Effects of short-chain fatty acid-butyrate supplementation on expression of circadian-clock genes, sleep quality, and inflammation in patients with active ulcerative colitis: a double-blind randomized controlled trial.

BACKGROUND: The regulation of the circadian clock genes, which coordinate the activity of the immune system, is disturbed in inflammatory bowel disease (IBD). Emerging evidence suggests that butyrate, a short-chain fatty acid produced by the gut microbiota is involved in the regulation of inflammatory responses as well as circadian-clock genes. This study was conducted to investigate the effects of sodium-butyrate supplementation on the expression of circadian-clock genes, inflammation, sleep and life quality in active ulcerative colitis (UC) patients. METHODS: In the current randomized placebo-controlled trial, 36 active UC patients were randomly divided to receive sodium-butyrate (600 mg/kg) or placebo for 12-weeks. In this study the expression of circadian clock genes (CRY1, CRY2, PER1, PER2, BMAl1 and CLOCK) were assessed by real time polymerase chain reaction (qPCR) in whole blood. Gene expression changes were presented as fold changes in expression (2^-ΔΔCT) relative to the baseline. The faecal calprotectin and serum level of high-sensitivity C-reactive protein (hs-CRP) were assessed by enzyme-linked immunosorbent assay method (ELIZA). Moreover, the sleep quality and IBD quality of life (QoL) were assessed by Pittsburgh sleep quality index (PSQI) and inflammatory bowel disease questionnaire-9 (IBDQ-9) respectively before and after the intervention. RESULTS: The results showed that sodium-butyrate supplementation in comparison with placebo significantly decreased the level of calprotectin (-133.82 ± 155.62 vs. 51.58 ± 95.57, P-value < 0.001) and hs-CRP (-0.36 (-1.57, -0.05) vs. 0.48 (-0.09-4.77), P-value < 0.001) and upregulated the fold change expression of CRY1 (2.22 ± 1.59 vs. 0.63 ± 0.49, P-value < 0.001), CRY2 (2.15 ± 1.26 vs. 0.93 ± 0.80, P-value = 0.001), PER1 (1.86 ± 1.77 vs. 0.65 ± 0.48, P-value = 0.005), BMAL1 (1.85 ± 0.97 vs. 0.86 ± 0.63, P-value = 0.003). Also, sodium-butyrate caused an improvement in the sleep quality (PSQI score: -2.94 ± 3.50 vs. 1.16 ± 3.61, P-value < 0.001) and QoL (IBDQ-9: 17.00 ± 11.36 vs. -3.50 ± 6.87, P-value < 0.001). CONCLUSION: Butyrate may be an effective adjunct treatment for active UC patients by reducing biomarkers of inflammation, upregulation of circadian-clock genes and improving sleep quality and QoL.

Bacillus subtilis-derived peptides disrupt quorum sensing and biofilm assembly in multidrug-resistant Staphylococcus aureus.

Multidrug-resistant Staphylococcus aureus is one of the most clinically important pathogens in the world, with infections leading to high rates of morbidity and mortality in both humans and animals. The ability of S. aureus to form biofilms protects cells from antibiotics and promotes the transfer of antibiotic resistance genes; therefore, new strategies aimed at inhibiting biofilm growth are urgently needed. Probiotic species, including Bacillus subtilis, are gaining interest as potential therapies against S. aureus for their ability to reduce S. aureus colonization and virulence. Here, we search for strains and microbially derived compounds with strong antibiofilm activity against multidrug-resistant S. aureus by isolating and screening Bacillus strains from a variety of agricultural environments. From a total of 1,123 environmental isolates, we identify a single strain B. subtilis 6D1, with a potent ability to inhibit biofilm growth, disassemble mature biofilm, and improve antibiotic sensitivity of S. aureus biofilms through an Agr quorum sensing interference mechanism. Biochemical and molecular networking analysis of an active organic fraction revealed multiple surfactin isoforms, and an uncharacterized peptide was driving this antibiofilm activity. Compared with commercial high-performance liquid chromatography grade surfactin obtained from B. subtilis, we show these B. subtilis 6D1 peptides are significantly better at inhibiting biofilm formation in all four S. aureus Agr backgrounds and preventing S. aureus-induced cytotoxicity when applied to HT29 human intestinal cells. Our study illustrates the potential of exploring microbial strain diversity to discover novel antibiofilm agents that may help combat multidrug-resistant S. aureus infections and enhance antibiotic efficacy in clinical and veterinary settings. IMPORTANCE: The formation of biofilms by multidrug-resistant bacterial pathogens, such as Staphylococcus aureus, increases these microorganisms' virulence and decreases the efficacy of common antibiotic regimens. Probiotics possess a variety of strain-specific strategies to reduce biofilm formation in competing organisms; however, the mechanisms and compounds responsible for these phenomena often go uncharacterized. In this study, we identified a mixture of small probiotic-derived peptides capable of Agr quorum sensing interference as one of the mechanisms driving antibiofilm activity against S. aureus. This collection of peptides also improved antibiotic killing and protected human gut epithelial cells from S. aureus-induced toxicity by stimulating an adaptive cytokine response. We conclude that purposeful strain screening and selection efforts can be used to identify unique probiotic strains that possess specially desired mechanisms of action. This information can be used to further improve our understanding of the ways in which probiotic and probiotic-derived compounds can be applied to prevent bacterial infections or improve bacterial sensitivity to antibiotics in clinical and agricultural settings.

