Exploring Socioeconomic Disparities in Health through Microbial Pathways: Insights from Metagenomics

In this project, I have three aims: to investigate the relationship between socio-economic position (SEP) and the gut microbiome across different life stages; examine the association between gut microbiome profiles and inflammatory biomarkers and mental health, and explore the gut microbiome as a mediator between SEP and inflammation and mental health.

Socioeconomic disparities in health and mortality are widely acknowledged, yet the biological mechanisms driving these associations remain unclear. Recently, the gut microbiome has emerged as a potentially significant mediating pathway between the social environment and both physical and mental health, due to its involvement in the stress response and the bidirectional communication network between the gut and the brain, known as the gut-brain axis (Foster et al., 2017). While recent studies have shown that individual and area-level SEP can affect gut microbiome composition (Bowyer et al., 2019; Zuniga-Chaves et al., 2023), these associations have not yet been examined across different life stages or in relation to health outcomes. Additionally, existing research has primarily relied on 16S rRNA sequencing, which identifies and quantifies bacterial types in a sample but has limitations. A more comprehensive approach using shotgun metagenomic sequencing, which identifies all genetic material in a sample and their functions is needed. This project proposes a comprehensive approach utilising metagenomics as well as other omics data such as metatranscriptomics and metabolomics, to deepen our understanding of how SEP influences the gut microbiome and to explore whether the gut microbiome may serve as a potential mediator across the socioeconomic health gradient.

We will explore how individual-level SEP, including income, occupation, and education, influences the gut microbiome across different life stages, examining both its functional implications and its impact on inflammatory biomarkers and mental health. This study will utilise data from Lifelines and Understanding Society, with Understanding Society planning to collect gut microbiome data in 2025. Lifelines is a multi-disciplinary, three-generation, population-based cohort study, that delves into the health and health-related behaviours of 167,729 individuals residing in the North of the Netherlands. Employing a wide array of investigative methods, Lifelines assesses various biomedical, socio-demographic, behavioural, physical, and psychological factors affecting the health and well-being of the general population.
The Lifelines study is unique in offering a gut microbiome dataset that includes multi-omics data. For example, the first gut microbiome assessment (DAG1/DEEP), collected from April 2012 to August 2013, includes metagenomic sequencing, metatranscriptomics, metabolomics, and inflammatory biomarkers such as CRP and cytokines for around 1500 participants. Metagenomic data was collected from Lifelines participants in 2015 and 2016 in the following microbiome assessment (DAG3), involving approximately 8,200 participants. Therefore, a comprehensive multi-omics approach is only feasible using Lifelines data. It enables us to identify the microbial species present, their functional roles, and the metabolites they produce-crucial insights for understanding the gut microbiota's impact on the gut-brain axis and inflammatory processes. Furthermore, the participants in the DAG3 assessment range in age from 8 to 84, allowing us to examine the relationship between SEP and the gut microbiome across different life stages, a field that has not been researched.