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The therapeutic effect of gamma-aminobutyric acid (GABA) on diabetes was spread as one of the alarming epidemics worldwide. The study aims to investigate the function of Lactobacillus brevis KLDS1.0727 and KLDS1.0373 strains as glutamic acid decarboxylase 65 (GAD65) carriers capable of generating GABA by comparing in vitro free and freeze-dried models and GABA intervention in vivo. PCR amplification of gad and in vitro i.e., (growth rate, viability at different pH, bile tolerance, and survivability in simulated gastric juice) were performed. In vivo experiments were conducted in 7 groups of C57BL/6J mice. Each group was injected with streptozotocin (ContSTZ, INSSTZ, LAC1STZ, LAC1MFDSTZ, LAC2STZ, LAC2MFDSTZ) daily except for the control (Cont). One group was injected with insulin (INSSTZ). The body weight and hyperglycemia in the blood were assessed weekly, post-euthanasia blood plasma parameters, insulin, and histological examination were evaluated. Results indicated L. brevis strains demonstrated a great tolerance to bile and simulated gastric juice in vitro (P

Background Hypertension is a prevalent chronic disease worldwide that remains poorly controlled. Recent studies support the concept that the gut microbiota is involved in the development of hypertension and that dietary fibre intake may act through the gut microbiota to lower blood pressure (BP). Resistant starch is a type of prebiotic fibre which is metabolised by commensal bacteria in the colon to produce short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. Previous work in pre-clinical models provides strong evidence that both prebiotic fibre as well as SCFAs (i.e. postbiotics) can prevent the development of hypertension. The aim of this clinical trial is to determine if acetylated and butyrylated modified resistant starch can decrease BP of hypertensive individuals via the modulation of the gut microbiota and release of high levels of SCFAs. Methods This is a phase IIa double-blinded, randomised, cross-over, placebo controlled trial. Participants are randomly allocated to receive either a diet containing 40 g/day of the modified resistant starch or placebo (corn starch or regular flour) for 3 weeks on each diet, with a 3-week washout period between the two diets. BP is measured in the office, at home, and using a 24-h ambulatory device. Arterial stiffness is measured using carotid-to-femoral pulse wave velocity. Our primary endpoint is a reduction in ambulatory daytime systolic BP. Secondary endpoints include changes to circulating cytokines, immune markers, and modulation to the gut microbiome. Discussion The findings of this study will provide the first evidence for the use of a combination of pre- and postbiotics to lower BP in humans. The results are expected at the end of 2021. Trial registration Australia and New Zealand Clinical Trial Registry ACTRN12619000916145. Registered on 1 July 2019.

Mastitis is one of the most important and multi-factorial diseases affecting dairy cows. This study was conducted to evaluate the effect of postbiotics secreted by lactic acid bacteria on mastitis. Within this aim, a total of 10 raw milk samples of healthy dairy cows were processed for the isolation of microbiota-derived bacteria. Following the isolation protocol, 24 isolates showing phenotypic characters similar to Lactobacillus species on specific MRS agar were selected and screened for their antibacterial activity against important mastitis-causing pathogens using the agar well diffusion method. According to the screening of the isolates, only one strain was found effective against all tested pathogens and selected for further assays. The isolate that exhibited a remarkable inhibitory effect was then identified as Lactobacillus sakei by 16S rRNA sequence analysis. The minimum inhibitory concentration of the postbiotics secreted by L. sakei into the culture medium was defined between the range of 40–50 mg/L. The antibacterial activity was also determined to be an acid-dependent effect, and HPLC analysis confirmed the presence of lactic acid (21.42 mg/mL) as the most common acid in the postbiotics. Among the 37 fatty acids, only oleic acid, palmitic acid, and stearic acid were detected. In addition to its antibacterial activity, postbiotics significantly reduced the biofilm formation of pathogens following the co-incubation, pre-treatment, and eradication assays, confirmed by confocal-laser and scanning electron microscopy. In conclusion, postbiotics with antibacterial and antibiofilm activity against important mastitis-causing pathogens can be used as a promising and natural agent in the prevention of mastitis.HIGHLIGHTSLactobacillus sakei EIR/CM-1 was isolated from Holstein cow’s milk microbiota.Postbiotics from the strain EIR/CM-1 displayed the highest antibacterial activity against ruminant mastitis-causing pathogens.Co-incubation with postbiotics at 5 mg/mL and above concentrations reduced the biofilm formation of ruminant mastitis-causing pathogens by more than 70%.Lactic acid was found to be the highest organic acid in postbiotics. Lactobacillus sakei EIR/CM-1 was isolated from Holstein cow’s milk microbiota. Postbiotics from the strain EIR/CM-1 displayed the highest antibacterial activity against ruminant mastitis-causing pathogens. Co-incubation with postbiotics at 5 mg/mL and above concentrations reduced the biofilm formation of ruminant mastitis-causing pathogens by more than 70%. Lactic acid was found to be the highest organic acid in postbiotics.

