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Longitudinal multi-omics of host-microbe dynamics in prediabetes.

ABSTRACT: Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host-microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.

SUBMITTER: Zhou W

PROVIDER: S-EPMC6666404 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Evidence has shown that gut microbiota play a key role in host metabolism and health; however, little is known about the microbial community in the donkey hindgut as well as the interactions that occur between gut microbes and the host. This study aimed to explore the gut microbiome differences by analyzing the microbial community and differentially expressed genes (DEGs) related to lipid metabolism and the immune system along the donkey hindgut. The hindgut tissues (cecum, ventral colon, and dorsal colon) were separated, and the contents of each section were collected from six male donkeys for multi-omics analysis. There were significant differences in terms of dominant bacteria among the three sections, especially between the cecum and dorsal colon sites. For instance, species belonging to Prevotella and Treponema were most abundant in the cecum, while the Clostridiales_bacterium, Streptococcus_equinus, Ruminococcaceae_bacterium, etc., were more abundant in the dorsal colon. Apart from propionate, the concentrations of acetate, isobutyrate, valerate and isovalerate were all lower in the cecum than in the dorsal colon (p < 0.05). Furthermore, we identified some interesting DEGs related to lipid metabolism (e.g., ME1, MBOAT1, ACOX1, ACOX2 and LIPH) and the immune system (e.g., MUC3B, mucin-2-like, IL17RC, IL1R2, IL33, C1QA, and MMP9) between the cecum and dorsal colon and found that the PPAR pathway was mainly enriched in the cecum. Finally, we found a complex relationship between the gut microbiome and gene expression, especially with respect to the immune system, and combined with protein-protein interaction (PPI) data, suggesting that the PPAR pathway might be responsible, at least in part, for the role of the hindgut microbiota in the donkeys' gut homeostasis. Our data provide an in-depth understanding of the interaction between the microbiota and function in the healthy equine hindgut and may also provide guidance for improving animal performance metrics (such as product quality) and equine welfare.

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Longitudinal multi-omics of host-microbe dynamics in prediabetes.

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