With modern medicine and an awareness of healthy lifestyle practices, people are living longer and generally healthier lives than their ancestors. These successes of modern medicine have resulted in an increasing proportion of elderly in society. Research groups around the world have investigated the contribution of gut microbial communities to human health and well-being. It was established that the microbiota composition of the human gut is modulated by lifestyle factors, especially diet. The microbiota composition and function, acting in concert with direct and indirect effects of habitual diet, is of great importance in remaining healthy and active. This is not a new concept, but until now the scale of the potential microbiota contribution was not appreciated. There are an estimated ten times more bacteria in an individual than human cells. The bacterial population is relatively stable in adults, but the age-related changes that occur later in life can have a negative impact on host health. This loss of the adult-associated microbiota correlates with measures of markers of inflammation, frailty, co-morbidity and nutritional status. This effect may be greater than that of diet or in some cases genetics alone. Collectively, the recent studies show the importance of the microbiota and associated metabolites in healthy aging and the importance of diet in its modulation.

Older people constitute a growing proportion of the worldwide population. Despite this, older people are often excluded from clinical research and are generally underrepresented in intervention studies. This severely restricts the ability to generalise outcomes from research involving younger populations, which may impact on the progression of knowledge and the development of best practice guidelines for the care of older people. This opinion piece outlines the challenges and practical difficulties experienced and overcome by the ELDERMET project. The ELDERMET project has recruited almost 500 subjects, aged 65 years and older, across a range of health states from the very frail to the very fit, half of whom have been studied at multiple time points. All ELDERMET subjects have participated in an extensive protocol and supplied multiple biological sample types. The challenges and obstacles faced by both researchers in recruiting older subjects and older people engaging with research and intervention studies are set out. Strategies are discussed for: the recruitment and retention of older subjects; recruiting subjects with physical or cognitive impairment; recruitment from specific locations; collecting accurate and robust data, particularly from subjects with mild to severe cognitive impairment; intervention product design, delivery and compliance. Practical and realistic solutions for maximising the engagement of older people with research and intervention studies are offered. The increased benefit brought by the generalisation and application of research and intervention outcomes to older populations is discussed. Copyright (c) 2012 S. Karger AG, Basel

The human intestinal microbiota has defined health-promoting properties. Alterations in the composition of the microbiota have been linked to common health problems, particularly at dynamic life stages such as older age. Environmental conditions, including diet, shape the composition of the intestinal microbiota. Recent studies have begun to link dietary intake with distinct microbiota compositional profiles and to link these profiles with health parameters in older populations. Defining the role of diet in supporting health-promoting microbiota profiles provides the foundation for the development of dietary interventions specifically targeted at sustaining health in older age.

OBJECTIVES The human intestinal microbiota composition alters naturally with age, but is unusually perturbed by antibiotic therapy. The impact of antibiotic therapy on the composition of the intestinal microbiota of a cross-section of elderly Irish subjects (n = 185, ≥ 65 years) was investigated, taking into consideration their residence location. METHODS Forty-two of the 185 elderly subjects were treated with at least one antibiotic within 1 month prior to faecal microbiota profiling. The residence locations of the subjects varied from long-term nursing care and rehabilitation wards to day hospitals and the community. RESULTS Culture-dependent methods indicated that faecal Bifidobacterium spp. numbers were significantly reduced following antibiotic treatment (P = 0.004, 7-fold reduction), while levels of Lactobacillus spp. and Enterobacteriaceae were unaffected. The largest decrease in Bifidobacterium spp. numbers was linked to the administration of nucleic acid synthesis inhibitors (P = 0.004, 23-fold reduction). Microbiota profiling revealed a significant compositional change across nine genera following antibiotic therapy, including a relative increase in Lactobacillus spp. (P = 0.031), as well as a decrease in the number of genera identified in the antibiotic-treated subjects (n = 58), when compared with untreated subjects (n = 79). More alterations in the intestinal microbiota were observed post-nucleic acid synthesis inhibitor therapy, most notably a decrease in relative Faecalibacterium spp. numbers (P < 0.001). CONCLUSIONS The impact of antibiotic therapy on the intestinal microbiota in the elderly should be considered for long-term health effects, and differential susceptibility may require the development of products (e.g. prebiotics and probiotics) for at-risk subjects.

Constipation is a common problem affecting many older people's quality of life. The aim of the study was to describe and compare the frequency of use of laxative medication in Irish adults, aged 65 years and older, from the community and a long-term care setting. Participants (n=207) were part of the Irish ELDERMET project. The project aims to find out how diet and lifestyle influence, and are influenced by, the bacteria in the gut, and how this knowledge can be used to promote health in older Irish people. It has recruited over 450 people, aged 65 and older, and will use the information gathered from the extensive proforma to develop recommendations, as well as functional foods/functional food ingredients specifically designed to promote and support health in older populations. Data were collected between June 2008 and April 2010 using a survey questionnaire. A quantitative descriptive correlational design was used. Analysis was conducted using PASW Statistics 18.0. Participants in long-term care received a greater number of both laxatives and prescribed medications than community-dwelling participants. Increased polypharmacy was also seen in participants taking laxatives, with participants in long-term care significantly (p<0.001) more likely to take multiple laxatives. Nurses are in a key position to develop proactive approaches to the prevention and treatment of constipation.

Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing.

The specific health benefits of probiotic supplementation in aging populations remain relatively undefined. Although some probiotic research performed to date has focused on specific populations – particular disease groups or those in dynamic life stages such as the very young and older adults – dedicated studies of older subjects with a typical range of age-related conditions are few. Published studies also feature a narrow range of probiotic strains. Exploitation of strain specificity to modulate the composition and function of the microbiota is crucial to maximize the potential benefit of probiotics. A combination of prebiotic (dietary) and probiotic agents may prove most effective in targeted modulation of the microbiota. The efficacy of specific probiotic strains in modulating the microbiota of older populations is worth pursuing, although the role of antibiotics and polypharmacy (use of multiple medications) in influencing the potential benefits of probiotic intervention requires more dedicated study.

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The composition of the dynamic infant microbiota is shaped by environmental factors that establish the basis of the microbiota of later life. They influence the composition of the stable adult microbiota and, later, the potential of the older microbiota to support health. Examining the role of the microbiota in maintaining and promoting health throughout life has been revolutionised by the relatively recent development of culture-independent methods for determining microbiota composition. Defining the composition of the human gut microbiota - from infancy to old age, provides the potential for its manipulation in the promotion and maintenance of health.

Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides , with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria , Actinobacteria , and Faecalibacteria . The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability.

Peak bone mass is a major determinant of osteoporosis risk in later life. It is under strong genetic control; however, little is known about the identity of the genes involved. In the present study, we investigated the relationship between polymorphisms in the genes encoding the vitamin D receptor (VDR) (FokI, TaqI) and estrogen receptor-α (ERα) (PvuII, XbaI), and bone mineral density (BMD), bone mineral content (BMC), and markers of bone turnover in 224 Danish girls aged 11–12 years. BMD and BMC were measured by dual-energy X-ray absorptiometry. Serum osteocalcin, 25(OH)D, and parathyroid hormone (PTH) were measured by ELISA assays and urinary pyridinium cross-links by HPLC. Physical activity, dietary calcium, and Tanner stage were assessed by questionnaire. In general, there were no significant differences in anthropometrical variables, physical activity, dietary calcium, serum 25(OH)D, or PTH among genotype groups. BMD or BMC of lumbar spine or whole body (adjusted for body and bone size and pubertal status) were not associated with VDR or ERα genotypes or the combination of these genotypes. This lack of association remained even after adjustment for dietary and environmental factors. VDR genotypes had no effect on bone turnover markers. XX and PP ERα genotypes were associated (P < 0.05) with reduced levels of urinary pyridinium cross-links, whereas serum osteocalcin was similar among genotypes. These findings suggest that the rate of bone resorption was influenced by ERα genotypes, even though these biochemical differences were not evident in bone mass indices.

Studies in experimental animals and murine osteoblast cells in culture have produced conflicting findings on the effect of conjugated linoleic acid (CLA) on bone formation. The present study investigated the influence of CLA on viability and metabolism of two human osteoblast-like cell lines (SaOS2 and MG63). Both cell lines were exposed to increasing concentrations (0–50μM) of CLA either as pure cis (c) 9: trans (t) 11 and t10:c12 CLA isomers or a blend of isomers, or linoleic acid (C18:2). Cell cytotoxicity and degree of DNA fragmentation were unaffected by any fatty acid treatment. PGE2 biosynthesis by both cell lines was variably reduced by CLA isomer blend and t10:c12 CLA, but not c9:t11 CLA. Alkaline phosphatase activity was variably increased by all CLA treatments. These results suggest a lack of cytotoxic effect of CLA on human osteoblast-like cells and tentatively suggest a possible beneficial effect on bone formation in humans.

Background Screening for sensorial impairment is a secondary objective in the context of neurodegenerative diseases, including dementias. For example, olfactory dysfunction is among the first signs of Alzheimer's disease. There has been no study of olfactory function in Irish subjects at risk of dementia.Aim To investigate olfactory function in non-demented Irish persons, who carry genetic risk factors for dementia.Methods Thirty-eight Irish adult subjects, who are at risk of dementia, were recruited. Cognitive performance and olfactory function were assessed and apolipoprotein E (APOE) genotype determined.Results Three and six subjects had a Mini Mental State Examination (MMSE) and Brief Smell Identification Test (B-SIT) score, respectively, outside the normal range. While five out of the fifteen epsilon-4 allele positive subjects had B-SIT scores outside the normal range, only one out of the twenty-three epsilon-4 allele negative subjects had; the difference in this frequency was significant (P=0.025). There was no significant difference (P=0.266) in the frequency of abnormal MMSE scores between epsilon-4 allele groups.Conclusion Further investigation is required to explore the reasons for the higher prevalence of olfactory dysfunction in epsilon-4 allele positive subjects.