Postbiotic lactobacilli induce cutaneous antimicrobial response and restore the barrier to inhibit the intracellular invasion of Staphylococcus aureus in vitro and ex vivo.

Intracellular pathogens including Staphylococcus aureus contribute to the non-healing phenotype of chronic wounds. Lactobacilli, well known as beneficial bacteria, are also reported to modulate the immune system, yet their role in cutaneous immunity remains largely unknown. We explored the therapeutic potential of bacteria-free postbiotics, bioactive lysates of lactobacilli, to reduce intracellular S. aureus colonization and promote healing. Fourteen postbiotics derived from various lactobacilli species were screened, and Latilactobacillus curvatus BGMK2-41 was selected for further analysis based on the most efficient ability to reduce intracellular infection by S. aureus diabetic foot ulcer clinical isolate and S. aureus USA300. Treatment of both infected keratinocytes in vitro and infected human skin ex vivo with BGMK2-41 postbiotic cleared S. aureus. Keratinocytes treated in vitro with BGMK2-41 upregulated expression of antimicrobial response genes, of which DEFB4, ANG, and RNASE7 were also found upregulated in treated ex vivo human skin together with CAMP exclusively upregulated ex vivo. Furthermore, BGMK2-41 postbiotic treatment has a multifaceted impact on the wound healing process. Treatment of keratinocytes stimulated cell migration and the expression of tight junction proteins, while in ex vivo human skin BGMK2-41 increased expression of anti-inflammatory cytokine IL-10, promoted re-epithelialization, and restored the epidermal barrier via upregulation of tight junction proteins. Together, this provides a potential therapeutic approach for persistent intracellular S. aureus infections.

Genome mining of Lactiplantibacillus plantarum PA21: insights into its antimicrobial potential.

BACKGROUND: The dramatic increase of antimicrobial resistance in the healthcare realm has become inexorably linked to the abuse of antibiotics over the years. Therefore, this study seeks to identify potential postbiotic metabolites derived from lactic acid bacteria such as Lactiplantibacillus plantarum that could exhibit antimicrobial properties against multi-drug resistant pathogens. RESULTS: In the present work, the genome sequence of Lactiplantibacillus plantarum PA21 consisting of three contigs was assembled to a size of 3,218,706 bp. Phylogenomic analysis and average nucleotide identity (ANI) revealed L. plantarum PA21 is closely related to genomes isolated from diverse niches such as dairy products, food, and animals. Genome mining through the BAGEL4 and antiSMASH database revealed four bacteriocins in a single cluster and four regions of biosynthetic gene clusters responsible for the production of bioactive compounds. The potential probiotic genes indirectly responsible for postbiotic metabolites production were also identified. Additionally, in vitro studies showed that the L. plantarum PA21 cell-free supernatant exhibited antimicrobial activity against all nine methicillin-resistant Staphylococcus aureus (MRSA) and three out of 13 Klebsiella pneumoniae clinical isolates tested. CONCLUSION: Results in this study demonstrates that L. plantarum PA21 postbiotic metabolites is a prolific source of antimicrobials against multi-drug resistant pathogens with potential antimicrobial properties.

Effects of sodium lauryl sulfate and postbiotic toothpaste on oral microecology.

