Lactococcus lactis

BACKGROUND: Plasmacytoid dendritic cells (pDCs) are a type of immune cell that play a crucial role in the defense against viral infection. Multiple randomized controlled trials (RCTs) have reported that oral intake of Lactococcus lactis strain Plasma (LC-Plasma) activates pDCs and reduces cold-like symptoms. This study conducted a meta-analysis to comprehensively evaluate the effects of oral LC-Plasma intake on pDC activation and cold-like symptoms by comparing healthy adults. METHOD: This study targeted RCTs that examined the effects of oral intake of LC-Plasma or placebo food products on pDC activation or common cold-like symptoms in healthy adult males and females. Data sources included PubMed, Cochrane Library, J-Dream III, UMIN-CTR, and the International Clinical Trials Registry Platform, with searches conducted up to June 21st, 2024. The primary outcome evaluated pDC activation, and the secondary outcome evaluated the subjective evaluation of common cold-like symptoms. A quantitative synthesis was performed by meta-analysis using random-effects models. Two authors independently assessed risk of bias using the revised Cochrane risk of bias tool (RoB2). RESULTS: Among the eight RCTs that met the eligibility criteria for this study, individual participant data (IPD) were obtained from seven. Since we were unable to obtain IPD from the remaining study, we integrated data from this study based on its final report. The meta-analysis in this study, conducted using data from 619 participants, revealed that the expression levels of pDC activation markers, CD86 and HLA-DR, were significantly maintained during LC-Plasma intake when compared to the placebo control group (CD86: SMD = 0.37, 95% CI (confidence interval): 0.17 to 0.57; HLA-DR: SMD = 0.47, 95% CI: 0.21 to 0.73). In addition, LC-Plasma intake significantly reduced the cumulative number of days per 28 days of cough and feverishness compared to the control group, according to the meta-analysis using data from 555 participants (Cough: MD=-0.69, 95%CI: -1.24 to -0.14; Feverishness: MD=-0.26, 95%CI: -0.52 to -0.0038). CONCLUSION: This study is the first to present, through integrated analyses using identical ana

Lactic acid bacteria (LAB) are fundamental in the production of fermented foods and several strains are regarded as probiotics. Large quantities of live LAB are consumed within fermented foods, but it is not yet known to what extent the LAB we ingest become members of the gut microbiome. By analysis of 9445 metagenomes from human samples, we demonstrate that the prevalence and abundance of LAB species in stool samples is generally low and linked to age, lifestyle, and geography, with Streptococcus thermophilus and Lactococcus lactis being most prevalent. Moreover, we identify genome-based differences between food and gut microbes by considering 666 metagenome-assembled genomes (MAGs) newly reconstructed from fermented food microbiomes along with 154,723 human MAGs and 193,078 reference genomes. Our large-scale genome-wide analysis demonstrates that closely related LAB strains occur in both food and gut environments and provides unprecedented evidence that fermented foods can be indeed regarded as a possible source of LAB for the gut microbiome.

BACKGROUND: Recent years have witnessed the emergence of a novel research direction in the field of tumor vaccines. An in situ vaccine known as FOLactis, comprised of genetically engineered Lactococcus lactis expressing a fusion protein of Fms-like tyrosine kinase 3 ligand (Flt3L) and co-stimulator OX40 ligand (OX40L), was developed by the Oncology Centre of Nanjing Drum Tower Hospital. The present study was designed to evaluate the efficacy and safety of combination therapy based on intratumoral injection of the in situ vaccine FOLactis and intravenous PD-1 monoclonal antibody in combination with immunoradiotherapy or low-dose chemotherapy in the treatment of advanced hepatic malignancies. METHODS: In this exploratory clinical study, patients with advanced hepatic malignancies were enrolled and randomly assigned to Group A and Group B, corresponding to different treatment regimens. The treatment regimen in Group A consisted of the in situ vaccine FOLactis combined with a PD-1 monoclonal antibody and immunoradiotherapy (5Gy/fraction×3fractions). In contrast, the regimen in Group B included the in situ vaccine FOLactis, a PD-1 monoclonal antibody, and low-dose chemotherapy (cisplatin plus vincristine). All treatments were given in 21-day cycles. The primary observation indicator of the study was the objective response rate (ORR) as defined by RECIST v1.1. Secondary observation indicators included the disease control rate (DCR) and the incidence of adverse events. RESULTS: A total of 18 eligible patients were included in the study. In Group A, the ORR and DCR for targeted lesions were 33.3%(95%CI:12.1-64.6%) and 77.8%(95%CI:45.3-96.1%), while the ORR and DCR for non-targeted lesions were 22.2%(95%CI:3.9-54.7%) and 66.7%(95%CI:35.4-87.9%), respectively. Targeted and non-targeted lesions in Group B did not reduce significantly, and their respective DCRs were 66.7%(95%CI:35.4-87.9%) and 22.2%(95%CI:3.9-54.7%). Patients in Group A experienced no significant adverse events. Patients in Group B experienced grade 1-2 hyperthermia as a side effect. CONCLUSIONS: The combination therapy based on the in situ vaccine FOLactis and intravenous PD-1 monoclonal antibody showed a

