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Case Study

Metabolomics To Profile Pathways Involved In Noncommunicable Disease Multimorbidity

Integration of in-depth metabolic and phenotypic profiling in a large cohort of individuals identified groups of metabolites that influence noncommunicable disease (NCD) networks.

A study in Nature Medicine aimed to better understand the onset of chronic disease conditions and multimorbidity identified several metabolites that influence the development of NCDs. The study sheds light on the metabolic overlaps of disease-causing pathways and human physiology, thus laying the groundwork for early disease prevention.

A study in Nature Medicine aimed to better understand the onset of chronic disease conditions and multimorbidity identified several metabolites that influence the development of NCDs.   The study sheds light on the metabolic overlaps of disease-causing pathways and human physiology, thus laying the groundwork for early disease prevention.

Metabolomics to profile pathways involved in noncommunicable disease multimorbidity

The Challenge: Understanding the Sources of Multimorbidity

With increasing age, many people suffer from several chronic, noncommunicable conditions at the same time, which is called multimorbidity. Although multimorbidity is increasing globally, we’re only just starting to understand the causes of co-occurring conditions—which often involve the same metabolic pathways.

Currently, detailed information is lacking on environmental or lifestyle factors that may drive the development of these conditions. Insights into modifiable factors and predispositions might help prevent and manage these conditions. To help fill this knowledge gap, this study profiled the blood of older adults to link the identified metabolites to lifestyle choices and present chronic conditions. These metabolic insights provide comprehensive knowledge on both human physiology and disease-causing factors.

The Metabolon Insight: Identifying Metabolites Associated with Multimorbidity

As part of the large EPIC-Norfolk cohort study, researchers sampled the blood of 11,966 men and women of a mean age of 60 years. Using Metabolon’s Global Discovery Panel, the researchers performed global metabolomic profiling to better understand the metabolites and pathways contributing to multimorbidity and their relationship with environmental and lifestyle risk factors.

The Solution: Linking Multimorbidity to Modifiable Risk Factors

This study linked 1,014 metabolites measured cross-sectionally to the onset of 27 noncommunicable disease conditions, mortality, and multimorbidity. Of the identified metabolites, 220 were associated with only one disease condition, 268 were associated with mortality, and 420 were associated with at least two different diseases or all-cause mortality.

The findings from this cohort study helped the researchers understand the metabolic overlaps between different diseases. Some metabolites were linked to several—and often seemingly unrelated—diseases. Thus, new metabolic connections among cardiometabolic and respiratory diseases including coronary heart disease, heart failure, type 2 diabetes, cerebral stroke, peripheral arterial disease, renal and liver diseases, chronic obstructive pulmonary disease, and lung cancer were identified.

Metabolomics further helped connect actionable risk factors with multimorbidity. Almost every metabolite was successfully linked to a prevalent condition, anthropometric marker, or lifestyle marker. These relationships between risk factors and metabolites represent potential targets for disease prevention and intervention.

The Outcome: Revealing Risk Factors for Mortality

This study integrated metabolomic and phenotypic profiling with the detailed assessment of several chronic disease conditions over a long time period. New associations between plasma levels of certain metabolites and actionable risk factors were identified. Hence, the study concluded that several modifiable or actionable factors, like obesity, smoking, impaired glucose homeostasis, low-grade inflammation, lipoprotein metabolism, and liver and kidney function, contribute to multimorbidity. These data set the stage to allow clinicians to focus on improving liver and kidney function, lipid and glucose metabolism, low-grade inflammation, and gut microbial diversity to address multimorbid conditions earlier in their development. Data from this study may also be useful for investigators trying to understand specific chronic conditions.

References

1. Pietzner, M., Stewart, I.D., Raffler, J. et al. Plasma metabolites to profile pathways in noncommunicable disease multimorbidity. Nat Med. 2021; 27, 471–479. doi: 10.1038/s41591-021-01266-0. PubMed PMCID: PMC8127079.

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