The causal relationship between gut microbiota and biliary tract cancer: comprehensive bidirectional Mendelian randomization analysis.

Background: Growing evidence has shown that gut microbiome composition is associated with Biliary tract cancer (BTC), but the causality remains unknown. This study aimed to explore the causal relationship between gut microbiota and BTC, conduct an appraisal of the gut microbiome's utility in facilitating the early diagnosis of BTC. Methods: We acquired the summary data for Genome-wide Association Studies (GWAS) pertaining to BTC (418 cases and 159,201 controls) from the Biobank Japan (BBJ) database. Additionally, the GWAS summary data relevant to gut microbiota (N = 18,340) were sourced from the MiBioGen consortium. The primary methodology employed for the analysis consisted of Inverse Variance Weighting (IVW). Evaluations for sensitivity were carried out through the utilization of multiple statistical techniques, encompassing Cochrane's Q test, the MR-Egger intercept evaluation, the global test of MR-PRESSO, and a leave-one-out methodological analysis. Ultimately, a reverse Mendelian Randomization analysis was conducted to assess the potential for reciprocal causality. Results: The outcomes derived from IVW substantiated that the presence of Family Streptococcaceae (OR = 0.44, P = 0.034), Family Veillonellaceae (OR = 0.46, P = 0.018), and Genus Dorea (OR = 0.29, P = 0.041) exerted a protective influence against BTC. Conversely, Class Lentisphaeria (OR = 2.21, P = 0.017), Genus Lachnospiraceae FCS020 Group (OR = 2.30, P = 0.013), and Order Victivallales (OR = 2.21, P = 0.017) were associated with an adverse impact. To assess any reverse causal effect, we used BTC as the exposure and the gut microbiota as the outcome, and this analysis revealed associations between BTC and five different types of gut microbiota. The sensitivity analysis disclosed an absence of empirical indicators for either heterogeneity or pleiotropy. Conclusion: This investigation represents the inaugural identification of indicative data supporting either beneficial or detrimental causal relationships between gut microbiota and the risk of BTC, as determined through the utilization of MR methodologies. These outcomes could hold significance for the formulation of individualized therapeutic strategies aimed at BTC prevention and survival enhancement.

Comparative analysis of biofilm characterization of probiotic Escherichia coli.

Biofilms are thought to play a vital role in the beneficial effects of probiotic bacteria. However, the structure and function of probiotic biofilms are poorly understood. In this work, biofilms of Escherichia coli (E. coli) Nissle 1917 were investigated and compared with those of pathogenic and opportunistic strains (E. coli MG1655, O157:H7) using crystal violet assay, confocal laser scanning microscopy, scanning electron microscopy and FTIR microspectroscopy. The study revealed significant differences in the morphological structure, chemical composition, and spatial heterogeneity of the biofilm formed by the probiotic E. coli strain. In particular, the probiotic biofilm can secrete unique phospholipid components into the extracellular matrix. These findings provide new information on the morphology, architecture and chemical heterogeneity of probiotic biofilms. This information may help us to understand the beneficial effects of probiotics for various applications.

Dual effects of a bacteriocin-producing Lactiplantibacillus pentosus CF-6HA, isolated from fermented aloreña table olives, as potential probiotic and antimicrobial agent.

The probiotic potential of Lactiplantibacillus pentosus CF-6HA isolated from traditionally fermented Aloreña table olives was analyzed in vitro and in silico. Results obtained suggested that this strain can be catalogued as "talented" bacterium exhibiting bacteriocin production with antimicrobial activity against human/animal and plant pathogens, such as Pseudomonas syringae and Verticillium dahliae. The robustness, safety and probiotic potential of L. pentosus CF-6HA was confirmed by in silico analysis. In addition, a plethora of coding genes for defense and adaptability to different life styles besides functional properties were identified. In this sense, defense mechanisms of L. pentosus CF-6HA consist of 17 ISI elements, 98 transposases and 13 temperate phage regions as well as a CRISPR (clustered regularly interspaced short palindromic repeats)/cas system. Moreover, the functionality of this strain was confirmed by the presence of genes coding for secondary metabolites, exopolysaccharides and other bioactive molecules. Finally, we demonstrated the ability of L. pentosus CF-6HA to biotransform selenite to nanoparticles (SeNPs) highlighting its potential role in selenium bioremediation to be exploited in foods, agriculture and the environment; but also for the bio-enrichment of fermented foods with selenium.

Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study.

Background: Multiple observational studies suggest a connection between the composition of the gut microbiota and hypothyroidism. However, it has yet to be determined whether the gut microbiota has a causal effect on hypothyroidism. Methods: To investigate the connection between the gut microbiota and hypothyroidism, two-sample Mendelian randomization was performed using data from a genome-wide association study meta-analysis (n = 18,430) conducted by the MiBioGen consortium. Summary statistics for hypothyroidism (26,342 cases and 59,827 controls) were obtained using the data from the FinnGen consortium R8 release data. To investigate the causal link between the gut microbiota and hypothyroidism, various methods, including MR-Egger, weighted median, weighted model, simple model, MR-PRESSO, and inverse variance weighted (IVW), were employed. The bacteria that were causally linked to hypothyroidism in forward Mendelian randomization analysis were subjected to reverse Mendelian randomization analysis. Cochran's Q statistics were utilized to gauge the heterogeneity of the instrumental variables. Results: The results indicated that Akkermansia had a positive impact on hypothyroidism, with an odds ratio of 0.84 (95% CI 0.74-0.95, p = 0.01) based on the inverse variance-weighted estimates. Additionally, Anaerostipes (OR = 1.17, 95% CI 1.01-1.36, p = 0.04), Butyrivibrio (OR = 0.93, 95% CI 0.88-0.99, p = 0.02), Holdemania (OR = 0.89, 95% CI 0.81-0.99, p = 0.03), Intestinimonas (OR = 1.13, 95% CI 1.02-1.26, p = 0.03), Ruminiclostridium5 (OR = 1.19, 95% CI 1.01-1.41, p = 0.04), and Ruminococcaceae UCG-011 (OR = 0.91, 95% CI 0.84-0.99, p = 0.03) were identified. The gut microbiota was not significantly affected by hypothyroidism, as indicated by the results of the reverse MR analysis. There was no significant variation in the instrumental variables or horizontal pleiotropy. Conclusion: The findings of this study using two-sample Mendelian randomization indicate a causal relationship between Akkermansia and hypothyroidism. Increased Akkermansia inhibits the onset and progression of hypothyroidism. Additional randomized controlled experiments are necessary to elucidate the beneficial impact of probiotics on hypothyroidism and their distinct protective mechanisms.

Genome-based assessment of safety characteristics of Lacticaseibacillus paracasei NY1301 and genomic differences in closely related strains marketed as probiotics.

The probiotic attributes of Lacticaseibacillus paracasei NY1301 were comprehensively characterized, and a comparison between the closely related LcA (Actimel) and LcY (Yakult) probiotic strains was conducted using genomic tools. All strains exhibited high genetic similarity and likely shared a common ancestor; differences were primarily expressed as minor chromosomal re-arrangements, substitutions, insertions, and deletions. Compared with LcY, NY1301 exhibited 125 single-nucleotide polymorphisms. NY1301 lacked virulence factors, antibiotic resistance genes, and mutations associated with antibiotic resistance and had a 46-kbp prophage. This prophage is spontaneously induced at low levels and remains in a non-lytic state under standard culture conditions. The observed causal adaptive mutations were likely related to niche adaptation within the respective laboratory or manufacturing processes that occurred during the maintenance of the strains. However, the phenotypic effects of these genomic differences remain unclear. To validate the safety of NY1301, we conducted an open-label trial with healthy participants who consumed excessive amounts of NY1301 (3.0 × 1011 cfu) daily for 28 days. The results of this trial and those of other in vivo studies, coupled with the long history of human consumption without established risks to humans, provide strong evidence confirming the safety of NY1301.

