Age-related degeneration gives rise to a number of pathologies, many of them associated with imbalances of the microbiota and the gut-associated immune system. Thus, the intestine is considered a key target organ to improve the quality of life in senescence. Gut microbiota can have a powerful impact in the deterioration linked to aging by its nutritional and immunomodulatory activity. Reduced numbers of beneficial species and low microbial biodiversity in the elderly have been linked with pathogenesis of many diseases. A healthy lifestyle with an elderly customized diet including probiotics can contribute to reducing the chronic proinflammatory status and other age-related pathologies. Beneficial effects of probiotic lactic acid bacteria and bifidobacteria to alleviate some of these disorders based on their immunomodulatory properties as well as their capacity to produce bioactive metabolites from dietary phytoestrogens are summarized. On one hand, the preservation of gut barrier integrity and an increased ability to fight infections are the main reported immune benefits of probiotics. On the other hand, the intake of a diet rich in phytoestrogens along with the presence of selected probiotic bacteria may lead to the production of equol, enterolignans, and urolithins, which are considered protective against chronic diseases related to aging.
The time-dependent biological complex processes that produce a gradual generalized deterioration of the anatomy and physiological functions of organisms are defined as aging. It led to weakness to environmental stress and therefore increases the risk of disease and death. Among multicellular organisms, aging is marked by a progressive decline in the function of multiple cells and tissues. Apparently, the event of aging is genetically determined and modulated by the environment, but the causes of those irreversible changes are still an unresolved challenge. Understanding aging is an important objective that may help to modify the aging process or the senescence effects. The aging rate could be determined by two major circumstances: the accumulation of damage and the effectiveness of somatic maintenance mechanisms [
The main aim of aging research is to improve the quality of life. Age-related degeneration gives rise to a number of pathologies, such as osteoarthritis, atherosclerosis, lung emphysema, malignancies (gastrointestinal, prostate), and dementias. The aging process is dependent on antistress responses, which act as antiaging mechanisms. Furthermore, immunosenescence, which can be defined as a decline in the functionality of the immune system, contribute to a chronic state of basal inflammatory activity (inflammaging) [
The most studied and reproducible nongenetic intervention in aging research is dietary restriction. However, the importance of diet composition has been highlighted when applying a reduction in calorie intake to regulate the lifespan [
The gastrointestinal (GI) tract is characterized by its complexity, being the main and largest site for interaction with the external environment. The GI tract is covered by a single layer of epithelial cells, which are responsible for the digestion and absorption of nutrients and electrolytes, as well as homeostasis. Moreover, the gut-associated lymphoid tissue provides an important first line of defence that controls the equilibrium between tolerance and immunity against orally acquired food and microbes. The human gut contains the enteric microbiota, whose mutualistic relationship contributes to the maintenance of health, including digestion of complex carbohydrates, intestinal homeostasis, synthesis of essential nutrients and vitamins, protection against pathogens, and stimulation of the immune system [
A distinguishing characteristic of the aging gut is the overexpression of proinflammatory cytokine IL-6, which has an effect on the intestinal barrier function and mucosal immune system [
Physical and immunological impairments of intestinal barrier are correlated with age-related diseases and lifespan. The cross-talk between gut microbiota and the gut-associated lymphoid tissue has a powerful effect on the host immune response which can lead to systemic metabolic effects [
Alterations in morphology and physiological functions modify the physical environment of the elderly gut, which affect the composition of the intestinal microbiota. Moreover, antibiotics are still an irreplaceable therapy for the elderly, which have also a huge influence on the intestinal microbiota composition. Dysbiosis is associated with various metabolic, infectious, and inflammatory disorders including malnutrition, diabetes, bowel diseases,
Gut microbiota has a strong impact in human physiology and, therefore, on the health status in the elderly and age-related diseases [
Host age, health status, and environmental factors can modulate our microbiota composition. Improving the profile of the gut microbiota during human aging, mainly lifestyle factors and nutritional habits, would have an impact on human health and longevity since longevity process is associated with human gut microbiota changes [
Probiotics can be applied to modulate the age-related gut microbiota imbalance and to introduce strains with specific health-promoting effects. The principal claimed benefits of probiotics in elderly people are prevention of diarrheal diseases, protection against pathogens, enhancement of the intestinal barrier function, improvement of gastrointestinal motility and inflammatory intestinal disorders, immunomodulatory effects, and prevention of colon cancer [
Probiotic intervention, with or without a specific diet composition, would help to improve the microbiota functionality in order to obtain health benefits during the old age. In this context, a diet rich in phytoestrogens can be considered an interesting therapeutic approach against aging due to their estrogenic and antioxidant actions. Here we summarize two promising beneficial effects of probiotics to alleviate some age-related pathologies based on their immunomodulatory properties as well as their capacity to produce bioactive metabolites from dietary compounds, such us phytoestrogens.
