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Practical Application Paraprobiotics are inactivated microbial cells that improve the health status of consumers when taken in adequate doses. They can be used instead of probiotics to eliminate disadvantages such as instability in production and storage difficulties. They can also be an alternative nutritional supplement for individuals sensitive to fermented products. In this study, a paraprobiotic supplement obtained from Lactobacillus plantarum was added to a soy dairy‐free beverage at two concentrations of 108 and 109 CFU/mL. Then, total soluble solids, pH, color, titratable acidity, antioxidant activity, and total phenolic content of the beverage were measured, and sensory analysis was also performed. The results indicate that paraprobiotic addition significantly increased (p < 0.05) the antioxidant activity (75.44 ± 0.23 µmol TE/g sample), total phenolic content (834.32 ± 6.69 mg GAE/g), protein (3.28 ± 0.18%), fat (2.35 ± 0.06), and ash content (0.57 ± 0.08). These results were also validated using the Raman spectroscopy technique. The paraprobiotic‐supplemented soy dairy‐free beverage had the highest taste and overall impression values. Since the parabiotic addition did not affect the physicochemical properties of the beverage, manufacturers can develop commercial products containing paraprobiotics without altering the production process.Paraprobiotics provide an alternative for individuals sensitive to fermented products but still desire the health benefits of probiotics. They additionally provide practical and technological advantages, including a longer shelf life without a need for a cold chain to preserve the viability and stability of microorganisms. The results of this study can be a reference for the industry to develop food products containing paraprobiotics with increased antioxidative and nutritional properties. [ABSTRACT FROM AUTHOR]

Purpose: Paraprobiotics are a non-viable form of probiotics that are reported to provide significant health benefits. Nevertheless, little is known about the beneficial effects of paraprobiotics on inflammatory bowel disease. Although probiotics show potential as therapeutic agents for a range of diseases, including inflammatory bowel disease (IBD), there are certain risks associated with their use. These risks include toxin production, hemolytic potential, antibiotic resistance, and the need to analyze metabolic activities. Hence Using paraprobiotic with the lower aforementioned risk would therefore be the preferable option. Here, we conducted an in vivo study to evaluate the preventive effect of our native paraprobiotic cocktail against dextran sulfate sodium (DSS)-induced murine colitis by affecting the autophagy signaling pathway. Methods: Four-week-old male C57Bl/6 mice were randomly divided into three groups after a two-week acclimation period with normal standard laboratory food diet. Mice were administered PBS (PBS group as control), PBS along with DSS (DSS group, as a control), and a cocktail of paraprobiotics along with DSS (Para group). The severity of colitis, length and histopathology of the colon were evaluated. In addition, the expression of autophagy was assessed using real-time PCR. Results: The results showed that administration of the paraprobiotic cocktail to DSS-treated mice inhibited the severity of colitis symptoms, as evidenced by the inhibition of weight loss and DAI, as well as histopathological scores in the study colon, as well as shortening of colon length caused by DSS. In contrast to the DSS group, the cocktail was able to modulate inflammation through upregulation of autophagy-related genes (becline 1, atg5, atg7, atg12, and atg13). Conclusion: Although there are some limitations in our investigation, such as the dosage and duration of treatments, our native paraprobiotic blend effectively prevented the advancement of colitis. This suggests that it plays a vital role in regulating inflammation and preventing colitis by promoting the autophagy mechanism in cases where the consumption of probiotics may have negative consequences. [ABSTRACT FROM AUTHOR]

In recent years, the probiotic product market has experienced rapid growth driven by the increasing consumer demand for functional products. Probiotics, defined as 'live microorganisms that have positive effects on host health when taken in sufficient amounts' are widely used in the production of functional foods. Studies have demonstrated that probiotic cells can provide beneficial health effects even when they are not active. The terms paraprobiotic and postbiotic have emerged as alternatives to probiotics, offering potential opportunities in the functional food market. Paraprobiotics are defined as non-living microbial cells that confer health benefits on the host when administered in sufficient quantities. To obtain paraprobiotics, the living cell must be inactivated while preserving its intact structure. Postbiotics are metabolic products secreted by beneficial microorganisms or low molecular weight soluble compounds released into the environment because of microbial cell lysis. Paraprobiotics and postbiotics, which are reported to possess beneficial properties such as antimicrobial, anti-inflammatory, anticarcinogenic, antiproliferative, and immunomodulatory effects, are applied in the food and pharmacology industries. This study evaluates the definitions of paraprobiotics and postbiotics, their uses in the food and pharmaceutical industries, and their effects on health. [ABSTRACT FROM AUTHOR]

The aim of this study was to produce Bacillus subtilis subsp. spizizenii as a paraprobiotic for the nutrition of rainbow trout (Oncorhynchus mykiss). Fifty-four trout (74.51 ± 3.15 g) were transferred to nine 300-liter tanks and fed PRO (live freeze-dried form), PAR (irradiated freeze-dried form) and control feed (n=3) for 8 weeks. Growth, hematological, immunological and enzymatic liver functions, as well as antioxidant capacity were then analyzed. Kidney, liver, and intestinal tissue as well as the expression of cytokines (TNF-1, TNF-2, IL-1β1, and IL-1β2) in spleen, and kidney were analyzed. The growth indices, white, and red blood cells, neutrophils, monocytes and granulocytes, total protein and globulin improved in the PAR and PRO groups compared to the control group (p

Background and purpose: Stress is a behavioral process that helps humans to increase survival. Stress refers to any biological response to an internal or external stimulator. Stress is difficult to study because of its widespread effect on different parts of the body. A good diet is essential for maintaining mental and physical health. During stress time, eating habits are greatly disrupted and this can cause nutritional deficiencies that may lead to more stress on the body. In stressful situations, the body uses more nutrients than usual. So a good diet is required, as a poor diet causes deficiencies that lead to more stress and health problems. Since 2004, many scientific studies have proven the functional and health-promoting properties of non-living probiotics. In recent years, research has been conducted on the consumption of deactivated cells of probiotics (paraprobiotics) whose positive effects have been proven in some studies. In the current research, lactobacillus plantarum paraprobiotic cells have been used in Shahani grape drinks to reduce stress in master's degree students. Materials and methods: The production of paraprobiotics is done in different ways, including heating, applying ultrasound, ultraviolet radiation, infrared radiation, ionizing rays, applying high hydrostatic pressure, and using some chemical compounds. Each of these inactivation methods cause changes in the structure and functional characteristics of non-living probiotic cells. High-power ultrasound was used for deactivation. the suspension containing parapsychobiotic was evaluated for the amount of the active ingredient gamma-aminobutyric acid using a high- performance liquid chromatography. Inactivated cells were added to the reconstituted Shahani grape juice. 32 healthy students consumed a control drink and a drink containing paraprobiotics daily for 10 weeks during the end-of-semester exams. Results: The use of paraprobiotics obtained from inactivation methods is useful when the health-giving compounds and metabolites are not completely reduced or destroyed under the influence of the inactivation method. Gamma-aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the central nervous system and plays an important role in coordinating brain function and reducing anxiety and stress. The results showed that the amount of gamma-aminobutyric acid in the suspension of parapsychobiotics was higher than in the suspension of live bacteria. Subjects who consumed a grape juice drink containing parapsychobiotics had higher general health scores than the control group during exams. The use of paraprobiotics in drinks improved the quality of sleep. At the end of the test, the amount of cortisol in the saliva of the control group was higher than the parapsychobiotic treated group. Conclusion: The results of this research showed that Lactobacillus plantarum paraprobiotic has potential benefits for improving mental health. Based on the results of this research, paraprobiotics, by affecting the human brain axis, reduce the secretion of stress hormones such as cortisol and, as a result, increase mental stability during the final semester exams of students. (Clinical Trials Registry Number: IRCT20240128060833N1)