Background Probiotics can release bioactive substances known as postbiotics, which can inhibit pathogenic microorganisms, improve immunomodulation, reduce antioxidant production, and modulate the gut microbiota. Methods In this study, we evaluated the in vitro antimicrobial effects, antioxidant activity, and anti-inflammatory potential of 10 lyophilized cell-free supernatants (LCFS) of Lactobacillus isolates. LCFS was obtained via centrifugation and subsequent lyophilization of the supernatant collected from the culture medium ofeach isolate. The antibacterial and antibiofilm activities of the LCFS were determined using broth microdilution. The antioxidant potential was evaluated by measuring the total phenolic and flavonoid contents and 2,2-Diphennyl-1-picrylhydrazyl (DPPH) and 2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS+) radical scavenging activities. Results All the isolates were able to inhibit the four tested pathogens. The isolates exhibited strong antibiofilm activity and eradicated the biofilms formed by Acinetobacter buamannii and Escherichia coli. All the prepared Lactobacillus LCFS contained phenols and flavonoids and exhibited antioxidant activities in the DPPH and ABTS+ radical scavenging assays. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay revealed that LCFS was not cytotoxic to RAW 264.7 cells. In addition, the ten Lactobacillus LCFS decreased the production of nitric oxide. Conclusions All the isolates have beneficial properties. This research sheds light on the role of postbiotics in functional fermented foods and pharmaceutical products. Further research to elucidate the precise molecular mechanisms of action of probiotics is warranted.

An imbalance in the crosstalk between the host and gut microbiota affects the intestinal barrier function, which results in inflammatory diseases and colorectal cancer. The colon epithelium protects itself from a harsh environment and various pathogenic organisms by forming a double mucus layer, primarily comprising mucins. Recent studies are focusing on how dietary patterns alter the gut microbiota composition, which in turn regulates mucin expression and maintains the intestinal layers. In addition, modulation of gut microbiota by microbiotic therapy (involving fecal microbiota transplantation) has emerged as a significant factor in the pathologies associated with dysbiosis. Therefore, proper communication between host and gut microbiota via different dietary patterns (prebiotics and probiotics) is needed to maintain mucus composition, mucin synthesis, and regulation. Here, we review how the interactions between diet and gut microbiota and bacterial metabolites (postbiotics) regulate mucus layer functionalities and mucin expression in human health and disease.

Metabolic diseases are serious threats to public health and related to gut microbiota. Probiotics, prebiotics, synbiotics, and postbiotics (PPSP) are powerful regulators of gut microbiota, thus possessing prospects for preventing metabolic diseases. Therefore, the effects and mechanisms of PPSP on metabolic diseases targeting gut microbiota are worth discussing and clarifying. Generally, PPSP benefit metabolic diseases management, especially obesity and type 2 diabetes mellitus. The underlying gut microbial-related mechanisms are mainly the modulation of gut microbiota composition, regulation of gut microbial metabolites, and improvement of intestinal barrier function. Moreover, clinical trials showed the benefits of PPSP on patients with metabolic diseases, while the clinical strategies for gestational diabetes mellitus, optimal formula of synbiotics and health benefits of postbiotics need further study. This review fully summarizes the relationship between probiotics, prebiotics, synbiotics, postbiotics, and metabolic diseases, presents promising results and the one in dispute, and especially attention is paid to illustrates potential mechanisms and clinical effects, which could contribute to the next research and development of PPSP.

Simple Summary Allogenic hematopoietic stem cell transplantation (allo-HSCT) represents a significant part of the treatment for hematologic malignancies and other types of diseases. Allo-HSCT-related complications, such as conditioning chemotherapy, graft-versus-host disease, mucositis, irradiation, administration of antibiotics, recurrent Clostridioides difficile infection, and many others, can alter the gut microbiota composition, leading to its imbalance. Consequently, the disruption of gut microbiota homeostasis and loss of gut-barrier integrity affect therapy efficacy. Thus, restoring gut microbiota diversity and maintaining its balance seem to be strongly needed in these cases. Promising effects were observed after fecal microbiota transplantation (FMT). Notwithstanding, FMT efficacy was confirmed in Clostridium difficile infection treatment in HSCT recipients. Gut microbiota may be also modified by prebiotics, probiotics, synbiotics, and postbiotics. However, the administration of fungal probiotics is associated with the risk of fungemia/septicemia, especially in immunocompromised patients. Abstract Nowadays, allogenic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy that is mainly recommended for hematologic malignancies. However, complications (such as graft-versus-host disease, mucositis, disease relapse, and infections) associated with the HSCT procedure contribute to the development of gut microbiota imbalance, gut-barrier disruption, and increased intestinal permeability. In the present narrative review, the crosstalk between gut microbiota products and intestinal homeostasis is discussed. Notably, gut-microbiota-related aspects have an impact on patients’ clinical outcomes and overall survival. In accordance with the most recent published data, gut microbiota is crucial for the treatment effectiveness of many diseases, not only gastrointestinal cancers but also hematologic malignancies. Therefore, it is necessary to indicate a therapeutic method allowing to modulate gut microbiota in HSCT recipients. Currently, fecal microbiota transplantation (FMT) is the most innovative method used to alter/restore gut microbiota composition, as well as modulate its activity. Despite the fact that some previous data have shown promising results, the knowledge regarding FMT in HSCT is still strongly limited, except for the treatment of Clostridium difficile infection. Additionally, administration of prebiotics, probiotics, synbiotics, and postbiotics can also modify gut microbiota; however, this strategy should be considered carefully due to the high risk of fungemia/septicemia (especially in case of fungal probiotics).

