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Relationship between Diet, Microbiota, and Healthy Aging

Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, CIBERFES-ISCIII, INCLIVA, 46010 Valencia, Spain
Department of Biomedical Sciences, Faculty of Health Sciences, Cardenal Herrera CEU University, 46115 Valencia, Spain
Freshage Research Group, Department of Physiotherapy, Faculty of Physiotherapy, University of Valencia, CIBERFES-ISCIII, INCLIVA, 46010 Valencia, Spain
Author to whom correspondence should be addressed.
Biomedicines 2020, 8(8), 287;
Received: 21 July 2020 / Revised: 4 August 2020 / Accepted: 6 August 2020 / Published: 14 August 2020


Due to medical advances and lifestyle changes, population life expectancy has increased. For this reason, it is important to achieve healthy aging by reducing the risk factors causing damage and pathologies associated with age. Through nutrition, one of the pillars of health, we are able to modify these factors through modulation of the intestinal microbiota. The Mediterranean and Oriental diets are proof of this, as well as the components present in them, such as fiber and polyphenols. These generate beneficial effects on the body thanks, in part, to their interaction with intestinal bacteria. Likewise, the low consumption of products with high fat content favors the state of the microbiota, contributing to the maintenance of good health.
Keywords: Mediterranean diet; Oriental diet; nutrition; polyphenols; microbiota; aging; health Mediterranean diet; Oriental diet; nutrition; polyphenols; microbiota; aging; health

1. Introduction

One of the most significant changes in today’s society is that the population is aging more slowly than in the past. We live longer; the majority of the population has a life expectancy of 60 years or more. According to data from the World Health Organization (WHO), the percentage of people over 60 years will be duplicated on a worldwide scale before 2050 [1]. In 2020 the number of people of more than 60 years of age has been reported to be higher than those under five years, and by 2050 the number of elderly adults requiring help with daily tasks will quadruplicate [2].
Advances in medicine and public health care, as well as lifestyle changes, have had positive effects on life expectancy, mortality rates, and chronic disease prevalence, thereby causing an aging of the population [3].
Whether or not the impact of these factors on society is positive depends on the health status of the elderly. Therefore, it is important to prevent diseases associated with age, such as diabetes and cardiovascular diseases, to promote an active aging of the population and maintain social, mental, and physical wellbeing. In this regard, three pillars of active aging have been postulated: Participation, health and security [4,5]. We will focus our study around health.
It is important to keep in mind that the risk factors causing age related diseases can be modified. One of the factors that can act upon the health pillar is nutrition [6]. What, when, and how much we eat affects the quality of life. A well-balanced diet can modulate the proliferation of specific bacteria within the gut microbiota, which has been related to an improved health status for the elderly.


In this century, research related to microbiota has increased due to two primary advances: The holobiont theory of evolution, and metagenomics. The former one plays an important role in the physiology of superior organisms, and the latter one allows for the identification of microorganisms without a need for cultivation. As a result of these advances and of the increasing interest in this field of study, the concept of the “intestinal–brain axis” was created, with a tight relation between the intestinal microbiota and neurodegenerative diseases such as Parkinson, Alzheimer, stroke, and epilepsy [7]. Actually, a study performed in mice proved the presence of bacteria in the brain of these mice [8]. Furthermore, Roberts et al. obtained a micrography of a human brain where bacteria were visible in all the cerebral blood vessels, proving the existence of a brain microbiota [9]. Further supporting the idea of the presence of bacteria in the brain, a study using epilepsy patients demonstrated a reduction of convulsion frequency by antibiotic treatment [10]. All these data suggest that there might be a brain microbiota, and by extrapolation a whole organism microbiota.
The gastrointestinal tract is colonized by a set of microorganisms that include not only bacteria but also viruses, fungi, and protozoa. Unlike other microorganisms, these are not identified as pathogens by our immune system, but rather coexist symbiotically with the enterocytes [11]. So far, it is known that its composition contains a total of 52 different phyla and up to 35,000 different bacterial species [12], the large majority being Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria (Figure 1).
It is worth mentioning that there are differences in composition and number depending on the location along the gastrointestinal tract such that at the stomach level they are estimated at a density of 102 bacteria/mL and in the colon at around 1011 bacteria/mL [14].
Originally, the intestinal microbiota is formed in the placenta, where there are low levels of non-pathogenic bacteria, the majority being Firmicutes and Bacteroidetes. After birth, the child’s intestine becomes rapidly colonized by the microbiota. Several studies show that this could already happen at the level of the uterus. Depending on whether the delivery is vaginal or by caesarean section, the intestine of the infant will be colonized by organisms from the maternal vagina or from the maternal skin flora. Another factor that influences the acquired microorganism is the type of diet the infant receives, breast milk or formula foods [11]. During the first three years of life, the child’s microbiota is unstable and has little diversity. After the third year it acquires a milieu similar to that of the adult stage. In the case of older adults (>65 years), the microbiota is characterized by a decrease in Firmicutes and Bifidobacterium, with diversity in the patterns of abundance for Clostridium [15]. In relation to centenarians, differences in the composition of the microbiota are also evident, especially at the level of the Firmicutes subgroups, with a decrease in Clostridium and an increase in Bacilli. In addition, it is enriched by the edge Proteobacteria. Thus, as we age, progressive changes are produced in the morphology and function of the microbiota. This could alter its diversity and provoke inflammatory and metabolic disruption, causing inflammatory diseases in the intestine, such as irritable bowel, obesity, etc. [16]. The relation Firmicutes/Bacteroidetes is altered when the Firmicutes proportion is augmented over Bacteroides and generates consequences such as those found in obesity. However, this association is still polemic and under investigation [17,18]. While, on a global level, the Firmicutes and Bacteroidetes seem to decrease, Clostridium is increased in elderly adults [19]. In the last years, bacteria of the Clostridium genera have provoked a big interest for their impact on morbidity and mortality in the older generation [20]. They can act as opportunistic pathogens and cause diseases like intoxication through alimentation, necrotizing enterocolitis, or necrotic enteritis [21]. Furthermore, their incidence is increasing, and they have become the most frequent cause for nosocomial diarrhea, which can lead to the production of toxic megacolon and sepsis, and even to death [22].
However, through nutrition we can modify the microbiota to maintain intestinal health by stimulating beneficial bacteria, such as the Bacteroidetes and Firmicutes in balanced proportions, and diminishing prejudicial bacteria like Clostridium [16,23]. Additionally, maintaining a healthy diet throughout a lifespan might be beneficial for healthy aging.