Background and purpose: Stress is a behavioral process that helps humans to increase survival. Stress refers to any biological response to an internal or external stimulator. Stress is difficult to study because of its widespread effect on different parts of the body. A good diet is essential for maintaining mental and physical health. During stress time, eating habits are greatly disrupted and this can cause nutritional deficiencies that may lead to more stress on the body. In stressful situations, the body uses more nutrients than usual. So a good diet is required, as a poor diet causes deficiencies that lead to more stress and health problems. Since 2004, many scientific studies have proven the functional and health-promoting properties of non-living probiotics. In recent years, research has been conducted on the consumption of deactivated cells of probiotics (paraprobiotics) whose positive effects have been proven in some studies. In the current research, lactobacillus plantarum paraprobiotic cells have been used in Shahani grape drinks to reduce stress in master's degree students. Materials and methods: The production of paraprobiotics is done in different ways, including heating, applying ultrasound, ultraviolet radiation, infrared radiation, ionizing rays, applying high hydrostatic pressure, and using some chemical compounds. Each of these inactivation methods cause changes in the structure and functional characteristics of non-living probiotic cells. High-power ultrasound was used for deactivation. the suspension containing parapsychobiotic was evaluated for the amount of the active ingredient gamma-aminobutyric acid using a high- performance liquid chromatography. Inactivated cells were added to the reconstituted Shahani grape juice. 32 healthy students consumed a control drink and a drink containing paraprobiotics daily for 10 weeks during the end-of-semester exams. Results: The use of paraprobiotics obtained from inactivation methods is useful when the health-giving compounds and metabolites are not completely reduced or destroyed under the influence of the inactivation method. Gamma-aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the central nervous system and plays an important role in coordinating brain function and reducing anxiety and stress. The results showed that the amount of gamma-aminobutyric acid in the suspension of parapsychobiotics was higher than in the suspension of live bacteria. Subjects who consumed a grape juice drink containing parapsychobiotics had higher general health scores than the control group during exams. The use of paraprobiotics in drinks improved the quality of sleep. At the end of the test, the amount of cortisol in the saliva of the control group was higher than the parapsychobiotic treated group. Conclusion: The results of this research showed that Lactobacillus plantarum paraprobiotic has potential benefits for improving mental health. Based on the results of this research, paraprobiotics, by affecting the human brain axis, reduce the secretion of stress hormones such as cortisol and, as a result, increase mental stability during the final semester exams of students. [ABSTRACT FROM AUTHOR]

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Cancer chemotherapy has allowed many patients to survive, but not without risks derived from its adverse effects. Drugs, such as 5-fluorouracil, irinotecan, oxaliplatin, methotrexate, and others, as well as different drug combinations trigger intestinal mucositis that may cause or contribute to anorexia, pain, diarrhea, weight loss, systemic infections, and even death. Dysbiosis is a hallmark of chemotherapy-induced intestinal mucositis and diarrhea, and, therefore, strategies aimed at modulating intestinal microbiota may be useful to counteract and prevent those dreadful effects. This narrative review offers an overview of the studies performed to test the efficacy of probiotics and probiotic-like agents against chemotherapy-induced intestinal mucositis and its consequences. Microbiota modulation through the oral administration of different probiotics (mainly strains of Lactobacillus and Bifidobacterium), probiotic mixtures, synbiotics, postbiotics, and paraprobiotics has been tested in different animal models and in some clinical trials. Regulation of dysbiosis, modulation of epithelial barrier permeability, anti-inflammatory effects, modulation of host immune response, reduction of oxidative stress, or prevention of apoptosis are the main mechanisms involved in their beneficial effects. However, the findings are limited by the great heterogeneity of the preclinical studies and the relative lack of studies in immunocompromised animals, as well as the scarce availability of results from clinical trials. Despite this, the results accumulated so far are promising. Hopefully, with the aid of these agents, intestinal mucositis will be less impactful to the cancer patient in the near future. [ABSTRACT FROM AUTHOR]

Studies describing antagonistic activity and disease resistance efficacy of potential probiotics towards lactococcosis caused by Lactococcus garvieae, Lactococcus lactis, Lactococcus piscium, and Lactococcus raffinolactis are limited. Most studies have focused on lactic acid bacteria (LAB), and less attention has been paid to Bacillus probiotics or other gram-positive or gram-negative members. Lactobacillus, Lactococcus, Leuconostoc, and Enterococcus are the most common genera of LAB tested towards L. garvieae either in in vitro or in vivo assays, and the obtained results are promising. Although strains of Flavobacterium, Pseudomonas, Aeromonas, and Vibrio genera have shown antibacterial activity against L. garvieae, further work is required to confirm such inhibition activity, particularly by disease resistance bioassays. recently, gram-positive or gram-negative bacteria strains have demonstrated antimicrobial inhibition towards L. garvieae in postbiotics, but details of their mode of action warranted further studies. This review addresses the probiotic therapy for lactococcosis in aquaculture and discusses the present gaps. [ABSTRACT FROM AUTHOR]