The diversity and delicate balance of the oral microbiome contribute to oral health, with its disruption leading to oral and systemic diseases. Toothpaste includes elements like traditional additives such as sodium lauryl sulfate (SLS) as well as novel postbiotics derived from probiotics, which are commonly employed for maintaining oral hygiene and a healthy oral cavity. However, the response of the oral microbiota to these treatments remains poorly understood. In this study, we systematically investigated the impact of SLS, and toothpaste containing postbiotics (hereafter, postbiotic toothpaste) across three systems: biofilms, animal models, and clinical populations. SLS was found to kill bacteria in both preformed biofilms (mature biofilms) and developing biofilms (immature biofilms), and disturbed the microbial community structure by increasing the number of pathogenic bacteria. SLS also destroyed periodontal tissue, promoted alveolar bone resorption, and enhanced the extent of inflammatory response level. The postbiotic toothpaste favored bacterial homeostasis and the normal development of the two types of biofilms in vitro, and attenuated periodontitis and gingivitis in vivo via modulation of oral microecology. Importantly, the postbiotic toothpaste mitigated the adverse effects of SLS when used in combination, both in vitro and in vivo. Overall, the findings of this study describe the impact of toothpaste components on oral microflora and stress the necessity for obtaining a comprehensive understanding of oral microbial ecology by considering multiple aspects.

The Effect of Microbiome-Modulating Agents (MMAs) on Type 1 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Gut microbiome-modulating agents (MMAs), including probiotics, prebiotics, postbiotics, and synbiotics, are shown to ameliorate type 1 diabetes (T1D) by restoring the microbiome from dysbiosis. The objective of this systematic review and meta-analysis was to assess the impact of MMAs on hemoglobin A1c (HbA1c) and biomarkers associated with (T1D). A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, National Knowledge Infrastructure, WeiPu, and WanFang Data up to 30 November 2023. Ten randomized controlled trials (n = 630) were included, with study quality evaluated using the Cochrane risk-of-bias tool. Random-effect models with standardized mean differences (SMDs) were utilized. MMA supplementation was associated with improvements in HbA1c (SMD = -0.52, 95% CI [-0.83, -0.20]), daily insulin usage (SMD = -0.41, 95% confidence interval (CI) [-0.76, -0.07]), and fasting C-peptide (SMD = 0.99, 95% CI [0.17, 1.81]) but had no effects on FBG, CRP, TNF-α, IL-10, LDL, HDL, and the Shannon index. Subgroup analysis of HbA1c indicated that a long-term intervention (>3 months) might exert a more substantial effect. These findings suggest an association between MMAs and glycemic control in T1D. Further large-scale clinical trials are necessary to confirm these findings with investigations on inflammation and gut microbiota composition while adjusting confounding factors such as diet, physical activity, and the dose and form of MMA intervention.

Insights into the Mechanisms of Action of Akkermansia muciniphila in the Treatment of Non-Communicable Diseases.

This comprehensive review delineates the extensive roles of Akkermansia muciniphila in various health domains, spanning from metabolic and inflammatory diseases to neurodegenerative disorders. A. muciniphila, known for its ability to reside in the mucous layer of the intestine, plays a pivotal role in maintaining gut integrity and interacting with host metabolic processes. Its influence extends to modulating immune responses and potentially easing symptoms across several non-communicable diseases, including obesity, diabetes, inflammatory bowel disease, and cancer. Recent studies highlight its capacity to interact with the gut-brain axis, suggesting a possible impact on neuropsychiatric conditions. Despite the promising therapeutic potential of A. muciniphila highlighted in animal and preliminary human studies, challenges remain in its practical application due to stability and cultivation issues. However, the development of pasteurized forms and synthetic mediums offers new avenues for its use in clinical settings, as recognized by regulatory bodies like the European Food Safety Authority. This narrative review serves as a crucial resource for understanding the broad implications of A. muciniphila across different health conditions and its potential integration into therapeutic strategies.

Gut Microbiota Modulation by Selenium and Zinc Enrichment Postbiotic on Dysbiosis Associated with Hypertension.

BACKGROUND: Targeting gut dysbiosis to treat chronic diseases or to alleviate the symptoms is a new direction for medical adjuvant therapies. Recently, postbiotics have received considerable attention as they are non-viable probiotic preparations that confer various health benefits to the host without the safety problems associated with using live microbial cells. OBJECTIVE: The aim of the study is to obtain selenium (Se) and zinc (Zn) enriched Saccharomyces boulardii postbiotic biomass and to analyze its modulation effect because these minerals play an important role in reducing gut dysbiosis linked to cardiovascular (CV) diseases. METHOD: The effect of the S. boulardii and Se/Zn enriched yeast postbiotics on CV microbial fingerprint was studied in vitro using the gastrointestinal system (GIS 1) and analyzed by microbiological, chemical, and qPCR methods. RESULT: There was a 2.2 log CFU/mL increase in the total bacterial load after SeZn postbiotic treatment and in the qPCR counts of Firmicutes phyla for both treatments. Beneficial taxa, Bifidobacterium spp. and Lactobacillus spp., as well as Bacteroides spp. were up to 1.5 log higher after mineral- enriched postbiotic application, while the acetic acid level increased. CONCLUSION: These preliminary studies highlight the therapeutic potential of using Se/Zn enriched yeast postbiotics as adjuvants for clinical treatments of CV diseases.

