Eldermet

Eldermet

Studying the relationship between diet, gut bacteria and health status in the elderly

Background

The human gut microbiota is home to an estimated 1014 bacteria that have a key role in promoting and maintaining health[1]. This microbiota plays essential roles in aiding metabolism of dietary ingredient (especially lipids and fibre)[2], regulating energy balance[3], producing vitamins[4], and both priming and regulating the immune defences to protect against pathogenic invasion[5]. There is increasing evidence that alterations in the microbiota are linked to obesity[6], inflammatory bowel disease[7, 8], and Irritable Bowel Syndrome[9, 10].With the realisation in recent years that the gut microbiota was essentially a 'forgotten organ' with a profound impact on general health, Paul O'Toole and colleagues set up technology platforms to examine the gut microbiota in a range of diseases including IBD, IBS, infants, and the elderly. The core technology is based upon next-generation sequencing, and required specialist hardware andexpertise to be built up[11, 12]. The ELDERMET project, see ELDERMET, aims to correlate diversity, composition, and metabolic potential of the faecal microbial metagenome with health, diet and lifestyle indices that are a) likely to be influenced by the microbiota or b) to influence the microbiota. We then examined the baseline microbiota in 161 subjects over 65 years recruited in Munster [13]. We found striking differences between individuals of the overall microbiota composition; an aggregate microbiota that was very different form younger adults; some subjects had very high or low levels of bacteria associated with health (Actinobacteria, Faecalobacteria) and disease (Enterobacteriaceae). New data published by the ELDERMET group in Nature, see Claesson, O Toole et al, shows that individual microbiota of people in long-stay ,nursing home, care is significantly less diverse than that of community dwellers and that this loss of community-associated microbiota correlates with increased frailty,supporting a relationship between diet, microbiota and health status, indicating a role for diet-driven microbiota alterations in varying rates of health decline upon ageing [14].

The Project

In the ELDERMET project, we are now examining correlations between diet, microbiota and health parameters, from the vast amount of data collected, to develop recommendations for specific dietary ingredients, foodstuffs, functional foods and/or dietary supplements, that will improve the health of elderly consumers. We see possibilities for acting as a reference centre with UCC partners in the area of dietary aspects of healthy aging, particularly with regard to how diet and microbiota may impact on inflammation, frailty, sarcopaenia and cognitive function.

We are also major partners in a European-wide project called Nu-Age, see www.nu-age.eu, that will examine the role of diet on health in 2,500 older persons in 5 recruitment centres across Europe. The main objective is to test the effect of switching to a Mediterranean diet upon a wide panel of clinical markers. Paul O'Toole leads the Work Package on Metagenomics and Microbiota analysis in the Nu-Age project, which is anchored by Univ. Bologna. He is actively pursuing opportunities for developing two additional EU projects, in collaboration with colleagues at the UCC CGR,and he is participatingrecently participated in a workshop at the National Institute for Aging this July 2012 in Washington DC Bethesda MD that may inform future US finding policy in this area. 

Timeline

The establishment of well phenotyped elderly subject cohorts in Cork, and the accrual of a massive database of diet-microbiota-health information, puts us in a strong position to act as a reference centre. We are currently expanding our activities to include metabolomics (identification of bacterial metabolites by NMR or Mass Spec) that are diagnostic for various stages of healthy or unhealthy aging. Our aim is to identify biomarkers for healthy ageing for point-of-care diagnostics. We are also well positioned, alongside our European colleagues, to examine microbiota human-genome interactions, which will be an important element in developing personalized healthcare for older persons.

Funding

The ELDERMET project is funded by the (Govt. of Ireland) Dept. Food, Agriculture and Marine till December 2013, and the Nu-Age project isFP7 funded until 2017.

Pillars Targeted

ELDERMET targets action A3 and the Care & Cure pillar, specifically B2:Multi-morbidity and R&D.

References

O'Toole, P.W. and M.J. Claesson, Gut Microbiota: changes throughout the lifespan from infancy to elderly. Internat. Dairy J., 2010. 20: p. 281-291.

Sekirov, I., et al., Gut microbiota in health and disease. Physiol Rev, 2010. 90(3): p. 859-904.

Murphy, E.F., et al., Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut, 2010. 59(12): p. 1635-42.

Hill, M.J., Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev, 1997. 6 Suppl 1: p. S43-5.

Guarner, F., et al., Mechanisms of disease: the hygiene hypothesis revisited. Nat. Clin. Pract. Gastroenterol. Hepatol., 2006. 3(5): p. 275-84.

Ley, R.E., et al., Microbial ecology: human gut microbes associated with obesity. Nature, 2006. 444(7122): p. 1022-3.

Manichanh, C., et al., Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut, 2006. 55(2): p. 205-11.

Qin, J., et al., A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 2010. 464(7285): p. 59-65.

Jeffery, I.B., et al., An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut, 2012. on-line early: p. 10.1136/gutjnl-2011-301501.

Kassinen, A., et al., The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology, 2007. 133(1): p. 24-33.

Claesson, M.J., et al., Comparative analysis of pyrosequencing and a phylogenetic microarray for exploring microbial community structures in the human distal intestine. PLoS One, 2009. 4(8): p. e6669.

Claesson, M.J., et al., Comparison of two next-generation sequencing technologies for resolving highly complex microbiota composition using tandem variable 16S rRNA gene regions. Nucleic Acids Res., 2010. 38(22): p. e200.

Claesson, M.J., et al., Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc. Natl. Acad. Sci. U S A, 2011. 108 Suppl 1: p. 4586-91.

Claesson MJ, Jeffery IB, Conde S, Power SE, O'Connor EM, Cusack S, Harris HM, Coakley M, Lakshminarayanan B, O'Sullivan O, Fitzgerald GF, Deane J, O'Connor M, Harnedy N, O'Connor K, O'Mahony D, van Sinderen D, Wallace M, Brennan L, Stanton C, Marchesi JR, Fitzgerald AP, Shanahan F, Hill C, Ross RP, O'Toole PW. Gut microbiota composition correlates with diet and health in the elderly.Nature 2012; doi: 10.1038/nature11319.

CHARGE-UCC

Centre for Gerontology and Rehabilitation , School of Medicine, UCC The Bungalow, Block 13, St. Finbarr's Hospital, Douglas Rd., Cork, Ireland

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