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Tindjau, Ricco, Jian-Yong Chua, and Shao-Quan Liu. "Growth, Substrate, and Metabolite Changes of Probiotic Bifidobacterium animalis subsp. lactis in Soy (Tofu) Whey." Fermentation 9, no. 12 (2023): 1024. http://dx.doi.org/10.3390/fermentation9121024.
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Soy (tofu) whey is one of the two side-streams from tofu processing, which has been shown to be suitable for microbial growth. In this work, probiotic Bifidobacterium animalis subsp. lactis Bl-04 and B94 were used to ferment soy whey with different supplements to explore the possibility of harnessing Bifidobacterium fermentation to upcycle soy whey. Soy whey was supplemented with different supplements (control, CN; glucose, G; glucose + cysteine, GC; glucose + cysteine + yeast extract, GCY) and inoculated with either B. lactis Bl-04 or B94. Growth, substrate utilization, and metabolic products were monitored before and after fermentation. Bl-04 managed to grow in all four media, while B94 needed cysteine to grow. The contents of sucrose, cysteine, methionine, and succinic acid decreased in the fermented samples. Acetic and lactic acids were produced in fermented soy whey ranging from 0.49–2.66 g/L and 0.58–2.88 g/L, respectively, with vitamin B12 at 2.06–4.56 μg/L. Increases in isoflavone aglycones (0.19–25.05 mg/L) and iron (0.03–0.12 mg/L) were observed. The PCA analysis of volatiles showed a distinct clustering due to short-chain fatty acids (acetic, butyric, and isovaleric acid), 2,3-butanedione (diacetyl), H2S, and 3-methylthiophene. Overall, the selection of suitable bifidobacterial strains and supplements for soy whey fermentation can open avenues to upcycle soy whey.
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Andersen, Joakim Mark, Rodolphe Barrangou, Maher Abou Hachem, et al. "Transcriptional analysis of oligosaccharide utilization by Bifidobacterium lactis Bl-04." BMC Genomics 14, no. 1 (2013): 312. http://dx.doi.org/10.1186/1471-2164-14-312.
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Zabel, Bryan, Sanna M. Mäkelä, Derek Nedveck, et al. "The Effect of Bifidobacterium animalis subsp. lactis Bl-04 on Influenza A Virus Infection in Mice." Microorganisms 11, no. 10 (2023): 2582. http://dx.doi.org/10.3390/microorganisms11102582.
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Influenza A virus infection is a major global disease requiring annual vaccination. Clinical studies indicate that certain probiotics may support immune function against influenza and other respiratory viruses, but direct molecular evidence is scarce. Here, mice were treated with a placebo or Bifidobacterium animalis subsp. lactis Bl-04 (Bl-04) orally via food (cereal) and also by gavage and exposed to Influenza A virus H1N1 (H1N1). The symptoms of the infection were observed, and tissues and digesta were collected for viral load RT-qPCR, transcriptomics, and microbiomics. The treatment decreased the viral load by 48% at day 3 post-infection in lungs and symptoms of infection at day 4 compared to placebo. Tissue transcriptomics showed differences between the Bl-04 and placebo groups in the genes in the Influenza A pathway in the intestine, blood, and lungs prior to and post-infection, but the results were inconclusive. Moreover, 16S rRNA gene profiling and qPCR showed the presence of Bl-04 in the intestine, but without major shifts in the microbiome. In conclusion, Bl-04 treatment may influence the host response against H1N1 in a murine challenge model; however, further studies are required to elucidate the mechanism of action.
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Barrangou, Rodolphe, Elizabeth P. Briczinski, Lindsay L. Traeger, et al. "Comparison of the Complete Genome Sequences of Bifidobacterium animalis subsp. lactis DSM 10140 and Bl-04." Journal of Bacteriology 191, no. 13 (2009): 4144–51. http://dx.doi.org/10.1128/jb.00155-09.
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ABSTRACT Bifidobacteria are important members of the human gut flora, especially in infants. Comparative genomic analysis of two Bifidobacterium animalis subsp. lactis strains revealed evolution by internal deletion of consecutive spacer-repeat units within a novel clustered regularly interspaced short palindromic repeat locus, which represented the largest differential content between the two genomes. Additionally, 47 single nucleotide polymorphisms were identified, consisting primarily of nonsynonymous mutations, indicating positive selection and/or recent divergence. A particular nonsynonymous mutation in a putative glucose transporter was linked to a negative phenotypic effect on the ability of the variant to catabolize glucose, consistent with a modification in the predicted protein transmembrane topology. Comparative genome sequence analysis of three Bifidobacterium species provided a core genome set of 1,117 orthologs complemented by a pan-genome of 2,445 genes. The genome sequences of the intestinal bacterium B. animalis subsp. lactis provide insights into rapid genome evolution and the genetic basis for adaptation to the human gut environment, notably with regard to catabolism of dietary carbohydrates, resistance to bile and acid, and interaction with the intestinal epithelium. The high degree of genome conservation observed between the two strains in terms of size, organization, and sequence is indicative of a genomically monomorphic subspecies and explains the inability to differentiate the strains by standard techniques such as pulsed-field gel electrophoresis.
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Sánchez, María Carmen, Ana Herráiz, Sindy Tigre, et al. "Evidence of the Beneficial Impact of Three Probiotic-Based Food Supplements on the Composition and Metabolic Activity of the Intestinal Microbiota in Healthy Individuals: An Ex Vivo Study." Nutrients 15, no. 24 (2023): 5077. http://dx.doi.org/10.3390/nu15245077.