Anticancer Potential of Postbiotic Derived from Lactobacillus brevis and Lactobacillus casei: In vitro Analysis of Breast Cancer Cell Line.

Breast cancer has emerged as the most widespread and dangerous type of malignancy among women worldwide. Postbiotics have recently emerged as a promising novel adjunct in breast cancer therapy, due to their immunomodulatory effects and the potential to mitigate the adverse effects of conventional treatments. This study aims to investigate the therapeutic effects of postbiotics derived from Lactobacillus brevis (CSF2) and Lactobacillus casei (CFS5), specifically examining their ability to inhibit cell proliferation and induce apoptosis in MCF-7 breast cancer cells. In the current study, the anticancer activity of the cell-free supernatant of L. brevis and L. casei was investigated against MCF-7 cells using MTT assay, flow cytometry, and qRT-PCR technique. Both bacteria showed a high potential for the induction of cell death in MCF-7 cells. However, CFS2 cytotoxicity was significantly higher than CFS5. Flow cytometry results showed significant induction of early apoptosis in cells treated with both CFS2 and CFS5 within 48 h. The induction was notably higher in cells treated with CFS2 compared to CFS5. Overall, CFS2 therapy resulted in a greater increase in BAX and CASP9 gene expression, as well as an elevated BAX/BCL2 ratio within 48 h. These findings indicate that the CFS2 treatment showed a higher level of apoptotic activity than the CFS5 treatment. High biocompatibility was demonstrated following treatment with CFS2 and CFS5. These CFSs may serve as adjunctive medications for suppressing the proliferation of cancer cells. The results of the current study highlight the potential of postbiotics in cancer treatment and suggest that supernatants may serve as effective agents for suppressing cancer cell growth and viability.

The comparative anti-oxidant and anti-inflammatory efficacy of postbiotics and probiotics through Nrf-2 and NF-kB pathways in DSS-induced colitis model.

IBD is a disorder which could be caused by oxidative stress. This investigation aims to determine if probiotics and postbiotics can control oxidative stress and inflammation and compare the effectiveness of these two probiotic and postbiotic mixtures of substances. 88 strains of Lactobacillus and Bifidobacterium were tested for antioxidant activity. Male wild-type C57BL/6 mice were divided into four experimental groups, namely high fat diet (HFD) + PBS, HFD + DSS, HFD + DSS + 109 cfu/ml of probiotics, and HFD + DSS + 109 cfu/ml of postbiotics. The phenotypical indices and pathological scores were assessed. The expression of genes related to NF-kB and Nrf2 signaling pathways and enzymes associated with oxidant/anti-oxidant activities, and proinflammatory/inflammatory cytokines were assessed. In contrast to the groups exposed to DSS, mice treated with probiotics mixture and postbiotics mixture alongside DSS displayed alleviation of DSS-induced adverse effects on phenotypical characteristics, as well as molecular indices such as the Nrf2 and NF-kB related genes, with a greater emphasis on the postbiotics component. In accordance with the findings of the present investigation, it can be inferred that even in using a high-fat dietary regimen as an inducer of oxidative stress, the emergence of inflammation can be effectively addressed through the utilization of probiotics and, more specifically, postbiotics.

Oral supplementation with postbiotics modulates the immune response produced by myxomatosis vaccination in wild rabbits.

Rabbits (Oryctolagus cuniculus) are vitally important species in the Iberian Peninsula ecosystem. However, since 1950, there has been a significant population decline, with major repercussions. This situation is mainly due to the presence of infectious diseases, such as myxomatosis, which is expanding and is characterized by severe and fatal clinical manifestations. Current control measures, mainly those based on vaccinations, are ineffective. Therefore, new strategies need to be developed and implemented. This study aimed to evaluate whether supplementation with postbiotic products modulates the immune response in wild rabbits vaccinated against myxomatosis. For this purpose, two groups of rabbits were established: a control group fed with standard feed ad libitum from weaning (28 days) until two months of age, and a treated group, which was fed under the same conditions but supplemented with postbiotics (3 kg/Tm). All the studied rabbits were vaccinated against this disease during weaning. In addition, a blood samples were obtained from all animals immediately before vaccination and 30 days later, which allowed us to evaluate the level of antibodies against myxomatosis virus (ELISA detection) and the relative expression of gene encoding to cytokines related to the immune response (IL6, TNFα and IFNγ), at both times of the experience. Weight and length measurements were also taken at both times to calculate body index and mean daily gain (MDG). No statistically significant differences in growth parameters were observed. There were also no differences in the serological response among groups. However, a relative underexpression of gene codifying to TNFα (p-value = 0.03683) and a higher expression on IFNγ (p-value = 0.045) were observed in the treated group. This modulation in cytokines could lead to less severe lesions in wild rabbit naturally infected with myxomatosis virus.