Intestinal mucositis (IM) is a common side effect resulting from cancer treatment. However, the management so far has not been very effective. In the last years, the role of the gut microbiota in the development and severity of mucositis has been studied. Therefore, the use of probiotics and paraprobiotics could have a potential therapeutic effect on IM. The aim of our study was to investigate the impact of the administration of Lacticaseibacillus rhamnosus (L. rhamnosus) CGMCC1.3724 and the paraprobiotic on IM in mice. For 13 days, male Balb/c mice were divided into six groups: control (CTL) and mucositis (MUC)/0.1 mL of saline; CTL LrV and MUC LrV/0.1 mL of 108 CFU of viable Lr; CTL LrI and MUC LrI/0.1 mL of 108 CFU of inactivated Lr. On the 10th day, mice from the MUC, MUC LrV, and MUC LrI groups received an intraperitoneal injection (300 mg/kg) of 5-fluorouracil to induce mucositis. The results showed that the administration of the chemotherapeutic agent increased the weight loss and intestinal permeability of the animals in the MUC and MUC LrV groups. However, administration of paraprobiotic reduced weight loss and maintained PI at physiological levels. The paraprobiotic also preserved the villi and intestinal crypts, reduced the inflammatory infiltrate, and increased the mucus secretion, Muc2 gene expression, and Treg cells frequency. [ABSTRACT FROM AUTHOR]

Tempeh is an Indonesian traditional food made from fermented soybeans, which offers wide culinary use in East Asian countries. Similar to all fermented foods, its preparation offers the purpose of food preservation. However, preclinical studies have highlighted that microbial action leads to a modification in the nutritional composition of the food’s matrix. Although there is a wide availability of data on the beneficial effect of soy, tempeh remains relatively unexplored, perhaps due to its limited diffusion in the world, which limits its research availability. However, available data suggest that tempeh may confer beneficial health effects due to the high bioavailability of nutrients and phytochemicals, showing ameliorative action on oxidative stress, glycaemic control, and blood lipid levels. Furthermore, the high biological value of tempeh means it can be used to optimize protein and caloric intake in athletes, vegetarians, and children. Moreover, the microbial fermentation used in the production of tempeh, in addition to improving the bioavailability of minerals, proteins, fibre, vitamins, and isoflavones, produces biopeptides whose biological effect is currently of great interest. Tempeh can be employed in traditional preparations as well as second-generation foods, such as plant-based meat substitutes, to provide functional and nutritional properties and a higher eco-friendly option compared to animal foods. This review aims to provide an overview of tempeh’s properties, regarding human data and future research perspectives.

Abstract Critical development period of intestinal microbiota occurs concurrently with brain development, and their interaction is influenced by the microbiota–gut–brain axis. This study examined how antibiotics exposure affected gut microbiota and brain development and analyzed the possible benefits of heat-inactivated Lacticaseibacillus paracasei N1115 (N1115). Thirty neonatal male mice were randomly divided into three groups and treated with sterilized water (control), an antibiotic cocktail (Abx), or antibiotics plus heat-inactivated N1115 (Abx + N1115) for 84 days. We found that while the mRNA levels of GABAAα1, GABAb1, and glucocorticoid receptor (GR) in the hippocampus and brain-derived neurotrophic factor (BDNF), GABAAα1, GABAb1, and nerve growth factor (NGF) in the prefrontal cortex were higher, the mRNA levels of 5-HT1A were lower in the Abx group. The Abx + N1115 group had lower mRNA levels of GABAAα1, GABAb1, and GR in the hippocampus and BDNF, GABAb1, and NGF in the prefrontal cortex than the Abx group. The latency period was longer in the Morris water maze test while longer rest time was seen in tail suspension test in the Abx group than the control and Abx + N1115 groups. In the open field test, the moving time and distance of the Abx group were reduced. Further, the alpha-diversity indexes of the Abx and Abx + N1115 groups were significantly lower than the control. Further, long-term exposure to antibiotics disrupted the intestinal microbiota as evidenced by decreased Bacteroides, Firmicutes, and Lactobacillus, and increased Proteobacteria and Citrobacter. However, N1115 significantly decreased the abundance of Citrobacter when compared with those in the Abx group. These results indicate that antibiotics can substantially damage the intestinal microbiota and cognitive function, causing anxiety and depression, which can be alleviated by heat-inactivated N1115 via modulation of the microbiota–gut–brain axis.

Long-term dietary habits are of great importance in the composition of the intestinal microbiota, which is represented by microorganisms that affect metabolic, physiological and immunological processes. The use of probiotics and prebiotics for the microbiota associated with nutrition is very popular. The fact that probiotics contain live microorganisms, which contribute significantly to the expansion of the food sector, can cause problems in industrial processes and storage. In recent years, in addition to probiotics and prebiotics, symbiotics in which probiotics and prebiotics are used in combination; postbiotics, which are metabolic by-products secreted by microorganisms, and paraprobiotics, which are non-living microbial cells, have started to attract a lot of attention. In the study, a literature review was conducted on the functions, health effects and uses of symbiotics, postbiotics and paraprobiotics in the food industry. [ABSTRACT FROM AUTHOR]

Abstract This study highlights the cytotoxic effect of three L. casei strains on colorectal cell lines in invitro conditions. Different concentrations of live, heat killed (HK) and cell free supernatant (CFS) of three L.casei strains were subjected to CaCo2 and MRC5 cell lines. The viability of the treated and untreated cells was determined after 72 hrs by MTT assay, and IC50 estimated. Apoptosis was evaluated by Annexin V-propidium iodide method using flow cytometry. The live, HK and CFS of the L. casei strains showed cytotoxic effects on colorectal cell lines with significant differences. The cytotoxicity effects of live cells on CaCo2 cells were significantly higher (p˂0.01) than the HK cells. A dose dependent response was observed, as higher concentrations resulted in enhanced cytotoxicity effects. Live L.casei 1296-2cells inhibited 91% of CaCo2 cell growth, with IC50 of less than 108 cfu/ml. MRS medium and concentrations of CFS at above 20% v/v, were cytotoxic to the normal cell lines. Flow cytometry analyses of L. casei 1296-2 indicated that cytotoxicity effects on CaCo2 cells is related to apoptotic induction. Invitro studies indicate that Live and CFS of L. casei 1296-2 might be promising candidate for the control of colorectal cancers.