Probiotics such as various strains of Lactobacillaceae have been shown to have antimicrobial and immunomodulatory activity. In vitro studies have shown that Lactobacilli can decrease bacterial biofilm formation. Effects on immune cells have been unclear with most studies showing anti-inflammatory activity. The mechanism of effects has not been clearly elucidated. In these studies, we used different concentrations of live Lactobacillus acidophilus as well as cell free filtrate (CFF) derived from different concentrations of bacteria. Use of CFF is advantageous as a therapeutic because in vivo it can directly contact immune cells and its concentration is fixed. Both live cells and CFF inhibited Pseudomonas aeruginosa biofilm formation. Importantly, we show that high concentration CFF destroyed mature biofilm. This activity was not due to a lowered pH per se, as pH matched HCl did not remove mature biofilm. High concentration CFF totally inhibited P. aeruginosa growth and was bactericidal (>99.99%), but low concentration CFF was not bactericidal. To examine the immunomodulatory effects of L. acidophilus, we incubated THP-1 monocytes and derived macrophages with CFF and measured TNFα production. CFF did not significantly increase TNFα production in THP-1 monocytes. When cells were prestimulated with LPS, high concentration CFF increased TNFα production even further. In macrophages, high concentration CFF alone increased TNFα production but did not affect LPS prestimulated cells. In contrast, low concentration CFF decreased TNFα production in LPS prestimulated cells. To elucidate the possible mechanisms for these effects, we repeated the experiments using a NF-κB reporter THP-1 cell line. High concentration CFF increased NF-κB activity in monocytes and macrophages. In LPS prestimulated macrophages, only low concentration CFF reduced NF-κB activity. These results suggest that high concentration CFF alone induced NF-κB expression which could account partially for an increase in TNFα production. On the other hand, in macrophages, the lower non-bactericidal concentration of CFF reduced NF-κB expression and decreased TNFα production after LPS prestimulation. Taken together, the results provide evidence that different concentrations of L. acidophilus CFF possess varying bactericidal, anti-biofilm and immunomodulatory effects. This is important in vivo to evaluate the possible use of L. acidophilus CFF in different conditions.

Microbial therapeutics, which include gut biotics and fecal transplantation, are interventions designed to improve the gut microbiome. Gut biotics can be considered as the administration of direct microbial populations. The delivery of this can be done through live microbial flora, certain food like fiber, microbial products (metabolites and elements) obtained through the fermentation of food products, or as genetically engineered substances, that may have therapeutic benefit on different health disorders. Dietary intervention and pharmacological supplements with gut biotics aim at correcting disruption of the gut microbiota by repopulating with beneficial microorganism leading to decrease in gut permeability, inflammation, and alteration in metabolic activities, through a variety of mechanisms of action. Our understanding of the pharmacokinetics of microbial therapeutics has improved with in vitro models, sampling techniques in the gut, and tools for the reliable identification of gut biotics. Evidence from human studies points out that prebiotics, probiotics and synbiotics have the potential for treating and preventing mental health disorders, whereas with paraprobiotics, proteobiotics and postbiotics, the research is limited at this point. Some animal studies point out that gut biotics can be used with conventional treatments for a synergistic effect on mental health disorders. If future research shows that there is a possibility of synergistic effect of psychotropic medications with gut biotics, then a gut biotic or nutritional prescription can be given along with psychotropics. Even though the overall safety of gut biotics seems to be good, caution is needed to watch for any known and unknown side effects as well as the need for risk benefit analysis with certain vulnerable populations. Future research is needed before wide spread use of natural and genetically engineered gut biotics. Regulatory framework for gut biotics needs to be optimized. Holistic understanding of gut dysbiosis, along with life style factors, by health care providers is necessary for the better management of these conditions. In conclusion, microbial therapeutics are a new psychotherapeutic approach which offer some hope in certain conditions like dementia and depression. Future of microbial therapeutics will be driven by well-done randomized controlled trials and longitudinal research, as well as by replication studies in human subjects.

Cardiovascular diseases (CVDs) can originate from early life. Accumulating evidence suggests that gut microbiota in early life is linked to CVDs in later life. Gut microbiota-targeted therapy has gained significant importance in recent decades for its health-promoting role in the prevention (rather than just treatment) of CVDs. Thus far, available gut microbiota-based treatment modalities used as reprogramming interventions include probiotics, prebiotics, and postbiotics. The purpose of this review is, first, to highlight current studies that link dysbiotic gut microbiota to the developmental origins of CVD. This is followed by a summary of the connections between the gut microbiota and CVD behind cardiovascular programming, such as short chain fatty acids (SCFAs) and their receptors, trimethylamine-N-oxide (TMAO), uremic toxins, and aryl hydrocarbon receptor (AhR), and the renin-angiotensin system (RAS). This review also presents an overview of how gut microbiota-targeted reprogramming interventions can prevent the developmental origins of CVD from animal studies. Overall, this review reveals that recent advances in gut microbiota-targeted therapy might provide the answers to reduce the global burden of CVDs. Still, additional studies will be needed to put research findings into practice.