Selection of Fermentation Supernatant from Probiotic Strains Exhibiting Intestinal Epithelial Barrier Protective Ability and Evaluation of Their Effects on Colitis Mouse and Weaned Piglet Models.

The intestinal epithelial barrier can prevent the invasion of pathogenic microorganisms and food antigens to maintain a consistent intestinal homeostasis. However, an imbalance in this barrier can result in various diseases, such as inflammatory bowel disease, malnutrition, and metabolic disease. Thus, the aim of this study was to select probiotic strains with epithelial barrier-enhancing ability in cell-based model and further investigate them for their improving effects on colitis mouse and weaned piglet models. The results showed that selected specific cell-free fermentation supernatants (CFSs) from Ligilactobacillus salivarius P1, Lactobacillus gasseri P12, and Limosilactobacillus reuteri G7 promoted intestinal epithelial cell growth and proliferation, strengthening the intestinal barrier in an intestinal epithelial cell line Caco-2 model. Further, the administration of CFSs of L. salivarius P1, L. gasseri P12, and L. reuteri G7 were found to ameliorate DSS-induced colitis in mice. Additionally, spray-dried powders of CFS from the three strains were examined in a weaned piglet model, only CFS powder of L. reuteri G7 could ameliorate the feed/gain ratio and serum levels of D-lactate and endotoxin. In conclusion, a new potential probiotic strain, L. reuteri G7, was selected and showed ameliorating effects in both colitis mouse and weaned piglet models.

Glycoprotein Matrix Zinc Exhibits Improved Absorption: A Randomized Crossover Trial.

Biotransformation of minerals via glycosylation by microorganisms such as yeast and/or probiotics yields nutrients bound to a food matrix, resulting in increased bioavailability. The purpose of this study was to compare the effects of glycoprotein matrix-bound zinc (GPM) on absorption compared to inorganic zinc oxide. Sixteen participants ingested 11 mg of zinc as either GPM™ Soy-Free Zinc (GPM, Ashland, Kearny, NJ, USA) or zinc oxide (USP). Blood samples were taken at 0 (i.e., baseline), 30, 60, 90, 120, 180, 240, 300, 360, 420, and 480 min post-ingestion. GPM zinc concentrations were significantly higher at 120 min (p = 0.02; 12.4 ± 5.1 mcg/dL), 180 min (p = 0.002; 16.8 ± 5.1 mcg/dL), and 240 min (p = 0.007; 14.6 ± 5.1 mcg/dL) in comparison to USP zinc oxide. In addition, GPM zinc significantly increased iAUC by 40% (5840 ± 2684 vs. 4183 ± 1132 mcg/dL * 480 min, p = 0.02), and Cmax values were 10% higher in GPM compared to USP (148 ± 21 mcg/dL vs. 135 ± 17.5 mcg/dL, p = 0.08). Tmax was 12% slower in GPM compared to USP (112.5 ± 38.7 min vs. 127.5 ± 43.1 min); however, differences in Tmax failed to reach statistical significance (p = 0.28). Zinc bound to a glycoprotein matrix significantly increased absorption compared to zinc oxide.

Metabolite profiling and bioactivity guided fractionation of Lactobacillaceae and rice bran postbiotics for antimicrobial-resistant Salmonella Typhimurium growth suppression.