Supplementation of High-Strength Oral Probiotics Improves Immune Regulation and Preserves Beta Cells among Children with New-Onset Type 1 Diabetes Mellitus: A Randomised, Double-Blind Placebo Control Trial.

OBJECTIVES: To investigate the mechanism of glycemic control in children with type 1 diabetes (T1D) following high-strength probiotics supplementation by assessing immune-regulatory markers. METHODS: In this single-centre randomised double-blinded placebo-controlled study, children with new-onset T1D on regular insulin therapy were randomised into probiotic or placebo groups with 30 children each. The probiotics group received oral powder of Vivomixx®, and the placebo group received corn starch for six months. The primary outcome parameters included induced T regulatory cells (i-Tregs) percentage, insulin autoantibodies (IAA), insulinoma associated 2 autoantibodies (IA2), glutamic acid decarboxylase autoantibodies (GAD 65) and plasma interleukin-10 (IL-10) levels. The secondary outcome variables were changes in plasma C-peptide levels and glycemic control parameters. RESULTS: Twenty-three children in the placebo group and 27 in the probiotic group completed the study. There was a significant increase in the percentage of iTregs (3.40 in the probiotic vs. 2.46 in the placebo group; p = 0.034). Median glycated hemoglobin (HbA1c) levels significantly decreased from 68 mmol/mol (8.35%) in the placebo group to 60 mmol/mol (7.55%) in the probiotic group (p = 0.017). Median C-peptide levels were significantly higher in probiotics (0.72 ng/ml) vs. placebo group (0.11 ng/ml) (p = 0.036). The plasma IL-10 levels significantly increased in the probiotic group after six months of treatment (p = 0.002). CONCLUSIONS: The high-strength probiotics improved the immunoregulatory milieu, thereby preserving the beta-cell function and better glycemic control.

Safety and Beneficial Properties of Bacteriocinogenic Lactococcus lactis and Pediococcus pentosaceus Strains, and Their Effect Versus Oral Cavity Related and Antibiotic-Resistant Pathogens.

Pediococcus pentosaceus 732, Lactococcus lactis subsp. lactis 431, and Lactococcus lactis 808, bacteriocinogenic strains previously isolated from kimchi and banana, were investigated for their safety, beneficial properties and in vitro inhibition of pathogens such as Listeria monocytogenes ATCC 15313 and Staphylococcus simulans KACC 13241 and Staphylococcus auricularis KACC 13252. The results of performed physiological, biochemical, and biomolecular tests suggest that these strains can be deemed safe, as no virulence genes were detected in their DNA. Notably, only the gad gene associated with GABA production was identified in the DNA isolated of Lc. lactis 808 and Lc. lactis subsp. lactis 431 strains. All tested LAB strains exhibited γ-hemolysins and were non-producers of gelatinase and biogenic amines, which suggested their safety potential. Additionally, they were relatively susceptible to antibiotics except for streptomycin, tobramycin, and vancomycin for Pd. pentosaceus 732. The growth of Pd. pentosaceus 732, Lc. lactis subsp. lactis 431, and Lc. lactis 808 and their survival were minimally affected by up to 3% ox bile and low pH (except pH 2.0 and 4.0). Moreover, these LAB strains were not inhibited by various commercial extracts as well as most of the tested medications tested in the study. They did not produce proteolytic enzymes but exhibited production of D/L-lactic acid and ß-galactosidase. They were also hydrophilic. Furthermore, their survival in artificial saliva, gastric simulation, and enteric passage was measured followed by a challenge test to assess their ability to inhibit the selected oral pathogens in an oral saliva model conditions.

The effects of prebiotic, probiotic or synbiotic supplementation on overweight/obesity indicators: an umbrella review of the trials' meta-analyses.