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Scientific evidence has increasingly supported the beneficial effects of probiotic-based food supplements on human intestinal health. This ex vivo study investigated the effects on the composition and metabolic activity of the intestinal microbiota of three probiotic-based food supplements, containing, respectively, (1) Bifidobacterium longum ES1, (2) Lactobacillus acidophilus NCFM®, and (3) a combination of L. acidophilus NCFM®, Lactobacillus paracasei Lpc-37™, Bifidobacterium lactis Bi-07™, and Bifidobacterium lactis Bl-04™. This study employed fecal samples from six healthy donors, inoculated in a Colon-on-a-plate® system. After 48 h of exposure or non-exposure to the food supplements, the effects were measured on the overall microbial fermentation (pH), changes in microbial metabolic activity through the production of short-chain and branched-chain fatty acids (SCFAs and BCFAs), ammonium, lactate, and microbial composition. The strongest effect on the fermentation process was observed for the combined formulation probiotics, characterized by the significant stimulation of butyrate production, a significant reduction in BCFAs and ammonium in all donors, and a significant stimulatory effect on bifidobacteria and lactobacilli growth. Our findings suggest that the combined formulation probiotics significantly impact the intestinal microbiome of the healthy individuals, showing changes in metabolic activity and microbial abundance as the health benefit endpoint.
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Huuskonen, Laura, Heli Anglenius, Ilmari Ahonen та Kirsti Tiihonen. "Effects of Bacterial Lysates and Metabolites on Collagen Homeostasis in TNF-α-Challenged Human Dermal Fibroblasts". Microorganisms 11, № 6 (2023): 1465. http://dx.doi.org/10.3390/microorganisms11061465.
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During skin aging, the production of extracellular matrix (ECM) proteins, such as type I collagen, decreases and the synthesis of ECM-degrading matrix metalloproteinases (MMPs) rises, leading to an imbalance in homeostasis and to wrinkle formation. In this study, we examined the effects of bacterial lysates and metabolites from three bifidobacteria and five lactobacilli on collagen homeostasis in human dermal fibroblasts during challenge with tumor necrosis factor alpha (TNF-α), modeling an inflammatory condition that damages the skin’s structure. Antiaging properties were measured, based on fibroblast cell viability and confluence, amount of type I pro-collagen, ratio of MMP-1 to type I pro-collagen, cytokines, and growth factors. The TNF-α challenge increased the MMP-1/type I pro-collagen ratio and levels of proinflammatory cytokines, as expected. With the probiotics, differences were clearly dependent on bacterial species, strain, and form. In general, the lysates elicited less pronounced responses in the biomarkers. Of all strains, the Bifidobacterium animalis ssp. lactis strains Bl-04 and B420 best maintained type I pro-collagen production and the MMP-1/collagen type I ratio under no-challenge and challenge conditions. Metabolites that were produced by bifidobacteria, but not their lysates, reduced several proinflammatory cytokines (IL-6, IL-8, and TNF-α) during the challenge, whereas those from lactobacilli did not. These results indicate that B. animalis ssp. lactis-produced metabolites, especially those of strains Bl-04 and B420, could support collagen homeostasis in the skin.
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Huuskonen, Laura, Anna Lyra, Eunju Lee, et al. "Effects of Bifidobacterium animalis subsp. lactis Bl-04 on Skin Wrinkles and Dryness: A Randomized, Triple-Blinded, Placebo-Controlled Clinical Trial." Dermato 2, no. 2 (2022): 30–53. http://dx.doi.org/10.3390/dermato2020005.
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The effects of orally consumed probiotics on skin wrinkles and dryness are not fully known. A randomized, placebo-controlled, triple-blinded study was conducted with 148 healthy Korean female volunteers aged between 33 and 60 years, who were administered 1.75 × 109 colony-forming units (CFUs) of Bifidobacterium animalis subsp. lactis Bl-04 (Bl-04) (N = 74) or matching placebo (N = 74) for 12 weeks. Facial wrinkles (with 3-dimensional (3D) imaging), skin hydration, transepidermal water loss (TEWL), elasticity, and gloss were assessed at baseline and after every 4 weeks of the intervention. Questionnaire-based subjective evaluations of product efficacy and usability were also analyzed. The consumption of Bl-04 was safe and ameliorated significantly facial skin wrinkle parameters (total wrinkle area and volume, average depth of wrinkles, and arithmetic average roughness (Ra)) versus placebo at 4 weeks, but there were no differences at Week 8 or 12 between groups. Skin hydration, TEWL, elasticity, and gloss were similar between treatment groups, as were the subjective evaluation scores. Oral consumption of Bl-04 indicated promising short-term effects on skin appearance from the winter toward the spring. In future study designs, special attention should be paid to environmental conditions as well as to the skin condition and age of the participants.
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Forssten, Sofia D., Nicolas Yeung, and Arthur C. Ouwehand. "Fecal Recovery of Probiotics Administered as a Multi-Strain Formulation during Antibiotic Treatment." Biomedicines 8, no. 4 (2020): 83. http://dx.doi.org/10.3390/biomedicines8040083.
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The present study aimed to investigate whether probiotic recovery is affected when consumed together with antibiotics. Fecal samples were collected from an earlier antibiotic associated diarrhea, randomized, placebo-controlled study with a product consisting of a combination of Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, and Bifidobacterium lactis Bi-07, B. lactis Bl-04 at equal numbers and at a total dose of 1010 CFU. Fecal samples were collected during the screening visit (T0), i.e., at the time of antibiotic prescription, and then on the last day of the antibiotic treatment (T1) as well as seven days after the subject had stopped taking the antibiotic treatment (T2) and at two weeks after completing antibiotic treatment and one week after probiotic/placebo consumption stopped (T3). Samples were analyzed for the presence of the four administered strains. The study was registered at clinicaltrials.gov as NCT01596829. Detection levels of all four strains were significantly increased from T0 to T1 and returned to baseline level from T2 to T3. There were also significantly more subjects with detectable levels of L. paracasei Lpc-37, B. lactis Bi-07, and B. lactis Bl-04 at T1 and T2 compared to T0 and T3, and compared to placebo. Each of the four strains could be detected in the feces of patients apparently unaffected by the simultaneous consumption of antibiotics.
