Skip Navigation
Metabolic Health @discuss.online
jet @hackertalks.com
Paper

Longitudinal multi-omics of host–microbe dynamics in prediabetes - 2019

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.

Full Paper : https://doi.org/10.1038/s41586-019-1236-x

1 comments

  • What a title! ha, talk about impenetrable

    Prediabetes and T2D are often associated with insulin resistance, where individuals produce insulin but are hyperglycaemic because their cells do not respond toinsulin.

    Sadly some cells do still respond to insulin, but others require more signaling, this is why poor metabolic health is characterized by huge hormonal imbalances (the signal strength to resolve blood glucose is so high that it messes with other hormones)

    performed a detailed longitudinal analysis of individuals with various early impairments in glucose control (for example, insulin resistance). We carried out deep profiling of the human gut and nasal microbiomes, as well as host circulating blood during periods of health and stress. Our study reveals that many host biochemical and microbial components are stable over time when healthy, but can undergo dynamic and marked changes in response to viral infection and other perturbations. Notably, these changes differ between insulin-sensitive and insulin-resistant individuals.

    This is very important to emphasize, long before metabolic ill-health is obvious to people the body already starts changing, having worse immune response, longer recovery times, etc. It's a very long road to T2D, but the subtle effects start early (with elevated insulin levels).

    This graph is super interesting, so the SSPG on the top (steady state plasma gluclose) is a proxy measurement for how insulin sensitive someone is, the lower the better.

    triglycerides were positively associated with SSPG, whereas high-density lipoprotein (HDL) was inversely correlated with SSPG15,16 . We also found that SSPG positively associated with increased inflammation and immune responses, as evident by neutrophil absolute count (q = 0.028) and white blood cell count (q = 0.066) from clinical laboratory tests. Although these complete blood count values were still in the normal range, these observations highlight the association between inflammation and insulin resistance

    Notably, most immune-related pathways were upregulated at the EE stage in insulin-sensitive participants, whereas almost no immune responses were evident until the EL stage in the insulin-resistant group. One key difference is that the acute phase response, which is a rapid inflammatory response that protects against infection using non-specific defence mechanisms, was activated and sustained through the EL stage in insulin-sensitive individuals but not in insulin-resistant individuals (Extended Data Fig. 5d). Furthermore, in agreement with the impaired host response in the insulin-resistant group, we observed fewer changes in nasal microbiota taxa and predicted genes in the insulin-resistant group during RVI.

    We know that T2D impacts immune response, its very helpful to see it quantified in terms of SSPG (insulin sensitivity). Impacted metabolic health means a weaker immune response as least for respiratory viruses.

    These data reveal extensive differences in molecular path-way changes upon RVI and immunization, and identify dysregulated pathways that include immune responses, metabolic and neurological pathways, as well as gut and nasal microorganisms

    The sad implication is that a infection can cause more inflammation (cytokine storm?) which speeds up the insulin resistance and T2D onset.