Background: There is controversial data on the effects of prebiotic, probiotic, or synbiotic supplementations on overweight/obesity indicators. Thus, we aimed to clarify this role of biotics through an umbrella review of the trials' meta-analyses. Methods: All meta-analyses of the clinical trials conducted on the impact of biotics on overweight/obesity indicators in general populations, pregnant women, and infants published until June 2023 in PubMed, Web of Sciences, Scopus, Embase, and Cochrane Library web databases included. The meta-analysis of observational and systematic review studies without meta-analysis were excluded. We reported the results by implementing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flowchart. The Assessment of Multiple Systematic Reviews-2 (AMSTAR2) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) systems were used to assess the methodological quality and quality of evidence. Results: Overall, 97 meta-analysis studies were included. Most studies were conducted on the effect of probiotics in both genders. Consumption of prebiotic: 8-66 g/day, probiotic: 104 -1.35×1015 colony-forming unit (CFU)/day, and synbiotic: 106-1.5×1011 CFU/day and 0.5-300 g/day for 2 to 104 weeks showed a favorable effect on the overweight/obesity indicators. Moreover, an inverse association was observed between biotics consumption and overweight/obesity risk in adults in most of the studies. Biotics did not show any beneficial effect on weight and body mass index (BMI) in pregnant women by 6.6×105-1010 CFU/day of probiotics during 1-25 weeks and 1×109-112.5×109 CFU/capsule of synbiotics during 4-8 weeks. The effect of biotics on weight and BMI in infants is predominantly non-significant. Prebiotics and probiotics used in infancy were from 0.15 to 0.8 g/dL and 2×106-6×109 CFU/day for 2-24 weeks, respectively. Conclusion: It seems biotics consumption can result in favorable impacts on some anthropometric indices of overweight/obesity (body weight, BMI, waist circumference) in the general population, without any significant effects on birth weight or weight gain during pregnancy and infancy. So, it is recommended to intake the biotics as complementary medications for reducing anthropometric indices of overweight/obese adults. However, more well-designed trials are needed to elucidate the anti-obesity effects of specific strains of probiotics.

Prospects of probiotics in beekeeping: a review for sustainable approach to boost honeybee health.

Honeybees are vital for global crop pollination, making indispensable contributions to agricultural productivity. However, these vital insects are currently facing escalating colony losses on a global scale, primarily attributed to parasitic and pathogenic attacks. The prevalent response to combat these infections may involve the use of antibiotics. Nevertheless, the application of antibiotics raises concerns regarding potential adverse effects such as antibiotic resistance and imbalances in the gut microbiota of bees. In response to these challenges, this study reviews the utilization of a probiotic-supplemented pollen substitute diet to promote honeybee gut health, enhance immunity, and overall well-being. We systematically explore various probiotic strains and their impacts on critical parameters, including survival rate, colony strength, honey and royal jelly production, and the immune response of bees. By doing so, we emphasize the significance of maintaining a balanced gut microbial community in honeybees. The review also scrutinizes the factors influencing the gut microbial communities of bees, elucidates the consequences of dysbiosis, and evaluates the potential of probiotics to mitigate these challenges. Additionally, it delineates different delivery mechanisms for probiotic supplementation and elucidates their positive effects on diverse health parameters of honeybees. Given the alarming decline in honeybee populations and the consequential threat to global food security, this study provides valuable insights into sustainable practices aimed at supporting honeybee populations and enhancing agricultural productivity.

Probiotics-A Promising Novel Therapeutic Approach in the Management of Chronic Liver Diseases.

An increased incidence of liver diseases has been observed in recent years and is associated with gut dysbiosis, which causes bacterial infection, intestinal permeability, and further leads to disease-related complications. Probiotics, active microbial strains, are gaining more clinical importance due to their beneficial effect in the management of many diseases, including liver diseases. Clinical scenarios show strong evidence that probiotics have efficacy in treating liver diseases due to their ability to improve epithelial barrier function, prevent bacterial translocation, and boost the immune system. Moreover, probiotics survive both bile and gastric acid to reach the gut and exert their health benefit. Evidence shows that probiotics are a promising approach to prevent several complications in clinical practice. Herein, we discuss the recent evidence, challenges, and appropriate use of probiotics in managing advanced liver diseases, which may have an impact on future therapeutic strategies. Furthermore, the superior effect of strain-specific probiotics and their efficacy and safety in managing liver diseases are discussed.