2. Interplay between Aging and Microbiota

The composition and function of the microbiota changes in individuals of advanced age (>65 years), as has been mentioned earlier. Between physiological changes and lifestyles associated with aging, we find a decrease in dentures, a reduction in digestion and absorption, changes in appetite due to medication, and changes in living conditions such as hospitalization or elderly residences [24]. These factors might be responsible for changes in alimentation habits, and thereby nutrition.
The mechanism by which the microbiota changes with age is not yet fully understood. Lifestyle changes, and particularly diet, play an important role. As aging is often accompanied by a reduction in quantity and variety of aliments containing fiber, it often leads to a risk of malnourishment [25].
Additionally, the microbiota can modulate changes in aging related to innate immunity, sarcopenia, and cognitive function, which are essential components of the frailty syndrome [26]. This syndrome, was defined for the first time by Linda Fried in 2004 as “the physiological state characterized by an increase in vulnerability to external aggressors, as the result of a decrease or deregulation of the physiological reserves of multiple systems, which causes difficulties in maintaining homeostasis” [27]. Recent studies have suggested that the loss of intestinal microbiota is more related to age associated frailty than to chronological age [28]. In this context, elderly people can experience comorbidity affecting the intestine and its bacteria.
In 2007, a study performed by the ELDERMET group in Cork, Ireland, proved the existence of a correlation between diet, the microbiota, and health in elderly volunteers. The microbiota in relation to aging was studied in both community and long-stay residential care elderly subjects. The first group showed a loss in bacterial diversity due to a higher intake of medication, and a recuperation of microbial diversity when reducing antibiotics, whereas the second group showed a loss in microbial components associated with bad health, and a gain in microbiota associated with aging. Therefore, the previous correlation can be used to measure the difference between elderly that live in elderly homes or rehabilitation centers and those who live by themselves in the long run [29]. Claesson et al. supported these findings on the relation between diet, microbiota, and health status. Through analysis of separated fecal microbiota composition, they showed that in 178 subjects of advanced age a change in diet associated with that found when moving to a care facility generated a change in the composition of intestinal bacteria significantly correlated with measures of frailty, comorbidity, nutritional status, and inflammatory markers [15].
The most noticeable changes in the intestinal microbiota are produced during the transition from adult to elderly. In comparison to younger individuals, a decrease in microbial diversity is observed, specifically in Bifidobacterium, Firmicutes, and Clostridium [15]. These changes in the microbiota associated to age are a factor of high relevance in several diseases, such as chronic inflammation, neurodegeneration, cognitive deterioration, frailty, and diabetes types 1 and 2 [30]. In regard to extreme longevity, the microbiota of centenarians differs from that of elderly adults. Bacteroidetes and Firmicutes dominate their intestinal microbiota, making up more than 93% of the overall bacteria flora. However, comparing to younger adults, specific changes in the subgroups of Firmicutes are observed: Clostridium is decreased, and Bacilli augmented. Moreover, the intestinal microbiota of centenarians in enriched in Proteobacteria, a group containing bacteria recently redefined as “pathobionts”, benign endogenous microbes which in dysbiosis can lead to pathologies [31,32].
Taken together, intestinal microbiota is subjected to constant changes throughout life and continues to change in old age and is closely linked to diet and health status, suggesting the possibility that microbial profiling may serve as a clinically useful biomarker in geriatric care. Predomination of one type of bacteria, or the over proliferation of bad bacteria upon good bacteria will have negative consequences. Thus, maintaining intestinal microbiota diversity seems to be a key point when seeking geriatric health [33]. Figure 2 shows microbiota evolution through aging.

3. The Influence of Nutrition on the Microbiota and Aging

In this paragraph, we will comment on the two diets that are the most associated with healthy aging: the Mediterranean and the Oriental diets.

3.1. The Mediterranean Diet

The Mediterranean diet (MD) is characterized by a high daily consumption of fruits and vegetables, whole grains and legumes, and a lower consumption of meat, fish, and lactose-rich products. Additionally, it is also associated with olive oil as the major source of fats, and moderate intake of red wine [34,35,36].
It has been shown that following an MD can have multiple benefits as it delays the appearance of chronic diseases associated with age such as cancer, diabetes type 2, and neurodegenerative diseases [36,37,38]. Furthermore, recent data suggest that the MD promotes beneficial effects on the intestinal microbiota, favoring the diversity of the colon microbiota by increasing Bacteroidetes and Firmicutes and reducing Clostridium [37]. Another study carried out on 27 healthy subjects, who were monitored for MD compounds, showed how MD eating habits modified the composition and diversity of the microbiota. More specifically, they observed an increase in Bacteroidetes and a higher Bacteroidetes/Firmicutes ratio. This modification of the different microbiota populations has proven to exert anti-inflammatory effects. Accordingly, how MD can decrease the transcription factor E2F1 in colon cancer cells in order to decrease the proliferation of these cells has been studied. Additionally, it activates factors with protective effects against oxidative stress such as the transcription factor NRF2 [39,40].
Other studies support the beneficial effects of MD on cardiovascular diseases [39,41,42,43,44]. In one of these, low levels of triglycerides, high HDL cholesterol levels, and lower arterial pressures were found in those following the MD in comparison to a control group consuming a low-fat diet [43]. In the “Lyon Diet Study”, the risk of severe cardiovascular events was reduced by 76% in the MD group. Additionally, a multicenter randomized study in Spain obtained similar results [44]. Moreover, how the risk of several types of cancer is decreased has also been studied, although the underlying mechanisms are still not clear [45,46]. This is reflected in the 605 patient cohort participating in the Lyon Heart Study, where the cancer risk decreased by 61% in the MD group in comparison to the control group [47]. One of the components of the MD is hydroxityrosol, a compound present in olive oil with antioxidant properties. It has been demonstrated that it reduces proliferation and induces apoptosis of certain cancer cells in the colon [48,49], prostate [50], and pancreas [51]. Furthermore, a clinical trial performed in Spain showed that the combination of the nutrients related to MD reduced pain and the inflammatory marker C-reactive in patients with breast cancer [52,53]. Likewise, various studies have analyzed the correlation between MD and diabetes type 2. MD has been seen to attenuate the augmentation of postprandial glycemia, reduce high peaks of insulin secretion, as well as diminish hyperlipidemia in patients with type 2 diabetes [54]. The PREDIMEM study “Prevention with the Mediterranean Diet” found that a bigger adherence to MD was inversely associated with the incidence of type 2 diabetes, which was reduced by 52% in the MD group compared to the control group [55]. In relation to neurodegenerative diseases, a high adherence to MD has been associated with improved cognitive function and lower risk of dementia [56,57,58,59]. However, many of these studies are observational, and can therefore not display a cause–effect relation. Moreover, other studies confirm the improvement in cognitive function in comparison to low-fat diet groups [47,60,61].
As we have previously described, MD reduces the risk of several diseases associated with aging. Furthermore, many studies demonstrate that MD promotes changes in the intestinal microbiota associated with healthy beneficial bacteria [34,37,39]. Consequently, the manipulation of the microbiota through MD should improve or benefit the treatment of these diseases [62,63,64,65]. However, the mechanisms through which MD promotes healthy changes on the intestinal microbiota are still not completely known.