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Latvala, Sinikka, Markus J. Lehtinen, Sanna M. Mäkelä, et al. "The effect of probiotic Bifidobacterium lactis Bl-04 on innate antiviral responses in vitro." Heliyon 10, no. 8 (2024): e29588. http://dx.doi.org/10.1016/j.heliyon.2024.e29588.
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Shulpekova, Yu O., and V. Yu Rusyaev. "Daily probiotics: benefits and reasonable application." Meditsinskiy sovet = Medical Council, no. 15 (October 19, 2021): 136–43. http://dx.doi.org/10.21518/2079-701x-2021-15-136-143.
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This article reviewed the mechanisms of action of probiotics and the possible effects of individual strains on the general wellbeing if they are taken daily.The content and activity of bacteria in food products should be regulated by special guidelines. The balanced nutrition allows us to get healthy strains in a natural way. Daily consumption of certain strains as part of functional food products is promising for the prevention of obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, functional intestinal disorders, colon cancer, cardiovascular diseases and depression. The issues of safety of novel probiotic strains newly introduced in clinical practice require careful consideration. Synbiotics can comprise probiotic strains of bacteria (Lactobacillus acidophilus La-14, Lactobacillus rhamnosus Lr-32, Bifidobacterium lactis Bl-04) with tolerance to acid, pepsin and bile salts, as well as the prebiotic inulin and vitamins B1, B2, B6 and B12 contributing to survival of beneficial bacteria. L. acidophilus is a common probiotic that occurs in the natural environment and food products, no cases of antibiotic resistance of this species have been established. Strains Lactobacillus acidophilus La-14, Lactobacillus rhamnosus Lr-32, Bifidobacterium lactis Bl-04 have a high adhesion capacity, strong inhibitory effects on intestinal pathogens, including fungi, anti-inflammatory effects, help to eliminate oxalates. As can be seen from the above, the use of probiotics and synbiotics is one of the most promising preventive fields of medicine.
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Martinez, Fabio Andres Castillo, José Manuel Domínguez, Attilio Converti, and Ricardo Pinheiro de Souza Oliveira. "Production of bacteriocin-like inhibitory substance by Bifidobacterium lactis in skim milk supplemented with additives." Journal of Dairy Research 82, no. 3 (2015): 350–55. http://dx.doi.org/10.1017/s0022029915000163.
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Bacteriocins are natural compounds used as food biopreservatives instead of chemical preservatives. Bifidobacterium animalis subsp. lactis (Bifid. lactis) was shown to produce a bacteriocin-like inhibitory substance (BLIS) able to inhibit the growth of Listeria monocytogenes selected as an indicator microorganism. To enhance this production by the strain Bifid. lactis BL 04, skim milk (SM) was used as a fermentation medium either in the presence or in the absence of yeast extract, Tween 80 or inulin as stimulating additives, and the results in terms of bacterial growth and BLIS production were compared with those obtained in a traditional high cost complex medium such as Man, Rogosa and Sharpe (MRS). To this purpose, all the cultivations were carried out in flasks at 200 rpm under anaerobic conditions ensured by a nitrogen flowrate of 1·0 L/min for 48 h, and BLIS production was quantified by means of a modified agar diffusion assay at low values of both temperature and concentration of List. monocytogenes. Although all these ingredients were shown to exert positive influence on BLIS production in both media, yeast extract and SM were by far the best ingredient and the best medium, respectively, allowing for a BLIS production at the late exponential phase of 2000 AU/ml.
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Marushko, Yurii, Tetiana Hyshchak, and Olha Chabanovich. "The Main Mechanisms of the Effect of Intestinal Microflora on the Immune System and Their Importance in Clinical Practice." Family Medicine, no. 4 (October 28, 2021): 19–27. https://doi.org/10.30841/2307-5112.4.2021.249409.
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The intestinal microflora protects humans from colonization by pathogenic microorganisms and inhibits their growth. It is known that one of the functions of normal flora is to activate not only the local immunity of the intestine, but also the system of the whole organism. Today, probiotic preparations with immunomodulatory effects are widely used in medical practice, containing Lactobacillus Acidophilus NCFMTM, Bifidobacterium Lactis BL-04, which support local and general immunity. Research results indicate that probiotics are effective in the treatment of many pathological conditions in both children and adults due to their various positive effects on health, including due to their immunomodulatory effects. The use of probiotics in complex therapy allows you to quickly achieve a stable normalization of the composition of the intestinal microflora and eliminate pathological manifestations of the disease. The fundamental importance of probiotics is that they allow the treatment of disorders of intestinal microecology, caused by both the external environment and oral antimicrobial therapy. Several probiotics have been shown to shorten the duration and ease the course of bacterial or viral respiratory infections. The effect of probiotics on the immune system is multifaceted and promising for the correction of cytokine production, which is especially important in the context of the SARS-CoV2 pandemic.
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Briczinski, Elizabeth P., Joseph R. Loquasto, Rodolphe Barrangou, Edward G. Dudley, Anastasia M. Roberts, and Robert F. Roberts. "Strain-Specific Genotyping of Bifidobacterium animalis subsp. lactis by Using Single-Nucleotide Polymorphisms, Insertions, and Deletions." Applied and Environmental Microbiology 75, no. 23 (2009): 7501–8. http://dx.doi.org/10.1128/aem.01430-09.