Schizophrenia is a chronic, heterogeneous neurodevelopmental disorder that has complex symptoms and uncertain etiology. Mounting evidence indicates the involvement of genetics and epigenetic disturbances, alteration in gut microbiome, immune system abnormalities, and environmental influence in the disease, but a single root cause and mechanism involved has yet to be conclusively determined. Consequently, the identification of diagnostic markers and the development of psychotic drugs for the treatment of schizophrenia faces a high failure rate. This article surveys the etiology of schizophrenia with a particular focus on gut microbiota regulation and the microbial signaling system that correlates with the brain through the vagus nerve, enteric nervous system, immune system, and production of postbiotics. Gut microbially produced molecules may lay the groundwork for further investigations into the role of gut microbiota dysbiosis and the pathophysiology of schizophrenia. Current treatment of schizophrenia is limited to psychotherapy and antipsychotic drugs that have significant side effects. Therefore, alternative therapeutic options merit exploration. The use of psychobiotics alone or in combination with antipsychotics may promote the development of novel therapeutic strategies. In view of the individual gut microbiome structure and personalized response to antipsychotic drugs, a tailored and targeted manipulation of gut microbial diversity naturally by novel prebiotics (non-digestible fiber) may be a successful alternative therapeutic for the treatment of schizophrenia patients.

Fermented products are permanently under the attention of scientists and consumers, both due to nutritional importance and health promoting effects. The fermented functional foods contribute to a more balanced diet and increase the immune responses (among many other health effects) with positive implications for quality of life. In this sense, improving the sourdough’s fermentation to boost the biotic (postbiotic and paraprobiotic) properties of the sourdough-based products has positive impacts on the nutritional and functional properties of the final baked products. These enhanced sourdoughs can be obtained in controlled fermentation conditions and used as sourdough bread improvers or novel bioingredients. In this context, our work aimed to optimize, using statistical tools, a gluten-free sourdough based on chickpea, quinoa, and buckwheat fermentation with selected lactic acid bacteria (LAB) to enhance its postbiotic properties. The most important biotechnological parameters were selected by Plackett–Burman Design (PBD) and then Response Surface Methodology (RSM) was applied to evaluate the interactions between the selected factors to maximize the gluten-free sourdough’s properties. As a result, the optimized fermented sourdough had antimicrobial activity with inhibition ratios between 71 and 100% against the Aspergillus niger, Aspergillus flavus, Penicillium spp. molds and against the Bacillus spp endospore-forming Gram-positive rods. The optimized variant showed a total titratable acidity (TTA) of 40.2 mL NaOH 0.1N. Finally, the high-performance liquid chromatography (HPLC) analysis highlighted a heterofermentative profile for the organic acids from the optimized sourdough. Among flavonoids and polyphenols, the level of caffeic and vanillic acids increased after lactic acid fermentation. The comparison between the optimized sourdough and the control evidenced significant differences in the metabolite profiles, thus highlighting its potential postbiotication effect.

Background Post-menopausal osteoporosis is a concern of health organizations, and current treatments do not seem enough. Postbiotics as bioactive compounds produced by probiotics may be an attractive alternative for bone health. In this study, we prepared, formulated, and compared the effects of cell lysate and supernatant of five native probiotic strains (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, Bifidobacterium longum, and Bacillus coagulans) in ovariectomized (OVX) rats. Methods The probiotic strains were isolated, and their cell-free supernatants and biomasses as postbiotics were extracted and formulated using standard microbial processes. The Sprague-Dawley rats were fed by 1 × 109 CFU/ml/day postbiotic preparations for 4 weeks immediately after ovariectomy. Dual-energy X-ray absorptiometry (DEXA) scans were accomplished to evaluate femur, spine, and tibia BMD. The serum biochemical markers [calcium, phosphorus, and alkaline phosphatase] were assessed. Results Postbiotics could considerably improve the global and femur area in OVX rats. In the case of global bone mineral density (BMD), Lactobacillus casei lysate and supernatant, Bacillus coagulans lysate and supernatant, lysate of Bifidobacterium longum and Lactobacillus acidophilus, and Lactobacillus reuteri supernatant significantly increased BMD. We found Bacillus coagulans supernatant meaningfully enriched tibia BMD. Conclusion Postbiotic could ameliorate bone loss resulting from estrogen deficiency. Also, the effects of postbiotics on different bone sites are strain-dependent. More clinical studies need to explore the optimal administrative dose and duration of the specific postbiotics in protecting bone loss.

Tuberculosis (TB), caused by Mycobacterium tuberculosis attacking the lungs and other organs, is one of the most common infectious disease worldwide. According to the WHO's 2020 report, a quarter of the world's population were infected with M. tuberculosis, and ~1.4 million people died of TB. Therefore, TB is a significant public health concern, which requires cost-effective strategies for prevention and treatment. The microbiota has been considered as a “forgotten organ” and a complex dynamic ecosystem, which plays a significant role in many physiological processes, and its dysbiosis is closely associated with infectious disease. Recently, a few studies have indicated associations between TB and microbiota. This review summarizes studies concerning the alterations of the gut and respiratory microbiota in TB, and their relationship with host susceptibility to M. tuberculosis infection, indicating that microbiota signatures in different stages in TB progression could be considered as biomarkers for TB diagnosis and control. In addition, the potential role of probiotics and postbiotics in TB treatment was discussed.