3.2. The Oriental Diet

The Oriental Diet (OD) is well known for its health benefits. It has been demonstrated that the population following this diet has a longer lifespan, to the point where Japan has become one of the countries with the highest life expectancy rate. In addition to the long lifespan, the diet is also associated with a long health span. In the OD, one of the most common aliments is soy.
It is known that soy consumption has positive effects on the organism due to its ability to increase intestinal bacteria diversity. Tamura et al. divided rats in three groups based on diet for a two week period. The different diets were enriched either with casein protein, soy protein, or soy protein and high fat. After studying the microbiota through genes of 16S rRNA of feces, they were able to see how soy protein induced a bigger variety in intestinal bacteria, which is associated with a healthy microflora. Specifically, they observed an increase in Bacteroidetes and Proteobacteria, as well as in Bifidobacterium and Enterococcus. On the other hand, they also addressed a decrease in Firmicutes and Lactococcus [66].
Soy contains a variety of polyphenols, genistein being one of them. Of all groups of polyphenols (stilbene, ligand, alcoholic polyphenols, etc.), genistein is an isoflavone, the structure of which is similar to that of estrogen, and is therefore also classified as a phytoestrogen [67]. Genistein is found almost exclusively in legumes, such as chickpeas and peas, and majorly in soy and its derivatives [68].
It has been observed that genistein consumption can have multiple benefits, within these the promotion of cardiovascular health, and thereby flexibility of blood vessels and reduction in cholesterol concentration [69]. As with many polyphenols, it is transformed and modified by the microbiota to enable its actions in the organism. It interacts with estrogenic receptors to alleviate symptoms associated with menopause, hot flashes, and osteoporosis, as well as exerting antiaromatase activity, which is key in the protection against breast cancer [70]. Several studies performed on rats have shown how the administration of genistein at early age counteracts dysbiosis in the intestinal microbiota provoked by a high fat diet [71]. These data are supported by research by Zhou et al. where they observed beneficial bacteria proliferation through perinatal supplementation [72]. López et al. also found that genistein can regulate the intestinal microbiota by reducing metabolic endotoxemia and the neuroinflammatory response to a high fat diet [73]. Additionally, genistein has antioxidative effects, as it blocks the formation of free radicals, hydrogen peroxide, and superoxide anion, and by overexpressing antioxidant enzymes [74]. Through these effects, it also has protective effects against ischemic stroke and neuroprotective effects against Alzheimer Disease by reducing the hyperphosphorylation of Tau protein [75,76]. Lastly, it has anti-inflammatory and antitumoral effects through its ability to inhibit key enzymes in the appearance and progression of tumors. It also regulates the tumoral microenvironment, causing a higher sensitivity to therapies by modulating the production of cytokines and chemokines, and activating immune cells [77,78].
Another polyphenol present in soy is daidzein; similarly to genistein, it is modified and transformed by the microbiota to equol, a compound with anti-inflammatory and anticarcinogenic properties. This has been demonstrated in several studies where it has been shown how daidzein inhibits the production of IL-2 and how the proliferation of tumoral cells in breast cancer is regulated by the blockage of PI3K/AKT [79]. Furthermore, it has been determined that equol protects β-pancreatic cells against streptozotocin-induced diabetes in rats [80].
Curcumin, a polyphenol found in turmeric root, is also abundantly present in OD. It has proven to be capable of exerting anti-inflammatory and anti-tumor effects, among others [81,82]. Regarding its role in the microbiota, it has been seen to directly modify it. Since its absorption and bioavailability is low, it can be found in significant amounts in the gastrointestinal tract after its consumption. In fact, curcumin administration considerably changed the relationship between beneficial and pathogenic bacteria by increasing the abundance of Bifidobacteria and Lactobacili and reducing the loads of Prevotellaceae, Choriobacteria, Enterobacteriaceae, and Enterococci [83].
Thereby, the OD reduces the risk of several diseases associated with aging. Additionally, numerous studies have shown how following an OD has positive effects on the microbiota by increasing the number of beneficial bacteria. However, as with the MD, the mechanisms by which this diet promotes healthy changes in the intestinal microbiota are still not fully known.

3.3. Effects on the Microbiota by Compounds Present in Diet: Fiber, Fats, and Polyphenols

As we have previously described, Mediterranean and Oriental diets have modulatory effects on intestinal microbiota. These diets include a wide variety of nutrients in balanced proportions that promote gut bacteria diversification and thus a healthy microflora. While practically all compounds we ingest through diet can have effects on the microbiota, in this review we will only focus on food compounds that are similar in the two diets, which include a high consumption of polyphenols and fibers, and a higher proportion of unsaturated fats (Table 1).
In the upcoming paragraphs, we will discuss in depth the beneficial effects of each one of these compounds.

3.3.1. Fibers

Diets rich in fibers such as, β-glucan, arabinoxylan, galactomannan, and pectines facilitate weight control, decrease systemic inflammation, and are fundamental in the maintenance of intestinal health by supplementing substrates for the health promoting bacteria (Bifidobacterium and Lactobacillus) [84].
Studies have shown that a diet rich in fiber generates beneficial effects for elderly adults, especially on the cardiovascular system. Fiber-rich diets reduce the risks for cardiovascular disease, such as obesity, diabetes, and hypertension. The inverse correlation between high consumption of fiber and weight gain risk has been demonstrated [38]. Additionally, fiber seems to have a positive impact on the composition of the intestinal microbiota, augmenting the number of beneficial bacteria, inhibiting the growth of pathogens, and reducing atherogenic serum cholesterol in the microbiome. Furthermore, it prohibits the intolerance to glucose by reducing postprandial hyperglycemia through the formation of a viscous layer around the small intestine, thereby slowing down the chyme transition. This in turn augments the thickness of the aqueous layer where solutes must pass to reach the enterocytic membrane, causing a decrease in glucose, lipids, and amino acid absorption. As a result, less biliary acids are absorbed, and in turn cholesterol levels are decreased, which employs the synthesis of new biliary acids [85].
In this manner, a high consumption of soluble and insoluble fibers is associated with lower risk of stroke, as shown in a study performed over 12 years [86]. Another study demonstrated that the ingestion of total fiber, cereal fiber, and vegetable fiber was associated with a lower risk of hypertension [87]. Not only that, a study about the association between ingested fiber in the diet per 1000 kcal and leucocyte telomere length showed that adults consuming high quantities of fiber had longer telomeres, which suggests that biological aging was significatively lower [88].
In conclusion, a diet rich in fiber facilitates the presence of beneficial intestinal bacteria, and thereby lowers the risk of diseases in elderly adults, leading to healthy aging.

3.3.2. Fats

Classic epidemiologic studies have demonstrated the relation between diets with a high content of saturated fats, and a higher risk of age-related diseases [89,90].
Studies with animals have shown that a high fat diet can determine the microbiome composition and affect the proportion of various families of bacteria in the intestine. In particular, rats that received a high fat diet showed a lower number of Bacteroidetes and a higher number of Firmicutes and Proteobacteria, which is a characteristic of obesity [91]. This change in the microbiota composition could occur rapidly. For example, the change from a diet poor in saturated fats and rich in vegetal polysaccharides to a diet high in fats and sugars changes the structure of the microbiota in one single day. Additionally, a diet high in saturated fats is related to increased risk of chronic diseases, such as metabolic syndrome, hypertension, and atherosclerosis due to the alterations of the microbiota [92,93,94].
More importantly, if we compare humans with two different diets, it is clear that the microbiome diversity in our intestines is affected by what we eat. An example of this is the proportion of Bacteroidetes/Firmicutes which was much higher in African children compared to Italian, as they follow a diet of less fats and sugars [95]. This is further confirmed in a study by Wan et al. where they showed that healthy young adults consuming high quantities of fats had adverse effects on the intestinal microbiota, fecal metabolites, and plasmatic proinflammatory factors derived from the intestine, which could serve as potential factors to modify long term health [96].
In conclusion, it is clear that fiber has a protective effect in the elderly, especially at the cardiovascular level, and can contribute to healthier biological aging, whereas a diet high in fats induces a dysbiosis which can trigger metabolic alterations associated with chronic diseases and those related to age. Additionally, it has also been shown to have protective effects in younger individuals.