Probiotic-fermented supplements (postbiotics) are becoming increasingly explored for their activity against antibiotic-resistant enteropathogens. Prebiotics are often incorporated into postbiotics to enhance their efficacy, but due to strain differences in probiotic activity, postbiotic antimicrobial effects are poorly understood. To improve postbiotic antimicrobial efficacy, we investigated and compared metabolite profiles of postbiotics prepared with three lactic acid bacteria strains (L. fermentum, L. paracasei, and L. rhamnosus) cultured with and without rice bran, a globally abundant, rich source of prebiotics. At their minimum inhibitory dose, L. fermentum and L. paracasei postbiotics + rice bran suppressed S. Typhimurium growth 42-55% more versus their respective probiotic-alone postbiotics. The global, non-targeted metabolome of these postbiotics identified 109 metabolites increased in L. fermentum and L. paracasei rice bran postbiotics, including 49 amino acids, 20 lipids, and 12 phytochemicals metabolites. To identify key metabolite contributors to postbiotic antimicrobial activity, bioactivity-guided fractionation was applied to L. fermentum and L. paracasei rice bran-fermented postbiotics. Fractionation resulted in four L. fermentum and seven L. paracasei fractions capable of suppressing S. Typhimurium growth more effectively versus the negative control. These fractions were enriched in 15 metabolites that were significantly increased in the global metabolome of postbiotics prepared with rice bran versus postbiotic alone. These metabolites included imidazole propionate (enriched in L. fermentum + rice bran, 1.61-fold increase; L. paracasei + rice bran 1.28-fold increase), dihydroferulate (L. fermentum + rice bran, 5.18-fold increase), and linoleate (L. fermentum + rice bran, 1.82-fold increase; L. paracasei + rice bran, 3.19-fold increase), suggesting that they may be key metabolite drivers of S. Typhimurium growth suppression. Here, we show distinct mechanisms by which postbiotics prepared with lactic acid bacteria and rice bran produce metabolites with antimicrobial activity capable of suppressing S. Typhimurium growth. Probiotic strain differences contributing to postbiotic antimicrobial activity attract attention as adjunctive treatments against pathogens.

A randomized double-blind, placebo-controlled trial to evaluate the safety and efficacy of live Bifidobacterium longum CECT 7347 (ES1) and heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in participants with diarrhea-predominant irritable bowel syndrome.

To determine the efficacy of the probiotic Bifidobacterium longum CECT 7347 (ES1) and postbiotic heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in improving symptom severity in adults with diarrhea-predominant irritable bowel syndrome (IBS-D), a randomised, double-blind, placebo-controlled trial with 200 participants split into three groups was carried out. Two capsules of either ES1, HT-ES1 or placebo were administered orally, once daily, for 84 days (12 weeks). The primary outcome was change in total IBS-Symptom Severity Scale (IBS-SSS) score from baseline, compared to placebo. Secondary outcome measures were stool consistency, quality of life, abdominal pain severity and anxiety scores. Safety parameters and adverse events were also monitored. The change in IBS-SSS scores from baseline compared to placebo, reached significance in the ES1 and HT-ES1 group, on Days 28, 56 and 84. The decrease in mean IBS-SSS score from baseline to Day 84 was: ES1 (-173.70 [±75.60]) vs placebo (-60.44 [±65.5]) (p < .0001) and HT-ES1 (-177.60 [±79.32]) vs placebo (-60.44 [±65.5]) (p < .0001). Secondary outcomes included changes in IBS-QoL, APS-NRS, stool consistency and STAI-S and STAI-T scores, with changes from baseline to Day 84 being significant in ES1 and HT-ES1 groups, compared to the placebo group. Both ES1 and HT-ES1 were effective in reducing IBS-D symptom severity, as evaluated by measures such as IBS-SSS, IBS-QoL, APS-NRS, stool consistency, and STAI, in comparison to the placebo. These results are both statistically significant and clinically meaningful, representing, to the best of the authors' knowledge, the first positive results observed for either a probiotic or postbiotic from the same strain, in this particular population.

What is already known on this topicIBS is a chronic functional gastrointestinal disorder characterized by abdominal pain, bloating and abnormalities in stool frequency or form. The gut microbiota of people living with IBS differs markedly to the microbiota of healthy individuals. Gut microbiota may play a key role in IBS aetiology and IBS symptoms may be alleviated by modulating the gut microbiota. Several proposed ways to modulate gut health include normalizing the gut microbiota, preventing the overgrowth of pathogenic bacteria, modulating visceral afferent pathways, and enhancing intestinal barrier function. However, significant heterogeneity between studies, study quality and population, study design and concerns about sample size have limited national and supranational bodies from recommending probiotics for IBS. Further well-powered, randomized, repeatable and controlled trials are warranted.What this study addsThe results of this study substantially contribute to the IBS research field, firstly by providing clinically meaningful and statistically significant results from a rigorous, well designed randomized, placebo-controlled trial and secondly, by exploring the use of postbiotics in IBS, an area of research still in its infancy. Probiotic (ES1) and postbiotic (HT-ES1) supplementation significantly reduced IBS symptom severity scores compared to placebo. This study met primary and secondary outcomes and strongly suggest that ES1 and HT-ES1 could be beneficial in the management of IBS.How this study might affect research, practice, or policyThis study adds to the current evidence base, supporting the use of probiotic/postbiotics for IBS. This research could be used to inform health professionals about using probiotics in IBS and help improve the quality of life and wellbeing for people living with the condition.

