Uncovering the relationship between gut microbial dysbiosis, metabolomics, and dietary intake in type 2 diabetes mellitus and in healthy volunteers: a multi-omics analysis

Abstract Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis among people with diabetes. While the assumption is that abnormal metabolomic signatures would often accompany microbial...

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Main Authors: Mohammad Tahseen Al Bataineh, Axel Künstner, Nihar Ranjan Dash, Habiba S. Alsafar, Mohab Ragab, Franziska Schmelter, Christian Sina, Hauke Busch, Saleh Mohamed Ibrahim
Format: Article
Language:English
Published: Nature Portfolio 2023-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-45066-7
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author Mohammad Tahseen Al Bataineh
Axel Künstner
Nihar Ranjan Dash
Habiba S. Alsafar
Mohab Ragab
Franziska Schmelter
Christian Sina
Hauke Busch
Saleh Mohamed Ibrahim
author_facet Mohammad Tahseen Al Bataineh
Axel Künstner
Nihar Ranjan Dash
Habiba S. Alsafar
Mohab Ragab
Franziska Schmelter
Christian Sina
Hauke Busch
Saleh Mohamed Ibrahim
author_sort Mohammad Tahseen Al Bataineh
collection DOAJ
description Abstract Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis among people with diabetes. While the assumption is that abnormal metabolomic signatures would often accompany microbial dysbiosis, the connection remains largely unknown. In this study, we investigated how diet changed the gut bacteriome, mycobiome and metabolome in people with and without type 2 Diabetes.1 Differential abundance testing determined that the metabolites Propionate, U8, and 2-Hydroxybutyrate were significantly lower, and 3-Hydroxyphenyl acetate was higher in the high fiber diet compared to low fiber diet in the healthy control group. Next, using multi-omics factor analysis (MOFA2), we attempted to uncover sources of variability that drive each of the different groups (bacterial, fungal, and metabolite) on all samples combined (control and DM II). Performing variance decomposition, ten latent factors were identified, and then each latent factor was tested for significant correlations with age, BMI, diet, and gender. Latent Factor1 was the most significantly correlated. Remarkably, the model revealed that the mycobiome explained most of the variance in the DM II group (12.5%) whereas bacteria explained most of the variance in the control group (64.2% vs. 10.4% in the DM II group). The latent Factor1 was significantly correlated with dietary intake (q < 0.01). Further analyses of the impact of bacterial and fungal genera on Factor1 determined that the nine bacterial genera (Phocaeicola, Ligilactobacillus, Mesosutterella, Acidaminococcus, Dorea A, CAG-317, Caecibacter, Prevotella and Gemmiger) and one fungal genus (Malassezia furfur) were found to have high factor weights (absolute weight > 0.6). Alternatively, a linear regression model was fitted per disease group for each genus to visualize the relationship between the factor values and feature abundances, showing Xylose with positive weights and Propionate, U8, and 2-Hydroxybutyrate with negative weights. This data provides new information on the microbially derived changes that influence metabolic phenotypes in response to different diets and disease conditions in humans.