Water-soluble microencapsulation using gum Arabic and skim milk enhances viability and efficacy of Pediococcus acidilactici probiotic strains for application in broiler chickens.

Objective: This study aimed to develop and evaluate the effectiveness of a water-soluble microencapsulation method for probiotic strains using gum Arabic (GA) and skim milk (SKM) over a three-month storage period following processing. Methods: Four strains of Pediococcus acidilactici (BYF26, BYF20, BF9, and BF14) that were typical lactic acid bacteria (LAB) isolated from the chicken gut were mixed with different ratios of gum Arabic (GA) and skim milk (SKM) as coating agents before spray drying at an inlet temperature 140°C. After processing, the survivability and probiotic qualities of the strains were assessed from two weeks to three months of storage at varied temperatures, and de-encapsulation was performed to confirm the soluble properties. Finally, the antibacterial activity of the probiotics was assessed under simulated gastrointestinal conditions. Results: As shown by scanning electron microscopy, spray-drying produced a spherical, white-yellow powder. The encapsulation efficacy (EE percent) was greatest for a coating containing a combination of 30% gum Arabic: 30% skim milk (w/v) (GA:SKM30) compared to lower concentrations of the two ingredients (p<0.05). Coating with GA:SKM30 (w/v) significantly enhanced (p<0.05) BYF26 survival under simulated gastrointestinal conditions (pH 2.5-3) and maintained higher survival rates compared to non-encapsulated cells under an artificial intestinal juices (AIJ) condition of pH 6. De-encapsulation tests indicated that the encapsulated powder dissolved in water while keeping viable cell counts within the effective range of 106 for 6 hours. In addition, following three months storage at 4°C, microencapsulation of BYF26 in GA:SKM30 maintained both the number of viable cells (p<0.05) and the preparation's antibacterial efficacy against pathogenic bacteria, specifically strains of Salmonella. Conclusion: Our prototype water-soluble probiotic microencapsulation GA:SKM30 effectively maintains LAB characteristics and survival rates, demonstrating its potential for use in preserving probiotic strains that can be used in chickens and potentially in other livestock.

Utilization of Probiotics Among Dental Students: A KAP Study.

Aim: The aim of the study is to know about the awareness of probiotics among undergraduate dental students. Materials and Methods: We conducted cross-sectional research where we had distributed a questionnaire consisting of ten open-ended questions, among 150 dental students through emails. The questions were based on the utilization of probiotics in dentistry. The data obtained was statistically analyzed with the help of Chi-square test. Results: In our study, we noted that most of the participants were aware of the term probiotics and had general ideas but were not fully aware of its pathogenesis. Around 83.2% of the participants were aware of probiotics and general concepts. We also noted that only 42.5% of the students agreed that probiotics can be used in the management of halitosis as well as periodontitis. Conclusion: We concluded that most of the dental students had a lack of awareness as well as were not familiar with the usage of probiotics in dentistry.

Oral delivery of probiotics using single-cell encapsulation.