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ABSTRACT Several probiotic strains of Bifidobacterium animalis subsp. lactis are widely supplemented into food products and dietary supplements due to their documented health benefits and ability to survive within the mammalian gastrointestinal tract and acidified dairy products. The strain specificity of these characteristics demands techniques with high discriminatory power to differentiate among strains. However, to date, molecular approaches, such as pulsed-field gel electrophoresis and randomly amplified polymorphic DNA-PCR, have been ineffective at achieving strain separation due to the monomorphic nature of this subspecies. Previously, sequencing and comparison of two B. animalis subsp. lactis genomes (DSMZ 10140 and Bl-04) confirmed this high level of sequence similarity, identifying only 47 single-nucleotide polymorphisms (SNPs) and four insertions and/or deletions (INDELs) between them. In this study, we hypothesized that a sequence-based typing method targeting these loci would permit greater discrimination between strains than previously attempted methods. Sequencing 50 of these loci in 24 strains of B. animalis subsp. lactis revealed that a combination of nine SNPs/INDELs could be used to differentiate strains into 14 distinct genotypic groups. In addition, the presence of a nonsynonymous SNP within the gene encoding a putative glucose uptake protein was found to correlate with the ability of certain strains to transport glucose and to grow rapidly in a medium containing glucose as the sole carbon source. The method reported here can be used in clinical, regulatory, and commercial applications requiring identification of B. animalis subsp. lactis at the strain level.
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Marttinen, Maija, Mehreen Anjum, Markku T. Saarinen, et al. "Enhancing Bioaccessibility of Plant Protein Using Probiotics: An In Vitro Study." Nutrients 15, no. 18 (2023): 3905. http://dx.doi.org/10.3390/nu15183905.
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As plant-based diets become more popular, there is an interest in developing innovations to improve the bioaccessibility of plant protein. In this study, seven probiotic strains (Bifidobacterium animalis subsp. lactis B420, B. lactis Bl-04, Lactobacillus acidophilus NCFM, Lacticaseibacillus rhamnosus HN001, Lacticaseibacillus paracasei subsp. paracasei Lpc-37, Lactiplantibacillus plantarum Lp-115, and Lactococcus lactis subsp. lactis Ll-23) were evaluated for their capacity to hydrolyze soy and pea protein ingredients in an in vitro digestion model of the upper gastrointestinal tract (UGIT). Compared to the control digestion of protein without a probiotic, all the studied strains were able to increase the digestion of soy or pea protein, as evidenced by an increase in free α-amino nitrogen (FAN) and/or free amino acid concentration. The increase in FAN varied between 13 and 33% depending on the protein substrate and probiotic strain. The survival of probiotic bacteria after exposure to digestive fluids was strain-dependent and may have affected the strain’s capacity to function and aid in protein digestion in the gastrointestinal environment. Overall, our results from the standardized in vitro digestion model provide an approach to explore probiotics for improved plant protein digestion and bioaccessibility of amino acids; however, human clinical research is needed to evaluate the efficacy of probiotics on amino acid absorption and bioavailability in vivo.
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Forssten, Sofia, and Arthur C. Ouwehand. "Dose-Response Recovery of Probiotic Strains in Simulated Gastro-Intestinal Passage." Microorganisms 8, no. 1 (2020): 112. http://dx.doi.org/10.3390/microorganisms8010112.
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The probiotic definition stipulates “adequate amounts”. Here, we investigated the metabolic output and recovery rate of probiotic strains using a simulated upper gastro-intestinal passage and colonic fermentation. Two different doses, 7 × 109 colony forming units (CFU) and 7 × 1010 CFU, of a probiotic mixture (Bifidobacterium lactis Bl-04, Lactobacillus acidophilus La-14, Lactobacillus paracasei Lpc-37, and Lactobacillus plantarum Lp-115) or placebo were tested. The four strains were quantified by qPCR and the metabolites analyzed by gas chromatography. There was a dose-response in the detection of all four strains. There was a slightly larger increase between the two doses for L. paracasei Lpc-37 as compared with the other strains; this may suggest a greater robustness of this strain. Compared with the placebo, the high dose simulations generated more propionic acid and a higher total of short chain fatty acids (SCFA). Higher doses of a species are required to reach measurable increases above the baseline level of this species.
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Turner, R. B., J. A. Woodfolk, L. Borish, et al. "Effect of probiotic on innate inflammatory response and viral shedding in experimental rhinovirus infection – a randomised controlled trial." Beneficial Microbes 8, no. 2 (2017): 207–15. http://dx.doi.org/10.3920/bm2016.0160.
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Ingestion of probiotics appears to have modest effects on the incidence of viral respiratory infection. The mechanism of these effects is not clear; however, there is evidence from animal models that the probiotic may have an effect on innate immune responses to pathogens. The purpose of this randomised, placebo-controlled study was to determine the effect of administration of Bifidobacterium animalis subspecies lactis Bl-04 on innate and adaptive host responses to experimental rhinovirus challenge. The effect on the response of chemokine (C-X-C motif) ligand 8 (CXCL8) to rhinovirus infection was defined as the primary endpoint for the study. 152 seronegative volunteers who had been supplemented for 28 days, 73 with probiotic and 79 with placebo, were challenged with RV-A39. Supplement or placebo administration was then continued for five days during collection of specimens for assessment of host response, infection, and symptoms. 58 probiotic and 57 placebo-supplemented volunteers met protocol-defined criteria for analysis. Probiotic resulted in higher nasal lavage CXCL8 on day 0 prior to virus challenge (90 vs 58 pg/ml, respectively, P=0.04, ANCOVA). The CXCL8 response to rhinovirus infection in nasal lavage was significantly reduced in the probiotic treated group (P=0.03, ANCOVA). Probiotic was also associated with a reduction in nasal lavage virus titre and the proportion of subjects shedding virus in nasal secretions (76% in the probiotic group, 91% in the placebo group, P=0.04, Fisher Exact test). The administration of probiotic did not influence lower respiratory inflammation (assessed by exhaled nitric oxide), subjective symptom scores, or infection rate. This study demonstrates that ingestion of Bl-04 may have an effect on the baseline state of innate immunity in the nose and on the subsequent response of the human host to rhinovirus infection. Clinicaltrials.gov registry number: NCT01669603.