Postbiotic characterization of a potential probiotic yeast isolate, and its microencapsulation in alginate beads coated layer-by-layer with chitosan.

Considering biosafety concerns and survivability limitations of probiotics (PRO) under different stresses, application of postbiotics and encapsulated PRO has received considerable attentions. Accordingly, the objective of the present study was to investigate the postbiotic capabilities of a potential PRO yeast isolate and the effect of encapsulation with alginate (Alg) and chitosan (Ch) on its survival under SGI conditions. Sequencing results of the PCR products led to the identification of Saccharomyces cerevisiae as the selected potential PRO yeast isolated from wheat germ sourdough. High survival of the isolate under simulated gastrointestinal (SGI) conditions (95.74%), its proper adhesion abilities, as well as its potent inhibitory activity against Listeria monocytogenes (75.84%) and Aspergillus niger (77.35%) were approved. Interestingly, the yeast cell-free supernatant (CFS) showed the highest antioxidant (84.35%) and phytate-degrading (56.19%) activities compared to the viable and heat-dead cells of the isolate. According to the results of the HPLC-based assay, anti-ochratoxin A (OTA) capability of the dead cells was also significantly (P < 0.05) higher than that of the viable cell. Meanwhile, the yeast CFS had no anti-OTA and antimicrobial activities against the foodborne bacteria and fungi tested. Further, microencapsulation of the yeast isolate in Alg beads coated layer-by-layer with Ch (with 77.02% encapsulation efficacy and diameter of 1059 µm based on the field emission scanning electron microscopy analysis) significantly enhanced its survivability under SGI conditions in comparison with the free cells. In addition, electrostatic cross-linking between negatively charged carboxylic groups of Alg and positively charged amino groups of Ch was verified in accordance with Fourier transform infrared and zeta potential data. Human and/or industrial food trials in future are needed for practical applications of these emerging ingredients.

An ex vivo Approach in European Seabass Leucocytes Supports the in vitro Regulation by Postbiotics of Aip56 Gene Expression of Photobacterium damselae subsp. piscicida.

Shewanella putrefaciens Pdp11 (SpPdp11) is a probiotic strain assayed in aquaculture; however, its postbiotic potential is unknown. Postbiotics are bacterial metabolites, including extracellular products (ECPs) that improve host physiology and immunity. Their production and composition can be affected by different factors such as the growing conditions of the probiotics. Photobacterium damselae subsp. piscicida strain Lg 41/01 (Phdp) is one of the most important pathogens in marine aquaculture. The major virulent factor of this bacterium is the exotoxin aip56, responsible for inducing apoptosis of fish leucocytes. Viable SpPdp11 cells have been reported to increase resistance to challenges with Phdp. This work aimed to evaluate the effect of two ECPs, T2348-ECP and FM1548-ECP, obtained from SpPdp11 grown under different culture conditions that previously demonstrated to exert different degradative and non-cytotoxic activities, as well as the effect on pathogens biofilm formation. These SpPdp11-ECPs were then analyzed by their effect on the viability, phagocytosis, respiratory burst and apoptogenic activity against European sea bass leucocytes infected or not with Phdp supernatant. Both ECPs, T2348-ECP and FM1548-ECP, were not cytotoxic against leucocytes and significantly reduced their apoptosis. Phagocytosis and respiratory burst of leucocytes were significantly reduced by incubation with Phdp supernatant, and not influenced by incubation with T2348-ECP or FM1548-ECP. However, both activities were significantly increased after leucocyte incubation with combined T2348-ECP and FM1548-ECP with Phdp supernatant, compared to those incubated only with Phdp supernatant. Finally, both T2348-ECP and FM1548-ECP significantly reduced the relative in vitro expression of the Phdp aip56 encoding gene.

Diet composition influences probiotic and postbiotic effects on broiler growth and physiology.

