**1. Introduction**

In recent years, great progress has been made in characterizing bidirectional interactions between central nervous system (CNS), enteric nervous system and gastrointestinal tract. Dr Michael Gershon has defined the gut as "the second brain" [1] for several reasons: the enteric nervous system may function autonomously (it is capable of reflexes in the absence of CNS input), it can communicate with CNS through the parasympathetic (via vagal nerve) and sympathetic (via paravertebral ganglia) nervous system and is susceptible to neurotrophic and neuromodulators signaling.

Studies on GF mice also highlighted another surprising relationship between gut microbiota and aging and in the occurrence of aging-related-diseases. It has been shown that GF mice live significantly longer than normal animals, probably due to the reduction of pathological infections, with a first report back in the mid 1960s [21], followed by others in mice [22, 23]

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

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

249

We shall further detail some topics related to the gut-brain axis in the elderly, like gut-brain alterations observed in preclinical and clinical studies, some data about neuro-nutraceuticals with a focus on mechanisms and gut-brain axis modulation with a final reference to

**2. Evidence-based data of gut-brain axis alteration in aged laboratory** 

Aging is (so far) an irreversible process which impacts on all cell populations, with several common denominators such as genomic instability, epigenetic alterations and oxidative stress [26]. It equally affects gut lining and brain cells, but it also changes the gut microbiota composition [27, 28] which in turn is associated with behavioral and physiological modifications. An anxious behavioral phenotype was observed while transferring fecal microbiota between two strains of mice [10]. Also, fecal microbiota transplantation from depressed patients to microbiota-depleted rats may have the potential to provoke behavioral and physiological features specific to depression, including anhedonia, anxiety-like behaviors, as well as modifications in tryptophan metabolism, suggesting that gut microbiota could be an important player in neurobehavioral changes in the rat [29]. Reduced anxiety and depression-related comportment in mice were connected to dysregulated GABA signaling by metabolizing dietary glutamate through certain strains of *Lactobacillus* and *Bifidobacteria* [30]. Another study focused on the analysis of microbiota of aged mice. It is reported that, although composition differed significantly, there was only an insignificant overall increase in bacterial taxa, from that of young mice. At phylum level, the most common microbial taxa were *Bacteroidetes* and *Firmicutes*. A few statistically significant differences in bacterial groups were noticed in aged mice. At the phylum level, TM7 was significantly higher, while at family level abundance less than 1%, significant increases in *Porphyromondaceae*, TM7 uncultured, *Clostridiaceae*, *Thermoanaerobacteraceae*, *Desulfovibrionaceae* and *Oxalobacteraceae* were seen in aged mice compared to young. Genera *Odoribacter* was much higher in the aged group whereas, other bacterial genera, including *Butyricimonas*, TM7 uncultured, *Gelria*, *Anaerosporobacter*, *Clostridium* and *Oxalobacter* had significant increases in aged mice. The Chao 1 index (which estimates species richness), the number of observed species and the phylogenetic diversity, the Shannon Index (alpha diversity) and beta diversity were higher in the aged compared with young groups. Also, gut permeability in young and aged mice prior to and after 1 h of restraint stress was assessed, proved that aged mice had significantly greater basal intestinal permeability

*Drosophila melanogaster* [24], *Caernohabditis elegans* [25].

clinical trials.

**animals**

than young mice [31].

The term gut-brain axis is often extended to include the role of intestinal flora in the system, in which case the axis is called microbiota-gut-brain axis. The microbiota is not limited to bacteria but also includes protozoa, fungi, nematodes and viruses, so that in the intestinal tract there are over 1000 species of bacteria out of a total of approximately 100 trillion organisms [2]. To maintain the homeostasis of such complex system, permanent correlation between the gut and the brain is essential.

The gastrointestinal microbiota has a symbiotic relationship with enteric cells and contributes to basic physiological processes such as digestion, growth and immune defense. The composition of an individual's microbiota depends on the mode of delivery at birth, genetic predisposition, age, nutrition, physical activity, environmental factors, stress, infections, other diseases and the use of antibiotics [3].