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Piątek, J., M. Bernatek, H. Krauss, et al. "Effects of a nine-strain bacterial synbiotic compared to simethicone in colicky babies – an open-label randomised study." Beneficial Microbes 12, no. 3 (2021): 249–57. http://dx.doi.org/10.3920/bm2020.0160.
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The aim of the study was to determine effects of administration of simethicone and a multi-strain synbiotic on the crying behaviour of colicky babies. The study design consisted of an open-label, two parallel treatment group study involving 87 infants aged 3-6 weeks with infantile colic (defined as crying episodes lasting 3 or more hours per day and occurring at least 3 days per week within 3 weeks prior to enrolment) randomly, unequally [1:1.5] assigned to receive simethicone (n=33) or a multi-strain synbiotic (n=54) orally for 4 weeks. The multi-strain synbiotic contained Lactobacillus acidophilus LA-14, Lacticaseibacillus casei R0215, Lacticaseibacillus paracasei Lp-115, Lacticaseibacillus rhamnosus GG, Ligilactobacillus salivarius Ls-33, Bifidobacterium lactis Bl-04, Bifidobacterium bifidum R0071, Bifidobacterium longum R0175 and fructooligosaccharides). Primary outcome measures were the responder rates (effect ≥50% reduction from baseline) of the measures ‘crying days last 3 weeks’, ‘average evening crying duration last 3 weeks’ and ‘reduction of average number of crying phases per day last three weeks’ at the end of treatment. The study is registered at ClinicalTrials.gov under NCT 04487834. Significantly higher responder rates (effect ≥50% reduction from baseline) of the multi-strain synbiotic compared to simethicone were found for the measures ‘crying days last 3 weeks’ (72% vs 18%, P<0.0001) and ‘average evening crying duration last 3 weeks’ (85% vs 39%, P=0.0001). No significant difference was found for the measure ‘reduction of average number of crying phases per day last three weeks’ (50% vs 42%, P=0.4852). No adverse effects were reported for the two treatment groups. Based on these results, the multi-strain synbiotic can be considered as an interesting therapeutic possibility for the treatment of infantile colic, worthwhile to be investigated further in non-clinical and clinical studies.
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Turner, Ronald B., Liisa Lehtoranta, Ashley Hibberd, et al. "Effect of Bifidobacterium animalis spp. lactis Bl-04 on Rhinovirus-Induced Colds: A Randomized, Placebo-Controlled, Single-Center, Phase II Trial in Healthy Volunteers." eClinicalMedicine 43 (January 2022): 101224. http://dx.doi.org/10.1016/j.eclinm.2021.101224.
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Airaksinen, K., N. Yeung, A. Lyra, et al. "The effect of a probiotic blend on gastrointestinal symptoms in constipated patients: a double blind, randomised, placebo controlled 2-week trial." Beneficial Microbes 10, no. 6 (2019): 617–27. http://dx.doi.org/10.3920/bm2018.0163.
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Selected strains of lactobacilli and bifidobacteria are known to ameliorate constipation-related symptoms and have previously shown efficacy on digestive health. In this clinical trial, the safety and effectiveness of a probiotic blend containing lactobacilli and bifidobacteria were evaluated in adults with self-reported bloating and functional constipation. Constipation was diagnosed by the Rome III criteria. A total of 156 adults were randomised into this double-blind and placebo-controlled trial. Participants consumed the combination of Lactobacillus acidophilus NCFM (1010 cfu), Lactobacillus paracasei Lpc-37 (2.5×109 cfu), Bifidobacterium animalis subsp. lactis strains Bl-04 (2.5×109 cfu), Bi-07 (2.5×109 cfu) and HN019 (1010 cfu) (n=78), or placebo (microcrystalline cellulose) (n=78) for two weeks. After treatment the following were measured: primary outcome of bloating and secondary outcomes of colonic transit time, bowel movement frequency, stool consistency, other gastrointestinal symptoms (flatulence, abdominal pain, and burbling), constipation-related questionnaires (PAC-SYM and PAC-QoL) and product satisfaction. Faecal recovery of consumed strains was determined. The enrolled population was defined as constipated, however, the initial bloating severity was lower than in previous similar studies. No clinically significant observations related to the safety of the product were reported. Product efficacy was not shown in the primary analysis for bloating nor for the secondary efficacy analyses. The placebo functioned similarly as the probiotic product. In post-hoc analysis, a statistically significant decrease in flatulence in favour of the probiotic group was observed; day 7 (intention-to-treat (ITT): P=0.0313; per-protocol (PP): 0.0253) and on day 14 (ITT: P=0.0116; PP: P=0.0102) as measured by area under the curve (AUC) analysis. The mean AUC of all symptoms decreased in favour of the probiotic group, indicating less digestive discomfort. The study was registered at the ISRCTN registry (ISRCTN41607808).
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Barbaro, Maria Raffaella, Francesca Bianco, Cesare Cremon, Giovanni Marasco, Vincenzo Stanghellini, and Giovanni Barbara. "A Probiotic Mixture of Lactobacillus rhamnosus LR 32, Bifidobacterium lactis BL 04, and Bifidobacterium longum BB 536 Counteracts the Increase in Permeability Induced by the Mucosal Mediators of Irritable Bowel Syndrome by Acting on Zonula Occludens 1." International Journal of Molecular Sciences 26, no. 6 (2025): 2656. https://doi.org/10.3390/ijms26062656.