Critical development period of intestinal microbiota occurs concurrently with brain development, and their interaction is influenced by the microbiota-gut-brain axis. This study examined how antibiotics exposure affected gut microbiota and brain development and analyzed the possible benefits of heat-inactivated Lacticaseibacillus paracasei N1115 (N1115). Thirty neonatal male mice were randomly divided into three groups and treated with sterilized water (control), an antibiotic cocktail (Abx), or antibiotics plus heat-inactivated N1115 (Abx + N1115) for 84 days. We found that while the mRNA levels of GABAAα1, GABAb1, and glucocorticoid receptor (GR) in the hippocampus and brain-derived neurotrophic factor (BDNF), GABAAα1, GABAb1, and nerve growth factor (NGF) in the prefrontal cortex were higher, the mRNA levels of 5-HT1A were lower in the Abx group. The Abx + N1115 group had lower mRNA levels of GABAAα1, GABAb1, and GR in the hippocampus and BDNF, GABAb1, and NGF in the prefrontal cortex than the Abx group. The latency period was longer in the Morris water maze test while longer rest time was seen in tail suspension test in the Abx group than the control and Abx + N1115 groups. In the open field test, the moving time and distance of the Abx group were reduced. Further, the alpha-diversity indexes of the Abx and Abx + N1115 groups were significantly lower than the control. Further, long-term exposure to antibiotics disrupted the intestinal microbiota as evidenced by decreased Bacteroides, Firmicutes, and Lactobacillus, and increased Proteobacteria and Citrobacter. However, N1115 significantly decreased the abundance of Citrobacter when compared with those in the Abx group. These results indicate that antibiotics can substantially damage the intestinal microbiota and cognitive function, causing anxiety and depression, which can be alleviated by heat-inactivated N1115 via modulation of the microbiota-gut-brain axis. [ABSTRACT FROM AUTHOR]

Heat-killed probiotics offer an alternative approach to enhance growth and disease resistance in farmed fish. In this study, we isolated Lactiplantibacillus plantarum VSG3 from the gut of Labeo rohita to investigate the effects of heat-killed L. plantarum (HK-LP) on the health and growth performance of Cyprinus carpio fingerlings. Different concentrations of HK-LP (0, 50, 100, 200, 300, and 400 mg/kg) were administered to the fish, followed by a challenge with Aeromonas hydrophila after 8 weeks of feeding. Notably, the LP200 group exhibited significantly improved percentage weight gain and specific growth rate, accompanied by the lowest feed conversion ratio. Post-challenge survival rates were considerably enhanced in the LP200 group, reaching 60.65%. Moreover, serum analysis indicated significantly higher levels of total protein and albumin in the LP200 group than in the control group. Although HK-LP had no substantial impact on certain serum parameters (glucose, total cholesterol, cortisol, and alanine aminotransferase), aspartate aminotransferase levels were considerably low in the LP200 group. Intestinal protease and trypsin activities significantly increased in the LP200 group, while no significant changes were observed in lipase and amylase activities post-pathogen challenge. Serum immunological indices, including lysozyme, alternative complement pathway, and phagocytic activity, improved considerably in the LP200 group. Additionally, serum antioxidant enzyme activities (superoxide dismutase [SOD], glutathione peroxidase [GPx], catalase [CAT], and myeloperoxidase) were significantly elevated in the LP200 group, while malondialdehyde level was reduced. Gene expression analysis in liver tissue indicated strong upregulation of antioxidant-related genes (SOD, CAT, nuclear factor erythroid 2 [NFE2]-related factor 2 [Nrf2], Kelch-like ECH-associated protein 1[Keap1]) in the LP100 and LP200 groups. Pro-inflammatory cytokines (IL-1β and TNF-α) were considerably downregulated in the kidneys of the LP200 post-challenged fish, although the anti-inflammatory cytokine IL-10 showed an increased expression. Quadratic regression analysis identified the optimal dietary HK-LP level for maximizing growth and immune performance (200.381–270.003 mg/kg). In summary, our findings underscore the potential of HK-LP as a valuable dietary supplement for enhancing carp aquaculture, particularly at the appropriate concentration. • Dietary heat-killed Lactiplantibacillus plantarum (HK-LP) benefits Cyprinus carpio health. • HK-LP enhances fish resistance against Aeromonas hydrophila challenge. • Study offers sustainable solution for aquaculture health. • Insights into HK probiotics' role in fish growth performance. • Novel research on probiotic impact on fish antioxidant status. [ABSTRACT FROM AUTHOR]

Recent researches have reported that pasteurized Akkermansia muciniphila , as a paraprobiotic, still plays an active role in various metabolic diseases. However, its role in alcoholic liver disease (ALD) remains unexplored. This study aims to evaluate the impact and mechanisms of pasteurized A. muciniphila on ALD. Its effects on ALD were assessed by phenotypic, biochemical parameters, and histological features in a mouse model. Further investigations into underlying mechanisms were conducted through gut microbiome, metabolomics analyses and quantitative real-time polymerase chain reaction (qRT-PCR) technology. Heterologously expressed outer membrane protein Amuc_1100 was utilized to explore the molecular action mechanism. Our research demonstrated that pasteurized A. muciniphila can indeed alleviate alcohol-induced liver damage by modulation of gut microbiota and host metabolism. It suppressed the proliferation of pathogenic microbes and fostered the growth of probiotics. Additionally, it rectified alcohol-induced abnormalities in serum metabolic patterns, particularly in lipid metabolism. Specifically, pasteurized A. muciniphila elevated serum levels of 3-hydroxybutyric acid, palmitoleic acid, acetylcarnitine, DHA, and arachidonic acid in alcohol-fed mice. qRT-PCR results showed that it reversed the alcohol-induced upregulation of mRNA expression of hepatic fatty acid synthesis genes and decreased mRNA expression of fatty acid oxidation and transport genes. Importantly, we identified that Amuc_1100 could partially recapitulate the protective effects of pasteurized A. muciniphila on ALD, especially regarding hepatic lipid metabolism. This study enhances our comprehension of the function of pasteurized A. muciniphila and underscores its potential therapeutic application, along with Amuc_1100, in the treatment of ALD. [Display omitted] [ABSTRACT FROM AUTHOR]