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spelling doaj.art-6b8fcce7819843b181c0bb8d98c0265e2023-11-19T13:06:08ZengNature PortfolioScientific Reports2045-23222023-10-0113111110.1038/s41598-023-45066-7Uncovering the relationship between gut microbial dysbiosis, metabolomics, and dietary intake in type 2 diabetes mellitus and in healthy volunteers: a multi-omics analysisMohammad Tahseen Al Bataineh0Axel Künstner1Nihar Ranjan Dash2Habiba S. Alsafar3Mohab Ragab4Franziska Schmelter5Christian Sina6Hauke Busch7Saleh Mohamed Ibrahim8Department of Genetics and Molecular Biology, College of Medicine and Health Sciences, Khalifa University of Science and TechnologyLübeck Institute of Experimental Dermatology, University of LübeckDepartment of Clinical Sciences, College of Medicine, University of SharjahDepartment of Genetics and Molecular Biology, College of Medicine and Health Sciences, Khalifa University of Science and TechnologyInstitute of Nutritional Medicine, University of LübeckInstitute of Nutritional Medicine, University of LübeckInstitute of Nutritional Medicine, University of LübeckLübeck Institute of Experimental Dermatology, University of LübeckDepartment of Genetics and Molecular Biology, College of Medicine and Health Sciences, Khalifa University of Science and TechnologyAbstract Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis among people with diabetes. While the assumption is that abnormal metabolomic signatures would often accompany microbial dysbiosis, the connection remains largely unknown. In this study, we investigated how diet changed the gut bacteriome, mycobiome and metabolome in people with and without type 2 Diabetes.1 Differential abundance testing determined that the metabolites Propionate, U8, and 2-Hydroxybutyrate were significantly lower, and 3-Hydroxyphenyl acetate was higher in the high fiber diet compared to low fiber diet in the healthy control group. Next, using multi-omics factor analysis (MOFA2), we attempted to uncover sources of variability that drive each of the different groups (bacterial, fungal, and metabolite) on all samples combined (control and DM II). Performing variance decomposition, ten latent factors were identified, and then each latent factor was tested for significant correlations with age, BMI, diet, and gender. Latent Factor1 was the most significantly correlated. Remarkably, the model revealed that the mycobiome explained most of the variance in the DM II group (12.5%) whereas bacteria explained most of the variance in the control group (64.2% vs. 10.4% in the DM II group). The latent Factor1 was significantly correlated with dietary intake (q < 0.01). Further analyses of the impact of bacterial and fungal genera on Factor1 determined that the nine bacterial genera (Phocaeicola, Ligilactobacillus, Mesosutterella, Acidaminococcus, Dorea A, CAG-317, Caecibacter, Prevotella and Gemmiger) and one fungal genus (Malassezia furfur) were found to have high factor weights (absolute weight > 0.6). Alternatively, a linear regression model was fitted per disease group for each genus to visualize the relationship between the factor values and feature abundances, showing Xylose with positive weights and Propionate, U8, and 2-Hydroxybutyrate with negative weights. This data provides new information on the microbially derived changes that influence metabolic phenotypes in response to different diets and disease conditions in humans.https://doi.org/10.1038/s41598-023-45066-7
spellingShingle Mohammad Tahseen Al Bataineh
Axel Künstner
Nihar Ranjan Dash
Habiba S. Alsafar
Mohab Ragab
Franziska Schmelter
Christian Sina
Hauke Busch
Saleh Mohamed Ibrahim
Uncovering the relationship between gut microbial dysbiosis, metabolomics, and dietary intake in type 2 diabetes mellitus and in healthy volunteers: a multi-omics analysis
Scientific Reports
title Uncovering the relationship between gut microbial dysbiosis, metabolomics, and dietary intake in type 2 diabetes mellitus and in healthy volunteers: a multi-omics analysis
title_full Uncovering the relationship between gut microbial dysbiosis, metabolomics, and dietary intake in type 2 diabetes mellitus and in healthy volunteers: a multi-omics analysis
title_fullStr Uncovering the relationship between gut microbial dysbiosis, metabolomics, and dietary intake in type 2 diabetes mellitus and in healthy volunteers: a multi-omics analysis
title_full_unstemmed Uncovering the relationship between gut microbial dysbiosis, metabolomics, and dietary intake in type 2 diabetes mellitus and in healthy volunteers: a multi-omics analysis
title_short Uncovering the relationship between gut microbial dysbiosis, metabolomics, and dietary intake in type 2 diabetes mellitus and in healthy volunteers: a multi-omics analysis
title_sort uncovering the relationship between gut microbial dysbiosis metabolomics and dietary intake in type 2 diabetes mellitus and in healthy volunteers a multi omics analysis
url https://doi.org/10.1038/s41598-023-45066-7
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