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Irritable Bowel Syndrome (IBS) is a disorder of gut- brain interaction characterized by recurrent abdominal pain associated with altered bowel habits. The therapeutic options for IBS patients include the use of probiotics. The aim of this study was to assess the effect of a multi-strain probiotic made up by Lactobacillus rhamnosus LR 32, Bifidobacterium lactis BL 04, and Bifidobacterium longum BB 536 (Serobioma, Bromatech s.r.l., Milano, Italy) on an in vitro model of the intestinal epithelial barrier in the presence of mucosal mediators that are released by IBS patients. IBS (n = 28; IBS with predominant diarrhea, IBS-D = 10; IBS with predominant constipation, IBS-C = 9; and IBS with mixed bowel habits, IBS-M = 9) patients, diagnosed according to the Rome IV criteria, and asymptomatic controls (ACs, n = 7) were enrolled. Mucosal mediators that were spontaneously released by colonic biopsies were collected (supernatants). Two doses of Serobioma were tested with/without IBS/AC mediators. RNA was extracted from Caco-2 cells to evaluate the tight junction (TJ) expression. Serobioma (106 CFU/mL) significantly reinforced the Caco-2 monolayer compared to growth medium alone (p < 0.05). IBS supernatants significantly increased Caco-2 paracellular permeability compared to the AC supernatants. The co-incubation of Caco-2 cells with IBS supernatants and Serobioma (106 CFU/mL) avoided the paracellular permeability alterations that were induced by IBS supernatants alone (p < 0.001), and, in particular, IBS-D and IBS-M ones. The co-incubation of Serobioma (106 CFU/mL) and IBS-D supernatants significantly increased ZO-1 expression compared to Caco-2 cells incubated with supernatants alone (p < 0.05), as confirmed via qPCR analyses. Serobioma (106 CFU/mL) counteracts the paracellular permeability changes that are induced by IBS supernatants, in particular IBS-D and IBS-M supernatants, likely modulating ZO-1 expression.
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Morovic, Wesley, Jason M. Roper, Amy B. Smith, et al. "Safety evaluation of HOWARU ® Restore ( Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Bifidobacterium animalis subsp. lactis Bl-04 and B. lactis Bi-07) for antibiotic resistance, genomic risk factors, and acute toxicity." Food and Chemical Toxicology 110 (December 2017): 316–24. http://dx.doi.org/10.1016/j.fct.2017.10.037.
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Cappellucci, Giorgio, Giulia Baini, Elisabetta Miraldi та ін. "Investigation on the Efficacy of Two Food Supplements Containing a Fixed Combination of Selected Probiotics and β-Glucans or Elderberry Extract for the Immune System: Modulation on Cytokines Expression in Human THP-1 and PBMC". Foods 13, № 3 (2024): 458. http://dx.doi.org/10.3390/foods13030458.
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Several herbal and other natural products are used as ingredients in food supplements to strengthen immunity even if, very often, marketed products are proposed without a clear rationale or experimental evidence. In this study, we aimed to investigate the effect on human monocytes (THP-1) and on ex vivo human peripheral blood mononuclear cells (PBMC) of two formulations, one containing Bifidobacterium animalis subsp. lactis Bl-04® with β-glucans (for adults) and one containing Lactobacillus rhamnosus CRL1505 with elderberry extract (for children). We compared formulations with single ingredients, with bacterial lipopolysaccharide (LPS) and the drug pidotimod; cytokines expression level was evaluated testing different concentrations of samples at two exposure times. As expected, LPS caused a non-specific huge upregulation of cytokines expression both in THP-1 and in PBMC, whereas pidotimod mainly upregulated IL-2 in PBMC and IL-8 in THP-1. The two formulations showed a difference between a pro-inflammatory stimulus such as LPS, and also from an immunostimulant drug, such as pidotimod, as they mainly upregulated the expression of IL-6 and IL-10 in PBMC but not in THP-1, in a concentration-dependent mode. Probiotics were shown to play a major role, but β-glucans and elderberry extract exerted a synergistic activity. This work demonstrated that combining selected probiotics with other natural products having immunomodulatory properties is an interesting strategy to develop innovative formulations in the sector of food supplements.
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Ardatskaya, M. D., A. A. Anuchkin, L. I. Butorova, A. I. Pavlov, N. R. Nugayeva, and Zh V. Fadina. "Pathogenetic aspects of the development and treatment of antibiotic-associated diarrhea: the choice of a synbiotic from the standpoint of evidence-based medicine." Meditsinskiy sovet = Medical Council, no. 6 (May 5, 2023): 113–25. http://dx.doi.org/10.21518/ms2023-026.
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Introduction. In recent years, diarrheal syndrome is the most common clinically significant negative effect of the antibiotic therapy (ABT), which constitutes a first-priority medical and social problem. The prescription of any antibiotic for any duration of treatment may cause a potential risk of developing antibiotic-associated diarrhea (AAD). In that regard, there is a need for the systematization of the main pathogenetic aspects of the deveopment of AAD and the rationale for the use of probiotics to prevent its development and treatment. Aim. To conduct a comparative evaluation of the efficacy, adherence and tolerability of a synbiotic Floriosa containing Bifidobacterium lactis Bl-04, Lactobacillus acidophilus La-14, Lactobacillus rhamnosus Lr-32, inulin, B vitamins, and an eubiotic Bifiform containing Enterococcus faecium, Bifidobacterium longum for the prevention of the development of AAD during and after the use of ABT in inpatients. Materials and methods. A total of 60 patients, which was used for the ABT in the hospital settings, were included in the study: the 1st group (30 patients) received a synbiotic, the 2nd group (30 patients) received an eubiotic. The efficacy of the preventive administration of drugs was assessed by Day 12 and 28 of the therapy. The methods included the patients’ assessment of the efficacy and satisfaction with treatment, an assay of short-chain fatty acids (SCFAs) in feces via gas-liquid chromatography and a Clostridium difficile Toxin A + B rapid test. Results. No cases of AAD were detected in both groups. The study drugs were comparable in terms of their efficacy assessment by the doctor and patients. A trend towards a higher assessment of the therapeutic effect and satisfaction with synbiotic therapy was observed. Changes in the absolute and relative content of SCFAs in the patients’ feces from the baseline level were established. More pronounced positive changes in the quantitative and qualitative composition of acids due to the treatment were identified in the patients who received the synbiotic and had more than 3 risk factors. Conclusions. The synbiotic Floriosa and probiotic Bifiform are effective drugs to prevent AAD. The synbiotic has advantages in terms of the overall assessment of the efficacy of the treatment and patient satisfaction, provides a pronounced protective effect on the intestinal microbiocenosis status during and after the ABT (as evidenced by the changes in SCFAs level in the feces), can be the drug of choice for the prevention of AAD, including AAD associated with C. difficile in individuals with more than 3 risk factors for the development of AAD.