The proper functioning of the human organism is dependent on a number of factors. The health condition of the organism can be often enhanced through appropriate supplementation, as well as the application of certain biological agents. Probiotics, i.e., live microorganisms that exert a beneficial effect on the health of the host when administered in adequate amounts, are often used in commonly available dietary supplements or functional foods, such as yoghurts. Specific strains of microorganisms, administered in appropriate amounts, may find application in the treatment of conditions such as various types of diarrhoea (viral, antibiotic-related, caused by Clostridioides difficile), irritable bowel syndrome, ulcerative colitis, Crohn's disease, or allergic disorders. In contrast, live microorganisms capable of exerting influence on the nervous system and mental health through interactions with the gut microbiome are referred to as psychobiotics. Live microbes are often used in combination with prebiotics to form synbiotics, which stimulate growth and/or activate the metabolism of the healthy gut microbiome. Prebiotics may serve as a substrate for the growth of probiotic strains or fermentation processes. Compared to prebiotic substances, probiotic microorganisms are more tolerant of environmental conditions, such as oxygenation, pH, or temperature in a given organism. It is also worth emphasizing that the health of the host may be influenced not only by live microorganisms, but also by their metabolites or cell components, which are referred to as postbiotics and paraprobiotics. This work presents the mechanisms of action employed by probiotics, prebiotics, synbiotics, postbiotics, paraprobiotics, and psychobiotics, together with the results of studies confirming their effectiveness and impact on consumer health. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to evaluate the efficacy of paraprobiotics Lactobacillus acidophilus PIN7 supplementation against dextran sodium sulphate (DSS)–induced colitis in mice and to determine their mechanisms of the action. Methods and Results: Ten‐week‐old female BALB/C mice were randomly divided into five groups. Each group was administered with PBS (control and DSS group), live PIN7 (LIVE group), heat‐killed PIN7 (HEAT group) or lysozyme‐treated PIN7 (LYSOZYME group) for 10 days followed by 2.5% DSS supply in drinking water for 5 days except for the control group. Colitis‐associated DAI scores were significantly (p < 0.05) attenuated in HEAT and LYSOZYME group. The HEAT group exhibited significantly (p < 0.05) lower colonic tissue damage score compared to the DSS group. Furthermore, HEAT and LYSOZYME groups showed significantly (p < 0.05) higher colonic expressions of toll‐like receptor (TLR) 6 and intestinal junction protein E‐cadherin and occludin compared to the DSS group. LYSOZYME group showed significantly (p < 0.05) lower colonic expressions of Th2 cell‐associated pro‐inflammatory molecules, namely GATA3 and IL‐4, and higher expression of anti‐inflammatory NLRP6 and IL‐18 compared to the DSS group. Also, HEAT group exhibited significantly (p < 0.05) lower colonic p‐IκBα expression compared to the DSS group, while COX‐2 expression was significantly (p < 0.05) suppressed by both paraprobiotics supplementation. Paraprobiotics significantly altered the composition of the intestinal microbiota. Conclusion: Paraprobiotic L. acidophilus PIN7 ameliorated DSS‐induced colitis by regulating immune‐modulatory TLR6 signalling and gut microbiota composition. Significance and Impact of the Study: This study suggests paraprobiotic L. acidophilus PIN7 are superior candidates to prevent intestinal inflammation associated with dysregulated immune responses. [ABSTRACT FROM AUTHOR]

Haemonchus contortus is a critical parasite of goats and sheep. Infection by this blood-feeding gastrointestinal nematode (GIN) parasite has significant health consequences, especially in lambs and kids. The parasite has developed resistance to virtually all known classes of small molecule anthelmintics used to treat it, giving rise in some areas to multidrug resistant parasites that are very difficult to control. Thus, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal protein 5B (Cry5B), a naturally occurring protein made by a bacterium widely and safely used around the world as a bioinsecticide, represents a new non-small molecule modality for treating GINs. Cry5B has demonstrated anthelmintic activities against parasites of monogastric animals, including some related to those that infect humans, but has not yet been studied in a ruminant. Here we show that H. contortus adults are susceptible to Cry5B protein in vitro. Cry5B produced in its natural form as a spore-crystal lysate against H. contortus infections in goats had no significant efficacy. However, a new Active Pharmaceutical Ingredient (API) paraprobiotic form of Cry5B called IBaCC (Inactivated Bacterium with Cytosolic Crystals), in which Cry5B crystals are encapsulated in dead Bt cell wall ghosts, showed excellent efficacy in vitro against larval stages of H. contortus and relative protein stability in bovine rumen fluid. When given to sheep experimentally infected with H. contortus as three 60 mg/kg doses, Cry5B IBaCC resulted in significant reductions in fecal egg counts (90%) and parasite burdens (72%), with a very high impact on female parasites (96% reduction). These data indicate that Cry5B IBaCC is a potent new treatment tool for small ruminants in the battle against H. contortus.

In this study, the effects of Curtobacterium proimmune K3 lysates, isolated from Panax ginseng beverages, on splenocytes and cyclophosphamide (CTX)-induced immunosuppressed mice were investigated. Treatment with C. proimmune K3 lysates stimulated splenocyte proliferation and increased cytokine secretion in vitro and splenocytes ex vivo. Treatment with C. proimmune K3 lysates alleviated CTX-induced immunosuppression by modulating innate immunity in vivo, by recovering immune organ index and natural killer cell cytotoxicity, as well as by stimulating the adaptive immune system, via restoration of splenic lymphocyte proliferation, delayed-type hypersensitivity response, and IgG and IgA content. Moreover, C. proimmune K3 lysates treatment remarkably enhanced cytokine production in the spleen and thymus, compared with CTX-immunosuppressed mice. Our results suggest C. proimmune K3 lysates hold potential as a novel immunomodulatory agent for use in therapeutic purposes or as an ingredient in functional foods.

This study investigated the effects of consumption of wheat-durum pasta added of Bifidobacterium animalis inactivated by gamma-irradiation (paraprobiotic) on health and gut microbiota of rats. Twenty-one male rats were divided into three groups as follow: control (Control) receiving standard diet; pasta control (PC) receiving diet containing pasta, and paraprobiotic pasta Bifidobacterium-irradiated (PPBI), receiving paraprobiotic pasta. The serum levels of glucose and total cholesterol were reduced (p < 0.05) in PPBI when compared to the Control (p < 0.05). PPBI showed high abundance (p ˂ 0.05) of Firmicutes and Actinobacteria and a lower abundance of Bacteriodes compared to Control and PC. Besides, the PPBI showed high abundance (p ˂ 0.05) of Clostridiales, Lactobacillales; Bifidobacteriales, Bacillales, and Coriobacteriales in comparison to Control. Specific genera such as Bifibacterium, Lactobacillus, Ruminococcus, Allobaculum, and Blautia were more related to PPBI. Findings reveal wheat-durum pasta as a potential vehicle for delivering paraprobiotics B. animalis. [ABSTRACT FROM AUTHOR]

Bifidobacterium bifidum BGN4 has been shown to improve the immune system by regulating interleukin (IL)-6 in RAW 264.7 macrophage cells. In this study, the dead cells of B. bifidum BGN4 were produced by enzymatic and physical processing to enhance the inhibition properties of pro-inflammatory cytokines using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Notably, the secretion levels of cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α were decreased by the cell-wall disrupted extracts compared to heat-killed cells. The result suggests that the exposed interior-surface of B. bifidum BGN4 has a potential ability to regulate the immune-responses in the gastrointestinal tract due to major substances in inside-cell wall such as peptidoglycan and teichoic acids. In conclusion, the lysed and disrupted cells from the inside out of B. bifidum BGN4 have anti-inflammatory properties as paraprobiotic agents to control chronic inflammatory related-diseases. [ABSTRACT FROM AUTHOR]

Paraprobiotics are non-viable microbial cells that, when administered in adequate amounts, confer some health benefits to the consumer. Paraprobiotics can be obtained by subjecting probiotics to physical or chemical treatments, and inactivation of the microorganism would lead to the release of some compounds, such as exopolysaccharides, peptidoglycans, surface proteins, and lipoteichoic acids, all of which have a variety of positive health effects. Paraprobiotics also have numerous technological advantages. Therefore, paraprobiotics are promising components and have great potential for producing functional food products. However, there are limited studies, most of which concentrate on using paraprobiotics in clinical research and using them directly. The objective of this study is to summarize the ways to obtain paraprobiotics, their health benefits, technological advantages, and their potential for utilization in food products.

