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Probiotics have several health benefits by modulating gut microbiome; however, techno-functional limitations such as viability controls have hampered their full potential applications in the food and pharmaceutical sectors. Therefore, the focus is gradually shifting from viable probiotic bacteria towards non-viable paraprobiotics and/or probiotics derived biomolecules, so-called postbiotics. Paraprobiotics and postbiotics are the emerging concepts in the functional foods field because they impart an array of health-promoting properties. Although, these terms are not well defined, however, for time being these terms have been defined as here. The postbiotics are the complex mixture of metabolic products secreted by probiotics in cell-free supernatants such as enzymes, secreted proteins, short chain fatty acids, vitamins, secreted biosurfactants, amino acids, peptides, organic acids, etc. While, the paraprobiotics are the inactivated microbial cells of probiotics (intact or ruptured containing cell components such as peptidoglycans, teichoic acids, surface proteins, etc.) or crude cell extracts (i.e. with complex chemical composition)”. However, in many instances postbiotics have been used for whole category of postbiotics and parabiotics. These elicit several advantages over probiotics like; (i) availability in their pure form, (ii) ease in production and storage, (iii) availability of production process for industrial-scale-up, (iv) specific mechanism of action, (v) better accessibility of Microbes Associated Molecular Pattern (MAMP) during recognition and interaction with Pattern Recognition Receptors (PRR) and (vi) more likely to trigger only the targeted responses by specific ligand-receptor interactions. The current review comprehensively summarizes and discussed various methodologies implied to extract, purify, and identification of paraprobiotic and postbiotic compounds and their potential health benefits.

Probiotics are live microorganisms that confer health benefits on the host. However, in recent years, several concerns on their use have been raised. In particular, industrial processing and storage of probiotic products are still technological challenges as these could severely impair cell viability. On the other hand, safety of live microorganisms should be taken into account, especially when administered to vulnerable people, such as the elderly and immunodeficient individuals. These drawbacks have enhanced the interest toward new products based on non-viable probiotics such as paraprobiotics and postbiotics. In particular, paraprobiotics, defined as “inactivated microbial cells (non-viable) that confer a health benefit to the consumer,” hold the ability to regulate the adaptive and innate immune systems, exhibit anti-inflammatory, antiproliferative and antioxidant properties and exert antagonistic effect against pathogens. Moreover, paraprobiotics can exhibit enhanced safety, assure technological and practical benefits and can also be used in products suitable for people with weak immunity and the elderly. These features offer an important opportunity to prompt the market with novel functional foods or nutraceuticals that are safer and more stable. This review provides an overview of central issues on paraprobiotics and highlights the urgent need for further studies aimed at assessing safety and efficacy of these products and their mechanisms of action in order to support decisions of regulatory authorities. Finally, a definition is proposed that unambiguously distinguishes paraprobiotics from postbiotics.

This review delves into the increasing interest in probiotics and paraprobiotics as a viable alternative to antibiotics in aquaculture, highlighting their potential to enhance fish health and prevent diseases. As the aquaculture industry continues its global expansion, addressing the challenges associated with disease outbreaks in high-density fish populations becomes imperative. The review underscores the promising role of probiotics and paraprobiotics as a sustainable strategy to mitigate these challenges. The diverse positive impacts of various probiotic strains such as Arthrobacter , Bacillus , Lactobacillus , Bifidobacterium , Clostridium , and others emphasize their roles in enhancing growth, resistance to diseases (including bacterial, viral, and parasitic infections), stress reduction, water quality management, and environmental sustainability. Challenges such as stability, host specificity, and regulatory considerations must be addressed to optimize the use of probiotics in aquaculture. Additionally, paraprobiotics, or non-viable microbial cells, present a safer alternative to the criticized antibiotics and even live probiotics in environments where microbial viability poses a risk. These inactivated cells retain the ability to modulate the immune system and improve gut health, offering a promising complementary approach to fish disease prevention. The review advocates for a systematic approach combining research, innovation, and collaboration to effectively integrate probiotics and paraprobiotics into fish farming practices. Furthermore, the mechanisms by which probiotics and paraprobiotics modulate gut microbiota, produce antimicrobial compounds, and strengthen fish’s immune system have been elucidated. Moreover, the practical applications of probiotics in fish farming, including optimal administration methods and the challenges and limitations faced by the industry, have been discussed. Emphasis on the importance of continued research to explore new probiotic and paraprobiotic strains and develop innovative delivery systems to ensure the sustainability of aquaculture has been discussed. By enhancing fish health, reducing the need for antibiotics, and improving water quality, probiotics, and paraprobiotics contribute to more sustainable and environmentally responsible aquaculture operations.

