Dataset Information

Microbiome and metabolome features of the cardiometabolic disease spectrum.

ABSTRACT: Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.

SUBMITTER: Fromentin S

PROVIDER: S-EPMC8863577 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Microbiome and metabolome features of the cardiometabolic disease spectrum.

Fromentin Sebastien S Forslund Sofia K SK Chechi Kanta K Aron-Wisnewsky Judith J Chakaroun Rima R Nielsen Trine T Tremaroli Valentina V Ji Boyang B Prifti Edi E Myridakis Antonis A Chilloux Julien J Andrikopoulos Petros P Fan Yong Y Olanipekun Michael T MT Alves Renato R Adiouch Solia S Bar Noam N Talmor-Barkan Yeela Y Belda Eugeni E Caesar Robert R Coelho Luis Pedro LP Falony Gwen G Fellahi Soraya S Galan Pilar P Galleron Nathalie N Helft Gerard G Hoyles Lesley L Isnard Richard R Le Chatelier Emmanuelle E Julienne Hanna H Olsson Lisa L Pedersen Helle Krogh HK Pons Nicolas N Quinquis Benoit B Rouault Christine C Roume Hugo H Salem Joe-Elie JE Schmidt Thomas S B TSB Vieira-Silva Sara S Li Peishun P Zimmermann-Kogadeeva Maria M Lewinter Christian C Søndertoft Nadja B NB Hansen Tue H TH Gauguier Dominique D Gøtze Jens Peter JP Køber Lars L Kornowski Ran R Vestergaard Henrik H Hansen Torben T Zucker Jean-Daniel JD Hercberg Serge S Letunic Ivica I Bäckhed Fredrik F Oppert Jean-Michel JM Nielsen Jens J Raes Jeroen J Bork Peer P Stumvoll Michael M Segal Eran E Clément Karine K Dumas Marc-Emmanuel ME Ehrlich S Dusko SD Pedersen Oluf O

Nature medicine 20220217 2

Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogene ...[more]

PMID: 35177860

Similar Datasets

Project description:Background and aims: Gene mutations or variants leading to insufficient reactive oxygen species (ROS) production have been associated with inflammatory bowel disease (IBD). In particular, 40-50% of patients with chronic granulomatous disease have IBD (CGD-IBD). CGD is caused by inherited defects in any one of the 5 subunits forming the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived ROS production. While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection in this immune compromised population. Understanding the impact of NOX2 defects on the composition and function of the intestinal microbiota may lead to the identification of treatments for CGD-IBD. Methods: We evaluated GI symptom and quality of life scores, and clinical biomarkers of local (i.e. fecal occult blood and calprotectin) and systemic (i.e. CBC, CRP, ESR, and albumin) inflammation in a cohort of 79 patients with CGD, 8 mutation carriers and 17 healthy controls followed at the National Institutes of Health (NIH). We profiled the intestinal microbiome by 16S rRNA (V4 region) sequencing and the stool metabolome by mass spectrometry in all fecal samples, and further validated our findings by profiling the stool microbiome in a second cohort of 36 patients with CGD recruited from 11 centers across North-America through the Primary Immune Deficiency Treatment Consortium (PIDTC). Predictive functional profiling of the microbial communities based on 16S rRNA sequencing was also performed. Results: After controlling for significant variables, we show decreased alpha diversity and identified distinct intestinal microbiome and metabolomic profiles in patients with CGD compared to healthy individuals. In particular, we observed enrichment for Erysipelatoclostridium spp., Sellimonas spp. and Lachnoclostridium spp. in stool samples from patients with CGD. Despite differences in alpha and beta diversity in samples from the NIH compared to the PIDTC cohort, there were several bacterial taxa that correlated significantly between both cohorts. We further demonstrate that patients with active IBD and/or a history of IBD have a distinct microbiome and metabolomic profile compared to patients without CGD-IBD and identified bacterial taxa to be evaluated as potential markers of disease severity, as well as targets for future therapeutic interventions. Conclusions: Intestinal microbiome and metabolomic signatures distinguished patients with CGD and CGD-IBD and identified microbial and metabolomic candidates to be further evaluated as potential targets to improve the management of patients with CGD-IBD.

Dataset Information

Microbiome and metabolome features of the cardiometabolic disease spectrum.

Publications

Microbiome and metabolome features of the cardiometabolic disease spectrum.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets