# Probiotics and Paraprobiotics--New Proposal for Functional Food
## 3 Paraprobiotic Opportunities and Challenges
### Mechanism of Paraprobiotics' Health Benefits  
The human health benefits of paraprobiotics are usually confronted with the effects of probiotics. This is comprehensible because their bioactive mechanisms are not fully elucidated. In many aspects, they are similar to those of probiotics. In general, the main bioactivity exerted by paraprobiotics is due to the compounds that are present on the bacterial cell wall. These include peptidoglycans, teichoic acids, lipopolysaccharidesaccharides, and other cell surface proteins [7; 40; 41]. Retaining outermost compounds on non-viable cells can trigger similar immune activity stimulating the innate immune system like that produced by viable probiotics. Peptidoglycan is the main component of the cell walls of Gram-positive bacteria and in Gram-negative bacteria, along with lipopolysaccharidesaccharides, which constitute an important component of the cell wall structure [42]. However, the composition of peptidoglycans and lipopolysaccharidesaccharides differs significantly among bacterial species, and for this reason, different immunological effects are exerted [43]. Another cell wall compound of Gram-positive bacteria involved in immunomodulation is teichoic acid. The significance of external compounds was confirmed by much research. [PERSON] et al. [44] reported that intact _L. casei_ Shirota stimulated the production of IL-12 (interleukin 12), unlike the soluble peptidoglycan. Similar information was reported by [PERSON] et al. [45] with the _L. salivarius_ UCC118 when the stimulations of IL-8 were hampered only by intact cells. Paraprobiotics' immunomododulatory activities are bidirectional. They stimulate both the production of pro-inflammatory cytokines (IL-2, IL-3, IL-8, tumor necrosis factor-alpha (IFN-\(\alpha\)), interferon-gamma (IFN-\(\gamma\)) as well as anti-inflammatory cytokines (IL-10, IL-6, IL-13, IL-4) (Figure 2). Moreover, paraprobiotics were found to promote the production of immunoglobulin (IgE, IgA IgM, IgG1) [7]. It can be assumed that living probiotics, as well as paraprobiotics, through various mutualistic influences on human organisms, exert comparable immunomododulatory responses [46]. Most of the research on paraprobiotics focuses on those derived from probiotic bacterial strains. Reports on yeast-derived paraprobiotics are rare [47]. The main constituents of yeasts' cell wall construction are polysaccharides, especially \(\beta\)-glucan (55-65% of cell wall components) and mannan (35-40% of cell wall components) [48; 49]. In the study by [PERSON] et al. [50], heat-inactivated _S. cerevisiae_ and _S. bouulardii_ modified the immunological reaction of RAW 264.7 macrophages. They reported an increase in pro-inflammatory cytokines, including TNF \(\alpha\) and IL-6. Moreover, the raised secretion of anti-inflammatory IL-10 was also reported (Figure 2). The most effective in immunomododulation turned out to be _S. boulardii_. The authors explained that it was the result of the higher mannan content in the cell wall of _S. boulardii_ compared with _S. cerevisiae_. Another study highlighted the mechanism of paraprobiotic health benefits in competition with enteropathogenic bacteria for adhesion sites, which prevents pathogenic colonization. According to [PERSON] et al. [51], this activity is strain-specific and inhibits the adherence of selected pathogens [52]. The effects of paraprobiotics also include the enhancement of the gut epithelial barrier, preserving its integrity and function, and reducing permeability [53,54]. Some authors point out that paraprobiotics, like probiotics, exert antioxidant activity, protecting the host against oxidative damage (Table 1) [55].