Overweight and obesity are significant global public health concerns that are increasing in prevalence at an alarming rate. Numerous studies have demonstrated the benefits of probiotics against obesity. Postbiotics are the next generation of probiotics that include bacteria-free extracts and nonviable microorganisms that may be advantageous to the host and are being increasingly preferred over regular probiotics. However, the impact of postbiotics on obesity has not been thoroughly investigated. Therefore, the goal of this review is to gather in-depth data on the ability of postbiotics to combat obesity. Postbiotics have been reported to have significant potential in alleviating obesity. This review comprehensively discusses the anti-obesity effects of postbiotics in cellular, animal, and clinical studies. Postbiotics exert anti-obesity effects via multiple mechanisms, with the major mechanisms including increased energy expenditure, reduced adipogenesis and adipocyte differentiation, suppression of food intake, inhibition of lipid absorption, regulation of lipid metabolism, and regulation of gut dysbiosis. Future research should include further in-depth studies on strain identification, scale-up of postbiotics, identification of underlying mechanisms, and well-defined clinical studies. Postbiotics could be a promising dietary intervention for the prevention and management of obesity.

Paraprobiotics, inactivated microbial cells, regulate immune system and exhibit antioxidant and anti-inflammatory activities in patients with weakened immunity or the elderly. This study evaluated the anti-tumor effects of heat-killed Bifidobacterium and Lactobacillus on human gastric cancer MKN1 cells in vitro and in vivo in xenograft animal models. First, cytotoxicity and apoptosis in MKN1 cells of 11 different heat-killed Bifidobacterium or Lactobacillus strains were examined using the MTT assay or flow cytometry, respectively. Then, BALB/c nude mice xenograft animal models were implanted with human gastric cancer MKN1 cells and orally administered a selected single or a mixture of heat-killed bacterial strains to investigate their inhibitory effect on tumor growth. In addition, the expression of p-Akt, p53, Bax, Bak, cleaved caspase-9, -3, and PARP in the tumor tissues was analyzed using Western blotting assay or immunohistochemistry staining. The results show that heat-killed B. bifidum MG731 (MG731), L. reuteri MG5346 (MG5346), and L. rhamnosus MG5200 (MG5200) induced relatively greater apoptosis than other strains in MKN1 cells. Oral administration of a single dose or a mixture of MG731, MG5346, or MG5200 significantly delayed tumor growth, and MG731 had the most effective anti-tumor effect in the xenograft model. Protein expression of p-Akt, p53, Bax, cleaved caspase-3 and -9, and PARP in tumors derived from the xenograft model correlated with the results of the immunohistochemistry staining.

Background: The gut microbiota impacts on central nervous system (CNS) function via the microbiota–gut–brain axis. Thus, therapeutics targeting the gut microbiota such as probiotics have the potential for improving mental health. This meta-analysis synthesizes the evidence regarding the impacts of probiotics on psychological well-being, psychiatric symptoms and CNS functioning. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied for executing this review using the databases PubMed, Web of Science and Cochrane Library. The data were summarized at qualitative and quantitative level. Results: Fifty-four randomized placebo-controlled studies were included, of which 30 were eligible for meta-analysis. If investigated, the probiotics mostly exerted effects on CNS function. Most probiotics did not affect mood, stress, anxiety, depression and psychiatric distress when compared to placebo at the qualitative level. At quantitative level, depression and psychiatric distress improved slightly in the probiotic condition (depression: mean difference −0.37 (95% CI: −0.55, −0.20); p ≤ 0.0001; psychiatric distress: mean difference −0.33 (95% CI: −0.53, −0.13); p = 0.001). Conclusions: To date it is unclear to which extent and in which specific areas next generation probiotics selected and developed for their ability to improve psychiatric condition and potentially other CNS functions are promising.

Probiotics are living microorganisms that are beneficial to the host, enhancing the immune response by promoting antibody production, regulating cytokine secretion, and stimulating T cells. However, probiotics have limitations in that they require viability control and have a short shelf life. Recently, the use of paraprobiotics has gained attention. These include dead bacterial cells, bacterial fractions, and cell lysate that have health benefits and are stable and safe for use. Paraprobiotics comprise molecules of bacterial cell wall compounds, such as peptidoglycans, teichoic acids, polysaccharides, and cell surface proteins. Paraprobiotics are manufactured by a diverse range of techniques, including thermal treatments, high pressure, ultraviolet rays, sonication, ionizing radiation, and pH modification. Their beneficial health effects include immunomodulatory, intestinal balancing, anticancer, and antimicrobial activities. Therefore, this review summarizes and discusses the manufacturing methods and bioavailability of paraprobiotics and suggests their potential health advantages.