BACKGROUND: Despite the variety of antidiabetic therapies, many patients with type 2 diabetes (T2D) do not achieve optimal glycemic control. Therefore, there is a need to develop additional methods for managing T2D, including ones that regulate the gut microbiome. AIM: To assess the effect of AntiAGE-Biom probiotic on metabolic parameters in T2D patients during 3 months of therapy. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled, single-center study included patients with T2D with glycated hemoglobin - HbA1c<7,5% on stable antidiabetic therapy. Patients were randomized into groups receiving AntiAGE-Biom and placebo. The primary endpoint was the change in HbA1c from baseline, secondary endpoints included the dynamics in biochemical and anthropometric parameters, body composition, as well as HOMA-IR index. RESULTS: The study included 40 patients with T2D (n=20 in each group). There was a trend towards a decrease in HbA1c in AntiAGE-Biom group, that did not reach statistical significance. The use of the probiotic improved the body composition after 3 months: reduced the percentage of fat in men and a subgroup of patients with an initial HbA1c≥ 6.5%; also increased skeletal muscle mass and lean mass in the trunk segment in men (р<0,05). CONCLUSION: AntiAGE-Biom probiotic helps to maintain metabolic control and significantly improve body composition in T2D patients with initial HbA1c<7.5%. Publisher: Обоснование. Несмотря на наличие широкого спектра сахароснижающей терапии, многие пациенты с сахарным диабетом 2-го типа (СД 2) не достигают оптимального контроля гликемии. В связи с этим существует необходимость разработки дополнительных методов контроля СД 2, в том числе направленных на регуляцию кишечного микробиома. Цель. Изучить возможность коррекции метаболических показателей у пациентов с СД 2 при приеме пробиотика AntiAGE-Biom в течение 3 мес. Материалы и методы. Проведено двойное слепое рандомизированное плацебо-контролируемое одноцентровое исследование. Пациенты с СД 2 с удовлетворительным контролем гликемии (гликированный гемоглобин – HbA1c<7,5%), не требующим интенсификации сахароснижающей терапии, рандомизированы в группы приема AntiAG

BACKGROUND: Disruption in gut microbiota has been identified as a contributor to obesity-related inflammation and metabolic disorders. This study investigates the effects of preoperative probiotic supplementation on inflammation, endotoxemia, adipokines, and gastrointestinal peptides after bariatric surgery. METHODS: This randomized, double-blind, placebo-controlled clinical trial included patients undergoing laparoscopic sleeve gastrectomy (LSG) or one anastomosis gastric bypass (OAGB). Participants were randomized to receive a 12-week supplementation of either a probiotic mixture, Sanprobi Barrier, which contained nine strains of bacteria (Bifidobacterium bifidum W23, Bifidobacterium lactis W51 and W52, Lactobacillus acidophilus W37, Levilactobacillus brevis W63, Lacticaseibacillus casei W56, Ligilactobacillus salivarius W24, Lactococcus lactis W19, and Lactococcus lactis W58), or a placebo before surgery. The key outcomes measured at baseline and 6 months postoperatively included serum lipopolysaccharide (LPS), cytokines (interleukin-6 - IL-6, interleukin-2 receptor-IL-2R, and C-reactive-CRP protein), adipokines (leptin, adiponectin, resistin), and gastrointestinal peptides (glucagon-like peptide-1 - GLP-1, ghrelin, and trefoil factor 2). Relative mRNA expression of ghrelin and trefoil family factor 2 in gastric tissues was also analyzed at baseline and on the day of the surgery. RESULTS: Out of the initial 110 participants, serum samples of 18 individuals in the probiotic group and 24 in the placebo group were analyzed. Both groups showed significant reductions in serum LPS levels six months after surgery; however, no significant differences were observed between the two groups. Adiponectin levels increased significantly in the placebo group (4.2 ± 2.3 vs. 2.2 ± 1.1 pg/mL; p < 0.001), while leptin levels decreased significantly in both groups without intergroup differences. IL-6 levels were significantly lower in the probiotic group compared to the placebo group at 6 months (2.2 ± 1.1 vs 4.2 ± 2.3 pg/mL; p = 0.004). No significant differences were observed in the remaining cytokine levels between the groups. Gastrointestinal peptides showed no significant di

OBJECTIVES: To correlate the urinary excretion of equol with intestinal microbiota in response to isoflavone supplementation alone or in combination with probiotics, and to compare these results with those of hormone therapy in postmenopausal women. METHODS: A pilot study was conducted on 47 postmenopausal women aged 40-60 years. Participants were randomly assigned to one of three groups: (A) oral isoflavone (150 mg dry extract of Glycine max); (B) isoflavone plus probiotic (Lactobacillus acidophilus, Lactobacillus casei, Lactococcus lactis, Bifidobacterium bifidum, and Bifidobacterium lactis); or (C) hormone therapy (1 mg estradiol/0.5 mg norethisterone acetate). Fecal samples were collected to extract bacterial DNA, and equol and its intermediates were measured using gas chromatography coupled with mass spectrometry at baseline and after 16 weeks of treatment. RESULTS: In the isoflavone alone and isoflavone plus probiotic groups, no statistically significant correlations were found between bacterial phyla or genera and the urinary excretion of equol or its intermediate after 16 weeks of treatment. In the hormone therapy group, directly proportional correlation between Bacteroidetes (Spearman R=0.83, Pa=0.01), Cyanobacteria (Spearman R=0.89, Pa=0.002), Alistipes (Spearman R=0.81, Pa=0.04), Catenibacterium (Spearman R=0.81, Pa=0.04), Clostridium (Spearman R=0.84, Pa=0.02), Barnesiella (Spearman R=0.84, Pa=0.02), and the urinary excretion of the equol intermediate were observed. CONCLUSIONS: Only the hormone therapy group showed a significant increase in bacterial abundance involved in isoflavone metabolism.

