Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status : The NU-AGE 1-year dietary intervention across five European countries
Ghosh, Tarini Shankar ; Rampelli, Simone ; Jeffery, Ian B. ; Santoro, Aurelia ; Neto, Marta ; Capri, Miriam ; Giampieri, Enrico ; Jennings, Amy ; Candela, Marco ; Turroni, Silvia ; Zoetendal, Erwin G. ; Hermes, Gerben D.A. ; Elodie, Caumon ; Brugere, Corinne Malpuech ; Pujos-Guillot, Estelle ; Berendsen, Agnes M. ; Groot, Lisette C.P.G.M. De; Feskens, Edith J.M. ; Kaluza, Joanna ; Pietruszka, Barbara ; Bielak, Marta Jeruszka ; Comte, Blandine ; Maijo-Ferre, Monica ; Nicoletti, Claudio ; Vos, Willem M. de; Fairweather-Tait, Susan ; Cassidy, Aedin ; Brigidi, Patrizia ; Franceschi, Claudio ; O'Toole, Paul W. - \ 2020
Gut 69 (2020)7. - ISSN 0017-5749
ageing - diet - enteric bacterial microflora - inflammation - intestinal bacteria
Objective: Ageing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty. Design: We profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet). Results: Adherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks. Conclusion: Collectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.
A Novel Approach to Improve the Estimation of a Diet Adherence Considering Seasonality and Short Term Variability – The NU-AGE Mediterranean Diet Experience
Giampieri, Enrico ; Ostan, Rita ; Guidarelli, Giulia ; Salvioli, Stefano ; Berendsen, A.M. ; Brzozowska, Anna ; Pietruszka, Barbara ; Jennings, Amy ; Meunier, Nathalie ; Caumon, Elodie ; Fairweather-Tait, Susan J. ; Sicinska, Ewa ; Feskens, E.J.M. ; Groot, C.P.G.M. de; Franceschi, Claudio ; Santoro, Aurelia - \ 2019
Frontiers in Physiology 10 (2019). - ISSN 1664-042X
In this work we present a novel statistical approach to improve the assessment of the adherence to a 1-year nutritional intervention within the framework of the NU-AGE project. This was measured with a single adherence score based on 7-days food records, under limitations on the number of observations per subject and time frame of intervention. The results of the NU-AGE dietary intervention were summarized by variations of the NU-AGE index as described in the NU-AGE protocol. Food and nutrient intake of all participants was assessed by means of 7-days food records at recruitment and after 10 to 14 months of intervention (depending on the subject availability). Sixteen food groups and supplementations covering the dietary goals of the NU-AGE diet have been used to estimate the NU-AGE index before and after the intervention. The 7-days food record is a reliable tool to register food intakes, however, as with other tools used to assess lifestyle dietary compliance, it is affected by uncertainty in this estimation due to the possibility that the observed week is not fully representative of the entire intervention period. Also, due to logistic limitations, the effects of seasonality can never be completely removed. These variabilities, if not accounted for in the index estimation, will reduce the statistical power of the analyses. In this work we discuss a method to assess these uncertainties and thus improve the resulting NU-AGE index. The proposed method is based on Hierarchical Bayesian Models. This model explicitly includes country-specific averages of the NU-AGE index, index variation induced by the dietary intervention, and country based seasonality. This information is used to evaluate the NU-AGE index uncertainty and thus to estimate the “real” NU-AGE index for each subject, both before and after the intervention. These corrections reduce the possibility of misinterpreting measurement variability as real information, improving the power of the statistical tests that are performed with the resulting index. The results suggest that this method is able to reduce the short term and seasonal variability of the measured index in the context of multicenter dietary intervention trials. Using this method to estimate seasonality and variability would allow one to obtain better measurements from the subjects of a study, and be able to simplify the scheduling of diet assessments.
Gender-specific association of body composition with inflammatory and adipose-related markers in healthy elderly Europeans from the NU-AGE study
Santoro, Aurelia ; Guidarelli, Giulia ; Ostan, Rita ; Giampieri, Enrico ; Fabbri, Cristina ; Bertarelli, Claudia ; Nicoletti, Claudio ; Kadi, Fawzi ; Groot, Lisette C.P.G.M. De; Feskens, Edith ; Berendsen, Agnes ; Brzozowska, Anna ; Januszko, Olga ; Kozlowska, Katarzyna ; Fairweather-Tait, Susan ; Jennings, Amy ; Meunier, Nathalie ; Caumon, Elodie ; Napoli, Alessandro ; Mercatelli, Daniele ; Battista, Giuseppe ; Capri, Miriam ; Franceschi, Claudio ; Bazzocchi, Alberto - \ 2019
European Radiology 29 (2019)9. - ISSN 0938-7994 - p. 4968 - 4979.