Conjugated linoleic acid (CLA) increases paracellular permeability across human intestinal-like Caco-2 cell monolayers, which transport Ca predominantly by the transcellular route. In vivo, however, paracellular Ca transport is the predominant route of Ca transport. Therefore, the objective of this study was to investigate the effect of CLA on transepithelial Ca transport in Caco-2 cells transporting Ca predominantly by the paracellular route. Cells were seeded onto permeable transport membranes and allowed to differentiate, over 14d, into intestinal-like cell monolayers. Monolayers (n=9/treatment) were exposed to 0 (control) or 80μM- 18:2, -cis-9, trans-11 CLA or -trans-10, cis-12 CLA for 14d prior to Ca transport studies. Overall transepithelial Ca transport as well as transcellular and parcellular Ca transport was significantly increased (P<0.001) by exposure of Caco-2 cells to both isomers of CLA, an effect which appeared to be related to altered localization of zona occludens 1 (a tight junction protein).

The effect of polyunsaturated fatty acids (PUFA), in particular conjugated linoleic acid (CLA), on Ca and bone metabolism is unclear. In a 2 × 2 factorial design study, forty male 4-week-old rats were fed a control diet containing 70 g added fat (soyabean oil (SBO; n –6 PUFA-rich diet) or menhaden oil–safflower oil (MSO; n −3 PUFA-rich diet))/kg diet with 0 or 10 g CLA/kg for 8 weeks. Ex vivo prostaglandin E 2 biosynthesis by bone organ culture was significantly higher ( P <0·001) in rats consuming SBO compared with MSO, irrespective of CLA. Addition of the CLA treatment to either diet further lowered ( P <0·05) ex vivo prostaglandin E 2 production. Neither PUFA type nor CLA altered circulating or femoral mRNA levels of osteocalcin (a marker of bone formation) or insulin-like growth factor-I (a mediator of bone metabolism). While urinary pyridinium crosslinks levels (markers of bone resorption) were unaffected by CLA irrespective of PUFA type, they were significantly higher ( P <0·05) in rats consuming SBO compared with MSO irrespective of CLA. Net fractional (%) and absolute (mg) Ca absorption were significantly ( P <0·01 and P <0·05 respectively) higher in CLA-supplemented than unsupplemented animals fed on the n −3 PUFA-rich diet, whereas CLA had no effect in animals fed the n –6 PUFA-rich diet. There was no effect of CLA supplementation on bone mineral mass. In conclusion, CLA supplementation over 8 weeks appeared to enhance Ca absorption in young growing rats fed an n −3 PUFA-rich diet, but had no measurable effect on bone metabolism or bone mass over this time frame.

The beneficial effect of bovine whey protein (WP) on bone metabolism has been shown in adult human subjects and ovariectomised rats. However, its effect on bone formation in earlier life, particularly during periods of bone mineral accrual, has not been investigated. Twenty-one male rats (4 weeks old, Wistar strain) were randomised by weight into three groups of seven rats each and fed ad libitum on a semi-purified low-Ca diet (3.0 g Ca/kg diet) containing 0 (control), 10 (diet WP1) or 20 (diet WP2) g bovine WP/kg for 47 d. On day 34 of the dietary intervention, all rats had two gelatine capsules containing demineralised bone powder implanted subcutaneously in the thorax region (a well-established in vivo model of ectopic bone formation). At 14 d after implantation, alkaline phosphatase activity (reflective of bone formation) in the bone implants from animals fed WP1 and -2 diets was almost 2-fold (P<0.01) that of control animals. Insulin-like growth factor (IGF)-I mRNA levels were about 3-fold (P<0.05) higher in implants from animals fed the WP diets compared with those from control animals. Serum- and urine-based biomarkers of bone metabolism and bone mineral composition in intact femora were unaffected by WP supplementation. In conclusion, the present findings suggest that bovine WP can enhance the rate of ectopic bone formation in young growing rats fed a Ca-restricted diet. This effect may be mediated by an increased synthesis of IGF-I in growing bone. The effect of WP on bone formation warrants further investigation.

There is compelling evidence to suggest that both the development of bone to peak bone mass at maturity and subsequent loss depend on the interaction between genetic, hormonal, environmental and nutritional factors. The major part (≤80%) of the age-specific variation in bone turnover and bone density is genetically determined. However, the notion of genetic determinant is of little value unless the specific genes that are involved can be identified. Most work in this area of osteoporosis research has focused on the candidate gene approach, which has identified several candidate genes for osteoporosis, including genes encoding the vitamin D receptor (VDR), oestrogen receptors (α and β), apolipoprotein E, collagen type I α 1 and methylenetetrahydrofolate reductase, amongst many others. However, in general, findings from numerous studies of the association between such genes and various bone variables have been inconsistent. In addition to possible gene—gene interactions it is likely that there are interactions between these genes and certain environmental factors, especially nutrition, that may mediate expression of bone-related phenotypes. While these potential interactions add a level of complexity to our understanding of these apparent genetic effects on bone, identification of a role for genetic factors without knowledge of their interaction with nutrients can do little to advance prevention and treatment of osteoporosis. This information is especially important because, unlike genotype, diet and nutrition can be modified. The aim of the present review is to critically evaluate current knowledge relating to candidate genes for osteoporosis, with particular emphasis on their interaction with nutrients and dietary factors in determining bone health.