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Morovic, Wesley, Paige Roos, Bryan Zabel, Claudio Hidalgo-Cantabrana, Anthony Kiefer, and Rodolphe Barrangou. "Transcriptional and Functional Analysis of Bifidobacterium animalis subsp. lactis Exposure to Tetracycline." Applied and Environmental Microbiology 84, no. 23 (2018). http://dx.doi.org/10.1128/aem.01999-18.
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ABSTRACT Commercial probiotic bacteria must be tested for acquired antibiotic resistance elements to avoid potential transfer to pathogens. The European Food Safety Authority recommends testing resistance using microdilution culture techniques previously used to establish inhibitory thresholds for the Bifidobacterium genus. Many Bifidobacterium animalis subsp. lactis strains exhibit increased resistance to tetracycline, historically attributed to the ribosomal protection gene tet(W). However, some strains that harbor genetically identical tet(W) genes show various inhibition levels, suggesting that other genetic elements also contribute to observed differences. Here, we adapted several molecular assays to confirm the inhibition of B. animalis subsp. lactis strains Bl-04 and HN019 and employed RNA sequencing to assess the transcriptional differences related to genomic polymorphisms. We detected specific stress responses to the antibiotic by correlating ATP concentration to number of viable genome copies from droplet digital PCR and found that the bacteria were still metabolically active in high drug concentrations. Transcriptional analyses revealed that several polymorphic regions, particularly a novel multidrug efflux transporter, were differentially expressed between the strains in each experimental condition, likely having phenotypic effects. We also found that the tet(W) gene was upregulated only during subinhibitory tetracycline concentrations, while two novel tetracycline resistance genes were upregulated at high concentrations. Furthermore, many genes involved in amino acid metabolism and transporter function were upregulated, while genes for complex carbohydrate utilization, protein metabolism, and clustered regularly interspaced short palindromic repeat(s) (CRISPR)-Cas systems were downregulated. These results provide high-throughput means for assessing antibiotic resistances of two highly related probiotic strains and determine the genetic network that contributes to the global tetracycline response. IMPORTANCE Bifidobacterium animalis subsp. lactis is widely used in human food and dietary supplements. Although well documented to be safe, B. animalis subsp. lactis strains must not contain transferable antibiotic resistance elements. Many B. animalis subsp. lactis strains have different resistance measurements despite being genetically similar, and the reasons for this are not well understood. In the current study, we sought to examine how genomic differences between two closely related industrial B. animalis subsp. lactis strains contribute to different resistance levels. This will lead to a better understanding of resistance, identify future targets for analysis of transferability, and expand our understanding of tetracycline resistance in bacteria.
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Wieërs, Grégoire, Valérie Verbelen, Mieke Van Den Driessche, et al. "Do Probiotics During In-Hospital Antibiotic Treatment Prevent Colonization of Gut Microbiota With Multi-Drug-Resistant Bacteria? A Randomized Placebo-Controlled Trial Comparing Saccharomyces to a Mixture of Lactobacillus, Bifidobacterium, and Saccharomyces." Frontiers in Public Health 8 (March 8, 2021). http://dx.doi.org/10.3389/fpubh.2020.578089.
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Objective: Most infections with Enterobacteriaceae producing AmpC β-lactamase (AmpC)-, extended-spectrum β-lactamase (ESBL)-, and carbapenemase-producing bacteria, vancomycin-resistant Enterococcus as well as naturally resistant non-fermenting bacteria such as Pseudomonas aeruginosa, are related to a prior colonization of the gut microbiota. The objective of this study was to determine whether treatment with probiotics during an antibiotic treatment could prevent the colonization of the gut microbiota with multi-drug resistant bacteria.Method: In total, 120 patients treated for 10 days with amoxicillin-clavulanate antibiotics were included in a randomized, placebo-controlled, double-blinded trial, comparing the effects of a 30 days treatment with placebo Saccharomyces boulardii CNCM I-745® and a probiotic mixture containing Saccharomyces boulardii, Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Bifidobacterium lactis Bl-04, and Bifidobacterium lactis Bi-07 (Bactiol duo®). Study treatment was initiated within 48 h of the antibiotic being initiated. Most of the patients included were elderly with a mean age of 78 years old with multiple comorbidities. Stools were collected at the time of inclusion in the trial, at the end of the antibiotic treatment, and the end of the study treatment. These were cultured on selective antibiotic media.Results: Treatment with the probiotic mixture led to a significant decline in colonization with Pseudomonas after antibiotic treatment from 25 to 8.3% (p = 0.041). Colonization with AmpC-producing enterobacteria was transiently increased after the antibiotic treatment (p = 0.027) and declined after the probiotic intervention (p= 0.041). No significant changes were observed in the placebo and Saccharomyces groups. Up to 2 years after the trial, no infection with ESBL-producing bacteria was observed in the probiotic mixture group.Conclusion: The association of Saccharomyces boulardii with specific strains of Lactobacillus and Bifidobacterium influences antibiotic treatment by counteracting the colonization of the colon microbiota with antibiotic-resistant pathogens.
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Hansen, Sarah J. Z., Wesley Morovic, Martha DeMeules, Buffy Stahl, and Connie W. Sindelar. "Absolute Enumeration of Probiotic Strains Lactobacillus acidophilus NCFM® and Bifidobacterium animalis subsp. lactis Bl-04® via Chip-Based Digital PCR." Frontiers in Microbiology 9 (April 11, 2018). http://dx.doi.org/10.3389/fmicb.2018.00704.
