotics increase the fungal proportion in the gut and disturb the fungal composition, especially C. albicans, in a subject-dependent manner. Indeed, variations across subjects in C. albicans burden in response to β-lactam treatment could be partly explained by changes in the levels of endogenous fecal β-lactamase activity. This highlighted a potential new key factor for C. albicans overgrowth. Thus, the significance of our research is in providing a better understanding of the factors behind C. albicans intestinal overgrowth, which might lead to new means to prevent life-threatening secondary infections.
- Published
- 2022