3.3.3. Polyphenols

Polyphenols, which have been mentioned earlier in this review, can reach the intestinal microbiota and thereby modify the molecule itself, the metabolism of the bacteria, and the intestinal flora population. This seems to have beneficial effects, including anticarcinogen, anti-inflammatory, and antioxidant properties [97].
For example, ellagitannins are polyphenols present in walnuts, pomegranates, and raspberries, which, when in the intestine, are modified by the microbiota and transformed into different compounds. Urolithin is one of the most widely studied products, and it has been demonstrated that it can be absorbed through enterohepatic circulation and that it can be transported in blood, and thereby be distributed to different tissues and exert diverse actions. It possesses anticancer effects through the inhibition of the Wnt signalization pathway, which could have a protective effect against colon cancer [98]. It has also been attributed anti-inflammatory properties as it inhibits the formation of proinflammatory compounds, such as cyclooxygenase-2 (COX-2), prostaglandin synthase E (PGSE), and prostaglandin E2 (PGE2) [99]. An important finding in this regard was made by Selma MV et al. in 2014, when they discovered a new species of bacteria in the microbiota responsible for the synthesis of urolithin from ellagic acid, which is formed in the stomach, that they denominated Gordonibacter urolithinfaciens [100]. However, the metabolites obtained from polyphenols through diet vary between individuals depending on the microbiota. In fact, certain individuals do not synthesize urolithin at all after the ingestion of its precursors [100].
Other polyphenols, such as resveratrol and curcumin, exert specific changes on the intestinal microflora. Concretely, in a study where rats were administrated these two polyphenols, they observed alterations in the bacteria groups Bacteroidetes and Clostridium. This in turn provided metabolic benefits in these individuals such as glycemic control [101].
On the other hand, there are polyphenols, such as quercetin, caffeic acid, and rutin, that affect the fermentation balance between the principal groups of intestinal bacteria that influence health by proliferating Bifidobacterium and diminishing Bacteroidetes and Firmicutes. Additionally, these polyphenols stimulate the production of short chain fatty acids through these bacteria [102].
These findings indicate that there are specific populations of bacteria capable of synthesizing final products such as urolithin and equol. The population of these bacteria in individuals is heterogenous, meaning the bacteria population present in the microbiota in each individual is a personal characteristic trait.

4. Conclusions

Life expectancy is increasing considerably, directing us towards a model of an aging society, and it is therefore necessary to expand our knowledge on the effects of aging. Taking into account all repercussions on the intestinal microbiota, to study the role of the microbiota is an interesting path, as well as the potential benefits that can be achieved through diet. Through dietary interventions many diseases associated with age such as cardiovascular and neurodegenerative diseases, diabetes, chronic inflammation, and cancer risk could be prevented.
Therefore, it is important to continue researching different nutritional approaches to fight physiological damages that are produced in an organism by aging. In particular, chronic factors present in advanced stages of life, such as inflammation and oxidative stress, must be considered, as these factors can be diminished or augmented depending on the consumed diet.

Author Contributions

Conceptualization, J.G., E.S.-M. and C.M.-B.; methodology, L.G.-M., J.S.-R. and A.R.-D. software, S.P.-P. and M.I.; formal analysis, K.S. and J.G.; investigation, G.O., K.S., C.M.-B. and L.G.-M.; resources, J.G.; writing—original draft preparation, J.G., K.S. and C.M.-B.; writing—review and editing, E.S.-M., M.I., K.S. and J.G.; visualization, J.G., G.O. and L.G.-M.; supervision, J.G. and C.M.-B.; All authors have read and agreed to the published version of the manuscript


This work was supported by FEDER [PIE15/00013], SAF2016-75508-R (Ministerio de 281 Economía y Competitividad), CB16/10/00435 (CIBERFES-ISCIII), PROMETEOII2014/056 282 (Conselleria de Educación, Investigación, Cultura y Deporte), The FRAILOMIC Initiative 283 (FP7-HEALTH-2012-Proposal no. 305483-2), ADVANTAGE-724099 (HP-JA) – DIALBFRAIL284 LATAM (825546 H2020-SC1-BHC) and GV/2019/092 from “Conselleria d’Educació, Cultura i Esport de la Generalitat Valenciana” to C.M.-B. Finally, Dr. C.M.-B. is recipient of a postdoctoral grant financed by Generalitat Valenciana (APOSTD/2018/230) and FSE (European Social Fund).

Conflicts of Interest

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript or in the decision to publish the results.