Senescence is associated with a decline in immune function and an increase in inflammation [
Probiotics can exert beneficial effects on the preservation of gut barrier integrity and function stimulating the activity and growth of beneficial bacteria and regulating the expression of tight junction proteins [
Aging process affects innate immunity, with reduced activity or number of natural killer (NK) cells, and adaptive immunity, with reduced antigen-specific IgA antibody and cellular immune responses [
Lactic acid bacteria (LAB) and bifidobacteria are commonly found in the gut of humans and other animals as well as in probiotic supplements and foods. Their immunomodulatory properties can be applied in age-related disorders. Studies carried out on mice demonstrated the potential of probiotics to palliate the effects of aging on the immune system. Administration of
Several human studies also show a higher ability to fight infections following probiotic consumption.
Phytoestrogens are polyphenols present in plants or foods derived from plants foods such as soya, flaxseed, cereals, vegetables, fruit, chocolate, and tea [
Potential probiotic strains implicated in the metabolism of phytoestrogen.
Bacteria | Transformation/production | Reference |
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Daidzin to daidzein | [ |
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Daidzin to daidzein | [ |
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Daidzein to dihydrodaidzein | [ |
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Daidzin to dihydrodaidzein | [ |
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Daidzin to dihydrodaidzein | [ |
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Daidzein into equol | [ |
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Daidzein into equol | [ |
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Daidzein into equol | [ |
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Enterodiol production from flax seed | [ |
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Urolithin C from ellagic acid | [ |
The transformation of isoflavones, lignans, and ellagitannins by bacteria is an essential step because equol, enterolignans, and urolithins are more bioavailable than their respective dietary phytoestrogens [ equol, enterolignans, and urolithins have more estrogenic/antiestrogenic activities than their precursors. The biological action of these derived compounds is mediated primarily by estrogen receptors [ equol and enterolignans are more antioxidants than their precursors [ finally, equol, enterolignans, and urolithins have anti-inflammatory effects and exert antiproliferative and apoptosis-inducing activities [
Although specific bacteria responsible for the equol, enterolignans, and urolithin production are still being investigated, some LAB and bifidobacteria have been involved in the metabolism of these compounds [
Isoflavones, lignans, and ellagitannins intake are metabolized by potential probiotic bacteria to produce equol, enterolignans, and urolithins, respectively. These compounds are more bioavailable and bioactive than their precursors.
In soy and unfermented soy foods, isoflavones are as glycosides such as daidzin, genistin, or glycitin. These compounds are less estrogenic than their aglycones daidzein, genistein, and glycitein, respectively. Daidzin, genistin, or glycitin cannot be absorbed because of their higher molecular weights and hydrophilicity [
Benefits of soy in aging are derived from the isoflavones metabolism of bacteria, including protection against breast cancer [
LAB and bifidobacteria are very important in the transformation of naturally occurring isoflavones in the form of
Daidzein, genistein, dihydrodaidzein, and dihydrogenistein possess physiological properties of interest in healthy aging [
A mix of bacteria composed of
Lignans, which are the major phytoestrogens occurring in Western diets, have relevant health properties [
Deglycosylation of the secoisolariciresinol diglucoside (SDG) present in the lignan extracts into secoisolariciresinol (SECO) is the first step towards the formation of enterolignans. The production of SECO from lignan extracts and SDG is widespread within LAB and bifidobacteria isolates [
Nowadays, different bacteria such as
Ellagitannins are complex derivatives of ellagic acid, which are largely metabolized by the colon microbiota of different mammals [
To date, only two urolithin-producing strains,
Probiotics able to produce or to increase species related to the production of urolithins or other phytoestrogens such as equol and enterolignans can mean a step forward in the probiotic interventions, increasing the bioavailability of these compounds, and subsequently their therapeutic applications.
Age-related changes in nutritional behaviour and microbial diversity during aging result in a higher susceptibility to infections and diseases. Likewise, the presence of some beneficial microorganisms in the gut could help to prevent or delay some age-associated diseases by improving the immune response, or by the production of bioactive metabolites as equol, enterolignans, and urolithins. The evidence for intake of probiotics along with age specifically oriented diet to improve the health during aging is promising. However, further studies for a rational manipulation of the gut microbiota are needed to better define the role of probiotics and to assess the real potential of these interventions.
The authors declare that there are no conflicts of interest regarding the publication of this paper.
Financial support from the Spanish Ministry of Economy and Competitiveness (MINECO), Projects RM12-00004-00-00 and RTA2013-00029-00-00, is acknowledged.