Chronic Diseases in Multimorbidity May Share Origins, Study Finds

Using metabolomic profiling from more than 11 000 individuals, researchers identified common pathways linking seemingly unrelated diseases that often co-occur.

A new study by a team of UK researchers has identified shared small molecule profiles that increase the likelihood of individuals developing multiple non-communicable diseases (NCD), referred to as multimorbidity.

Multimorbidity is defined as co-occurrence of ≥2 chronic conditions which could include cardiovascular disease, cancer, chronic respiratory disease, diabetes. The study was published March 11, 2021, in the journal Nature Medicine.

In their effort to identify underlying biological links in individuals with multimorbidity, the team, led by Dr Claudia Langenberg at the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge and Berlin Institute of Health, Charité University Medicine Berlin, Germany, used baseline untargeted plasma metabalomic profiling that covered 1,014 metabolites from >11 000 participants in the European Prospective Investigation into Cancer (EPIC)-Norfolk study.

The small circulating molecules (eg, sugars, lipids, vitamins) serve as a "comprehensive readout of human physiology," the authors write, essentially providing an objective reflection of the influences and interactions of genetics, lifestyle, environment, medical treatment, and gut microbes.

The investigators identified and documented the association of the metabolites with 27 different NCD often seen in multimorbidity, observing that nearly half of the molecules examined were associated with at least one of the 27 diseases.

Nearly two-thirds (65.5%) of the disease-associated metabolites were shared by multiple diseases and, so, with the risk for multimorbidity. One example: elevated plasma levels of N-acetylneuraminate were associated with a higher risk of 14 diseases.

The team then integrated baseline data on more than 50 clinical risk factors and characteristics of EPIC-Norfolk study participants documented at study enrollment, to put metabolite-disease associations into context and identify shared pathways.

The analysis highlighted the following as precursors to common clusters of multimorbidity and as targets for prevention and early intervention.

  • Kidney and liver function
  • Lipid and glucose metabolism
  • Low-grade inflammation
  • Surrogates of gut microbial diversity
  • Specific health-related behaviors

"Such a deep understanding of molecular process has the potential to not only improve treatment of disease, but also aid earlier identification of individuals at risk," said lead author Lundenberg in a press release from UK Research and Innovation (UKRI). "For example, we found that several metabolites measured were better predictors of future kidney-related disease risk than the current standard clinical tests."

"Our observation that two-thirds of the small molecules were linked to at least 2, even seemingly unrelated, diseases strongly contrasts the disease-centric approach still common in biomedical research," said Dr Maik Pietzner, co-lead author of the study at the MRC, in the UKRI statement. "People do not usually develop just one long-term disease, so by taking a broader approach...we can gain a more useful understanding of the underlying biological processes." He notes that treatments that target pathways shared by several of a patient's conditions may provide a more consistent benefit that avoids increasing risk for other diseases.

“…identifying these metabolic footprints could help to develop preventive therapeutics in the future," commented Ivan Pavlov, program lead at MRC. “Importantly, the paper discovers possible links between seemingly unrelated diseases opening potential new avenues for research."