# Probiotics and Paraprobiotics--New Proposal for Functional Food
## 2 The Safety of Paraprobiotics  
With the growing popularity of functional foods among consumers, probiotic safety has become increasingly relevant. This is especially important in vulnerable populations, including infants, elderly people, pregnant women, and chronically ill or immunocompromised patients [17]. It should be emphasized that for more seriously ill patients, the benefit of probiotics usage may be greater. The safety issues cannot be neglected, and potential profits should be confronted with possible side effects [17].  
The list of probiotics intended for human use is recommended according to the approved status in the USA, Generally Recognized as Safe (GRAS), or in the European Union as Qualified Presumption of Safety (QPS) [18; 19]. These rules regulate their application and safety. Probiotics usage, including food products enriched with them, are under continuous surveillance by suitable agencies. Nowadays, molecular typing, including whole genome sequencing, is recommended for probiotic identification. Before probiotics are recognized as safe and obtain the status for human intended use, extended research should be scheduled. The approval requirements for new probiotic microorganisms are restrictive  
Figure 1: Family of bioactive food ingredients. FOSHU—foods for specified health uses.  
and are the same as for drugs. In 2012, the Food and Drug Administration (FDA) created a category of live microorganisms, such as bacteria called Live Biotherapeutic Products (LBPs). LBPs are intended for the prevention and treatment of diseases or conditions in human beings. LBP is recognized by the FDA as \"medicinal products containing live microorganisms (bacteria or yeasts) [20; 21]. Those regulations were followed in 2019 by the European Pharmacopoeia Commission of the European Directorate for the Quality of Medicines & HealthCare [22]. Therefore, the approval of LBPs requires a series of expensive pre-clinical and clinical research, including randomized controlled trials.  
Most probiotic reports are focused on health benefits, while adverse events are underreported [23; 24]. One of the potential threats related to the use of live microorganisms in functional food is the transfer of antibiotic-resistance genes. This is an essential issue in the scope of the widespread use or even overuse of antibiotics. Other adverse events of probiotics are local and systemic infections, including life-threatening sepsis [25]. Considering the possibility of probiotics and the occurrence of adverse events, paraprobiotics, and postbiotics are safer components of functional foods than live microorganisms. Their use is not related to the above-mentioned risks and is even harmless. This attribute seems to be particularly important in vulnerable patient populations. Other aspects that favor paraprobiotics over probiotics to whom viability at a high level is required are convenience related to food processing, storage, and transportation. Moreover, the interactions of paraprobiotics with the food matrix and food products are limited or even absent. This facilitates the extension of functional food products' shelf life with retained paraprobiotic bioactivity intended for the health benefits of consumers [26]. The paraprobiotic attributes of safety and stability offer the possibility of large-scale applications in functional food production and consumption. On the other hand, in comparison with live probiotic microorganisms, non-viable cells are not capable of producing and secreting many valuable bioactive metabolites, such as bacterios, lipopolysaccharide, exopolysaccharide, organic acids, etc. [27; 28].