Dietary ingredient and nutrient composition may affect the efficacy of additives in broilers. Specific feed ingredients can represent dietary challenging conditions for broilers, resulting in impaired performances and health, which might be alleviated by dietary probiotics and postbiotics. We assessed the effects of a Lactobacilli probiotic (Pro) and postbiotic (Post) when added to a standard (SD) and challenge (CD) diet. A completely randomized block study with 2 diets (SD, CD) and 3 additive conditions (Control, Pro and Post) involving 1,368 one-day-old Ross male broilers, equally distributed among 36 pens, from d1 to d42 was conducted. Both diets were formulated to contain identical levels of nutrients, with CD formulated to be richer than SD in nonstarch polysaccharides using rye and barley as ingredients. Readout parameters included growth performance parameters, footpad lesions score, blood minerals and biochemical parameters, and tibia health, strength, and composition. Compared to SD, CD decreased BW (1,936 vs. 2,033 g; p = 0.001), increased FCR (p < 0.01) and impaired tibia health and strength (p < 0.05) at d35, thereby confirming the challenging effect of CD. Pro and Post increased BW in CD (+4.7 and +3.2%, respectively, at d35; P < 0.05) but not in the SD group, without affecting FCR. Independently of the diet, Pro increased plasma calcium, phosphorus and uric acid at d21 (+6.2, +7.4, and +15.5%, respectively) and d35 (+6.6, +6.2 and +21.0%, respectively) (P < 0.05) while Post increased plasma magnesium only at d21 (+11.3%; P = 0.037). Blood bile acids were affected by additives in an age- and diet-dependent manner, with some opposite effects between dietary conditions. Diet composition modulated Pro and Post effects on broiler growth performance. Additionally, Pro and Post affected animal metabolism and leg health diet-dependently for some but not all investigated parameters. Our findings show that the effects of pro- and postbiotics on the growth performance and physiology of broilers can be dependent on diet composition and thus possibly other factors affecting diet characteristics.

New clues for postbiotics to improve host health: a review from the perspective of function and mechanisms.

Strain activity and stability severely limit the beneficial effects of probiotics in modulating host health. Postbiotics have emerged as a promising alternative as they can provide similar or even enhanced efficacy to probiotics, even under inactivated conditions. This review introduces the ingredients, preparation, and identification techniques of postbiotics, focusing on the comparison of the advantages and limitations between probiotics and postbiotics based on their mechanisms and applications. Inactivation treatment is the most significant difference between postbiotics and probiotics. We highlight the use of emerging technologies to inactivate probiotics, optimize process conditions to maintain the activity of postbiotics, or scale up their production. Postbiotics have high stability which can overcome unfavorable factors, such as easy inactivation and difficult colonization of probiotics after entering the intestine, and are rapidly activated, allowing continuous and rapid optimization of the intestinal microecological environment. They provide unique mechanisms, and multiple targets act on the gut-organ axis, co-providing new clues for the study of the biological functions of postbiotics. We summarize the mechanisms of action of inactivated lactic acid bacteria, highlighting that the NF-κB and MAPK pathways can be used as immune targeting pathways for postbiotic modulation of host health. Generally, we believe that as the classification, composition, and efficacy mechanism of postbiotics become clearer they will be more widely used in food, medicine, and other fields, greatly enriching the dimensions of food innovation. © 2024 Society of Chemical Industry.

Effects of dietary supplementation of postbiotic derived from Bacillus subtilis ACCC 11025 on growth performance, meat yield, meat quality, excreta bacteria, and excreta ammonia emission of broiler chicks.

The primary aim of this study was to explore the impact of dietary supplementation with a postbiotic derived from Bacillus subtilis ACCC 11025 on growth performance, meat yield, meat quality, excreta bacterial populations, and excreta ammonia emissions of broiler chicks. A total of 480 day-old Arbor Acre broiler chicks, initially weighing 52.83 ± 1.38 g, were randomly allocated into 4 distinct groups. Each group was housed in 6 separate cages, each containing 20 birds. The experimental phase spanned 42 d, divided into 2 periods (d 1-21 and d 22-42). Dietary interventions were based on a basal diet, with postbiotic supplementation at levels of 0.000, 0.015, 0.030, or 0.045%. Our findings indicate that dietary supplementation with postbiotic had a positive influence on body weight gain (BWG) and feed efficiency. The most substantial improvements in BWG and feed efficiency were observed in the group of broiler chicks fed a diet containing 0.015% postbiotic. Furthermore, the inclusion of postbiotic in the diet led to an increase in the yield of breast and leg muscles, with a significant difference in meat yields observed between the control group and the group receiving 0.015% postbiotic supplementation. It's noteworthy that dietary manipulation did not exert any discernible impact on the quality of breast and leg muscle samples. Concurrently, we observed an elevation in serum albumin and total protein contents corresponding to the increasing postbiotic dosage in the diet. Additionally, dietary supplementation with postbiotic effectively controlled the emission of ammonia from excreta and reduced the abundance of Salmonella in excreta while enhancing the presence of Lactobacillus bacteria. The group receiving 0.015% postbiotic supplementation displayed the lowest levels of ammonia emission and the highest counts of Lactobacillus bacteria in excreta. In light of these results, we conclude that dietary supplementation with 0.015% postbiotic represents an efficacious strategy for increasing BWG and meat yield of broiler chicks by enhancing feed efficiency as well as mitigating ammonia emissions from excreta by modulating the composition of excreta bacterial communities.