**1. Introduction**

The oral-gastro-intestinal-sex-skin can be classified as unique large and heterogeneous apparatus populated by a huge variety of microorganisms, bacteria, virus, fungi, and other single-celled creatures, that compose the totality of human microbiota that contributes together with bone/skeleton system, to maintain the body energy homeostasis. The human body hosts something like 10–100 trillion microbial cells that coexist in a strict fruitful symbiotic relationship that persists as long as the body is kept in a balanced healthy state [1, 2]. The gut plays an important role in regulating metabolic immune activities. The gut's essential task is the absorption of nutrients and the synthesis of important micromolecules obtained from food that cannot be assimilated by the stomach and small intestine [1–3]. Xyloglucans and fructo-oligosaccharides from vegetables and fruits, protein, and lipids; the assimilation of essential vitamins like vitamins B-12, D, and K; and the synthesis of hormones like serotonin from tryptophan amino acid take place right in the gut, thanks to the constant activity of its entire microbiota. The microbiota are able to produce 50–100 mmol·L—1 per day of extremely important short-chain fatty acids (SCFAs), such as acetic, propionic, and butyric acids—and serve as an energy source to the host intestinal epithelium and skeleton [1–4].

The importance of SCFAs has been well described by several studies during the last decade; the activity of acetic acid, for instance, has been found to be essential against infections, in blood pressure regulation and against sclerotic plaque deposition in arterial walls. The presence of butyric acid is an essential anti-IBS agent due to its immune-modulator properties and anti-inflammatory action, while propionic acid has been found to be important in preventing obesity and diabetes 2 [1–4].

Although bacteria, viruses, and fungi might be very harmful and dangerous, they are indispensable for life as well. This symbiotic coexistence throughout the millennia made a deep crucial biological impact on human species, and it has become essential not only for survival but for evolution as well. Accumulating evidences have clearly demonstrated how part of these specific microorganisms can resume specific immunomodulatory roles and the way they affect either composition function or migration of various immune cell subpopulations from one site to a different location. For instance, oral macrophages may migrate under the influence of specific signal induction of local microbiota from oral either to the lungs or even the brain passing through the blood brain barrier (BBB) [5–10].

The outcomes from experiments performed on germ-free (GF) mice confirmed the great role of gut microbiota in the upsurge of immune system deficiencies. GF animals were shown to have compromised Paneth cells and low levels of natural killer (NK) cells, dendritic cells (DCs), and α/β + and γ/δ + T cell populations that play an important role in defense and pathogenesis during inflammation and infection, especially against certain types of malignancies. In addition, GF animals were highly susceptible to frequent infections due to a decline in angiogenin-4 (Ang4), a powerful antimicrobial part of the class of microbicide proteins in Paneth cells [5–10].

The alteration of the gut microbiota may contribute to open up the invasion of exogenous pathogens that may destabilize the whole intestinal mucosa. The pathogen systematic overgrowth will trigger a cascade of strong inflammatory responses making intestinal mucosa highly susceptible and motile. The chronic inflammation will weaken the endothelial tide junction to the point that the walls become highly relaxed and permeable causing the phenomenon known as "leaky gut" that allows

**121**

*Probiotics in Health and Immunity: A First Step toward Understanding the Importance…*

the free, uncontrolled passage of microorganism into the system via the bloodstream and tissues where they start allocating. In fact, the presence of these typical gut residents could be found in eroded, inflamed, and degenerated joints and

**2. Gut dysbiosis: a modality to understand neurodegenerative diseases: the disruption of blood-brain barrier (BBB) may explain the** 

The high and uncontrolled levels of pathogenic microorganism colonizing the gut contribute to a condition known as dysbiosis [14]. Since few years the dysbiosis has been associated with a variety of degenerative patterns that tend to subvert the metabolic/neuro/hormonal/immune axis contributing to a variety of disorders that round to different body systems ranging from skeleton, cardiovascular, to neuro system. There are several mechanisms proposed that are able to trigger this state of systemic disorders; one of the possibilities is linked to bacterial metabolites and immune-modulating mediators that contribute to the high permeability of intestinal mucosa allowing local pathogens to get through the mucosal barriers triggering a huge variety of immune responses. A second and though related mechanism is the sabotage of SCFAs' production; the consequences of this mechanism are the abrupt breakdown of energy balance mechanism, a reduction of cell-bacteria signaling pathway, and the worsening of epithelial cell layer integrity due to the decreased production of tight junction proteins which allows the translocation of LPS into the submucosa as well. The significant presence of pro-inflammatory cytokines and interleukins such as TNFα, IFN-γ, IL-1β, IL-2, IL-4, IL-5, and IL-6 is the peculiar trait of a dysbiotic gut (**Figure 1**) [14–16]. A third way of dysbiosis transmission is through the vagus nerve (VN), the main component of parasympathetic nervous system (PSN) which also constitutes an effective bridge of the gut/CNS axis. This hypothesis, today supported by a concrete line of evidences, proposes the existence of a reciprocal interference way between the CNS and gut through the VN. In this view the VN is able to perceive microbiota movement, grade of activity, and therefore degradation; on the other hand, pathogens once out from the gut mucosa barrier are able to communicate and move to the CNS

These essential structural alterations are at the base of neurodegenerative pathologies. Though it is a unique pathological aspect, we may see the presence of a common configuration indeed, which is a shared neurological chronic inflammatory pattern. In all these cases, the chronic neuro-inflammatory condition is characterized by an abnormal hyperactive behavior of neural immune cells, the microglia, known as macrophages of the brain [18, 19]. The chronic inflammatory state that from the gut opens up the pathway of pathogenic microbiota invasion all the way through oral and brain compartment, which is the hallmark of neurodegenerative disorders' dynamic pathogenesis. Patients with Parkinson's disease (PD), Alzheimer's (AD), multiple sclerosis (MS), or amyotrophic lateral sclerosis all present a variety of disturbances in intestinal microbial compared to healthy individuals. Neurodegenerative-affected patients' intestinal and fecal analysis showed a clear clinical picture of microbiota dysbiosis. The test outcomes showed high level of coliform and gram-negative bacteria from *Ralstonia* genus concomitantly with low critical level of anti-inflammatory strains related to *Blautia*, *Coprococcus*, and *Roseburia* genera. Another indicator was also noted; it was the low presence of *Prevotella* generally seen as beneficial bacteria, involved in the metabolism of plant polysaccharides and vitamins strictly associated with the production of neuroactive

*DOI: http://dx.doi.org/10.5772/intechopen.88601*

**gut-oral-brain axis relationship**

through the VN pathway [14–18].

organs such as the lungs, heart, brain, and liver [11–13].

*Probiotics in Health and Immunity: A First Step toward Understanding the Importance… DOI: http://dx.doi.org/10.5772/intechopen.88601*

the free, uncontrolled passage of microorganism into the system via the bloodstream and tissues where they start allocating. In fact, the presence of these typical gut residents could be found in eroded, inflamed, and degenerated joints and organs such as the lungs, heart, brain, and liver [11–13].