Adequate intake of live probiotics is beneficial to human health and wellbeing because they can help treat or prevent a variety of health conditions. However, the viability of probiotics is reduced by the harsh environments they experience during passage through the human gastrointestinal tract (GIT). Consequently, the oral delivery of viable probiotics is a significant challenge. Probiotic encapsulation provides a potential solution to this problem. However, the production methods used to create conventional encapsulation technologies often damage probiotics. Moreover, the delivery systems produced often do not have the required physicochemical attributes or robustness for food applications. Single-cell encapsulation is based on forming a protective coating around a single probiotic cell. These coatings may be biofilms or biopolymer layers designed to protect the probiotic from the harsh gastrointestinal environment, enhance their colonization, and introduce additional beneficial functions. This article reviews the factors affecting the oral delivery of probiotics, analyses the shortcomings of existing encapsulation technologies, and highlights the potential advantages of single-cell encapsulation. It also reviews the various approaches available for single-cell encapsulation of probiotics, including their implementation and the characteristics of the delivery systems they produce. In addition, the mechanisms by which single-cell encapsulation can improve the oral bioavailability and health benefits of probiotics are described. Moreover, the benefits, limitations, and safety issues of probiotic single-cell encapsulation technology for applications in food and beverages are analyzed. Finally, future directions and potential challenges to the widespread adoption of single-cell encapsulation of probiotics are highlighted.

Co-administration of probiotic and vitamin D significantly improves cognitive function in schizophrenic patients: A double-blinded randomized controlled trial.

AIM: Manipulation of the intestinal microbiome and supplying vitamin D can attenuate psychiatric symptoms in schizophrenic patients. The current study tried to evaluate the effects of probiotic/vitamin D supplementation on the cognitive function and disease severity of schizophrenic patients. METHODS: In the present study, 70 patients (aged 18-65) with schizophrenia were recruited. Participants were randomly allocated to the placebo (n = 35) and intervention (probiotic supplements+400 IU vitamin D, n = 35) groups. Severity of disease and cognitive function (primary outcomes) were evaluated by Positive and Negative Syndrome Scale (PANSS) and Montreal Cognitive Assessment (MoCA) tests, respectively. Moreover, lipid profile, body mass index (BMI), gastrointestinal (GI) problems, serum C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were evaluated as secondary outcomes. RESULTS: A total of 69 patients completed the study. The MoCA score was increased by 1.96 units in the probiotic-containing supplement group compared to the placebo (p = 0.004). Also, the percentage of subjects with MoCA score ≥ 26 rose significantly in the intervention group (p = 0.031). Moreover, TC (p = 0.011), FBS (p = 0.009), and CRP (p < 0.001) significantly decreased in the supplement group compared to the placebo. Although the probiotic supplement reduced PANSS score by 2.82 units, the difference between the study groups was not statistically significant (p = 0.247). CONCLUSION: Co-administration of probiotics and vitamin D has beneficial effects on the improvement of cognitive function in schizophrenic patients.

T cell cascade regulation initiates systemic antitumor immunity through living drug factory of anti-PD-1/IL-12 engineered probiotics.

Immune checkpoint blockade (ICB) has revolutionized cancer therapy but only works in a subset of patients due to the insufficient infiltration, persistent exhaustion, and inactivation of T cells within a tumor. Herein, we develop an engineered probiotic (interleukin [IL]-12 nanoparticle Escherichia coli Nissle 1917 [INP-EcN]) acting as a living drug factory to biosynthesize anti-PD-1 and release IL-12 for initiating systemic antitumor immunity through T cell cascade regulation. Mechanistically, INP-EcN not only continuously biosynthesizes anti-PD-1 for relieving immunosuppression but also effectively cascade promote T cell activation, proliferation, and infiltration via responsive release of IL-12, thus reaching a sufficient activation threshold to ICB. Tumor targeting and colonization of INP-EcNs dramatically increase local drug accumulations, significantly inhibiting tumor growth and metastasis compared to commercial inhibitors. Furthermore, immune profiling reveals that anti-PD-1/IL-12 efficiently cascade promote antitumor effects in a CD8+ T cell-dependent manner, clarifying the immune interaction of ICB and cytokine activation. Ultimately, such engineered probiotics achieve a potential paradigm shift from T cell exhaustion to activation and show considerable promise for antitumor bio-immunotherapy.

Lactococcus lactis HkyuLL 10 suppresses colorectal tumourigenesis and restores gut microbiota through its generated alpha-mannosidase.

