Changes in the type 2 diabetes gut mycobiome associate with metformin treatment across populations.

Autor:	Van Syoc E; Department of Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.; Department of Animal Science, The Pennsylvania State University, University Park, Pennsylvania, USA.; One Health Microbiome Center, The Pennsylvania State University, University Park, Pennsylvania, USA., Nixon MP; College of Information Sciences and Technology, The Pennsylvania State University, University Park, Pennsylvania, USA., Silverman JD; One Health Microbiome Center, The Pennsylvania State University, University Park, Pennsylvania, USA.; College of Information Sciences and Technology, The Pennsylvania State University, University Park, Pennsylvania, USA.; Department of Statistics, The Pennsylvania State University, University Park, Pennsylvania, USA.; Department of Medicine, The Pennsylvania State University, Hershey, Pennsylvania, USA., Luo Y; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Gonzalez FJ; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA., Elbere I; Latvian Biomedical Research and Study Center, Riga, Latvia., Klovins J; Latvian Biomedical Research and Study Center, Riga, Latvia., Patterson AD; One Health Microbiome Center, The Pennsylvania State University, University Park, Pennsylvania, USA.; Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania, USA., Rogers CJ; Department of Nutritional Sciences, University of Georgia, Athens, Georgia, USA., Ganda E; Department of Animal Science, The Pennsylvania State University, University Park, Pennsylvania, USA.; One Health Microbiome Center, The Pennsylvania State University, University Park, Pennsylvania, USA.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2024 Jun 12; Vol. 15 (6), pp. e0016924. Date of Electronic Publication: 2024 May 20.
DOI:	10.1128/mbio.00169-24
Abstrakt:	The human gut teems with a diverse ecosystem of microbes, yet non-bacterial portions of that community are overlooked in studies of metabolic diseases firmly linked to gut bacteria. Type 2 diabetes mellitus (T2D) is associated with compositional shifts in the gut bacterial microbiome and the mycobiome, the fungal portion of the microbiome. However, whether T2D and/or metformin treatment underpins fungal community changes is unresolved. To differentiate these effects, we curated a gut mycobiome cohort spanning 1,000 human samples across five countries and validated our findings in a murine experimental model. We use Bayesian multinomial logistic normal models to show that T2D and metformin both associate with shifts in the relative abundance of distinct gut fungi. T2D is associated with shifts in the Saccharomycetes and Sordariomycetes fungal classes, while the genera Fusarium and Tetrapisipora most consistently associate with metformin treatment. We confirmed the impact of metformin on individual gut fungi by administering metformin to healthy mice. Thus, metformin and T2D account for subtle, but significant and distinct variation in the gut mycobiome across human populations. This work highlights for the first time that metformin can confound associations of gut fungi with T2D and warrants the need to consider pharmaceutical interventions in investigations of linkages between metabolic diseases and gut microbial inhabitants. Importance: This is the largest to-date multi-country cohort characterizing the human gut mycobiome, and the first to investigate potential perturbations in gut fungi from oral pharmaceutical treatment. We demonstrate the reproducible effects of metformin treatment on the human and murine gut mycobiome and highlight a need to consider metformin as a confounding factor in investigations between type 2 diabetes mellitus and the gut microbial ecosystem. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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