Dietary driven approaches to support healthy ageing: investigating the interactions between the gut microbiota, vitamin D and bone health

Diet is a critical factor in influencing bone health. Calcium and vitamin D are considered to be key nutrients in maintaining bone metabolism (as well as vitamin D being involved in intestinal calcium absorption). However, recent research has identified a decline in the consumption of foods containing these nutrients, with vitamin D deficiency in particular, becoming increasingly common worldwide.

The human gastrointestinal tract is inhabited by trillions of commensal bacteria that are known to impact on human health through a range of host-microorganism interactions including nutrient absorption and immune function. Illness, age and changes in diet and lifestyle factors can disrupt this complex ecosystem, and few studies have identified a link between gut dysbiosis and bone mineral density (BMD); hence, the gut microbiota may be an important modifiable factor to support bone health and prevent age-associated bone diseases such as osteoporosis.

Dietary interventions targeting the gut microbiota such as prebiotics and probiotics, are safe and well established approaches that improve health by positively altering the gut microbiota. Recent studies have demonstrated that combining these gut microbiota-targeted nutraceuticals with vitamin D, can enhance its bioavailability and result in greater health benefits.

This project aims to investigate the relationship between the gut microbiota, vitamin D and markers of bone health, and ultimately, develop a novel gut microbiota-targeted nutraceutical product containing vitamin D, to improve bone metabolism and support healthy ageing.

We hypothesise that gut bacteria are integral contributors to bone as well as intestinal health, and that combining gut microbiota-targeted dietary interventions such as pre- and probiotics with vitamin D, has the potential to improve bone health. We will apply a multidisciplinary approach. The specific objectives are:

1) Conduct a systematic and meta-analysis to assess the relationship between the gut microbiota, vitamin D and indices of bone health, and identify potential molecular mechanisms to target through dietary intervention (UoS).

2) Use multivariate statistical approaches to investigate the association between gut microbiota-targeted nutraceuticals and BMD in large scale (observational) population studies (UK Biobank, NHANES) and using data from previous FSA/BBSRC-funded nutrition and bone health studies (UoS).

3) Examine the impact of vitamin D on the gut microbiota in vitro, using a laboratory human gut model system. Dietary components of interest (identified in objectives 1 and 2) will also be tested, to ascertain their effect on vitamin D bioavailability. Samples will be analysed using microbial and metabolic phenotyping, to assess the impact of the intervention on gut microbial composition and activity respectively (UoR).

4) Design and deliver a randomised, placebo controlled, dietary intervention trial in 40 vitamin D-deficient adults (UoR), and better understand the impact of this potential dietary treatment strategy in modulating the gut microbiota to improve bone metabolism. This study number is powered around a 0.2 log10 increase in bifidobacteria (standard prebiotic intervention target).

Baseline and endline BMD will be measured using a DEXA scan, and blood, urine and stool samples collected at the same timepoints will be analysed using molecular phenotyping approaches. Microbial changes will be mapped with metabolic alterations and regressed against BMD, thus improving knowledge of microbes as well as biomarkers/molecular pathways involved in changes to bone health status.

This proposal combines analytical approaches to conduct a holistic assessment of dietary intervention on bone health, and establish whether changes in mechanisms are mediated by the gut microbiota. he results of this project could lead to possible health claims for the food products used, as well as scientific, clinical and societal interest