Multiomics signatures of type 1 diabetes with and without albuminuria.

Autor:	Clos-Garcia M; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; LEITAT Technological Center, Terrassa, Spain., Ahluwalia TS; Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark.; The Bioinformatics Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark., Winther SA; Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark., Henriksen P; Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark., Ali M; Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark., Fan Y; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Stankevic E; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Lyu L; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Vogt JK; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Clinical Microbiomics, Copenhagen, Denmark., Hansen T; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Legido-Quigley C; Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark., Rossing P; Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Pedersen O; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Center for Clinical Metabolic Research, Gentofte University Hospital, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2022 Dec 02; Vol. 13, pp. 1015557. Date of Electronic Publication: 2022 Dec 02 (Print Publication: 2022).
DOI:	10.3389/fendo.2022.1015557
Abstrakt:	Aims/hypothesis: To identify novel pathophysiological signatures of longstanding type 1 diabetes (T1D) with and without albuminuria we investigated the gut microbiome and blood metabolome in individuals with T1D and healthy controls (HC). We also mapped the functional underpinnings of the microbiome in relation to its metabolic role. Methods: One hundred and sixty-one individuals with T1D and 50 HC were recruited at the Steno Diabetes Center Copenhagen, Denmark. T1D cases were stratified based on levels of albuminuria into normoalbuminuria, moderate and severely increased albuminuria. Shotgun sequencing of bacterial and viral microbiome in stool samples and circulating metabolites and lipids profiling using mass spectroscopy in plasma of all participants were performed. Functional mapping of microbiome into Gut Metabolic Modules (GMMs) was done using EggNog and KEGG databases. Multiomics integration was performed using MOFA tool. Results: Measures of the gut bacterial beta diversity differed significantly between T1D and HC, either with moderately or severely increased albuminuria. Taxonomic analyses of the bacterial microbiota identified 51 species that differed in absolute abundance between T1D and HC (17 higher, 34 lower). Stratified on levels of albuminuria, 10 species were differentially abundant for the moderately increased albuminuria group, 63 for the severely increased albuminuria group while 25 were common and differentially abundant both for moderately and severely increased albuminuria groups, when compared to HC. Functional characterization of the bacteriome identified 23 differentially enriched GMMs between T1D and HC, mostly involved in sugar and amino acid metabolism. No differences in relation to albuminuria stratification was observed. Twenty-five phages were differentially abundant between T1D and HC groups. Six of these varied with albuminuria status. Plasma metabolomics indicated differences in the steroidogenesis and sugar metabolism and circulating sphingolipids in T1D individuals. We identified association between sphingolipid levels and Bacteroides sp. abundances. MOFA revealed reduced interactions between gut microbiome and plasma metabolome profiles albeit polar metabolite, lipids and bacteriome compositions contributed to the variance in albuminuria levels among T1D individuals. Conclusions: Individuals with T1D and progressive kidney disease stratified on levels of albuminuria show distinct signatures in their gut microbiome and blood metabolome. Competing Interests: PR reports personal fees from Bayer during the conduct of the study. He has received research support and personal fees from AstraZeneca and Novo Nordisk, and personal fees from Astellas Pharma, Boehringer Ingelheim, Eli Lilly, Gilead Sciences, Mundipharma, Sanofi, and Vifor Pharma. All fees are given to Steno Diabetes Center Copenhagen. Author MC-G was employed by company LEITAT Technological Center. Author JKV was employed by Clinical Microbiomics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Clos-Garcia, Ahluwalia, Winther, Henriksen, Ali, Fan, Stankevic, Lyu, Vogt, Hansen, Legido-Quigley, Rossing and Pedersen.)
Databáze:	MEDLINE
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