OBJECTIVE: Probiotic Lactococcus lactis is known to confer health benefits to humans. Here, we aimed to investigate the role of L. lactis in colorectal cancer (CRC). DESIGN: L. lactis abundance was evaluated in patients with CRC (n=489) and healthy individuals (n=536). L. lactis was isolated from healthy human stools with verification by whole genome sequencing. The effect of L. lactis on CRC tumourigenesis was assessed in transgenic Apc Min/+ mice and carcinogen-induced CRC mice. Faecal microbiota was profiled by metagenomic sequencing. Candidate proteins were characterised by nano liquid chromatography-mass spectrometry. Biological function of L. lactis conditioned medium (HkyuLL 10-CM) and functional protein was studied in human CRC cells, patient-derived organoids and xenograft mice. RESULTS: Faecal L. lactis was depleted in patients with CRC. A new L. lactis strain was isolated from human stools and nomenclated as HkyuLL 10. HkyuLL 10 supplementation suppressed CRC tumourigenesis in Apc Min/+ mice, and this tumour-suppressing effect was confirmed in mice with carcinogen-induced CRC. Microbiota profiling revealed probiotic enrichment including Lactobacillus johnsonii in HkyuLL 10-treated mice. HkyuLL 10-CM significantly abrogated the growth of human CRC cells and patient-derived organoids. Such protective effect was attributed to HkyuLL 10-secreted proteins, and we identified that α-mannosidase was the functional protein. The antitumourigenic effect of α-mannosidase was demonstrated in human CRC cells and organoids, and its supplementation significantly reduced tumour growth in xenograft mice. CONCLUSION: HkyuLL 10 suppresses CRC tumourigenesis in mice through restoring gut microbiota and secreting functional protein α-mannosidase. HkyuLL 10 administration may serve as a prophylactic measure against CRC.

Probiotics may alleviate intestinal damage induced by cardiopulmonary bypass in children.

OBJECTIVES: Intestinal ischemia-reperfusion injury induced by cardiopulmonary bypass causes intestinal epithelial barrier dysfunction, leading to dysbiosis and bacterial translocation. We conducted a randomized prospective study with two objectives: (1) to investigate epithelial barrier dysfunction and bacterial translocation induced by cardiopulmonary bypass and changes in the gut microbiota and (2) to verify whether probiotics can improve these conditions. METHODS: Between 2019 and 2020, patients 0-15 years old scheduled to undergo cardiac surgery using cardiopulmonary bypass were enrolled and randomly allocated to 2 groups: the intervention group received probiotics, and the control group did not receive probiotics. We analyzed the microbiota in feces and blood, organic acid concentrations in feces, plasma intestinal fatty-acid binding protein, and immunological responses. RESULTS: Eighty-two patients were enrolled in this study. The characteristics of the patients were similar in both groups. The total number of obligate anaerobes was higher in the intervention group than in the control group after postoperative day 7. We identified four clusters within the perioperative gut microbiota, and cluster changes showed a corrective effect of probiotics on dysbiosis after postoperative day 7. Organic acid concentrations in feces, incidence of bacterial translocation, Intestinal fatty-acid binding protein levels, and immunological responses, except for Interleukin -17A, were not markedly different between the two groups. CONCLUSIONS: Administration of probiotics was able to correct dysbiosis but did not sufficiently alleviate the intestinal damage induced by cardiopulmonary bypass. More effective methods should be examined to prevent disturbances induced by cardiac surgery using cardiopulmonary bypass.

Milk and Lacticaseibacillus casei BL23 effects on intestinal responses in a murine model of colitis.