Gut microbiota can influence the functioning of the CNS by the ability to synthesize or mimic some molecules such as host-signaling neuroactive molecules, for example, acetylcholine, catecholamine, g-aminobutyric acid (GABA), histamine, melatonin and serotonin [4]. Conversely, the composition of the microbiota is influenced by emotional and psychological stress [5], resulting, for example, in the decrease in *Lactobacilli* species or the increase of *Clostridium* species [6, 7]. Although communication between the components of the microbiota-gut-brain axis has been well established by preclinical and clinical studies (excellently reviewed in [8–11]), the exact mechanisms by which this communication is made remains largely unknown. The interest in this research area began to consistently grow since the early 2000s, when one of the first papers to be published showed that germ-free (GF) mice exhibit an exaggerated hypothalamus-pituitary axis (HPA) response to stress compared to a normal mouse [12]. These results were later on confirmed by other studies on rodents grown in a germ-free (GF) environment that showed how gut microbiota influences the development of emotional behavior, stress and pain systems modulation, and the functioning of neurotransmitter systems in the brain [13, 14]. This communication between gut and brain was proven to be dependent on at least two elements such as vagus nerve signaling and specific bacterial species [15–18]. Further on, the influence of gut microbiota composition on high cognitive processes and brain chemistry [19] was demonstrated by its modulation with probiotics and antibiotics [10, 20].

Studies on GF mice also highlighted another surprising relationship between gut microbiota and aging and in the occurrence of aging-related-diseases. It has been shown that GF mice live significantly longer than normal animals, probably due to the reduction of pathological infections, with a first report back in the mid 1960s [21], followed by others in mice [22, 23] *Drosophila melanogaster* [24], *Caernohabditis elegans* [25].

**1. Introduction**

248 Gerontology

and neuromodulators signaling.

gut and the brain is essential.

antibiotics [10, 20].

diseases and the use of antibiotics [3].

In recent years, great progress has been made in characterizing bidirectional interactions between central nervous system (CNS), enteric nervous system and gastrointestinal tract. Dr Michael Gershon has defined the gut as "the second brain" [1] for several reasons: the enteric nervous system may function autonomously (it is capable of reflexes in the absence of CNS input), it can communicate with CNS through the parasympathetic (via vagal nerve) and sympathetic (via paravertebral ganglia) nervous system and is susceptible to neurotrophic

The term gut-brain axis is often extended to include the role of intestinal flora in the system, in which case the axis is called microbiota-gut-brain axis. The microbiota is not limited to bacteria but also includes protozoa, fungi, nematodes and viruses, so that in the intestinal tract there are over 1000 species of bacteria out of a total of approximately 100 trillion organisms [2]. To maintain the homeostasis of such complex system, permanent correlation between the

The gastrointestinal microbiota has a symbiotic relationship with enteric cells and contributes to basic physiological processes such as digestion, growth and immune defense. The composition of an individual's microbiota depends on the mode of delivery at birth, genetic predisposition, age, nutrition, physical activity, environmental factors, stress, infections, other

Gut microbiota can influence the functioning of the CNS by the ability to synthesize or mimic some molecules such as host-signaling neuroactive molecules, for example, acetylcholine, catecholamine, g-aminobutyric acid (GABA), histamine, melatonin and serotonin [4]. Conversely, the composition of the microbiota is influenced by emotional and psychological stress [5], resulting, for example, in the decrease in *Lactobacilli* species or the increase of *Clostridium* species [6, 7]. Although communication between the components of the microbiota-gut-brain axis has been well established by preclinical and clinical studies (excellently reviewed in [8–11]), the exact mechanisms by which this communication is made remains largely unknown. The interest in this research area began to consistently grow since the early 2000s, when one of the first papers to be published showed that germ-free (GF) mice exhibit an exaggerated hypothalamus-pituitary axis (HPA) response to stress compared to a normal mouse [12]. These results were later on confirmed by other studies on rodents grown in a germ-free (GF) environment that showed how gut microbiota influences the development of emotional behavior, stress and pain systems modulation, and the functioning of neurotransmitter systems in the brain [13, 14]. This communication between gut and brain was proven to be dependent on at least two elements such as vagus nerve signaling and specific bacterial species [15–18]. Further on, the influence of gut microbiota composition on high cognitive processes and brain chemistry [19] was demonstrated by its modulation with probiotics and We shall further detail some topics related to the gut-brain axis in the elderly, like gut-brain alterations observed in preclinical and clinical studies, some data about neuro-nutraceuticals with a focus on mechanisms and gut-brain axis modulation with a final reference to clinical trials.