  1. World Health Organization. 10 Datos Sobre el Envejecimiento y la Salud. Available online: (accessed on 6 November 2019).
  2. World Health Organization. Envejecimiento y Salud. Available online: (accessed on 6 November 2019).
  3. Arc-Chagnaud, C.; Millan, F.; Salvador-Pascual, A.; Correas, A.G.; Olaso-Gonzalez, G.; De la Rosa, A.; Carretero, A.; Gomez-Cabrera, M.C.; Viña, J. Reversal of age-associated frailty by controlled physical exercise: The pre-clinical and clinical evidences. Sports Med. Health Sci. 2019, 1, 33–39. [Google Scholar] [CrossRef]
  4. Limón-Mendizábal, M.R.; Ortega Navas, M.C. Envejecimiento activo y mejora de la calidad de vida en adultos mayores. Rev. Psicol. Educ. 2011, 1, 225–238. [Google Scholar]
  5. Caballero-García, J.C. Aspectos generales de envejecimiento normal y patológico. In Terapia Ocupacional en Geriatría: Principios y Práctica; Elsevier Masson: Paris, France, 2010; pp. 41–60. [Google Scholar]
  6. Vaiserman, A.M.; Koliada, A.K.; Marotta, F. Gut microbiota: A player in aging and a target for anti-aging intervention. Ageing Res. Rev. 2017, 35, 36–45. [Google Scholar] [CrossRef] [PubMed]
  7. Castillo-Álvarez, F.; Marzo-Sola, M.E. Role of the gut microbiota in the development of various neurological diseases. Neurologia 2019. [Google Scholar] [CrossRef]
  8. Graham, F. Daily briefing: Hints of a microbiome in the brain. Gut bacteria might also live in our brain, new technique that turns mice transparent and mental-health first aid in the lab. Nature Briefing. 13 November 2018. Available online: (accessed on 6 November 2019).
  9. Servick, K. Do gut bacteria make a second home in our brains? Science 2018. [Google Scholar] [CrossRef]
  10. Braakman, H.M.H.; van Ingen, J. Can epilepsy be treated by antibiotics? J. Neurol. 2018, 265, 1934–1936. [Google Scholar] [CrossRef]
  11. Jandhyala, S.M.; Talukdar, R.; Subramanyam, C.; Vuyyuru, H.; Sasikala, M.; Nageshwar Reddy, D. Role of the normal gut microbiota. World J. Gastroenterol. 2015, 21, 8787–8803. [Google Scholar] [CrossRef]
  12. Frank, D.N.; St Amand, A.L.; Feldman, R.A.; Boedeker, E.C.; Harpaz, N.; Pace, N.R. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc. Natl. Acad. Sci. USA 2007, 104, 13780–13785. [Google Scholar] [CrossRef][Green Version]
  13. Unger, S.; Stintzi, A.; Shah, P.; Mack, D.; O’Connor, D.L. Gut microbiota of the very-low-birth-weight infant. Pediatr. Res. 2015, 77, 205–213. [Google Scholar] [CrossRef][Green Version]
  14. Tsai, Y.L.; Lin, T.L.; Chang, C.J.; Wu, T.R.; Lai, W.F.; Lu, C.C.; Lai, H.C. Probiotics, prebiotics and amelioration of diseases. J. Biomed. Sci. 2019, 26, 3. [Google Scholar] [CrossRef]
  15. Claesson, M.J.; Cusack, S.; O’Sullivan, O.; Greene-Diniz, R.; de Weerd, H.; Flannery, E.; Marchesi, J.R.; Falush, D.; Dinan, T.; Fitzgerald, G.; et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc. Natl. Acad. Sci. USA 2011, 108, 4586–4591. [Google Scholar] [CrossRef] [PubMed][Green Version]
  16. Power, S.E.; O’Toole, P.W.; Stanton, C.; Ross, R.P.; Fitzgerald, G.F. Intestinal microbiota, diet and health. Br. J. Nutr. 2014, 111, 387–402. [Google Scholar] [CrossRef]
  17. Cigarran Guldris, S.; González Parra, E.; Cases Amenós, A. Gut microbiota in chronic kidney disease. Nefrologia 2017, 37, 9–19. [Google Scholar] [CrossRef] [PubMed][Green Version]
  18. Arias, A.; Mach, N. Efecto de los probióticos en el control de la obesidad en humanos: Hipótesis no demostradas. Rev. Española Nutr. Hum. Dietética 2012, 16, 100–107. [Google Scholar] [CrossRef][Green Version]
  19. Ribera Casado, J.M. Intestinal microbiota and ageing: A new intervention route? Rev. Esp. Geriatr. Gerontol. 2016, 51, 290–295. [Google Scholar] [CrossRef] [PubMed]
  20. Morosini, M.I.; Cercenado, E.; Ardanuy, C.; Torres, C. Phenotypic detection of resistance mechanisms in gram-positive bacteria. Enferm. Infecc. Microbiol. Clin. 2012, 30, 325–332. [Google Scholar] [CrossRef]
  21. Morris, W.E.; Fernández-Miyakawa, M.E. Toxins of Clostridium perfringens. Rev. Argent. Microbiol. 2009, 41, 251–260. [Google Scholar]
  22. Monge, D.; Morosini, M.; Millán, I.; Pérez Canosa, C.; Manso, M.; Guzman, M.F.; Asensio, A. Risk factors for Clostridium difficile infections in hospitalized patients. Med. Clin. 2011, 137, 575–580. [Google Scholar] [CrossRef]
  23. Cardona, F.; Andrés-Lacueva, C.; Tulipani, S.; Tinahones, F.J.; Queipo-Ortuño, M.I. Benefits of polyphenols on gut microbiota and implications in human health. J. Nutr. Biochem. 2013, 24, 1415–1422. [Google Scholar] [CrossRef][Green Version]
  24. O’Toole, P.W.; Jeffery, I.B. Gut microbiota and aging. Science 2015, 350, 1214–1215. [Google Scholar] [CrossRef]
  25. Alang, N.; Kelly, C.R. Weight gain after fecal microbiota transplantation. Open Forum Infect. Dis. 2015, 2. [Google Scholar] [CrossRef] [PubMed]
  26. Mills, S.; Stanton, C.; Lane, J.A.; Smith, G.J.; Ross, R.P. Precision Nutrition and the Microbiome, Part I: Current State of the Science. Nutrients 2019, 11, 923. [Google Scholar] [CrossRef] [PubMed][Green Version]
  27. Fried, L.P.; Ferrucci, L.; Darer, J.; Williamson, J.D.; Anderson, G. Untangling the concepts of disability, frailty, and comorbidity: Implications for improved targeting and care. J. Gerontol. A Biol. Sci. Med. Sci. 2004, 59, 255–263. [Google Scholar] [CrossRef] [PubMed][Green Version]
  28. Rondanelli, M.; Giacosa, A.; Faliva, M.A.; Perna, S.; Allieri, F.; Castellazzi, A.M. Review on microbiota and effectiveness of probiotics use in older. World J. Clin. Cases 2015, 3, 156–162. [Google Scholar] [CrossRef]
  29. Jeffery, I.B.; Lynch, D.B.; O’Toole, P.W. Composition and temporal stability of the gut microbiota in older persons. ISME J. 2016, 10, 170–182. [Google Scholar] [CrossRef] [PubMed][Green Version]
  30. Claesson, M.J.; Jeffery, I.B.; Conde, S.; Power, S.E.; O’Connor, E.M.; Cusack, S.; Harris, H.M.; Coakley, M.; Lakshminarayanan, B.; O’Sullivan, O.; et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 2012, 488, 178–184. [Google Scholar] [CrossRef] [PubMed]
  31. Nagpal, R.; Mainali, R.; Ahmadi, S.; Wang, S.; Singh, R.; Kavanagh, K.; Kitzman, D.W.; Kushugulova, A.; Marotta, F.; Yadav, H. Gut microbiome and aging: Physiological and mechanistic insights. Nutr. Healthy Aging 2018, 4, 267–285. [Google Scholar] [CrossRef][Green Version]
  32. Sebastián Domingo, J.J.; Sánchez Sánchez, C. From the intestinal flora to the microbiome. Rev. Esp. Enferm. Dig. 2018, 110, 51–56. [Google Scholar] [CrossRef][Green Version]
  33. Kostic, A.D.; Howitt, M.R.; Garrett, W.S. Exploring host-microbiota interactions in animal models and humans. Genes Dev. 2013, 27, 701–718. [Google Scholar] [CrossRef][Green Version]