OBJECTIVE: To explore whether acupuncture combined with clomiphene can reduce the luteinizing hormone-to follicle-stimulating hormone ratio and impact the gut microbiota in patients with obese polycystic ovary syndrome. METHODS: This open-label, randomized, parallel-group controlled trial included 86 women aged 20-40 years with obese polycystic ovary syndrome and 19 healthy controls. Participants were randomly assigned to either an acupuncture combined with clomiphene group or a clomiphene-only group, with a healthy control group for comparison. The treatment lasted three menstrual cycles, with acupuncture administered three times weekly and clomiphene given daily from day five of menstruation for five consecutive days per cycle. The primary outcome was the change in the luteinizing hormone-to-follicle-stimulating hormone (LH/FSH) ratio. Secondary outcomes included levels of other sex hormones, glucose and lipid metabolism parameters, self-rating anxiety and depression scale scores, and gut microbiota composition. RESULTS: Intention-to-treat analysis showed that the adjusted mean luteinizing hormone-to follicle-stimulating hormone ratio decrease was -0.8 (95% CI: -1.14 to -0.46) in the acupuncture combined with clomiphene group and -0.22 (95% CI: -0.47 to 0.01) in the clomiphene group. The adjusted between-group difference was 0.53 (95% CI: 0.24 to 0.82, p < 0.001). The levels of Agathobacter faecis increased, and those of Erysipelatoclostridium spiroforme, Streptococcus lutetiensis, and Lactococcus lactis decreased after acupuncture combined with clomiphene treatment (p < 0.05). CONCLUSION: Acupuncture combined with clomiphene may be safe and effective, reduce the luteinizing hormone-to follicle-stimulating hormone ratio, and improve insulin resistance in obese polycystic ovary syndrome, and these outcomes may be related to the gut microbiota.

Emerging evidence suggests that microbiota plays a crucial role in the development, progression, and therapeutic options in obesity and its comorbidities. This study assessed preoperative probiotic therapy's impact on bariatric treatment outcomes. A 12-week randomized, double-blind, placebo-controlled trial with 48 patients undergoing bariatric surgery was conducted. Participants received probiotics-Sanprobi Barrier-which contained nine strains of bacteria: Bifidobacterium bifidum W23, Bifidobacterium lactis W51 and W52, Lactobacillus acidophilus W37, Levilactobacillus brevis W63, Lacticaseibacillus casei W56, Ligilactobacillus salivarius W24, Lactococcus lactis W19, and Lactococcus lactis W58. Primary outcomes included excess body weight loss, body weight loss, and excess body mass index loss, with secondary objectives focusing on metabolic profiles. Surgical treatment of obesity significantly improved anthropometric and metabolic parameters. No significant differences were observed in primary outcomes or in secondary outcomes between groups at any time point post-surgery. Preoperative probiotics administration did not affect clinical outcomes 1, 3, or 6 months following bariatric surgery.

Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO2max), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion (p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage (p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 (p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.

BACKGROUND: The stalling global progress in malaria control highlights the need for novel tools for malaria elimination, including transmission-blocking vaccines. Transmission-blocking vaccines aim to induce human antibodies that block parasite development in the mosquito and mosquitoes becoming infectious. The Pfs48/45 protein is a leading Plasmodium falciparum transmission-blocking vaccine candidate. The R0.6C fusion protein, consisting of Pfs48/45 domain 3 (6C) and the N-terminal region of P. falciparum glutamate-rich protein (R0), has previously been produced in Lactococcus lactis and elicited functional antibodies in rodents. Here, we assess the safety and transmission-reducing efficacy of R0.6C adsorbed to aluminium hydroxide with and without Matrix-M™ adjuvant in humans. METHODS: In this first-in-human, open-label clinical trial, malaria-naïve adults, aged 18-55 years, were recruited at the Radboudumc in Nijmegen, the Netherlands. Participants received four intramuscular vaccinations on days 0, 28, 56 and 168 with either 30 µg or 100 µg of R0.6C and were randomised for the allocation of one of the two different adjuvant combinations: aluminium hydroxide alone, or aluminium hydroxide combined with Matrix-M1™ adjuvant. Adverse events were recorded from inclusion until 84 days after the fourth vaccination. Anti-R0.6C and anti-6C IgG titres were measured by enzyme-linked immunosorbent assay. Transmission-reducing activity of participants' serum and purified vaccine-specific immunoglobulin G was assessed by standard membrane feeding assays using laboratory-reared Anopheles stephensi mosquitoes and cultured P. falciparum gametocytes. RESULTS: Thirty-one participants completed four vaccinations and were included in the analysis. Administration of all doses was safe and well-tolerated, with one related grade 3 adverse event (transient fever) and no serious adverse events occurring. Anti-R0.6C and anti-6C IgG titres were similar between the 30 and 100 µg R0.6C arms, but higher in Matrix-M1™ arms. Neat participant sera did not induce significant transmission-reducing activity in mosquito feeding experiments, but concentrated vaccine-specific IgGs purified from sera