Ascaris and Parascaris are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, e.g., Ascaris is passed from humans to pigs and vice versa. The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Bacillus thuringiensis Cry5B protein with known anthelmintic properties, against zoonotic Ascaris suum and Parascaris spp. This paraprobiotic, known as IBaCC, intoxicated A. suum larvae in vitro and was highly effective in vivo against intestinal A. suum infections in a new mouse model for this parasite. Fermentation was scaled up to 350 l to treat pigs and horses. Single dose Cry5B IBaCC nearly completely cleared A. suum infections in pigs. Furthermore, single dose Cry5B IBaCC drove fecal egg counts in Parascaris-infected foals to zero, showing at least parity with, and potential superiority to, current efficacy of anthelmintics used against this parasite. Cry5B IBaCC therefore represents a new, paraprobiotic One Health approach towards targeting Ascarididae that is safe, effective, massively scalable, stable, and useful in human and veterinary medicine in both the developed and developing regions of the world.

Probiotics have been widely studied due to their health benefits and technological effects. In recent years, paraprobiotic and postbiotics derived from probiotic strains stood out. The recently reclassified Lacticaseibacillus casei- 01 (former Lactobacillus casei- 01) may exert different health effects on the host and has an important role in the development of probiotic dairy and non-dairy foods. This review presents the general aspects, the classification and nomenclature of L. casei- 01 and summarizes the available scientific literature about this strain from 2011 to 2020. The health benefits associated with consumption of live and inactivated L. casei- 01 cells, the factors influencing its survival in food products, and the impact of its addition on the quality parameters of dairy and non-dairy products are discussed. The regular consumption of foods added with L. casei -01 promotes antihypertensive and anti-hyperglycemic effects, and improves lipid profile in human. The incorporation of L. casei -01 in dairy matrices can improve the quality parameters, while in non-dairy products the desired characteristics can be achieved if suitable L. casei -01 concentrations and other factors are optimized. However, the physiological and technological effects of paraprobiotics or postbiotics derived from L. casei -01 remain unexplored. • Lacticaseibacillus casei -01 has antihypertensive and anti-hyperglycemic effects. • L. casei -01 has antioxidant properties and improves lipid profile. • L. casei -01 improves the quality parameters in dairy matrices. • L. casei -01 effects on quality parameters vary in non-dairy products. • Little is known about paraprobiotics or postbiotics derived from L. casei -01. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of two inactivation methods on probiotic, and aimed to determine a suitable inactivation method and condition for obtaining beneficial paraprobiotics from Lactobacillus plantarum (LP) and Lactobacillus gasseri (LG). The effect of inactivation condition on culturability, physiological properties, and morphological characteristics was evaluated by a plating method, flow cytometry, and field emission-scanning electron microscopy, respectively. The result revealed that each strain conferred different resistance to inactivation methods. The heat-treated (75 and 90 °C for 15 and 30 min) LG lost its growth ability, but it's all sonicated samples (50 and 100 W for 5 and 10 min) were stable and maintained their growth ability. However, the ability to grow on culture media of sonicated (50 and 100 W for 5 and 10 min) LP was less than its heat-treated (75 and 90 °C for 15 min) specimens. According to flow cytometry data, the membrane integrity of each probiotic cell was affected by both inactivation methods; however, the severe heat process (90 for 30 min) causes the most serious membrane damage to LG cells (PI = 97.7%). Morphological properties of both strains were significantly affected by inactivation methods. After inactivation treatment, damaged cell, cell roughness, lysed cell, cell adhesions, cell disruption, and cell bending were increased, significantly. Results indicate that for obtaining a functional paraprobiotic the inactivation process should be optimized. Also, it should be noticed that a particular optimized inactivation method is not suitable for obtaining paraprobiotic from all probiotic strains. • Sonication and thermal process impose different effects on viable cells. • The flow cytometry method is a promising method for observing the viability of cells. • Selection of a proper inactivation method is very important for obtaining a health-benefit paraprobiotic. [ABSTRACT FROM AUTHOR]

The human gastrointestinal tract (GIT) contains a rich, complex microbiota that plays an important role in digestion, immunology, and the occurrence of certain diseases. Under normal conditions, the composition of the gut microbiota is stable. However, the composition of the microbiota may change due to changes in diet, use of certain medications and stress. Today, it is a common and known method to take probiotics, which are defined as living microorganisms such as bacteria, yeast, when taken in sufficient quantities to regulate the intestinal microbiota, in the form of food or as a food supplement. In recent years, the use of paraprobiotics, which are non-living (inactive) microorganisms, or postbiotics, which are metabolic by-products released from living bacteria or after bacterial degradation, have started to attract attention as an alternative to probiotics. Paraprobiotics and postbiotics demonstrate many health effects such as regulating intestinal health and strengthening the immune system, just like probiotics, in the hosts where they are applied. In this study, studies on paraprobiotics and postbiotics that can be used instead of probiotics and provide similar health effects are reviewed. [ABSTRACT FROM AUTHOR]

The proper functioning of the human organism is dependent on a number of factors. The health condition of the organism can be often enhanced through appropriate supplementation, as well as the application of certain biological agents. Probiotics, i.e., live microorganisms that exert a beneficial effect on the health of the host when administered in adequate amounts, are often used in commonly available dietary supplements or functional foods, such as yoghurts. Specific strains of microorganisms, administered in appropriate amounts, may find application in the treatment of conditions such as various types of diarrhoea (viral, antibiotic-related, caused by Clostridioides difficile), irritable bowel syndrome, ulcerative colitis, Crohn’s disease, or allergic disorders. In contrast, live microorganisms capable of exerting influence on the nervous system and mental health through interactions with the gut microbiome are referred to as psychobiotics. Live microbes are often used in combination with prebiotics to form synbiotics, which stimulate growth and/or activate the metabolism of the healthy gut microbiome. Prebiotics may serve as a substrate for the growth of probiotic strains or fermentation processes. Compared to prebiotic substances, probiotic microorganisms are more tolerant of environmental conditions, such as oxygenation, pH, or temperature in a given organism. It is also worth emphasizing that the health of the host may be influenced not only by live microorganisms, but also by their metabolites or cell components, which are referred to as postbiotics and paraprobiotics. This work presents the mechanisms of action employed by probiotics, prebiotics, synbiotics, postbiotics, paraprobiotics, and psychobiotics, together with the results of studies confirming their effectiveness and impact on consumer health.