  34. Biagi, E.; Nylund, L.; Candela, M.; Ostan, R.; Bucci, L.; Pini, E.; Nikkïla, J.; Monti, D.; Satokari, R.; Franceschi, C.; et al. Through ageing, and beyond: Gut microbiota and inflammatory status in seniors and centenarians. PLoS ONE 2010, 5, e10667. [Google Scholar] [CrossRef]
  35. Del Chierico, F.; Vernocchi, P.; Dallapiccola, B.; Putignani, L. Mediterranean diet and health: Food effects on gut microbiota and disease control. Int. J. Mol. Sci. 2014, 15, 11678–11699. [Google Scholar] [CrossRef]
  36. Huhn, S.; Kharabian Masouleh, S.; Stumvoll, M.; Villringer, A.; Witte, A.V. Components of a Mediterranean diet and their impact on cognitive functions in aging. Front. Aging Neurosci. 2015, 7, 132. [Google Scholar] [CrossRef][Green Version]
  37. Tosti, V.; Bertozzi, B.; Fontana, L. Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms. J. Gerontol. A Biol. Sci. Med. Sci. 2018, 73, 318–326. [Google Scholar] [CrossRef][Green Version]
  38. Franceschi, C.; Ostan, R.; Santoro, A. Nutrition and Inflammation: Are Centenarians Similar to Individuals on Calorie-Restricted Diets? Annu. Rev. Nutr. 2018, 38, 329–356. [Google Scholar] [CrossRef][Green Version]
  39. De Pablos, R.M.; Espinosa-Oliva, A.M.; Hornedo-Ortega, R.; Cano, M.; Arguelles, S. Hydroxytyrosol protects from aging process via AMPK and autophagy; a review of its effects on cancer, metabolic syndrome, osteoporosis, immune-mediated and neurodegenerative diseases. Pharmacol. Res. 2019, 143, 58–72. [Google Scholar] [CrossRef]
  40. Ortega, R.M.; Aparicio Vizuete, A.; Jiménez Ortega, A.I.; Rodríguez Rodríguez, E. Wholegrain cereals and sanitary benefits. Nutr. Hosp. 2015, 32, 25–31. [Google Scholar] [CrossRef]
  41. De Filippis, F.; Pellegrini, N.; Vannini, L.; Jeffery, I.B.; La Storia, A.; Laghi, L.; Serrazanetti, D.I.; Di Cagno, R.; Ferrocino, I.; Lazzi, C.; et al. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut 2016, 65, 1812–1821. [Google Scholar] [CrossRef]
  42. Estruch, R.; Ros, E.; Salas-Salvadó, J.; Covas, M.I.; Corella, D.; Arós, F.; Gómez-Gracia, E.; Ruiz-Gutiérrez, V.; Fiol, M.; Lapetra, J.; et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N. Engl. J. Med. 2018, 378, e34. [Google Scholar] [CrossRef]
  43. De Lorgeril, M.; Salen, P.; Martin, J.L.; Monjaud, I.; Delaye, J.; Mamelle, N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: Final report of the Lyon Diet Heart Study. Circulation 1999, 99, 779–785. [Google Scholar] [CrossRef]
  44. Wade, A.T.; Davis, C.R.; Dyer, K.A.; Hodgson, J.M.; Woodman, R.J.; Keage, H.A.D.; Murphy, K.J. A Mediterranean Diet with Fresh, Lean Pork Improves Processing Speed and Mood: Cognitive Findings from the MedPork Randomised Controlled Trial. Nutrients 2019, 11, 1521. [Google Scholar] [CrossRef][Green Version]
  45. De Lorgeril, M.; Salen, P.; Martin, J.L.; Mamelle, N.; Monjaud, I.; Touboul, P.; Delaye, J. Effect of a mediterranean type of diet on the rate of cardiovascular complications in patients with coronary artery disease. Insights into the cardioprotective effect of certain nutriments. J. Am. Coll. Cardiol. 1996, 28, 1103–1108. [Google Scholar] [CrossRef]
  46. Ostan, R.; Lanzarini, C.; Pini, E.; Scurti, M.; Vianello, D.; Bertarelli, C.; Fabbri, C.; Izzi, M.; Palmas, G.; Biondi, F.; et al. Inflammaging and cancer: A challenge for the Mediterranean diet. Nutrients 2015, 7, 2589–2621. [Google Scholar] [CrossRef][Green Version]
  47. Willis, A.; Greene, M.; Braxton-lloyd, K. An Experimental Study of a Mediterranean-style Diet Supplemented with Nuts and Extra-virgin Olive Oil for Cardiovascular Disease Risk Reduction: The Healthy Hearts Program (P12-021-19). Curr. Dev. Nutr. 2019, 3. [Google Scholar] [CrossRef]
  48. Tyrovolas, S.; Panagiotakos, D.B. The role of Mediterranean type of diet on the development of cancer and cardiovascular disease, in the elderly: A systematic review. Maturitas 2010, 65, 122–130. [Google Scholar] [CrossRef]
  49. Sun, L.; Luo, C.; Liu, J. Hydroxytyrosol induces apoptosis in human colon cancer cells through ROS generation. Food Funct. 2014, 5, 1909–1914. [Google Scholar] [CrossRef]
  50. Luo, C.; Li, Y.; Wang, H.; Cui, Y.; Feng, Z.; Li, H.; Wang, Y.; Wurtz, K.; Weber, P.; Long, J.; et al. Hydroxytyrosol promotes superoxide production and defects in autophagy leading to anti-proliferation and apoptosis on human prostate cancer cells. Curr. Cancer Drug Targets 2013, 13, 625–639. [Google Scholar] [CrossRef]
  51. Goldsmith, C.D.; Bond, D.R.; Jankowski, H.; Weidenhofer, J.; Stathopoulos, C.E.; Roach, P.D.; Scarlett, C.J. The Olive Biophenols Oleuropein and Hydroxytyrosol Selectively Reduce Proliferation, Influence the Cell Cycle, and Induce Apoptosis in Pancreatic Cancer Cells. Int. J. Mol. Sci. 2018, 19, 1937. [Google Scholar] [CrossRef][Green Version]
  52. Cruz-Lozano, M.; González-González, A.; Marchal, J.A.; Muñoz-Muela, E.; Molina, M.P.; Cara, F.E.; Brown, A.M.; García-Rivas, G.; Hernández-Brenes, C.; Lorente, J.A.; et al. Hydroxytyrosol inhibits cancer stem cells and the metastatic capacity of triple-negative breast cancer cell lines by the simultaneous targeting of epithelial-to-mesenchymal transition, Wnt/β-catenin and TGFβ signaling pathways. Eur. J. Nutr. 2019, 58, 3207–3219. [Google Scholar] [CrossRef]
  53. Sirianni, R.; Chimento, A.; De Luca, A.; Casaburi, I.; Rizza, P.; Onofrio, A.; Iacopetta, D.; Puoci, F.; Andò, S.; Maggiolini, M.; et al. Oleuropein and hydroxytyrosol inhibit MCF-7 breast cancer cell proliferation interfering with ERK1/2 activation. Mol. Nutr. Food Res. 2010, 54, 833–840. [Google Scholar] [CrossRef]
  54. Martínez, N.; Herrera, M.; Frías, L.; Provencio, M.; Pérez-Carrión, R.; Díaz, V.; Morse, M.; Crespo, M.C. A combination of hydroxytyrosol, omega-3 fatty acids and curcumin improves pain and inflammation among early stage breast cancer patients receiving adjuvant hormonal therapy: Results of a pilot study. Clin. Transl. Oncol. 2019, 21, 489–498. [Google Scholar] [CrossRef]
  55. Gomez-Marin, B.; Gomez-Delgado, F.; Lopez-Moreno, J.; Alcala-Diaz, J.F.; Jimenez-Lucena, R.; Torres-Peña, J.D.; Garcia-Rios, A.; Ortiz-Morales, A.M.; Yubero-Serrano, E.M.; Del Mar Malagon, M.; et al. Long-term consumption of a Mediterranean diet improves postprandial lipemia in patients with type 2 diabetes: The Cordioprev randomized trial. Am. J. Clin. Nutr. 2018, 108, 963–970. [Google Scholar] [CrossRef][Green Version]