AIMS/HYPOTHESIS: We hypothesised that islet beta cell antigen presentation in the gut along with a tolerising cytokine would lead to antigen-specific tolerance in type 1 diabetes. We evaluated this in a parallel open-label Phase 1b study using oral AG019, food-grade Lactococcus lactis bacteria genetically modified to express human proinsulin and human IL-10, as a monotherapy and in a parallel, randomised, double-blind Phase 2a study using AG019 in combination with teplizumab. METHODS: Adults (18-42 years) and adolescents (12-17 years) with type 1 diabetes diagnosed within 150 days were enrolled, with documented evidence of at least one autoantibody and a stimulated peak C-peptide level >0.2 nmol/l. Participants were allocated to interventions using interactive response technology. We treated 42 people aged 12-42 years with recent-onset type 1 diabetes, 24 with Phase 1b monotherapy (open-label) and 18 with Phase 2a combination therapy. In the Phase 2a study, after treatment of the first two open-label participants, all people involved were blinded to group assignment, except for the Data Safety Monitoring Board members and the unblinded statistician. The primary endpoint was safety and tolerability based on the incidence of treatment-emergent adverse events, collected up to 6 months post treatment initiation. The secondary endpoints were pharmacokinetics, based on AG019 detection in blood and faeces, and pharmacodynamic activity. Metabolic and immune endpoints included stimulated C-peptide levels during a mixed meal tolerance test, HbA1c levels, insulin use, and antigen-specific CD4+ and CD8+ T cell responses using an activation-induced marker assay and pooled tetramers, respectively. RESULTS: Data from 24 Phase 1b participants and 18 Phase 2a participants were analysed. No serious adverse events were reported and none of the participants discontinued AG019 due to treatment-emergent adverse events. No systemic exposure to AG019 bacteria, proinsulin or human IL-10 was demonstrated. In AG019 monotherapy-treated adults, metabolic variables were stabilised up to 6 months (C-peptide, insulin use) or 12 months (HbA1c) post treatment initiation. In participants treated

Recombinant LL-37 Lactococcus lactis (Oral LL-37) was designed to prevent progression of COVID-19 by targeting virus envelope, however, effectiveness and safety of Oral LL-37 in clinical application was unclear. A total of 238 adult inpatients, open-labelled, randomized, placebo-controlled, single-center study was conducted to investigate the primary end points, including negative conversion time (NCT) of SARS-CoV-2 RNA and adverse events (AEs). As early as intervened on 6th day of case confirmed, Oral LL-37 could significantly shorten NCT (LL-37 9.80 ± 2.67 vs. placebo 14.04 ± 5.89, p < 0.01). For Oral LL-37, as early as treated in 6 days, the adjusted hazard ratio (HR) for a primary event of nucleic acid negative outcome was 6.27-fold higher than 7-day-later (HR: 6.276, 95% confidence interval [CI]: 3.631-10.848, p < 0.0001), and the adjusted HR of Oral LL-37 within 6 days is higher than placebo (HR: 2.427 95% CI: 1.239-4.751, p = 0.0097). No severe AEs were observed during hospitalization and follow-up investigation. This study shows that early intervention of Oral LL-37 incredibly reduces NCT implying a potential for clearance of Omicron BA.5.1.3 without evident safety concerns. © 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.

Enterococcus faecalis is among the leading causes of hospital-acquired infections worldwide. This bacterium has both intrinsic and acquired resistance to various antibiotics. The continuous development of antibiotic resistance by pathogens poses a challenge that economically and technologically restricts the discovery of next-generation antibiotics. Therefore, many researchers aim to develop new strategies to combat this pathogen. The aim of this study was to evaluate the synergistic antimicrobial and antibiofilm effects of the combination of antimicrobial agents such as chlorhexidine (CHX), ethylenediaminetetraacetic acid (EDTA) and sodium hypochlorite (NaOCl) with nisin against clinical and food isolates of E.faecalis. Nisin produced by wild-type and recombinant Lactococcus lactis strains was purified and their activities were evaluated in comparison with commercial nisin. The minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) of the agents were determined using microplate dilution methods. Antibiofilm activities were visualized using scanning electron microscopy (SEM). The MIC values for CHX, EDTA, and NaOCl were determined as 0.0002%, 5 mM, and 0.50%, respectively. The MIC values of nisin for all tested strains and isolates ranged from 12.5 to 100 IU/ mL. Synergistic interactions of the antimicrobial agents were determined using the checkerboard method, revealing that the most effective combination was the combination of nisin and EDTA. Similarly, the most effective combination for eradicating 24-hour biofilms was nisin + EDTA (1000 IU/mL + 10 mM). The concentration of nisin in this combination was lower than its MBEC value (1500 IU/mL). While the combination of nisin with CHX and NaOCl achieved complete eradication of biofilms, the agents alone were ineffective in achieving such results. SEM images showed that although E.faecalis biofilms were not completely eradicated, they were significantly disrupted as a result of the combined application of nisin with antimicrobial agents. These in vitro findings indicate that the combination of nisin and EDTA may be effective against biofilm structures formed by clinical and fo

