**3. Evidence of gut-brain axis alteration in old patients**

Each human organism hosts a widely diverse population of microbes that form a "metaorganism" (comprising 10 bacterial cells for every one of our own) [32]. This metaorganism, which is now studied thoroughly in major scientific endeavors such as Human Microbiome Project [33], impacts on its host as much as the human host changes it back throughout different life stages. Microbial diversity and intestinal microflora stability decrease with age [27, 28] and are accompanied by a reduction in brain function and a decrease in cognitive abilities [34, 35]. Furthermore, alteration of gut microbiota homeostasis, through dietary or environmental factors, can lead to an imbalance between symbionts and pathobionts, resulting in reduced intestinal barrier function such as a dysbiosis state can be related to subsequent metabolic and inflammatory disorders, visceral pain and even alterations in brain functioning [36]. Other studies have shown that while the microbial composition of the gut changes with age, it is not a linear process. The two dominant phyla in younger persons, *Bacteroides* and *Firmicutes*, remain prominent at older ages, but there are supposed to be changes in the percentage of these phyla, a fact still under discussion. Other studies support the prevalence of potentially pathogenic bacteria (e.g. proteobacteria) that are detrimental for symbiotic beneficial bacteria (e.g. species of *Bifidobacteria*) [37]. In this regard, there is an increased interest in the putative role of microbial gut in the fragility and vulnerability associated with the aging process.

permeability via age-associated remodeling of intestinal epithelial tight junction proteins. On the opposite side is a recent report by Valentini et al. that found no correlation between aging and increased intestinal permeability (or altered intestinal barrier), but mentioned low-

Role of Nutraceuticals in Modulation of Gut-Brain Axis in Elderly Persons

http://dx.doi.org/10.5772/intechopen.73005

251

Age-related physiological modifications in the gastrointestinal tract undoubtedly affect the gut microbiota and high susceptibility to infections becomes an inevitable consequence. The gut microbiota homeostasis seem to play a crucial role for the gut well-being during the aging process and, in this perspective, dietary control of the gut microbiota of the elderly could be

Nutraceuticals are defined as "*food or food product that provides medical or health benefits including the prevention and treatment of diseases*" [46]. This concept is partially overlapping with the term "bioactive compounds" – "secondary plant metabolites eliciting pharmacological or toxicological effects in man and animals" [47]. Neuro-nutraceuticals are, by extrapolation, active compounds, obtained from food products or plants that exert effects on the CNS. They can be represented by vitamins, amino acids, minerals, trace elements, etc., with presumed health-promoting or disease-preventing effects. Oxidative stress, dysregulation of redox metals homeostasis and inflammation represent the main leading causes of brain aging and therefore the administration of antioxidant and anti-inflammatory molecules can be an important strategy for preventing brain aging and several brain age-related diseases such as Parkinson's

However, the evaluation of nutraceutical efficacy and safety represents a big challenge due to the complex chemical compositions and multiple mode of actions [50]. Starting from chemical classification of bioactive compounds [47], several classes have been repeatedly associated with beneficial neurological effects. *Flavonoids* consist of a central three-ring structure and may occur as oligomers *-proanthocyanidins*. All compounds contain phenol groups with antioxidant effect. Many different polyphenols have been reported to retard age-related declines in CNS function, cognition and behavior. A polyphenol with the ability to modulate a multitude of signaling molecules and with antibacterial, anti-inflammatory and neuroprotective properties is *curcumin,* the active ingredient in the spice turmeric. Curcumin acting as an antioxidant, anti-inflammatory and lipophilic agent can improve the cognitive functions in animal models and patients with Alzheimer's disease by several mechanisms. Short-term supplementation of curcumin to aged rats enhanced the frequency of polysialylated cells in the dentate infragranular zone and significantly improved both spatial learning and memory in adult and aged rats [51]. The long-term curcumin-supplemented diet had a important effects on hippocampal cellular proliferation, cognitive function and transcriptional responses in aged rats and this response is dependent of the length of curcumin treatment [52]. Curcumin administration supported the immune system to reduce beta-amyloid plaques, ensures the delayed degradation of neurons and decreased microglia activation resulting in the improvement of overall

an important target for preserving a healthy gut microbiota community [42].

disease, Alzheimer's disease, dementia and depression [48, 49].

**4. Neuro-nutraceuticals: definition, examples and mechanisms of** 

grade inflammation as a possible favoring factor [45].

**action**

Gut microbiota and extreme longevity are the main topics of several interesting studies. There are evidence that extreme aging might be supported by subdominant gut microbiota species, along with pro-inflammatory species and health-associated taxa [38]. Another study was focused on long-lived Chinese people and gut microbiota, with a special reference to the above-mentioned study. Significant differences in community membership and structures between the Italian and Chinese long-living groups were observed, attributed to many factors such as geography, genetics, diets and DNA-extraction methods [39].

