Identifying and targeting modifiable inflammatory factors underlying higher risk of frailty in individuals experiencing deprivation

Frailty is a big problem for public health, and it is especially common in poor communities. The Consensus on Healthy Ageing from Public Health England says that people who live in poverty have 20 fewer years of good health and are more likely to become weak as they age. People who are homeless, addicted to drugs or alcohol, have learning challenges, need mental health care, or are vulnerable migrants are more likely to become frail before they should.

The NIHR Innovations in Clinical Trials Design and Delivery for the Underserved (INCLUDE) project has been trying to find ways to include under-served groups in health and care studies (https://tinyurl.com/y6k4y9vd). Older people have been pointed out as a group that doesn't get enough help nor their views are always adequately represented in research about ageing.

This research proposal is in line with the advice recently given by experts in Geriatric medicine. The goal of that advice is to improve the inclusion of underserved groups in research, to reduce inequalities, and to learn more about the morbidity and mortality of diseases that affect these populations so that effective, real-world interventions can be developed.

The his project will address this need by identifying and characterising the specific inflammatory pathways involved in premature frailty which are modifiable by targeting gut microbes, to then develop interventions to reduce premature frailtyin deprived populations.

The study aims to develop effective interventions that consider the social and environmental factors that contribute to frailty and ageing, identifying first on common inflammatory mechanisms between aging and social deprivation, focusing then on those that are linked to the gut microbes carried by a person. This means that such mechanisms may be targeted by diet or exercise which modify the gut microbiome. The team will then use advance statistical techniques and data from hundreds of thousands of people in UK Biobank to ascertain a causal role of the inflammatory features identified on premature ageing and on frailty. Using microbiome and inflammation data from already completed dietary and exercise clinical interventions, it will be possible to determine which interventions or combinations of interventions are most likely to specifically tackle the inflammatory/microbiome pathways involved in premature ageing cause deprivation.
The feasibility and acceptability of interventions through qualitative research.
The views from deprived individuals, from frail people in care homes, from carers and charities working with these groups will all be incorporated to design a prototype intervention. This holistic approach recognises that there are multiple factors that can impact health outcomes and aims to develop interventions that are tailored to the needs of deprived populations.

The interdisciplinary team comprising of experts from various fields such as clinical experts (geriatricians, orthopaedic surgeons), social scientists, bioinformaticians, omics experts, and trialists can be highly beneficial in designing interventions to target the gut microbiome and reduce premature frailty in deprived populations. Such a team brings together a diverse range of expertise and skills to assess, plan, and manage care jointly, enabling a holistic approach to care and to addressing health inequalities with regards to premature ageing.

This project aims to investigate the hypothesis that specific inflammatory pathways involved in the development of premature frailty and unhealthy aging are upregulated in individuals who experience deprivation compared to those who don't. The goal is to develop targeted interventions, focused on dietary supplementation (omega-3, prebiotics, probiotics, protein) and physiotherapy, to reduce the likelihood of premature aging and frailty in deprived groups.

The project will use an interdisciplinary approach that incorporates microbiome and proteomic data from various dietary supplementation studies and a physiotherapy study and assess feasibility and acceptability to groups experiencing social deprivation through qualitative research. The specific aims and objectives of the project include assessing the links between socioeconomic deprivation, gut microbiome, and inflammation; establishing the relationship of microbiome and inflammatory features identified to clinical outcomes and causal validation; investigating the effect of protein supplementation, physiotherapy, omega-3 supplementation, pre- or probiotics on the selected inflammatory and microbiome features identified in previous studies; and identifying the core elements for a complex intervention following the MRC framework.

The project will use the principles of co-design and co-production to work with the communities of interest to better understand their context and how the interventions could work for them. This research has the potential to improve the quality of life for older adults enduring socioeconomic deprivation and to mitigate premature ageing, frailty, and eventually fractures and death.