Lymphoma remains a significant global health burden, necessitating innovative, targeted therapeutic strategies. Nisin (N), a bacteriocin produced by Lactococcus lactis, has demonstrated antimicrobial and anticancer properties through membrane disruption and apoptotic induction. Urolithin B (UB), a gut microbiota-derived metabolite of ellagitannins, has shown anti-inflammatory and antiproliferative activities in various cancer models. Vincristine (Vinc), a common anti-lymphoma drug, disrupts microtubule formation, leading to cell cycle arrest and apoptosis in cancer cells. This study explored the antiproliferative and pro-apoptotic effects of a triple combination therapy comprising N, UB, and Vinc against human lymphoma cell lines (HKB-11 and Hs 313.T). This study systematically evaluated the synergistic efficacy of both monotherapy and dual and triple combinations and molecular mechanisms using Alamar Blue viability assays, combination index (CI) modelling, reactive oxygen species (ROS) quantification, annexin V/7-AAD flow cytometry, and bottom-up label-free proteomics. The potential cytotoxicity of the combination on normal stromal HS-5 cells was also assessed using the Alamar Blue assay. The N: UB: Vinc combination at 2240: 210: 0.94 µM demonstrated potent synergy (CI values 0.31-0.50 at IC90 - IC95) and induced near-complete growth inhibition (> 99%) in both lymphoma cell lines with reduced toxicity (42.09 ± 1.21% viability) toward normal stromal HS-5 cells. ROS analysis revealed significant oxidative stress, while flow cytometry confirmed enhanced apoptosis (p < 0.0001) in the combination groups. Proteomic profiling of the combination N: UB: Vinc at 2450.94 µM uncovered distinct molecular responses, including upregulation of MAP1LC3B2 (Log2FC = 1.4), GMNN (Log2FC = 1.3), and SLC38A2 (Log2FC = 1.5), promoting apoptosis, cell cycle regulation, and mTOR signaling inhibition. Concurrently, key oncogenic and metabolic proteins were downregulated, including NNMT (Log2FC = -2.9), PLTP (Log2FC = -2.5), and CYP4X1 (Log2FC = -2.0), which implicated the suppression of MAPK-Akt signaling, ferroptosis activation, and lipid metabolism disruption. These results established

Clostridioides difficile is a major cause of nosocomial diarrhea. As current antibiotic treatment failures and recurrence of infections are highly frequent, alternative strategies are needed for the treatment of this disease. This study explores the use of bacteriocins, specifically lacticin 3147 and pediocin PA-1, which have reported inhibitory activity against C. difficile. We engineered Lactococcus lactis strains to produce these bacteriocins individually or in combination, aiming to enhance their activity against C. difficile. Our results show that lacticin 3147 and pediocin PA-1 display synergy, resulting in higher anti-C. difficile activity. We then evaluated the effects of these L. lactis strains in a Simplified Human Intestinal Microbiome (SIHUMI-C) model, a bacterial consortium of eight diverse human gut species that includes C. difficile. After introducing the bacteriocin-producing L. lactis strains into SIHUMI-C, samples were collected over 24 hours, and the genome copies of each species were assessed using qPCR. Contrary to expectations, the combined bacteriocins increased C. difficile levels in the consortium despite showing synergy against C. difficile in agar-based screening. This can be rationally explained by antagonistic inter-species interactions within SIHUMI-C, providing new insights into how broad-spectrum antimicrobials might fail to control targeted species in complex gut microbial communities. These findings highlight the need to mitigate off-target effects in complex gut microbiomes when developing bacteriocin-based therapies with potential clinical implications for infectious disease treatment.

Thiamine dilauryl sulphate (TDS) exerts a bacteriostatic effect against Gram-positive bacteria and is used as a food additive. The heartwood extract of the Indian kino tree (Pterocarpus marsupium), a medicinal tree native to India, shows weak antimicrobial effects against bacteria and superficial dermatophyte-infective fungi. Herein, we report that the combination of TDS and P. marsupium extract exerts an additive or synergistic antimicrobial effect against various food spoilage microorganisms. Among the 13 species tested, this combination showed synergistic antimicrobial effects against Bacillus subtilis, Lactococcus lactis, Lactobacillus plantarum, and Candida albicans in an agar dilution method. We also found that the combination promoted the production of reactive oxygen species against a model yeast Saccharomyces cerevisiae using a fluorescnt 2',7'-dichlorofluorescein diacetate. Furthermore, the combination restricted drug efflux from yeast cells via efflux pumps in an efflux assay using a fluorescent rhodamine 6 G. These results suggest that the antifungal effect of TDS is improved in combination with P. marsupium extract via oxidative stress induction and drug efflux restriction. The combination of TDS and P. marsupium extract has a low environmental impact and toxicity when used in foods; therefore, it is also expected to be used in food and industrial products in the future. © The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for skin and soft tissue infections with multi-resistance to many antibiotics. It is thus imperative to explore alternative antimicrobial treatments to ensure future treatment options. Nisin (NIS), an antibacterial peptide produced by Lactococcus lactis, was selected to combine with Oxacillin (OX), to evaluate the antimicrobial effect and potential mechanism against MRSA. The synergistic antimicrobial effect of OX and NIS was verified by Minimal Inhibitory Concentration (MIC) assays, checkerboard analysis, time-kill curve, biofilm producing ability, and mice skin infection model in vivo. For the potential synergistic antimicrobial mechanism, the microstructure and integrity change of MRSA cells were determined by Scanning and Transmission Electron Microscope (SEM and TEM), intracellular alkaline phosphatase activity and propidium iodide staining were assayed; And transcription of mecA, main gene of MRSA resistant to OX, were detected by qRT-PCR. The results showed NIS could restore the sensitivity of MRSA to OX and inhibit biofilm production; OX + NIS can make MRSA cell deform; NIS may recover OX sensitivity by inhibiting the transcription of mecA. In vivo, mice skin infection models indicate that OX + NIS can substantially alleviate MRSA infections. As a safe commercially available biological compound, NIS and the combination of antibiotics are worth developing as new anti-MRSA biomaterials.

