Multi-organ imaging demonstrates the heart-brain-liver axis in UK Biobank participants

Abstract

Medical imaging provides numerous insights into the subclinical changes that precede serious diseases such as heart disease and dementia. However, most imaging research either describes a single organ system or draws on clinical cohorts with small sample sizes. In this study, we use state-of-the-art multi-organ magnetic resonance imaging phenotypes to investigate cross-sectional relationships across the heart-brain-liver axis in 30,444 UK Biobank participants. Despite controlling for an extensive range of demographic and clinical covariates, we find significant associations between imaging-derived phenotypes of the heart (left ventricular structure, function and aortic distensibility), brain (brain volumes, white matter hyperintensities and white matter microstructure), and liver (liver fat, liver iron and fibroinflammation). Simultaneous three-organ modelling identifies differentially important pathways across the heart-brain-liver axis with evidence of both direct and indirect associations. This study describes a potentially cumulative burden of multiple-organ dysfunction and provides essential insight into multi-organ disease prevention.

Heart-brain connections: Phenotypic and genetic insights from magnetic resonance images

“…This paper specifically focuses on heart-brain connections. Because of the large amount of data collected in the UKB study, it is also possible to study the relationships between the brain and other human organs and systems ( 133 ). For example, increasing evidence supports the gut-brain axis, which involves complex interactions between the central nervous system and the enteric nervous system ( 134 ).…”

The Genetic Architecture of Biological Age in Nine Human Organ Systems

“…Previous research efforts have made progress in studying the interconnectedness of multiorgan systems in human health 3,[6][7][8][9][10][11][12][13] . In a recent study by McCracken et al, a heart-brain-liver axis was studied, highlighting direct and indirect associations among the three organs and their interconnectivity and shared biological pathways 11 .…”

“…Previous research efforts have made progress in studying the interconnectedness of multiorgan systems in human health 3,[6][7][8][9][10][11][12][13] . In a recent study by McCracken et al, a heart-brain-liver axis was studied, highlighting direct and indirect associations among the three organs and their interconnectivity and shared biological pathways 11 . A recent review highlighted the role of interorgan signals in metabolic control, including the secretion of peptides, small molecules, and lipid mediators by metabolic tissues and the involvement of the central nervous system in coordinating peripheral metabolic functions 9 .…”

Ten-organ developmental proteome atlas from infancy to adulthood mice

“…[34][35][36][37] The synchronization of organ development is evidenced by the analogous expression trends of proteins involved in the regulatory pathways of the four organs, namely lung, spleen, stomach and skin. The results of organ developmental synchrony may be further explored by the concepts of "organ-organ crosstalk" 38,39 and "organ axes" 40 .…”