Probiotic-containing fermented dairy foods have the potential to benefit human health, but the importance of the dairy matrix for efficacy remains unclear. We investigated the capacity of Lacticaseibacillus casei BL23 in phosphate-buffered saline (BL23-PBS), BL23-fermented milk (BL23-milk), and milk to modify intestinal and behavioral responses in a Dextran Sodium Sulfate (DSS, 3% w/v) mouse model of colitis. Significant sex-dependent differences were found such that female mice exhibited more severe colitis, greater weight loss, and higher mortality rates. Sex differences were also found for ion transport ex vivo, colonic cytokine and tight junction gene expression, and fecal microbiota composition. Measurements of milk and BL23 effects showed BL23-PBS consumption improved weight recovery in females, while milk resulted in better body weight recovery in males. Occludin and Claudin-2 gene transcript levels indicated barrier function was impaired in males, but BL23-milk was still found to improve colonic ion transport in those mice. Pro-inflammatory and anti-inflammatory gene expression levels were increased in both male and female mice fed BL23, and to a more variable extent, milk, compared to controls. The female mouse fecal microbiota contained high proportions of Akkermansia (average of 18.1%) at baseline, and females exhibited more changes in gut microbiota composition following BL23 and milk intake. Male fecal microbiota harbored significantly more Parasutterella and less Blautia and Roseburia after DSS treatment, independent of BL23 or milk consumption. These findings show the complex interplay between dietary components and sex-dependent responses in mitigating inflammation in the digestive tract.

Lacticaseibacillus casei K11 exerts immunomodulatory effects by enhancing natural killer cell cytotoxicity via the extracellular regulated-protein kinase pathway.

PURPOSE: Probiotics can serve as immunomodulators that regulate the activation of immune cells. This study aimed to screen potential probiotic strains that can enhance NK cell toxicity to improve host immunity. METHODS: In this investigation, we examined three potential probiotic strains, namely Lactiplantibacillus plantarum YZX21 (YZX21), Bifidobacterium bifidum FL-276.1 (FL-276.1) and Lacticaseibacillus casei K11 (K11), to assess their capacity in modulating NK cytotoxicity both in vitro and in vivo, while elucidating the underlying mechanisms involved. RESULTS: The findings demonstrated that K11 exhibited superior efficacy in enhancing NK cytotoxicity. Subsequent analysis revealed that K11 significantly augmented the secretion of perforin and granzyme B by NK cells through activation of receptors NKp30 and NKp46 via the extracellular signal-regulated kinase (ERK) pathway. Furthermore, heat-inactivated K11 also enhanced NK cell activity to an extent comparable to live bacteria, with lipoteichoic acid from K11 identified as a crucial factor mediating the activation of NK cell cytotoxicity. CONCLUSION: Our study suggests that K11 may have potential applications as probiotics or postbiotics for regulating NK cell cytotoxicity to enhance immunity.

Heat-Killed Lactilactobacillus sakei WB2305 and Lactiplantibacillus plantarum WB2324 Inhibited LPS-Induced Inflammation in Human Airway Epithelial Cells.

Asthma is characterized by inflammation of the airways, including the inflammatory and airway structural cells. Probiotics, which have diverse effects, even within the same species, are being studied to prevent and mitigate the severity of asthma. Lactilactobacillus sakei WB2305 and Lactiplantibacillus plantarum WB2324 were isolated from kimchi. These strains have acceptable probiotic properties and are safe. In addition, the anti-inflammatory potential of the heat-killed isolates against lipopolysaccharide (LPS)-induced inflammation in the human pulmonary epithelial cell line (A549) was investigated. The heat-killed Lact. sakei WB2305 and Lact. plantarum WB2324 reduced the chemokine and cytokines mRNA expression levels, as shown by the results of using real-time polymerase chain reaction. Western blotting results showed that the nuclear factor-kappa B (NF-κB) activation and mitogen-activated protein kinases (MAPK) signaling pathways were suppressed by treatment with the heat-killed strains. The production amounts of eotaxin, tumor necrosis factor-ɑ (TNF-α), and interleukin-6 (IL-6) were lower than those in LPS-only treated cells. Additionally, 2',7'-dichlorofluorescein diacetate (DCFH-DA) staining confirmed decreased reactive oxygen species (ROS) production in A549 cells. Therefore, the results of present study demonstrate the anti-inflammatory and anti-asthmatic activities of heat-killed Lact. sakei WB2305 and Lact. plantarum WB2324 in human airway epithelial cells.