  56. Prattichizzo, F.; De Nigris, V.; Spiga, R.; Mancuso, E.; La Sala, L.; Antonicelli, R.; Testa, R.; Procopio, A.D.; Olivieri, F.; Ceriello, A. Inflammageing and metaflammation: The yin and yang of type 2 diabetes. Ageing Res. Rev. 2018, 41, 1–17. [Google Scholar] [CrossRef]
  57. Caracciolo, B.; Xu, W.; Collins, S.; Fratiglioni, L. Cognitive decline, dietary factors and gut-brain interactions. Mech. Ageing Dev. 2014, 136-137, 59–69. [Google Scholar] [CrossRef]
  58. Féart, C.; Samieri, C.; Allès, B.; Barberger-Gateau, P. Potential benefits of adherence to the Mediterranean diet on cognitive health. Proc. Nutr. Soc. 2013, 72, 140–152. [Google Scholar] [CrossRef][Green Version]
  59. Lange, K.W.; Guo, J.; Kanaya, S.; Lange, K.M.; Nakamura, Y.; Li, S. Medical foods in Alzheimer’s disease. Food Sci. Hum. Wellness 2019, 8, 1–7. [Google Scholar] [CrossRef]
  60. Shannon, O.M.; Stephan, B.C.M.; Granic, A.; Lentjes, M.; Hayat, S.; Mulligan, A.; Brayne, C.; Khaw, K.T.; Bundy, R.; Aldred, S.; et al. Mediterranean diet adherence and cognitive function in older UK adults: The European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk) Study. Am. J. Clin. Nutr. 2019, 110, 938–948. [Google Scholar] [CrossRef]
  61. Martínez-Lapiscina, E.H.; Clavero, P.; Toledo, E.; Estruch, R.; Salas-Salvadó, J.; San Julián, B.; Sanchez-Tainta, A.; Ros, E.; Valls-Pedret, C.; Martinez-Gonzalez, M. Mediterranean diet improves cognition: The PREDIMED-NAVARRA randomised trial. J. Neurol. Neurosurg. Psychiatry 2013, 84, 1318–1325. [Google Scholar] [CrossRef][Green Version]
  62. Valls-Pedret, C.; Sala-Vila, A.; Serra-Mir, M.; Corella, D.; de la Torre, R.; Martínez-González, M.; Martínez-Lapiscina, E.H.; Fitó, M.; Pérez-Heras, A.; Salas-Salvadó, J.; et al. Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial. JAMA Intern. Med. 2015, 175, 1094–1103. [Google Scholar] [CrossRef][Green Version]
  63. Bhatt, A.P.; Redinbo, M.R.; Bultman, S.J. The role of the microbiome in cancer development and therapy. CA Cancer J. Clin. 2017, 67, 326–344. [Google Scholar] [CrossRef][Green Version]
  64. Esteve, E.; Ricart, W.; Fernández-Real, J.M. Gut microbiota interactions with obesity, insulin resistance and type 2 diabetes: Did gut microbiote co-evolve with insulin resistance? Curr. Opin. Clin. Nutr. Metab. Care 2011, 14, 483–490. [Google Scholar] [CrossRef]
  65. Tang, W.H.; Wang, Z.; Levison, B.S.; Koeth, R.A.; Britt, E.B.; Fu, X.; Wu, Y.; Hazen, S.L. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 2013, 368, 1575–1584. [Google Scholar] [CrossRef][Green Version]
  66. Tamura, K.; Sasaki, H.; Shiga, K.; Miyakawa, H.; Shibata, S. The Timing Effects of Soy Protein Intake on Mice Gut Microbiota. Nutrients 2019, 12, 87. [Google Scholar] [CrossRef][Green Version]
  67. Kuiper, G.G.; Lemmen, J.G.; Carlsson, B.; Corton, J.C.; Safe, S.H.; van der Saag, P.T.; van der Burg, B.; Gustafsson, J.A. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 1998, 139, 4252–4263. [Google Scholar] [CrossRef]
  68. Liggins, J.; Bluck, L.J.; Runswick, S.; Atkinson, C.; Coward, W.A.; Bingham, S.A. Daidzein and genistein content of fruits and nuts. J. Nutr. Biochem. 2000, 11, 326–331. [Google Scholar] [CrossRef]
  69. Bäckhed, F.; Ding, H.; Wang, T.; Hooper, L.V.; Koh, G.Y.; Nagy, A.; Semenkovich, C.F.; Gordon, J.I. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA 2004, 101, 15718–15723. [Google Scholar] [CrossRef][Green Version]
  70. Schwiertz, A.; Taras, D.; Schäfer, K.; Beijer, S.; Bos, N.A.; Donus, C.; Hardt, P.D. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 2010, 18, 190–195. [Google Scholar] [CrossRef]
  71. Zhou, L.; Xiao, X.; Zhang, Q.; Zheng, J.; Deng, M. Maternal Genistein Intake Mitigates the Deleterious Effects of High-Fat Diet on Glucose and Lipid Metabolism and Modulates Gut Microbiota in Adult Life of Male Mice. Front. Physiol. 2019, 10, 985. [Google Scholar] [CrossRef][Green Version]
  72. Zhou, L.; Xiao, X.; Zhang, Q.; Zheng, J.; Li, M.; Wang, X.; Deng, M.; Zhai, X.; Liu, J. Gut microbiota might be a crucial factor in deciphering the metabolic benefits of perinatal genistein consumption in dams and adult female offspring. Food Funct. 2019, 10, 4505–4521. [Google Scholar] [CrossRef][Green Version]
  73. López, P.; Sánchez, M.; Perez-Cruz, C.; Velázquez-Villegas, L.A.; Syeda, T.; Aguilar-López, M.; Rocha-Viggiano, A.K.; Del Carmen Silva-Lucero, M.; Torre-Villalvazo, I.; Noriega, L.G.; et al. Long-Term Genistein Consumption Modifies Gut Microbiota, Improving Glucose Metabolism, Metabolic Endotoxemia, and Cognitive Function in Mice Fed a High-Fat Diet. Mol. Nutr. Food Res. 2018, 62, e1800313. [Google Scholar] [CrossRef]
  74. Borras, C.; Gambini, J.; Gomez-Cabrera, M.C.; Sastre, J.; Pallardo, F.V.; Mann, G.E.; Vina, J. Genistein, a soy isoflavone, up-regulates expression of antioxidant genes: Involvement of estrogen receptors, ERK1/2, and NFkappaB. FASEB J. 2006, 20, 2136–2138. [Google Scholar] [CrossRef]
  75. Pryde, S.E.; Duncan, S.H.; Hold, G.L.; Stewart, C.S.; Flint, H.J. The microbiology of butyrate formation in the human colon. FEMS Microbiol. Lett. 2002, 217, 133–139. [Google Scholar] [CrossRef] [PubMed]
  76. David, L.A.; Materna, A.C.; Friedman, J.; Campos-Baptista, M.I.; Blackburn, M.C.; Perrotta, A.; Erdman, S.E.; Alm, E.J. Host lifestyle affects human microbiota on daily timescales. Genome Biol. 2014, 15, R89. [Google Scholar] [CrossRef] [PubMed][Green Version]
  77. Hamilton, M.J.; Weingarden, A.R.; Sadowsky, M.J.; Khoruts, A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am. J. Gastroenterol. 2012, 107, 761–767. [Google Scholar] [CrossRef]
  78. Aroniadis, O.C.; Brandt, L.J. Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. Gastroenterol. Hepatol. 2014, 10, 230–237. [Google Scholar]
  79. Zhang, J.; Ren, L.; Yu, M.; Liu, X.; Ma, W.; Huang, L.; Li, X.; Ye, X. S-equol inhibits proliferation and promotes apoptosis of human breast cancer MCF-7 cells via regulating miR-10a-5p and PI3K/AKT pathway. Arch. Biochem. Biophys. 2019, 672, 108064. [Google Scholar] [CrossRef] [PubMed]
  80. Horiuchi, H.; Usami, A.; Shirai, R.; Harada, N.; Ikushiro, S.; Sakaki, T.; Nakano, Y.; Inui, H.; Yamaji, R. S-Equol Activates cAMP Signaling at the Plasma Membrane of INS-1 Pancreatic β-Cells and Protects against Streptozotocin-Induced Hyperglycemia by Increasing β-Cell Function in Male Mice. J. Nutr. 2017, 147, 1631–1639. [Google Scholar] [CrossRef] [PubMed][Green Version]
  81. Bielak-Zmijewska, A.; Grabowska, W.; Ciolko, A.; Bojko, A.; Mosieniak, G.; Bijoch, Ł.; Sikora, E. The Role of Curcumin in the Modulation of Ageing. Int. J. Mol. Sci. 2019, 20, 1239. [Google Scholar] [CrossRef] [PubMed][Green Version]
