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 mediterranean diet mix has chemopreventive effects in a murine model of colorectal cancer modulating apoptosis and the gut microbiota
Piazzi, Giulia ; Prossomariti, Anna ; Baldassarre, Maurizio ; Montagna, Claudio ; Vitaglione, Paola ; Fogliano, Vincenzo ; Biagi, Elena ; Candela, Marco ; Brigidi, Patrizia ; Balbi, Tiziana ; Munarini, Alessandra ; Belluzzi, Andrea ; Pariali, Milena ; Bazzoli, Franco ; Ricciardiello, Luigi - \ 2019
Frontiers in Oncology 9 (2019)MAR. - ISSN 2234-943X
Chemoprevention - Colorectal cancer - Mediterranean diet - Microbiota - Omega-3
Objectives: Unhealthy dietary patterns have been associated with colorectal cancer (CRC) onset while Mediterranean Diet (MD) has been proposed for CRC prevention. This study evaluated the effect of a Mediterranean Diet Mix (MD-MIX) on colonic tumors development in A/J mice fed a low-fat (LFD) or a high-fat western diet (HFWD), and injected with the procarcinogen azoxymethane (AOM). Materials and Methods: Forty A/J male mice were randomly assigned into four feeding arms (10 mice/arm; LFD, LFD-MD-MIX, HFWD, HFWD-MD-MIX) to be treated with AOM. Ten mice were exposed to the diets alone (Healthy LFD and Healthy HFWD) to be used as control. Tumor incidence and multiplicity were evaluated at sacrifice. Mucosal fatty acid content and urinary phenolic compounds were assayed by mass spectrometry. Apoptosis was evaluated by TUNEL assay and gene expression markers. Cell proliferation was evaluated by Ki67 immunohistochemistry. Microbiota composition was assessed at different time points by 16S RNA sequencing. Results: A tumor incidence of 100% was obtained in AOM-treated mice. The MD-MIX supplementation was able to reduce the number of colonic lesions in both LFD and HFWD-fed mice and to induce apoptosis, in particular in the LFD-MD-MIX arm. Moreover, a preventive effect on low-grade dysplasia and macroscopical lesions (>1 mm) development was found in HFWD-fed mice together with a regulation of the AOM-driven intestinal dysbiosis. Conclusions: MD-MIX was able to counteract CRC development in mice under different dietary backgrounds through the regulation of apoptosis and gut microbiota.
Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia in colitis-associated colorectal cancer acting on Notch signaling and gut microbiota
Piazzi, G. ; Argenio, G. D'; Prossomariti, A. ; Lembo, V. ; Mazzone, G. ; Candela, M. ; Biagi, E. ; Brigidi, P. ; Vitaglione, P. ; Fogliano, V. ; Angelo and others, L. D' - \ 2014
International Journal of Cancer 135 (2014)9. - ISSN 0020-7136 - p. 2004 - 2013.
inflammatory-bowel-disease - dietary fish-oil - intestinal microbiota - mouse model - docosahexaenoic acid - mice - sodium - cells - differentiation - chemoprevention
Inflammatory bowel diseases are associated with increased risk of developing colitis-associated colorectal cancer (CAC). Epidemiological data show that the consumption of ¿-3 polyunsaturated fatty acids (¿-3 PUFAs) decreases the risk of sporadic colorectal cancer (CRC). Importantly, recent data have shown that eicosapentaenoic acid-free fatty acid (EPA-FFA) reduces polyp formation and growth in models of familial adenomatous polyposis. However, the effects of dietary EPA-FFA are unknown in CAC. We tested the effectiveness of substituting EPA-FFA, for other dietary fats, in preventing inflammation and cancer in the AOM-DSS model of CAC. The AOM-DSS protocols were designed to evaluate the effect of EPA-FFA on both initiation and promotion of carcinogenesis. We found that EPA-FFA diet strongly decreased tumor multiplicity, incidence and maximum tumor size in the promotion and initiation arms. Moreover EPA–FFA, in particular in the initiation arm, led to reduced cell proliferation and nuclear ß-catenin expression, whilst it increased apoptosis. In both arms, EPA-FFA treatment led to increased membrane switch from ¿-6 to ¿-3 PUFAs and a concomitant reduction in PGE2 production. We observed no significant changes in intestinal inflammation between EPA-FFA treated arms and AOM-DSS controls. Importantly, we found that EPA-FFA treatment restored the loss of Notch signaling found in the AOM-DSS control and resulted in the enrichment of Lactobacillus species in the gut microbiota. Taken together, our data suggest that EPA-FFA is an excellent candidate for CRC chemoprevention in CAC.
Maintenance of a healthy trajectory of the intestinal microbiome during aging: A dietary approach
Candela, M. ; Biagi, E. ; Brigidi, P. ; O'Toole, P.W. ; Vos, W.M. de - \ 2014
Mechanisms of Ageing and Development 136-137 (2014). - ISSN 0047-6374 - p. 70 - 75.
gut microbiota - fecal microbiota - immune-system - elderly-patients - human longevity - age - disease - immunosenescence - intervention - enterotypes
Sharing an intense transgenomic metabolism with the host, the intestinal microbiota is an essential factor for several aspects of the human physiology. However, several age-related factors, such as changes diet, lifestyle, inflammation and frailty, force the deterioration of this intestinal microbiota-host mutualistic interaction, compromising the possibility to reach longevity. In this scenario, the NU-AGE project involves the development of dietary interventions specifically tailored to the maintenance of a healthy trajectory of the intestinal microbiome, counteracting all processes connected to the pathophysiology of the human aging
|Diet-microbiota-health interactions in older persons - the ELDERMET study and probing causality in the NuAge project
O'Toole, P.W. ; Vos, W.M. de; Brigidi, P. - \ 2013
In: 20th International Congress of Nutrition (ICN), Granada, Spain, 15 - 20 September, 2013. - Granada, Spain : Karger - p. 41 - 41.
Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians
Biagi, E. ; Nylund, L. ; Candela, M. ; Ostan, R. ; Bucci, L. ; Pini, E. ; Nikkïla, J. ; Monti, D. ; Satokari, R.M. ; Franceschi, C. ; Brigidi, P. ; Vos, W.M. de - \ 2010
PLoS ONE 5 (2010)5. - ISSN 1932-6203 - 14 p.
ribosomal-rna gene - real-time pcr - butyrate-producing bacteria - fecal microbiota - eubacterium-limosum - human feces - human longevity - human colon - t-cells - age
BACKGROUND: Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections. METHODOLOGY/PRINCIPAL FINDINGS: By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians. CONCLUSIONS/SIGNIFICANCE: We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population