Yoghurt was produced using killed cells of Lactobacillus acidophilus ATCCSD 5221 and Bifidobacterium animalis subsp. lactis BB‐12. The rheological and sensory properties of the yoghurt were investigated at the end of the fermentation. The results revealed that the samples made with killed cells gave the lowest storage modulus, loss modulus, stress crossover point and loss tangent. The frequency‐sweep of yoghurt samples containing paraprobiotics added before fermentation showed the highest correlation coefficient. In the case of sensory assessment, significant differences were indicated among treatments. Adding killed cells of B. animalis subsp. lactis BB‐12 before fermentation produced yoghurt with the highest total score, whereas samples containing killed cells of L. acidophilus ATCCSD 5221 and B. animalis subsp. lactis BB‐12 added before fermentation exhibited the lowest total score. [ABSTRACT FROM AUTHOR]

Haemonchus contortus is a critical parasite of goats and sheep. Infection by this blood-feeding gastrointestinal nematode (GIN) parasite has significant health consequences, especially in lambs and kids. The parasite has developed resistance to virtually all known classes of small molecule anthelmintics used to treat it, giving rise in some areas to multidrug resistant parasites that are very difficult to control. Thus, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal protein 5B (Cry5B), a naturally occurring protein made by a bacterium widely and safely used around the world as a bioinsecticide, represents a new non-small molecule modality for treating GINs. Cry5B has demonstrated anthelmintic activities against parasites of monogastric animals, including some related to those that infect humans, but has not yet been studied in a ruminant. Here we show that H. contortus adults are susceptible to Cry5B protein in vitro. Cry5B produced in its natural form as a spore-crystal lysate against H. contortus infections in goats had no significant efficacy. However, a new Active Pharmaceutical Ingredient (API) paraprobiotic form of Cry5B called IBaCC (Inactivated Bacterium with Cytosolic Crystals), in which Cry5B crystals are encapsulated in dead Bt cell wall ghosts, showed excellent efficacy in vitro against larval stages of H. contortus and relative protein stability in bovine rumen fluid. When given to sheep experimentally infected with H. contortus as three 60 mg/kg doses, Cry5B IBaCC resulted in significant reductions in fecal egg counts (90%) and parasite burdens (72%), with a very high impact on female parasites (96% reduction). These data indicate that Cry5B IBaCC is a potent new treatment tool for small ruminants in the battle against H. contortus. Image 1 [ABSTRACT FROM AUTHOR]

In recent years, new probiotic-related concepts such as postbiotics and paraprobiotics have been coined to indicate that non-viable microorganisms or bacterial-free extracts may provide benefits to the host by offering additional bioactivities to probiotics, including but not limited to anti-inflammatory, immunomodulatory, anti-proliferative and antioxidant activities. Despite in vitro and in vivo studies that support the promising use of postbiotics and paraprobiotics as health promoters, the mechanism of action and the signaling pathway involved have not yet been fully elucidated. Therefore, the aim of this chapter is to provide an overview of novel probiotic-related concepts and the scientific evidence that supports their bioactivities as well as the possible mechanisms underlying their health-promoting effects. Additionally, current trends in food, feed, and pharmaceutical applications are discussed. [ABSTRACT FROM AUTHOR]

The contribution of cold water aquaculture for the world fish production is significant. Although sturgeon farming is an important part of China's cold water aquaculture industry, its production is less compared with the current potentiality of the country. There are many reasons for the lower production of cold water fish farming including feed and disease. The aim of the present study was to investigate the effect of a paraprobiotic and postbiotic feed supplement (Herpes Worry Free or HWF™) on the growth, feeding efficiency and gut microbiota balance of hybrid sturgeon. Besides, the effect of sturgeon gut microbiota fed on the diet supplemented with HWF™ on the expression of growth promoter, and immune regulatory genes of germ free (GF) zebrafish was evaluated. Sturgeon were fed for three weeks with HWF™ supplemented or basal diet. At the end of the experiment gut content of sturgeon, fed on either experimental diet was transferred and colonized to GF zebrafish. Sturgeon fed with HWF™ supplemented diet showed significantly higher weight gain rate and lower feed conversion ratio (FCR) as compared with the control (P < 0.05). Compared with the control group, the relative abundance of Firmicutes, were significantly higher in the HWF™ group (P < 0.05), whereas Proteobacteria, Actinobacteria and Chlamydiae were significantly higher in the control group (P < 0.05). Furthermore, at the genus level Clostridium (64.50 ± 5.99%) and Lactococcus (29.5 ± 3.05%) were the most dominant gut bacteria in the HWF™ group and the control group of sturgeon, respectively. The expression of genes related to growth, inflammation and non-specific immunity was significantly upregulated in GF zebrafish colonized with gut microbiota of HWF™ sturgeon group. In conclusion, HWF™ played significant role in growth, feed efficiency and modulation of gut microbiota of sturgeon. The gut microbiota of sturgeon fed on the diet supplemented with HWF™ upregulated the expression of genes related to growth, inflammation and non-specific immunity in GF zebrafish model. • Dietary HWF™ improved weight gain and feed conversion ratio of hybrid sturgeon. • Dietary HWF™ improved the composition of gut microbiota of hybrid sturgeon. • The expression of growth promoter and immune regulatory related genes was upregulated in GF zebrafish colonized with HWF™ induced gut microbiota. [ABSTRACT FROM AUTHOR]

Tempeh is an Indonesian traditional food made from fermented soybeans, which offers wide culinary use in East Asian countries. Similar to all fermented foods, its preparation offers the purpose of food preservation. However, preclinical studies have highlighted that microbial action leads to a modification in the nutritional composition of the food's matrix. Although there is a wide availability of data on the beneficial effect of soy, tempeh remains relatively unexplored, perhaps due to its limited diffusion in the world, which limits its research availability. However, available data suggest that tempeh may confer beneficial health effects due to the high bioavailability of nutrients and phytochemicals, showing ameliorative action on oxidative stress, glycaemic control, and blood lipid levels. Furthermore, the high biological value of tempeh means it can be used to optimize protein and caloric intake in athletes, vegetarians, and children. Moreover, the microbial fermentation used in the production of tempeh, in addition to improving the bioavailability of minerals, proteins, fibre, vitamins, and isoflavones, produces biopeptides whose biological effect is currently of great interest. Tempeh can be employed in traditional preparations as well as second-generation foods, such as plant-based meat substitutes, to provide functional and nutritional properties and a higher eco-friendly option compared to animal foods. This review aims to provide an overview of tempeh's properties, regarding human data and future research perspectives., Competing Interests: The author declares no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