Background: Probiotics are generally considered as safe, but infections may rarely occur in vulnerable patients. Alternatives to live microorganisms to manage dysbiosis may be of interest in these patients. Reuterin is a complex component system exhibiting broad spectrum antimicrobial activity and a possible candidate substance in these cases.Methods: Reuterin supernatant was cultured from Lentilactobacillus diolivorans in a bioreactor in a two-step process. Storage stability at −20°C and effect of repeated freeze-thaw cycles were assessed by high performance liquid chromatography (HPLC). Antimicrobial activity was tested against Clostridium difficile, Listeria monocytogenes, Escherichia coli, Enterococcus faecium, Staphylococcus (S.) aureus, Staphylococcus epidermidis, Streptococcus (S.) agalactiae, Propionibacterium acnes, and Pseudomonas aeruginosae. Male BALBc mice were gavage fed with reuterin supernatant (n = 10) or culture medium (n = 10). Fecal volatile organic compounds (VOC) were assessed by gas chromatography mass spectroscopy; the microbiome was examined by 16S rRNA gene sequencing.Results: The supernatant contained 13.4 g/L reuterin (3-hydroxypropionaldehyde; 3-HPA). 3-HPA content remained stable at −20°C for 35 days followed by a slow decrease of its concentration. Repeated freezing/thawing caused a slow 3-HPA decrease. Antimicrobial activity was encountered against S. aureus, S. epidermidis, and S. agalactiae. Microbiome analysis showed no differences in alpha and beta diversity markers. Linear discriminant effect size (LEfSe) analysis identified Lachnospiraceae_bacterium_COE1 and Ruminoclostridium_5_uncultured_Clostridiales_ bacterium (in the reuterin medium group) and Desulfovibrio_uncultured_ bacterium, Candidatus Arthromitus, Ruminococcae_NK4A214_group, and Eubacterium_xylanophilum_group (in the reuterin group) as markers for group differentiation. VOC analysis showed a significant decrease of heptane and increase of 3-methylbutanal in the reuterin group.Conclusion: The supernatant produced in this study contained acceptable amounts of 3-HPA remaining stable for 35 days at −20°C and exhibiting an antimicrobial effect against S. aureus, S. agalactiae, and S. epidermidis. Under in vivo conditions, the reuterin supernatant caused alterations of the fecal microbiome. In the fecal, VOC analysis decreased heptane and increased 3-methylbutanal were encountered. These findings suggest the high potential of the reuterin system to influence the intestinal microbiome in health and disease, which needs to be examined in detail in future projects.

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.

Summary Background & aims Microbiome-modulators can help positively steer early-life microbiota development but their effects on microbiome functionality and associated safety and tolerance need to be demonstrated. We investigated the microbiome impact of a new combination of bioactive compounds, produced by the food-grade microorganisms Bifidobacterium breve C50 and Streptococcus thermophilus ST065 during a fermentation process, and prebiotics in an infant formula. Tolerance and safety were also assessed. Methods An exploratory prospective, randomized, double-blind, controlled, multi-centre study was designed to investigate the effect of bioactive compounds and prebiotics (short-chain galacto-oligosaccharides (scGOS)/long-chain fructo-oligosaccharides (lcFOS) 9:1). Experimental formulas containing these bioactive compounds and prebiotics (FERM/scGOS/lcFOS), prebiotics (scGOS/lcFOS), or bioactive compounds (FERM), were compared to a standard cow's milk-based control formula (Control). Exclusively breastfed infants were included as a reference arm since exclusive breastfeeding is considered as the optimal feeding for infants. The study lasted six months and included visits to health care professionals at baseline, two, four and six months of age. Stool SIgA concentration was the primary study outcome parameter. Results There were 280 infants randomized over the experimental arms and 70 infants entered the breastfed-reference arm. Demographics were balanced, growth and tolerance parameters were according to expectation and adverse events were limited. At four months of age the median SIgA concentration in the FERM/scGOS/lcFOS group was significantly higher compared to the Control group (p = 0.03) and was more similar to the concentrations found in the breastfed-reference group. Bifidobacterium increased over time in all groups. The FERM/scGOS/lcFOS combination resulted in a microbiota composition and metabolic activity closer to the breastfed infants’ microbiome. Conclusion The FERM/scGOS/lcFOS combination showed a significant positive effect on SIgA levels. All formulas tested were associated with normal growth and were well-tolerated. Additionally, at four months of age the FERM/scGOS/lcFOS formula brought the microbiome composition and metabolic activity closer towards that of breastfed infants. Clinical trial registry Registration number NTR2726 (Netherlands Trial Register; www.trialregister.nl/ ).