  82. Skyvalidas, D.; Mavropoulos, A.; Tsiogkas, S.; Dardiotis, E.; Liaskos, C.; Mamuris, Z.; Roussaki-Schulze, A.; Sakkas, L.I.; Zafiriou, E.; Bogdanos, D.P. Curcumin mediates attenuation of pro-inflammatory interferon γ and interleukin 17 cytokine responses in psoriatic disease, strengthening its role as a dietary immunosuppressant. Nutr. Res. 2020, 75, 95–108. [Google Scholar] [CrossRef] [PubMed]
  83. Di Meo, F.; Margarucci, S.; Galderisi, U.; Crispi, S.; Peluso, G. Curcumin, Gut Microbiota, and Neuroprotection. Nutrients 2019, 11, 2426. [Google Scholar] [CrossRef][Green Version]
  84. Ticinesi, A.; Tana, C.; Nouvenne, A.; Prati, B.; Lauretani, F.; Meschi, T. Gut microbiota, cognitive frailty and dementia in older individuals: A systematic review. Clin. Interv. Aging 2018, 13, 1497–1511. [Google Scholar] [CrossRef][Green Version]
  85. Arana Cañedo-Argüelles, C. Fibra dietética. Rev. Pediatría Atención Primaria 2006, 8 (Suppl. 1), 83–97. [Google Scholar]
  86. Pascual, V.; Perez Martinez, P.; Fernández, J.M.; Solá, R.; Pallarés, V.; Romero Secín, A.; Pérez Jiménez, F.; Ros, E. SEA/SEMERGEN consensus document 2019: Dietary recommendations in the prevention of cardiovascular disease. Semergen 2019, 45, 333–348. [Google Scholar] [CrossRef] [PubMed]
  87. Casiglia, E.; Tikhonoff, V.; Caffi, S.; Boschetti, G.; Grasselli, C.; Saugo, M.; Giordano, N.; Rapisarda, V.; Spinella, P.; Palatini, P. High dietary fiber intake prevents stroke at a population level. Clin. Nutr. 2013, 32, 811–818. [Google Scholar] [CrossRef] [PubMed]
  88. Larsson, S.C.; Wolk, A. Dietary fiber intake is inversely associated with stroke incidence in healthy Swedish adults. J. Nutr. 2014, 144, 1952–1955. [Google Scholar] [CrossRef] [PubMed]
  89. Tucker, L.A. Dietary Fiber and Telomere Length in 5674 U.S. Adults: An NHANES Study of Biological Aging. Nutrients 2018, 10, 400. [Google Scholar] [CrossRef][Green Version]
  90. Kuller, L.H. Dietary fat and chronic diseases: Epidemiologic overview. J. Am. Diet. Assoc. 1997, 97, S9–S15. [Google Scholar] [CrossRef]
  91. Everitt, A.V.; Hilmer, S.N.; Brand-Miller, J.C.; Jamieson, H.A.; Truswell, A.S.; Sharma, A.P.; Mason, R.S.; Morris, B.J.; Le Couteur, D.G. Dietary approaches that delay age-related diseases. Clin. Interv. Aging 2006, 1, 11–31. [Google Scholar] [CrossRef]
  92. Turnbaugh, P.J.; Ridaura, V.K.; Faith, J.J.; Rey, F.E.; Knight, R.; Gordon, J.I. The effect of diet on the human gut microbiome: A metagenomic analysis in humanized gnotobiotic mice. Sci. Transl. Med. 2009, 1, 6ra14. [Google Scholar] [CrossRef][Green Version]
  93. Ma, J.; Li, H. The Role of Gut Microbiota in Atherosclerosis and Hypertension. Front. Pharmacol. 2018, 9, 1082. [Google Scholar] [CrossRef]
  94. Zhang, C.; Zhang, M.; Wang, S.; Han, R.; Cao, Y.; Hua, W.; Mao, Y.; Zhang, X.; Pang, X.; Wei, C.; et al. Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J. 2010, 4, 232–241. [Google Scholar] [CrossRef][Green Version]
  95. Brandsma, E.; Kloosterhuis, N.J.; Koster, M.; Dekker, D.C.; Gijbels, M.J.J.; van der Velden, S.; Ríos-Morales, M.; van Faassen, M.J.R.; Loreti, M.G.; de Bruin, A.; et al. A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis. Circ. Res. 2019, 124, 94–100. [Google Scholar] [CrossRef] [PubMed]
  96. De Filippo, C.; Cavalieri, D.; Di Paola, M.; Ramazzotti, M.; Poullet, J.B.; Massart, S.; Collini, S.; Pieraccini, G.; Lionetti, P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl. Acad. Sci. USA 2010, 107, 14691–14696. [Google Scholar] [CrossRef] [PubMed][Green Version]
  97. Larrosa, M.; Luceri, C.; Vivoli, E.; Pagliuca, C.; Lodovici, M.; Moneti, G.; Dolara, P. Polyphenol metabolites from colonic microbiota exert anti-inflammatory activity on different inflammation models. Mol. Nutr. Food Res. 2009, 53, 1044–1054. [Google Scholar] [CrossRef] [PubMed]
  98. Handy, D.E.; Castro, R.; Loscalzo, J. Epigenetic modifications: Basic mechanisms and role in cardiovascular disease. Circulation 2011, 123, 2145–2156. [Google Scholar] [CrossRef] [PubMed][Green Version]
  99. Larrosa, M.; González-Sarrías, A.; Yáñez-Gascón, M.J.; Selma, M.V.; Azorín-Ortuño, M.; Toti, S.; Tomás-Barberán, F.; Dolara, P.; Espín, J.C. Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism. J. Nutr. Biochem. 2010, 21, 717–725. [Google Scholar] [CrossRef]
  100. Selma, M.V.; Tomás-Barberán, F.A.; Beltrán, D.; García-Villalba, R.; Espín, J.C. Gordonibacter urolithinfaciens sp. nov., a urolithin-producing bacterium isolated from the human gut. Int. J. Syst. Evol. Microbiol. 2014, 64, 2346–2352. [Google Scholar] [CrossRef]
  101. Sreng, N.; Champion, S.; Martin, J.C.; Khelaifia, S.; Christensen, J.E.; Padmanabhan, R.; Azalbert, V.; Blasco-Baque, V.; Loubieres, P.; Pechere, L.; et al. Resveratrol-mediated glycemic regulation is blunted by curcumin and is associated to modulation of gut microbiota. J. Nutr. Biochem. 2019, 72, 108218. [Google Scholar] [CrossRef]
  102. Parkar, S.G.; Trower, T.M.; Stevenson, D.E. Fecal microbial metabolism of polyphenols and its effects on human gut microbiota. Anaerobe 2013, 23, 12–19. [Google Scholar] [CrossRef]
Figure 1. Taxonomy of microbiota. Black: Kingdom; green: Phylum; red: Class; blue: Order. Adapted from Unger et al., Pediatr. Res. 2015 [13]. Copyright © International Pediatric Research Foundation, Inc. 2015.
Figure 1. Taxonomy of microbiota. Black: Kingdom; green: Phylum; red: Class; blue: Order. Adapted from Unger et al., Pediatr. Res. 2015 [13]. Copyright © International Pediatric Research Foundation, Inc. 2015.
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Figure 2. Intestinal microbiota changes through life.Green arrows signify increase. Red arrows signify decrease.
Figure 2. Intestinal microbiota changes through life.Green arrows signify increase. Red arrows signify decrease.
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Table 1. Summaries of the main effects of each compound on the intestinal bacteria and the health consequences. Upward arrows signify increase. Downward arrows signify decrease.
Table 1. Summaries of the main effects of each compound on the intestinal bacteria and the health consequences. Upward arrows signify increase. Downward arrows signify decrease.
Diet CompoundMicrobiota ModificationHealth Consequences
↑ Lactobacillus
↓ Pathogens
↓ Inflammation
↓ Hypertension
↓ Obesity
Saturated fats↓ Bacteroides
↑ Firmicutes
↑ Proteobacteria
↑ Obesity
↑ Hypertension
↑ Atherosclerosis
Polyphenols↑ Bifidobacterium
↓ Firmicutes
↓ Clostridium
↓ Inflammation
↑ Antioxidants
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