First-generation cephalosporins such as cefazolin (CEZ) have been widely used for mastitis treatment in dairy cattle. However, the use of antibiotics results in the presence of antibiotic residues in milk, which is used for human consumption. Nisin A, a bacteriocin produced by Lactococcus lactis, has been used as a broad-spectrum food preservative for over 50 years. Therefore, a combination of CEZ and nisin A might provide an extended activity spectrum against mastitis pathogens and reduce the antibiotic dose for mastitis treatment. This study aimed to evaluate the combined effect of CEZ and nisin A against mastitis pathogens using the checkerboard and time-kill assays. In the checkerboard assay, the CEZ-nisin A combination exhibited a synergistic effect against Staphylococcus aureus (n=20/20) and Enterococcus faecalis (n=13/18), and meanwhile exhibited a mostly additive effect against Staphylococcus intermedius (n=12/20), Streptococcus agalactiae (n=10/10), Streptococcus dysgalactiae (n=18/18), and Escherichia coli (n=14/18). There were no indifferent or antagonistic effects between CEZ and nisin A. In the time-kill assay, the CEZ-nisin A combination at 0.5 × or 1 × minimum inhibitory concentration exhibited synergistic reduction of bacterial growth by over 3 log10 colony forming units per ml relative to that observed with either antimicrobial substance alone. These results suggest that the CEZ-nisin A combination can be used for developing an intramammary infusion for mastitis treatment, with lower antibiotic concentrations than normal.

Cysteine/histidine-dependent amidohydrolase/peptidase (CHAP) and amidase are known as catalytic domains of the bacteriophage-derived endolysin LysK and were previously reported to show lytic activity against methicillin-resistant Staphylococcus aureus (MRSA). In the current study, the in silico design and analysis of chimeric CHAP-amidase model was applied to enhance the stability and solubility of protein, which was achieved through improving the properties of primary, secondary and tertiary structures. The coding gene sequence of the chimeric CHAP-amidase was synthesized and subcloned into the pET-22(+) expression vector, and the recombinant protein was expressed in E. coli BL21 (DE3) strain. Subsequent affinity-based purification yielded ~12 mg soluble protein per liter of E. coli culture. Statistical analysis indicated that concentrations of ≥1 μg/mL of the purified protein have significant antibacterial activity against S. aureus MRSA252 cells. The engineered chimeric CHAP-amidase exhibited 3.2 log reduction of MRSA252 cell counts at the concentration of 10 μg/mL. A synergistic interaction between CHAP-amidase and vancomycin was detected by using checkerboard assay and calculating the fractional inhibitory concentration (FIC) index. This synergistic effect was shown by 8-fold reduction in the minimum inhibitory concentration of vancomycin. The chimeric CHAP-amidase displayed strong antibacterial activity against S. aureus, S. epidermidis, and enterococcus. However, it did not indicate any significant antibacterial activity against E. coli and Lactococcus lactis. Taken together, these findings suggest that our chimeric CHAP-amidase might represent potential to be used for the development of efficient antibacterial therapies targeting MRSA and certain Gram-positive bacteria.

Streptococcus suis serotype 2 is known to cause severe infections in pigs, including meningitis, endocarditis and pneumonia. Furthermore, this bacterium is considered an emerging zoonotic agent. Recently, increased antibiotic resistance in S. suis has been reported worldwide. The objective of this study was to evaluate the potential of nisin, a bacteriocin of the lantibiotic class, as an antibacterial agent against the pathogen S. suis serotype 2. In addition, the synergistic activity of nisin in combination with conventional antibiotics was assessed. Using a plate assay, the nisin-producing strain Lactococcus lactis ATCC 11454 proved to be capable of inhibiting the growth of S. suis (n=18) belonging to either sequence type (ST)1, ST25, or ST28. In a microdilution broth assay, the minimum inhibitory concentration (MIC) of purified nisin ranged between 1.25 and 5 μg/mL while the minimum bactericidal concentration (MBC) was between 5 and 10 μg/mL toward S. suis. The use of a capsule-deficient mutant of S. suis indicated that the presence of this polysaccharidic structure has no marked impact on susceptibility to nisin. Following treatment of S. suis with nisin, transmission electron microscopy observations revealed lysis of bacteria resulting from breakdown of the cell membrane. A time-killing curve showed a rapid bactericidal activity of nisin. Lastly, synergistic effects of nisin were observed in combination with several antibiotics, including penicillin, amoxicillin, tetracycline, streptomycin and ceftiofur. This study brought clear evidence supporting the potential of nisin for the prevention and treatment of S. suis infections in pigs.