In the last decade, the gastrointestinal microbiota has been recognised as being essential for health. Indeed, several publications have documented the suitability of probiotics, prebiotics, and symbiotics in the management of different diseases such as diabetes mellitus (DM). Advances in laboratory techniques have allowed the identification and characterisation of new biologically active molecules, referred to as “postbiotics”. Postbiotics are defined as functional bioactive compounds obtained from food-grade microorganisms that confer health benefits when administered in adequate amounts. They include cell structures, secreted molecules or metabolic by-products, and inanimate microorganisms. This heterogeneous group of molecules presents a broad range of mechanisms and may exhibit some advantages over traditional “biotics” such as probiotics and prebiotics. Owing to the growing incidence of DM worldwide and the implications of the microbiota in the disease progression, postbiotics appear to be good candidates as novel therapeutic targets. In the present review, we summarise the current knowledge about postbiotic compounds and their potential application in diabetes management. Additionally, we envision future perspectives on this topic. In summary, the results indicate that postbiotics hold promise as a potential novel therapeutic strategy for DM.

The underlying mechanisms of probiotics and postbiotics are not well understood, but it is known that both affect the adaptive and innate immune responses. In addition, there is a growing concept that some probiotic strains have common core mechanisms that provide certain health benefits. Here, we aimed to elucidate the signalization of the probiotic bacterial strains Lactobacillus paragasseri K7, Limosilactobacillus fermentum L930BB, Bifidobacterium animalis subsp. animalis IM386 and Lactiplantibacillus plantarum WCFS1. We showed in in vitro experiments that the tested probiotics exhibit common TLR2‐ and TLR10‐dependent downstream signalling cascades involving inhibition of NF‐κB signal transduction. Under inflammatory conditions, the probiotics activated phosphatidylinositol 3‐kinase (PI3K)/Akt anti‐apoptotic pathways and protein kinase C (PKC)‐dependent pathways, which led to regulation of the actin cytoskeleton and tight junctions. These pathways contribute to the regeneration of the intestinal epithelium and modulation of the mucosal immune system, which, together with the inhibition of canonical TLR signalling, promote general immune tolerance. With this study we identified shared probiotic mechanisms and were the first to pinpoint the role of anti‐inflammatory probiotic signalling through TLR10.

Inflammatory bowel disease (IBD) is a chronic and relapsing intestinal inflammatory condition with no effective treatment. Probiotics have gained wide attention because of their outstanding advantages in intestinal health issues. In previous studies, a novel soluble protein, HM0539, which is derived from Lactobacillus rhamnosus GG (LGG), showed significant protective effects against murine colitis, but no clear precise mechanism for this effect was provided. In this study, we hypothesized that the protective function of HM0539 might be derived from its modulation of the TLR4/Myd88/NF-κB axis signaling pathway, which is a critical pathway widely involved in the modulation of inflammatory responses. To test this hypothesis, the underlying anti-inflammatory effects and associated mechanisms of HM0539 were determined both in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and in dextran sulfate sodium (DSS)-induced murine colitis. Our results showed that HM0539 inhibited the expression of cyclooxygenase-2 (COX-2) and the expression inducible nitric oxide synthase (iNOS) by down-regulating the activation of their respective promoter, and as a result this inhibited the production of prostaglandin E2 (PGE2) and nitric oxide (NO). Meanwhile, we demonstrated that HM0539 could ultimately modulate the activation of distal NF-κB by reducing the activation of TLR4 and suppressing the transduction of MyD88. However, even though the overexpression of TLR4 or MyD88 obviously reversed the effect of HM0539 on LPS-induced inflammation, HM0539 still retained some anti-inflammatory activity. Consistent with the in vitro findings, we found that HM0539 inhibited to a great extent the production of inflammatory mediators associated with the suppression of the TLR4/Myd88/NF-κB axis activation in colon tissue. In conclusion, HM0539 was shown to be a promising anti-inflammatory agent, at least in part through its down-regulation of the TLR4-MyD88 axis as well as of the downstream MyD88-dependent activated NF-κB signaling, and hence might be considered as a potential therapeutic option for IBD.

Background Multiple studies suggest a key role for gut microbiota in IgE-mediated food allergy (FA) development, but to date, none has studied it in the persistent state. Methods To characterize the gut microbiota composition and short-chain fatty acid (SCFAs) profiles associated with major food allergy groups, we recruited 233 patients with FA including milk (N = 66), sesame (N = 38), peanut (N = 71), and tree nuts (N = 58), and non-allergic controls (N = 58). DNA was isolated from fecal samples, and 16S rRNA gene sequences were analyzed. SCFAs in stool were analyzed from patients with a single allergy (N = 84) and controls (N = 31). Results The gut microbiota composition of allergic patients was significantly different compared to age-matched controls both in α-diversity and β-diversity. Distinct microbial signatures were noted for FA to different foods. Prevotella copri (P. copri) was the most overrepresented species in non-allergic controls. SCFAs levels were significantly higher in the non-allergic compared to the FA groups, whereas P. copri significantly correlated with all three SCFAs. We used these microbial differences to distinguish between FA patients and non-allergic healthy controls with an area under the curve of 0.90, and for the classification of FA patients according to their FA types using a supervised learning algorithm. Bacteroides and P. copri were identified as taxa potentially contributing to KEGG acetate-related pathways enriched in non-allergic compared to FA. In addition, overall pathway dissimilarities were found among different FAs. Conclusions Our results demonstrate a link between IgE-mediated FA and the composition and metabolic activity of the gut microbiota.