It is now well known how the microbiota can positively or negatively influence humans health, depending on its composition. The microbiota’s countless beneficial effects have allowed it to be defined as a genuine symbiont for our species. In an attempt to positively influence the microbiota, research has focused on probiotics and prebiotics. Probiotics are viable beneficial bacteria of various strains. Prebiotics are specific substances able to favor the development of advantageous bacteria strains. Postbiotics are a new category of compounds capable of affecting the microbiota. According to the different definitions, postbiotics include both nonviable bacteria and substances deriving from bacterial metabolism. Postbiotics are particularly promising in pediatric settings, as they offer some advantages over probiotics, including the absence of the risk of intestinal translocation or worsening of local inflammation. For these reasons, their use in fragile population categories such as newborns, and even more prematures, seems to be the best solution for improving microbiota’s health in this population. This narrative review aims to collect the research conducted so far on postbiotics’ potential in the first stages of life.

Periodontal disease represents a progressive destruction of tooth-supporting tissues. Recently, paraprobiotics are regarded as an adjunctive therapy to the non-surgical Scaling-and-Root-Planing (SRP). The aim of this study is to evaluate the efficacy of two new formulations of paraprobiotics, a toothpaste and a mouthwash, respectively, for the domiciliary hygiene. A total of 40 patients were randomly assigned to the following domiciliary treatments: Group 1 (SRP + Curasept Intensive Treatment 0.2% chlorhexidine) (control) and Group 2 (SRP + Biorepair Peribioma toothpaste + Biorepair Peribioma Mousse mouthwash) (trial). At baseline (T0) and after 3 and 6 months (T1–T2), periodontal clinical (Bleeding on Probing, Probing Pocket Depth, Clinical Attachment Loss, Bleeding Score, Sulcus Bleeding Index, Plaque Index, Approximal Plaque Index, Adherent Gingiva, Gingival Recession, and Pathological Sites) and microbiological parameters (Pathological Bacteria, Saprophytic Bacteria, Enlarged Red Complex, Red Complex, Orange Complex, and counts of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythensys, Treponema denticola, Prevotella intermedia, and Fusobacterium nucleatum). The use of the experimental products resulted in a significant reduction of most of the clinical indices assessed, which occurred at a major degree with respect to the conventional chlorhexidine considered as control. Additionally, after 6 months of use, the abovementioned products significantly decreased the percentage of pathological bacteria and the counts of those bacteria constituting the “Red Complex”, more related to the periodontal disease. Accordingly, the paraprobiotics-based products tested in this study seem to represent a valid support to SRP with a benefit on both clinical indices and on specific periodontopathogens.

Background: This experiment was designed to investigate how replacing antibiotics with postbiotics and paraprobiotics could affect growth performance, small intestine morphology, immune status, and hepatic growth gene expression in broiler chickens. Methods: The experiment followed a completely randomized design (CRD) in which eight treatments were replicated six times with seven birds per replicate. A total of 336, one-day-old (COBB 500) chicks were fed with the eight treatment diets, which include T1 = negative control (Basal diet), T2 = positive control (Basal diet + 0.01% (w/w) Oxytetracycline), T3 = Basal diet + 0.2% (v/w) postbiotic TL1, T4 = Basal diet + 0.2% (v/w) postbiotic RS5, T5 = Basal diet + 0.2% (v/w) paraprobiotic RG11, T6 = Basal diet + 0.2% (v/w) postbiotic RI11, T7 = Basal diet + 0.2% (v/w) paraprobiotic RG14, T8 = Basal diet + 0.2% (v/w) paraprobiotic RI11, for 35 days in a closed house system. Results: The growth performance indicators (final body weight, cumulative weight gain, and feed conversion ratio) were not significantly (p > 0.05) affected by the dietary treatments. However, feed intake recorded a significant (p < 0.05) change in the starter and finisher phases across the dietary treatments. Paraprobiotic RG14 had significantly (p < 0.05) lower abdominal fat and intestines. Villi heights were significantly (p < 0.05) increased, while the crypt depth decreased significantly due to dietary treatments. The dietary treatments significantly influenced colon mucosa sIgA (p < 0.05). Similarly, plasma immunoglobulin IgM level recorded significant (p < 0.05) changes at the finisher phase. In this current study, the hepatic GHR and IGF-1 expressions were significantly (p < 0.05) increased by postbiotics and paraprobiotics supplementation. Conclusions: Therefore, it was concluded that postbiotics and paraprobiotics differ in their effect on broiler chickens. However, they can replace antibiotics without compromising the growth performance, carcass yield, and immune status of broiler chickens.