A bacteriocin-producing Lactococcus lactis subsp. lactis was isolated from the intestine of olive flounder. The bacteriocin was identified as nisin Z. It was active against Gram-positive bacteria. Nisin Z at 3,200 arbitrary units (AU) was more effective in seawater than in PBS; growth of Streptococcus iniae was completely inhibited within 3 h. Nisin Z preparations with 3.5% (w/v) NaCl was the most effective against S. iniae being similar to nisin Z in seawater. Nisin Z is thus a good alternative to antibiotics to prevent streptococcosis caused by S. iniae aquaculture systems.

Nisin, a bacteriocin produced during the exponential growth phase of Lactococcus lactis ATCC 11454, inhibits the growth of a broad range of Gram-positive bacteria. Gram-negative bacteria can also be inhibited by nisin with EDTA. In this study, nisin production was assayed by the agar diffusion method using Lactobacillus sake ATCC 15521 and a recombinant Escherichia coli DH5-alpha expressing the recombinant green fluorescent protein as the nisin-susceptible test organisms. The titers of nisin expressed and released in culture media were quantified and expressed in arbitrary units (AU/mL of medium) and converted to standard nisin concentration (Nisaplin, 25 mg of pure nisin with an activity of 1 x 10(6) AU/mL). The expression and release of nisin by L. lactis in skimmed milk (9.09% total solids) with Man Rugosa Shepeer-Bacto Lactobacilli broth (1:1) was monitored in a 5 L New Brunswick fermentor. Combining EDTA with nisin increased the bactericidal effect of nisin on the bacteria examined. The presence of EDTA was necessary to inhibit E. coli growth with nisin. L. sake was shown to be a good indicator for the evaluation of nisin release in the culture media, including with the addition of EDTA.

Erratum in J Neurogastroenterol Motil. 2023 Jan 30;29(1):125. doi: 10.5056/jnm21202E. BACKGROUND/AIMS: We aim to evaluate the differences in the microbiome of responders and non-responders, as well as predict the response to probiotic therapy, based on fecal microbiome data in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: A multi-strain probiotics that contains Lactobacillus acidophilus (KCTC 11906BP), Lactobacillus plantarum (KCTC11867BP), Lactobacillus rhamnosus (KCTC 11868BP), Bifidobacterium breve (KCTC 11858BP), Bifidobacterium lactis (KCTC 11903BP), Bifidobacterium longum (KCTC 11860BP), and Streptococcus thermophilus (KCTC 11870BP) were used. Patients were categorized into probiotic and placebo groups, and fecal samples were collected from all patients before and at the end of 8 weeks of treatment. The probiotic group was further divided into responders and non-responders. Responders were defined as patients who experienced adequate relief of overall irritable bowel syndrome symptoms after probiotic therapy. Fecal microbiota were investigated using Illumina MiSeq and analyzed using the EzBioCloud 16S database and microbiome pipeline (https://www.EZbiocloud.net). RESULTS: There was no significant difference in the alpha and beta diversity between the responder and non-responder groups. The abundances of the phylum Proteobacteria and genus Bacteroides significantly decreased after probiotic treatment. Bifidobacterium bifidum, Pediococcus acidilactici, and Enterococcus faecium showed a significantly higher abundance in the probiotic group after treatment compared to the placebo group. Enterococcus faecalis and Lactococcus lactis were identified as biomarkers of non-response to probiotics. The abundance of Fusicatenibacter saccharivorans significantly increased in the responders after treatment. CONCLUSIONS: Probiotic treatment changes some composition of fecal bacteria in patients with IBS-D. E. faecalis and L. lactis may be prediction biomarkers for non-response to probiotics. Increased abundance of F. sccharivorans is correlated to symptom improvement by probiotics in patients with IBS-D.

Lactococcus lactis strain Plasma (LC-Plasma) is reported to have anti-viral effects via direct activation of plasmacytoid dendritic cells, which upregulate the production of type I and III interferons. A randomized, placebo-controlled, double-blind, parallel group study was designed for elementary schoolchildren, grades 1 to 3, in Vietnam. LC-Plasma or a control were administered to schoolchildren as a beverage (1.0 × 1011 count LC-Plasma/day/person). The primary endpoint was to determine the efficacy of LC-Plasma in reducing the cumulative days absent from school due to upper respiratory disease (URID) and gastrointestinal disease (GID), and the secondary endpoint was to evaluate the potency of LC-Plasma on URID/GID symptoms and general well-being scores. LC-Plasma intake significantly reduced the cumulative days absent from school due to URID/GID (Odds ratio (OR) = 0.57, p = 0.004) and URID alone (OR = 0.56, p = 0.005); LC-Plasma also significantly reduced the number of cumulative fever positive days during the first 4 weeks of intervention (OR = 0.58, p = 0.001) and cumulative days with diarrhea during the last 4 weeks of the intervention period (OR = 0.78, p = 0.01). The number of positive general wellbeing days was significantly improved in the LC-Plasma group compared with the control throughout the intervention period (OR = 0.93, 0.93, p = 0.03, 0.04 in the first and last 4 weeks of the intervention, respectively). These data suggest that LC-Plasma seems to improve the health condition of elementary schoolchildren and reduces school absenteeism due to infectious disease, especially URID.