ObjectivesThe aim of this work was to examine the cross-sectional relationship between body composition (BC) markers for adipose and lean tissue and bone mass, and a wide range of specific inflammatory and adipose-related markers in healthy elderly Europeans. Methods A whole-body dual-energy X-ray absorptiometry (DXA) scan was made in 1121 healthy (65–79 years) women and men from five European countries of the “New dietary strategies addressing the specific needs of elderly population for a healthy aging in Europe” project (NCT01754012) cohort to measure markers of adipose and lean tissue and bone mass. Pro-inflammatory (IL-6, IL-6Rα, TNF-α, TNF-R1, TNF-R2, pentraxin 3, CRP, alpha-1-acid glycoprotein, albumin) and anti-inflammatory (IL-10, TGF-β1) molecules as well as adipose-related markers such as leptin, adiponectin, ghrelin, and resistin were measured by magnetic bead-based multiplex-specific immunoassays and biochemical assays. Results BC characteristics were different in elderly women and men, and more favorable BC markers were associated with a better adipose-related inflammatory profile, with the exception of skeletal muscle mass index. No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-β1, TNF-α, IL-6Rα, glycoprotein 130, TNF-α-R1, and TNF-α-R2.Conclusions The association between BC and inflammatory and adipose-related biomarkers is crucial in decoding aging and pathophysiological processes, such as sarcopenia. DXA can help in understanding how the measurement of fat and muscle is important, making the way from research to clinical practice.
A Cross-Sectional Analysis of Body Composition Among Healthy Elderly From the European NU-AGE Study: Sex and Country Specific Features
Santoro, Aurelia ; Bazzocchi, Alberto ; Guidarelli, Giulia ; Ostan, Rita ; Giampieri, Enrico ; Mercatelli, Daniele ; Scurti, M. ; Berendsen, A.M. ; Surala, Olga ; Jennings, Amy ; Meunier, Nathalie ; Caumon, Elodie ; Gillings, Rachel ; Kadi, Fawzi ; Capel, Frederic ; Cashman, Kevin D. ; Pietruszka, Barbara ; Feskens, E.J.M. ; Groot, C.P.G.M. de; Battista, Giuseppe ; Salvioli, Stefano ; Franceschi, Claudio - \ 2018
Frontiers in Physiology 9 (2018). - ISSN 1664-042X - 16 p.
Body composition (BC) is an emerging important factor for the characterization of metabolic status. The assessment of BC has been studied in various populations and diseases such as obesity, diabetes, endocrine diseases as well as physiological and paraphysiological conditions such as growth and aging processes, and physical training. A gold standard technique for the assessment of human BC at molecular level is represented by dual-energy X-ray absorptiometry (DXA), which is able to precisely assess the body mass (and areal bone mineral density-aBMD) on a regional and whole-body basis. For the first time, within the framework of the NU-AGE project, BC has been assessed by means of a whole-body DXA scan in 1121 sex-balanced free-living, apparently healthy older adults aged 65–79 years enrolled in 5 European countries (Italy, France, United Kingdom, Netherlands, and Poland). The aim of this analysis is to provide a complete profile of BC in healthy elderly participants from five European countries and to investigate country- and sex-related differences by state-of-the-art DXA technology. To compare BC data collected in different centers, specific indexes and ratios have been used. Non-parametric statistical tests showed sex-specific significant differences in certain BC parameters. In particular, women have higher fat mass (FM) (Fat/Lean mass ratio: by 67%, p < 2.2e-16) and lower lean mass (Lean Mass index: by -18%, p < 2.2e-16) than men. On the other hand, men have higher android FM than women (Android/gynoid FM ratio: by 56%, p < 2.2e-16). Interesting differences also emerged among countries. Polish elderly have higher FM (Fat/Lean mass ratio: by 52%, p < 2.2e-16) and lower lean mass (Skeletal Mass index: by -23%, p < 2.2e-16) than elderly from the other four countries. At variance, French elderly show lower FM (Fat/Lean mass ratio: by -34%, p < 2.2e-16) and higher lean mass (Skeletal Mass index: by 18%, p < 2.2e-16). Moreover, five BC profiles in women and six in men have been identified by a cluster analysis based on BC parameters. Finally, these data can serve as reference for normative average and variability of BC in the elderly populations across Europe.