Wild probiotic consortia of microorganisms (bacteria and yeasts) associated in the artisanal cultures’ microbiota (milk kefir grains, water kefir grains and kombucha) are considered valuable promoters for metabiotics (prebiotics, probiotics, postbiotics and paraprobiotics) production. The beneficial effects of the fermented products obtained with the artisanal cultures on human well-being are described by centuries and the interest for them is continuously increasing. The wild origin and microbial diversity of these above-mentioned consortia give them extraordinary protection capacity against microbiological contaminants in unusual physico-chemical conditions and unique fermentative behaviour. This review summarizes the state of the art for the wild artisanal cultures (milk and water kefir grains, respectively, kombucha—SCOBY), their symbiotic functionality, and the ability to ferment unconventional substrates in order to obtain valuable bioactive compounds with in vitro and in vivo beneficial functional properties. Due to the necessity of the bioactives production and their use as metabiotics in the modern consumer’s life, artisanal cultures are the perfect sources able to biosynthesize complex functional metabolites (bioactive peptides, antimicrobials, polysaccharides, enzymes, vitamins, cell wall components). Depending on the purposes of the biotechnological fermentation processes, artisanal cultures can be used as starters on different substrates. Current studies show that the microbial synergy between bacteria—yeast and/or bacteria—offers new perspectives to develop functional products (food, feeds, and ingredients) with a great impact on life quality.

Over the last decade, our understanding of the composition and functions of the gut microbiota has greatly increased. To a large extent, this has been due to the development of high-throughput genomic analyses of microbial communities, which have identified the critical contributions of the microbiome to human health., Over the last decade, our understanding of the composition and functions of the gut microbiota has greatly increased. To a large extent, this has been due to the development of high-throughput genomic analyses of microbial communities, which have identified the critical contributions of the microbiome to human health. Consequently, the intestinal microbiota has emerged as an attractive therapeutic target. The large majority of microbiota-targeted therapies aim at engineering the intestinal ecosystem by means of probiotics or prebiotics. Recently, a novel therapeutic approach has emerged which focuses on molecules that are secreted, modulated, or degraded by the microbiome and act directly on the host. Here, we discuss the advantages and challenges associated with the metabolite-based “postbiotic” approach, highlighting recent progress and the areas that need intensive attention and investigation over the next 5 years. The time is ripe for postbiotic therapies to be developed in the near future.

AIM:To determine the protective capacity against Salmonella infection in mice of the cell-free fraction (postbiotic) of fermented milk, produced at laboratory and industrial level.METHODS AND RESULTS:The proteolytic activity (PA) of five commercial cultures and eleven autochthonous Lactobacillus strains was evaluated. The DSM-100H culture displayed the highest PA and it was selected for further studies. The capacity of the postbiotics produced by pH-controlled fermentation to stimulate the production of secretory-IgA in faeces and to protect mice against Salmonella infection was evaluated. A significant increase of S-IgA in faeces of mice fed 14 days the postbiotic obtained at the laboratory (F36) was detected compared to control animals. A significantly higher survival was observed in mice fed the F36 and the FiSD (industrial product) compared to controls.CONCLUSION:The postbiotics obtained showed immunomodulatory and protective capacity against Salmonella infection in mice.SIGNIFICANCE AND IMPACT OF THE STUDY:The pH-controlled milk fermentation by the proteolytic DSM-100H culture could be a suitable strategy to obtain a food ingredient to be added to a given food matrix, not adequate to host viable cells of probiotics, to confer it enhanced functionality and thus expand the functional food market. This article is protected by copyright. All rights reserved. Fil: Dunnand, E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentina Fil: Burns, Patricia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentina Fil: Binetti, Ana Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentina Fil: Bergamini, Carina Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentina Fil: Peralta, Guillermo Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentina Fil: Forzani, Liliana Maria. Universidad Nacional del Litoral. Facultad de Ingeniería Química; Argentina Fil: Reinheimer, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentina Fil: Vinderola, Celso Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentina

Prebiotics are non-digestible food components able to modify host microbiota toward a healthy profile, concomitantly conferring general beneficial health effects. Numerous research works have provided wide evidence regarding the effects of prebiotics on the protection against different detrimental phenotypes related to cancer, immunity, and features of the metabolic syndrome, among others. Nonetheless, one topic less studied so far, but relevant, relates to the connection between prebiotics and energy metabolism regulation (and the prevention or treatment of obesity), especially by means of their impact on adaptive (non-shivering) thermogenesis in brown adipose tissue (BAT) and in the browning of white adipose tissue (WAT). In the present review, a key link between prebiotics and the regulation of adaptive thermogenesis and lipid metabolism (in both BAT and WAT) is proposed, thus connecting prebiotic consumption, microbiota selection (especially gut microbiota), production of microbiota metabolites, and the regulation of energy metabolism in adipose tissue, particularly regarding the effects on browning promotion, or on BAT recruitment. In this sense, various types of prebiotics, from complex carbohydrates to phenolic compounds, have been studied regarding their microbiota-modulating role and their effects on crucial tissues for energy metabolism, including adipose tissue. Other studies have analyzed the effects of the main metabolites produced by selected microbiota on the improvement of metabolism, such as short chain fatty acids and secondary bile acids. Here, we focus on state-of-the-art evidence to demonstrate that different prebiotics can have an impact on energy metabolism and the prevention or treatment of obesity (and its associated disorders) by inducing or regulating adaptive thermogenic capacity in WAT and/or BAT, through modulation of microbiota and their derived metabolites., This work was supported by the Spanish Government: INTERBIOBES-AGL2015-67019-P (MINECO/FEDER, EU).

