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The three levels of

Probiotic Action

 

There is a large variety in microbial species and strains and their properties vary amongst each other. Multiple microbe–microbe and microbe–host interactions account for the versatility of probiotic action. To provide insight in their working mechanisms we make use of the “3 levels of probiotic action” concept. In this concept the possible effects of the activities of microorganisms on our health are grouped in three levels. The levels correspond to the location on or in the body where their effects take place and the nature of the process that is influenced. In figure 1, a schematic overview of this 3 level concept is shown. Some probiotic activities are directly beneficial for the host, because their effects are directly mediated by metabolites produced by the probiotic microorganisms. Other activities are more indirectly beneficial, and a cascade (i.e. signalling pathways) of chemical reactions is necessary to finally result in health-benefits for the host.

 

 

Figure 1: The three levels of probiotic action concept 

 

COPY The function of a carrier material in probiotics_1517

 

 

 

1. Level 1: external effects. The effects that affect processes outside the body.

 

 

2. Level 2: local barrier effects. The effects that affect local barrier functioning.

 

 

3. Level 3: systemic internal effects. The effects that affect systemic processes inside the body.

 

 

Level 1: external effects

The probiotic effects that are grouped in this level affect processes that take place on the outside of the human body. Not only on those surfaces that we obviously consider to be the outside of our body, such as the skin, but also other surfaces of our body that we, in our ignorance, often think of as the inside. Examples of surfaces that we often incorrectly see as the inside of our body are: the inside of our mouth, the lumen of our gut, and the bladder. These body cavities are essentially extensions of the external space, as they are in direct contact to the external environment. At this level most of the probiotic actions affect microbe ↔ microbe interactions. These effects mainly revolve around maintaining or restoring microbiota homeostasis. An example of an important microbe–microbe interaction is a process known as cross-feeding. Cross-feeding is the nutritional interaction between microbial community members, e.g. the break-down of an indigestible polysaccharides by one microorganism results in the nutrients for another.

 

Other examples of effects on level 1, are the influences that microbial activities have on the:

 colonization and outgrowth of pathogens (e.g. by competition for nutrients, or the production of antimicrobial substances);

 direct communication between microorganisms (e.g. by production of quorum sensing molecules).

 

 

 

Level 2: local barrier effects

The probiotic effects that are grouped in this level affect processes that take place at the interface between the outside and the inside of the body. At this level most of the probiotic actions affect local microbe ↔ barrier interactions. The nature of these interactions depend on the body site, as the barrier formed by, for example, the skin has different properties than the intestinal or vaginal barrier. Furthermore, in this “3 levels of probiotic action” concept, the barrier is not only formed by a physical barrier consisting of epithelial cells, but also comprises e.g. the overlaying mucus layer, and underlying connective tissue. An example of an important microbe-barrier interaction is the effect of gut microorganism on the permeability of the intestinal barrier. The intestinal barrier is formed by a single layer of epithelial cells that constitutes the largest epithelial barrier that we have in our body. This epithelial cell layer permits the absorption of nutrients, electrolytes and water, while maintaining an effective defence against intraluminal toxins, antigens and microorganisms. The permeability of the intestinal barrier is amongst others regulated by so called tight junctions, protein structures that connect epithelial cells. Studies have shown that the intestinal microorganisms can target various intracellular pathways to change the expression and distribution of tight junction proteins, and thereby regulate intestinal barrier permeability.

 

Other examples of effects on level 2, are the effects of microbial activities on the:

  level of cytoprotective compound production (e.g. defences) by host cells;

  regulation of host mucus secretion;

  regulation of gut motility.

 

 

Level 3: systemic internal effects

The microbial effects that are grouped in this level affect processes that take place inside the human body. At this level most of the probiotic actions affect systemic microbe ↔ host interactions. An example of an important microbe–host interaction, is the effect a microorganism can have on our systemic immune system. It has been seen that microorganisms in the intestinal tract can promote host defence by priming and conditioning specific adaptive immune response such as for example steering specific cytokine production by T cells. This makes sense when you realize that the largest part of all immune cells in our body (60-70%) is located around our intestine. Systemic immune effects are first to come to mind when thinking about health effects of probiotics. However, microorganisms are able to affect many other physiological systems as well.

 

Other examples of effects on level 3, are the effects of microbial activities on the:

 endocrine system e.g. by influencing hormone levels;

  circulatory system e.g. by influencing systolic blood pressure;

  neurological system e.g. by influencing neurotransmitter levels.

These systemic effects of probiotic activities are not caused by live probiotic microorganisms entering the bloodstream -translocation of microorganisms into the body is usually an undesirable event- but they are mediated by microbial metabolites or are the outcome of a cascade of reactions.

 

 

 

 

 

The function of a carrier material in probiotics

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