Cross-Sectional Analysis of the Correlation Between Daily Nutrient Intake Assessed by 7-Day Food Records and Biomarkers of Dietary Intake Among Participants of the NU-AGE Study
Ostan, Rita ; Guidarelli, Giulia ; Giampieri, Enrico ; Lanzarini, Catia ; Berendsen, Agnes A.M. ; Januszko, Olga ; Jennings, Amy ; Lyon, Noëlle ; Caumon, Elodie ; Gillings, Rachel ; Sicinska, Ewa ; Meunier, Nathalie ; Feskens, Edith J.M. ; Pietruszka, Barbara ; Groot, Lisette C.P.G.M. de; Fairweather-Tait, Susan ; Capri, Miriam ; Franceschi, Claudio ; Santoro, Aurelia - \ 2018
Frontiers in Physiology 9 (2018). - ISSN 1664-042X
Methods for measuring diet composition and quantifying nutrient intake with sufficient validity are essential to study the association between nutrition and health outcomes and risk of diseases. 7-day food records provides a quantification of food actually and currently consumed and is interesting for its use in intervention studies to monitor diet in a short-term period and to guide participants toward changing their intakes. The objective of this study is to analyze the correlation/association between the daily intake of selected nutrients (collected by a 7-day food records plus a mineral/vitamin supplementation questionnaire) and estimates of energy expenditure as well as blood and urine biomarkers of dietary intakes in 1,140 healthy elderly subjects (65–79 years) at baseline of the NU-AGE intervention study (NCT01754012, clinicaltrials.gov). The results show that: the daily intake of energy correlated significantly with predicted total energy expenditure (pTEE) (ρ = 0.459, p < 0.001, and q < 0.001); protein intake correlated significantly with the ratio of 24 h urinary urea to creatinine excretion (ρ = 0.143 for total protein intake, ρ = 0.296 for animal protein intake, and ρ = 0.359 for protein intake/body weight, p < 0.001 and q < 0.001 for each correlation); vitamin B12 and folate intakes correlated significantly with their serum concentrations (ρ = 0.151 and ρ = 0.363, respectively; p < 0.001 and q < 0.001 for each correlation); sodium and potassium intakes correlated significantly with their 24 h urinary excretion (ρ = 0.298 and ρ = 0.123, respectively; p < 0.001 and q < 0.001 for each correlation); vitamin B12 and folate intakes were negatively associated with plasma homocysteine measure (p = 0.001 and p = 0.004, respectively); stratifying subjects by gender, the correlations between energy intake and pTEE and between potassium intake and its 24 h urinary excretion lost their significance in women. Even if the plasma and urinary levels of these nutrients depend on several factors, the significant correlations between daily reported intake of nutrients (protein, vitamin B12, folate, and sodium) and their blood/urinary markers confirmed that the 7-day food records (plus a supplementation questionnaire) provides reliable data to evaluate short-term current dietary intake in European elderly subjects and it can be exploited to guide and monitor NU-AGE participants through the shift of their diet according NU-AGE recommendations.
The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: a systems biology approach
Viegas Calcada, D.I. ; Vianello, D. ; Giampieri, E. ; Sala, C. ; Castellani, G. ; Graaf, A. de; Kremer, B. ; Ommen, B. van; Feskens, E.J.M. ; Santoro, A. ; Franceschi, C. ; Bouwman, J. - \ 2014
Mechanisms of Ageing and Development 136-137 (2014). - ISSN 0047-6374 - p. 138 - 147.
nf-kappa-b - microarray experiment miame - minimum information - innate immunity - quantitative-analysis - interaction networks - insulin-resistance - cell biology - data sets - t-cells
Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabolic function. Systems biology has helped in identifying the mediators and pathways involved in these phenomena, mainly through the application of high-throughput screening methods, valued for their molecular comprehensiveness. Nevertheless, inflammation and metabolic regulation are dynamical processes whose behavior must be understood at multiple levels of biological organization (molecular, cellular, organ, and system levels) and on multiple time scales. Mathematical modeling of such behavior, with incorporation of mechanistic knowledge on interactions between inflammatory and metabolic mediators, may help in devising nutritional interventions capable of preventing, or ameliorating, the age-associated functional decline of the corresponding systems