One of the main characteristics of probiotics is their ability to stimulate and modulate the immune response regardless of their viability. Lactobacillus casei (Lc) can stimulate local and systemic immunity, in addition to the activation of macrophages at sites distant from the intestine. Activated macrophages limit the replication of intracellular protozoa, such as Toxoplasma gondii, through the production of nitric oxide. The present study aimed to evaluate the protection generated by treatment with viable and non-viable Lc in the murine systemic toxoplasmosis model. CD1 male mice were treated with viable Lc (immunobiotic) and non-viable Lc (paraprobiotic), infected with tachyzoites of Toxoplasma gondii RH strain. The reduction of the parasitic load, activation of peritoneal macrophages, inflammatory cytokines, and cell populations was evaluated at 7 days post-infection, in addition to the survival. The immunobiotic and paraprobiotic reduced the parasitic load, but only the immunobiotic increased the activation of peritoneal macrophages, and the production of interferon-gamma (IFN-γ), tumor necrosis factor (TNF), and interleukin-6 (IL-6) while the paraprobiotic increased the production of monocyte chemoattractant protein-1 (MCP-1) and T CD4+CD44+ lymphocytes. Viable and non-viable Lc increases survival but does not prevent the death of animals. The results provide evidence about the remote immunological stimulation of viable and non-viable Lc in an in vivo parasitic model.

The present study evaluated the paraprobiotic effect of heat-inactivated Bacillus amyloliquefaciens FPTB16 on immunological response and immune relevant gene expression in catla ( Catla catla ). Heat inactivation of viable cells of B. amyloliquefaciens was done at 60 °C for 2 h. For preparation of paraprobiotic supplemented diet, the heat-inactivated bacteria were added to the basal diet (control) at three different inclusion levels i.e., 10 7 , 10 8 and 10 9 cells g −1 diet. Fish (25.98 ± 2.57 g) were fed with these diets and various immune responses and immune relevant gene expressions were measured after 4 weeks of feeding. Biochemical parameters were also measured along with the immunological responses. Immunological parameters viz. oxygen radical production, serum lysozyme activity and total serum protein content showed significant enhancement (p < 0.05) in fish fed with 10 8 and 10 9 cells g −1 diet. Significant enhancement in myeloperoxidase activity was observed in all the dietary groups compared to control. Alkaline phosphatase activity showed significant enhancement (p < 0.05) in fish fed with 10 7 and 10 8 cells g −1 diet. Biochemical parameters viz. GPT, GOT and glucose content did not show any significant difference in any of the dietary groups. Immune relevant genes viz. IL-1β, TNF-α, C3 and iNOS showed significantly higher expression in either liver or head-kidney tissues in most of the cases. However, IFN-γ expression showed a down-regulation pattern in both the tissues. In conclusion, the dietary supplementation of heat-inactivated B. amyloliquefaciens enhanced the immunity of catla, particularly at 10 8 cells g −1 diet. The results collectively suggest the paraprobiotic applicability of B. amyloliquefaciens in aquaculture. [ABSTRACT FROM AUTHOR]

High-density intensive farming is the development trend of modern aquaculture, which is characterized by high density culture environment and feeding of high-fat diet. The use of high-fat diet can increase the weight gain rate of some fish species, but it affects the health of fish. In this study, we investigated the beneficial effects of a compound of paraprobiotic and postbiotic (CPP) derived from autochthonous microorganisms supplemented diet on growth performance, epidermal mucus, liver and gut health, and gut microbiota profile of common carp (Cyprinus carpio). Common carp were fed with diets supplemented with 0, 1, 2 or 3 g/kg of CPP in the control diet for 14 weeks, with four replications in each group and 20 fish in each repetition. The results showed that fish fed with diet supplemented with CPP significantly decreased the hepatosomatic index (p < 0.05), even though no significant effects were observed in the growth performance of the fish. In the CPP1.0 and CPP2.0 groups the level of complement 4 and superoxide dismutase (SOD) activity in the epidermal mucus were significantly increased compared to the control group (p < 0.05). No significant values were recorded among the treatment groups in the level of Lysozyme activity and total antioxidant capacity (T-AOC) (p > 0.05). For liver health, dietary CPP2.0 were significantly decreased the Triacylglycerol content in the liver, compared with the control (p < 0.05). Furthermore, fish groups fed with CPP1.0 and CPP2.0 showed significant decreased in the number of vacuoles representing lipid droplets and the liver damage scores (p < 0.05), compared with the control group. The CPP2.0 group significantly decreased serum alanine aminotransferase (Alt) and aspartate aminotransferase (Ast) levels, and significantly increased liver antioxidant (total antioxidant capacity, superoxide dismutase and catalase (CAT)) levels compared to the control group (p < 0.05). The level of liver malondialdehyde (MDA) was significantly reduced in the CPP groups compared to the control (p < 0.05). Dietary CPP supplementation were significantly down-regulated the relative expression of pro-inflammatory cytokines (nf-κb p65 and tnf-α) and up-regulated anti-inflammatory cytokines (il-1β, il-10 and tgf-β), compared to the control group (p < 0.05). Similarly, intestinal hypoxia inducible factor 1 subunit alpha (hif-1α) expression was significantly increased in the CPP1.0 and 2.0 groups, compared with then control (p < 0.05). Combined with intestinal HE staining and inflammatory gene expression, it was found that the intestinal inflammatory cytokines (nf-κb p65 , il-1β, il-10 and tgf-β) in the CPP2.0 supplemented group were significantly higher than the control group (p < 0.05), and the intestinal villi were more orderly arranged. In the CPP3.0 group, the expression of nf-κb p65 , il-1β, il-10 were significantly higher compared with the control (p < 0.05). Furthermore, remarkably lower intestinal injury scores were recorded in the CPP groups verses the control (p < 0.05). The gut microbiota diversity index data showed that lower diversity index values were observed in the CPP2.0 group compared with the control (p < 0.05). The relative abundances of Fusobacteria and Cetobacterium in the CPP2.0 and 3.0 groups were significantly higher than those in the control group (p < 0.05). In conclusion, dietary CPP supplementation could enhance non-specific immunity and antioxidant levels, reduce liver lipid deposition, alleviate liver and intestinal damage and inflammation, and improve gut microbiota abundance and diversity in common carp fed with high-fat diet. The best positive effect was observed in common carp fed with diet supplemented at a level of 2 g/kg of basal diet. • The compound of paraprobiotic and postbiotic (CPP) ensured growth and reduced hepatosomatic index of common carp. • CPP2.0 group improved non-specific immunity and antioxidant levels of common carp. • CPP2.0 group effectively improved liver and intestinal health of common carp. • CPP2.0 group significantly enriched the relative abundances of Fusobacteria and Cetobacterium in gut. [ABSTRACT FROM AUTHOR]