The objective of this double-blind, placebo-controlled study was to elucidate the effects of fermented milk containing Lactococcus lactis subsp. cremoris FC (FC) on defaecation in healthy young women. We included 31 women (18-31 years old) who were randomly selected into two groups. Subjects in the test group consumed fermented milk containing FC, while subjects in the placebo group consumed non-fermented gelled milk. In the test group, defaecation frequency (both in days and times per week) and stool volume significantly increased during the consumption of fermented milk containing FC compared with before consumption. These effects were also observed in subjects with mild constipation. Furthermore, in subjects with mild constipation, stool ammonia concentration was significantly lower in the test group than that in the placebo group after 4 weeks. These results suggest that fermented milk containing FC is beneficial for improving defaecation and faecal properties.

This systematic review synthesizes current knowledge on nisin, an antimicrobial peptide produced by Lactococcus lactis, and explores its expanding applications across multiple fields. A structured search was conducted using databases such as PubMed, Web of Science, and Scopus, covering articles published between 2000 and 2024. Over 150 peer-reviewed studies were analyzed based on predefined inclusion criteria, focusing on molecular structure, biosynthesis, antimicrobial mechanisms, and applications. The review discusses nisin's established role in food preservation and highlights its emerging potential in therapeutic medicine and biotechnology. Recent advances in production strategies, particularly genetic engineering and fermentation optimization, are critically evaluated. Key findings include the elucidation of nisin's dual antimicrobial mechanisms and the successful development of various engineered nisin variants. Despite these advances, significant research gaps remain. In particular, the mechanisms underlying bacterial resistance to nisin and effective mitigation strategies are not yet fully understood. Additionally, the stability, scalability, and regulatory approval of nisin-loaded nanocarriers in real food systems remain underexplored. The review also assesses nisin's safety profile, regulatory status, and performance under diverse environmental conditions. Emphasis is placed on its potential to combat antimicrobial resistance and contribute to sustainable food systems. Overall, this analysis identifies current challenges and outlines future research priorities necessary to fully harness nisin's applications in food safety, medicine, and biotechnology.

Lactococcus lactis has potential as a mucosal vaccine delivery system. L. lactis can express antigens from bacteria or viruses, which are tightly controlled using nisin. Although L. lactis-based vaccine shows great promise, no product is ready for human use. Several studies have been conducted to develop L. lactis-based vaccine, and the efficacy of these vaccines has been evaluated in many scientific articles. This paper aims to review key aspects of current knowledge on the promising characteristics of L. lactis and to suggest its implications for vaccine design. Articles were obtained online using inclusion and exclusion criteria through Harzing's Publish or Perish. The article assessment used the Joanna Briggs Institute critical appraisal checklist for quasi-experimental studies. The efficacy evaluation of 24 articles showed that L. lactis-based vaccine can induce IgA and IgG as humoral immune responses; T CD4, T CD8, and B cells as cellular immune responses; and various proinflammatory cytokines such as IFN-γ, TNF-α, IL-2, IL-4, IL-8, IL-10, IL-12, IL-17. L. lactis is suitable as a vector carrier for oral or nasal mucosal vaccines targeting bacterial and viral infections. The development of L. lactis as a vaccine delivery system is promising.

OBJECTIVES: Oral mucositis (OM) is an acute and highly prevalent side effect of cancer treatments. Currently, there is no effective strategy for its prevention or treatment. This systematic review aimed to assess the effectiveness of biotics used as a therapeutic strategy for the management of OM. MATERIALS AND METHODS: The PRISMA checklist was followed and PubMed, Web of Science, and Scopus were screened for clinical and pre-clinical studies assessing the potential effects of biotics in OM. Inclusion criteria included in vivo studies related to oral mucositis evaluating the effect of biotics, and written in Portuguese, English, French, Spanish, or Dutch. The following exclusion criteria were used: systematic reviews and meta-analyses, reviews, case reports, opinion papers or comments, conference papers, letters without results, articles not related to oral therapy-induced mucositis or biotics, or in vitro articles that do not simulate oral mucositis. RESULTS: From a total of 1250 articles retrieved, 9 were included in this systematic review. Four clinical studies reported a reduction in oral mucositis occurrence with Lactobacillus species (Lactobacillus casei and Lactobacillus brevis CD2) and Bacillus clausii UBBC07. In pre-clinical studies, Lactococcus lactis genetically modified and Lactobacillus reuteri reduced the severity of OM and Streptococcus salivarius K12 also decreased the size of the ulcers. CONCLUSION: The findings of this systematic review suggest that probiotic supplementation may potentially reduce the incidence of therapy-induced OM and decrease its severity in patients undergoing cancer treatment. However, the available evidence is marred by significant heterogeneity across studies. © 2023. The Author(s).

Nisin, a member of class I bacteriocins known as lantibiotics, is produced by the lactic acid bacterium Lactococcus lactis and is characterized by a wide spectrum of antibacterial activity against gram-positive bacteria. This characteristic in conjunction with its low toxicity and safety of use in food has contributed to the worldwide success of nisin as a natural food preservative. This lantibiotic has attracted interest as a potential natural therapeutic agent for the control of bacterial infections. However, similar to other antimicrobial peptides of natural origin, the spectrum of biological activity of nisin surpasses its antibacterial properties, encompassing interesting and incompletely understood immunotropic characteristics. This paper is a systematic review of the current information about the potential immunomodulatory properties of nisin based on in vitro and in vivo studies in various experimental models. We also discuss the effect of potentially probiotic, nisin-producing L. lactis strains on the immune system of animals.