These findings emphasize the importance of sampling a healthy population, both in terms of age, geographic and cultural traditions in order to identify features of gut microbiomes signatures related to age [40].

Age-associated alterations in gut microbiota are associated with subsequent decline with age in the functionality of the immune system (immunosenescence) and a chronic lowgrade inflammatory status, partially due to increased intestinal permeability and increased colonic cytokine expression (inflammaging) [41]. The inflammaging process can undermine the homeostatic equilibrium and accelerate the changes in gut microbiota structure and composition that could be related to the progression of diseases and frailty in the elderly population [42].

Mabbott et al. in 2015 [43] provided an important advance in our understanding on the effects of aging on intestinal permeability and innate mucosal immune responsiveness in elderly patients. Using human terminal ileal biopsy tissues, they demonstrated that intestinal permeability to solutes, but not macromolecules, was significantly increased in the intestines of elderly humans. Tran and Greenwood-Van Meerveld in 2013 [44] showed for the first time a pivotal contributing factor to geriatric vulnerability to gastrointestinal dysfunction may increase colonic permeability via age-associated remodeling of intestinal epithelial tight junction proteins. On the opposite side is a recent report by Valentini et al. that found no correlation between aging and increased intestinal permeability (or altered intestinal barrier), but mentioned lowgrade inflammation as a possible favoring factor [45].

**3. Evidence of gut-brain axis alteration in old patients**

and vulnerability associated with the aging process.

signatures related to age [40].

population [42].

250 Gerontology

such as geography, genetics, diets and DNA-extraction methods [39].

Each human organism hosts a widely diverse population of microbes that form a "metaorganism" (comprising 10 bacterial cells for every one of our own) [32]. This metaorganism, which is now studied thoroughly in major scientific endeavors such as Human Microbiome Project [33], impacts on its host as much as the human host changes it back throughout different life stages. Microbial diversity and intestinal microflora stability decrease with age [27, 28] and are accompanied by a reduction in brain function and a decrease in cognitive abilities [34, 35]. Furthermore, alteration of gut microbiota homeostasis, through dietary or environmental factors, can lead to an imbalance between symbionts and pathobionts, resulting in reduced intestinal barrier function such as a dysbiosis state can be related to subsequent metabolic and inflammatory disorders, visceral pain and even alterations in brain functioning [36]. Other studies have shown that while the microbial composition of the gut changes with age, it is not a linear process. The two dominant phyla in younger persons, *Bacteroides* and *Firmicutes*, remain prominent at older ages, but there are supposed to be changes in the percentage of these phyla, a fact still under discussion. Other studies support the prevalence of potentially pathogenic bacteria (e.g. proteobacteria) that are detrimental for symbiotic beneficial bacteria (e.g. species of *Bifidobacteria*) [37]. In this regard, there is an increased interest in the putative role of microbial gut in the fragility

Gut microbiota and extreme longevity are the main topics of several interesting studies. There are evidence that extreme aging might be supported by subdominant gut microbiota species, along with pro-inflammatory species and health-associated taxa [38]. Another study was focused on long-lived Chinese people and gut microbiota, with a special reference to the above-mentioned study. Significant differences in community membership and structures between the Italian and Chinese long-living groups were observed, attributed to many factors

These findings emphasize the importance of sampling a healthy population, both in terms of age, geographic and cultural traditions in order to identify features of gut microbiomes

Age-associated alterations in gut microbiota are associated with subsequent decline with age in the functionality of the immune system (immunosenescence) and a chronic lowgrade inflammatory status, partially due to increased intestinal permeability and increased colonic cytokine expression (inflammaging) [41]. The inflammaging process can undermine the homeostatic equilibrium and accelerate the changes in gut microbiota structure and composition that could be related to the progression of diseases and frailty in the elderly

Mabbott et al. in 2015 [43] provided an important advance in our understanding on the effects of aging on intestinal permeability and innate mucosal immune responsiveness in elderly patients. Using human terminal ileal biopsy tissues, they demonstrated that intestinal permeability to solutes, but not macromolecules, was significantly increased in the intestines of elderly humans. Tran and Greenwood-Van Meerveld in 2013 [44] showed for the first time a pivotal contributing factor to geriatric vulnerability to gastrointestinal dysfunction may increase colonic Age-related physiological modifications in the gastrointestinal tract undoubtedly affect the gut microbiota and high susceptibility to infections becomes an inevitable consequence. The gut microbiota homeostasis seem to play a crucial role for the gut well-being during the aging process and, in this perspective, dietary control of the gut microbiota of the elderly could be an important target for preserving a healthy gut microbiota community [42].