Postbiotics are functional bioactive compounds, generated in a matrix during fermentation, which may be used to promote health. The term postbiotics can be regarded as an umbrella term for all synonyms and related terms of these microbial fermentation components. Therefore, postbiotics can include many different constituents including metabolites, short-chain fatty acids (SCFAs), microbial cell fractions, functional proteins, extracellular polysaccharides (EPS), cell lysates, teichoic acid, peptidoglycan-derived muropeptides and pili-type structures. Postbiotics is also a rather new term in the ‘-biotics’ field. Where consensus exists for the definitions of pre- and probiotics, this is not yet the case for postbiotics. Here we propose a working definition and review currently known postbiotic compounds, their proposed mechanisms, clinical evidence and potential applications. Research to date indicates that postbiotics can have direct immunomodulatory and clinically relevant effects and evidence can be found for the use of postbiotics in healthy individuals to improve overall health and to relief symptoms in a range of diseases such as infant colic and in adults atopic dermatitis and different causes of diarrhea.

Probiotics (Pro-life live entities) provide the health and well being with multitude of beneficial effects on humans and animals (and relief against varied disorders). Probiotics may manage lactose intolerance, elevate immune profile, prevent colorectal cancers, reduce cholesterol and triglyceride profile, lowering blood pressure and inflammatory process. They also prevent osteoporosis, allergic reactions and help suppress H. pylori infections and other pathological manifestations. Microbial metabolites (even in the absence of live entities) may exert (analogous) effects on signal pathways and barrier functions. Such substances are referred as ‘Postbiotics’ (the plain metabolic byproduct of probiotics, bioactive manifestations in the host). Generally, postbiotics include secondary metabolites such as bacteriocins, organic acids, ethanol, acetaldehyde, reactive oxygen species (ROS). Such metabolites are inhibitory against pathogenic strains of different broad spectrum drug resistant microbial groups (MDR, XDR etc). Postbiotics are safe, apathogenic which may resist hydrolysis by enzymes of mammalian origin. It has been described that micro-RNA profile of human milk may exert the inhibitory effects of probiotics. Our research group has been investigating the merits of mammalian milk as a viable source of probiotics that secrete bioactive peptides against MDR/biofilm producing strains (ref. Streptococcus thermophilus and Enterococcus faecalis, a GIT probiont). These peptides are in the range of 10-16KDa molecular mass (sensitive to proteolytic enzymes as well). Genes coding for these peptides are plasmid associated. Mode of action of these peptides is bacteriostatic. Molecular identification of these Probiotic strains is being followed. This, on the whole marks an emphasis on biological operation of novel strains of Probiotic and their applications in medico-clinical areas to improve the human health and wellness.

The aim of this study was to investigate the potential of postbiotics originated from Lactobacillus fermentum BGHV110 strain (HV110) to counteract acetaminophen (APAP)-induced hepatotoxicity in HepG2 cells. This strain was selected according to its autophagy inducing potential, based on previous studies reporting protective role of autophagy in APAP caused cellular damage. Cell viability was assessed using MTT and LDH assays, while autophagy was monitored by qPCR analysis of BECN1, Atg5, p62/SQSTM1, and PINK1 mRNA expression and by Western blot analysis of p62/SQSTM1 and lipidated LC3 accumulation. Our results showed that detrimental effect of APAP on cell viability was suppressed in the presence of HV110 which was linked with increased conversion of LC3 protein and p62/SQSTM1 protein degradation. Additionally, higher p62/SQSTM1 and PINK1 mRNA transcription were noticed in cells co-treated with APAP/HV110, simultaneously. In conclusion, this study suggests that HV110 enhances activation of PINK1-dependent autophagy in HepG2 cells and its eventual co-supplementation with APAP could be potentially used for alleviation of hepatotoxic side effects caused by APAP overdose.

Background: Some beneficial effects of probiotics may be due to secreted probiotic-derived factors, identified as "postbiotic" mediators. The aim of this study was to evaluate whether supernatants harvested from Lactobacillus rhamnosus GG (LGG) cultures (ATCC53103 strain) protect colonic human smooth muscle cells (HSMCs) from lipopolysaccharide (LPS)-induced myogenic damage. Materials and methods: LGG was grown in de Man, Rogosa, Share medium at 37°C and samples were collected in middle and late exponential, stationary, and overnight phases. Supernatants were recovered by centrifugation, filtered, and stored at -20°C. The primary HSMCs culture was exposed for 24 hours to purified LPS of a pathogen strain of Escherichia coli (O111:B4) (1 μg/mL) with and without supernatants. Postbiotic effects were evaluated on the basis of HSMCs morphofunctional alterations and interleukin-6 (IL-6) production. Data are expressed as mean±SE (P