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Morrill, Johan, Evelina Kulcinskaja, Anna Maria Sulewska та ін. "The GH5 1,4-β-mannanase from Bifidobacterium animalis subsp. lactis Bl-04 possesses a low-affinity mannan-binding module and highlights the diversity of mannanolytic enzymes". BMC Biochemistry 16, № 1 (2015). http://dx.doi.org/10.1186/s12858-015-0055-4.
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Гаус, О. В., and М. А. Ливзан. "Phenotypes of irritable bowel syndrome and strategies for patient-oriented curation of patient." Лечащий врач, no. 7-8(26) (August 30, 2023). http://dx.doi.org/10.51793/os.2023.26.8.006.
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Цель работы. Предложить пациентоориентированный подход к курации больного с синдромом раздраженного кишечника на основе выделенных фенотипов заболевания. Материалы и методы. На основе комплексного анализа взаимодействия факторов генетики и эпигенетики выделены и представлены характеристики фенотипов синдрома раздраженного кишечника. Для каждого фенотипа разработаны и апробированы индивидуализированные схемы терапии заболевания. Для оценки эффективности предложенных пациентоориентированных подходов проведено открытое когортное проспективное рандомизированное исследование в параллельных группах. Результаты. При постинфекционном синдроме раздраженного кишечника пациентам рекомендовано назначение штамма Lactobacillus paracasei CNCMI-1572, а также коррекция пищевых привычек с ограничением соли и продуктов, содержащих лактозу. При фенотипе синдрома раздраженного кишечника с избыточной массой тела и ожирением пациентам предложено ограничение продуктов с высоким гликемическим индексом, дополнительное назначение адеметионина, а также синбиотика, содержащего инулин, штаммы Bifidobacterium lactis Bl-04, Lactobacillus acidophilus La-14, Lactobacillus rhamnosus Lr-32 и витамины группы В. При коморбидном фенотипе целесообразно назначение цитопротектора ребамипида. Дополнительно необходима коррекция рациона питания с исключением продуктов-триггеров. При эссенциальном фенотипе пациентам рекомендован прием пробиотического штамма Bifidobacterium longum 35624. Применение предложенных пациентоориентированных стратегий дополнительно к стандартной терапии позволило достичь более эффективного купирования клинических проявлений и уменьшения степени тяжести синдрома раздраженного кишечника, повышения душевого благополучия, а также сократить частоту рецидивов заболевания. Заключение. Предложенные пациентоориентированные подходы к курации больного с синдромом раздраженного кишечника на основе выделенных фенотипов заболевания могут рассматриваться в качестве одного из возможных способов повышения эффективности терапии заболевания. Objective. To propose a patient-oriented approach to the management of a patient with irritable bowel syndrome based on the identified phenotypes of the disease. Materials and methods. Based on a comprehensive analysis of the interaction of genetic and epigenetic factors, the characteristics of the phenotypes of irritable bowel syndrome have been identified and presented. For each phenotype, individualized treatment regimens for the disease have been developed and tested. To evaluate the effectiveness of the proposed patient-oriented approaches, an open cohort, prospective, randomized study in parallel groups was conducted. Results. With post-infectious irritable bowel syndrome, patients are recommended to prescribe a strain of Lactobacillus paracasei CNCMI-1572, as well as correction of eating habits with restriction of salt and products containing lactose. With the phenotype of irritable bowel syndrome with overweight and obesity, patients were offered the restriction of foods with a high glycemic index, the additional appointment of ademetionine, as well as a synbiotic containing inulin, strains of Bifidobacteriumlactis Bl-04, Lactobacillusacidophilus La-14, Lactobacillusrhamnosus Lr-32 and B vitamins In the comorbid phenotype, it is advisable to prescribe the cytoprotector rebamipide. Additionally, a correction of the diet is necessary with the exclusion of trigger foods. With the essential phenotype, patients are recommended to take the probiotic strain Bifidobacterium longum 35624. The use of the proposed patient-oriented strategies in addition to standard therapy made it possible to achieve more effective relief of clinical manifestations and reduce the severity of irritable bowel syndrome, improve mental well-being, and reduce the frequency of relapses of the disease. Conclusion. The proposed patient-oriented approaches to the management of a patient with irritable bowel syndrome based on the identified disease phenotypes can be considered as one of the possible ways to improve the effectiveness of disease therapy.
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Gomaa, Ahmed, Martha Verghese, and Josh Herring. "Inhibition of Antimicrobial Resistant Salmonella Heidelberg by a Synbiotic Combination of Prebiotics and Probiotics in an in Vitro Model (P20-011-19)." Current Developments in Nutrition 3, Supplement_1 (2019). http://dx.doi.org/10.1093/cdn/nzz040.p20-011-19.
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Abstract Objectives The aim of this study was to compare effects of different probiotic strains with and without prebiotics on lowering Salmonella heidelberg CFU in vitro. Methods The different inhibition levels of three strains of probiotics, Bifidobacterium lactis (Danisco Bl-04), Lactobacillus rhamnosus (Danisco Lr-32™) and Lactobacillus acidophilus (Danisco La-14®) on S. heidelberg were assessed and compared in presence and absence of 2.5% prebiotic cocktail of mannose (Acros Organics), xylose (Fisher Scientific), and inulin (MP Biomedicals) using Mueller-Hinton agar wells diffusion (factorial experiment). Recommendations for growth of selected microorganisms such as temperature and oxygen conditions were taken into consideration. All the analysis was conducted in triplicates. Results The results showed that three probiotics strains were able to significantly (P < 0.05) inhibit growth of S. heidelberg with and without prebiotics. Moreover, results showed that zones of inhibition were significantly (P = 0.03) greater with addition of prebiotics regardless of probiotic strains used. Conclusions According to the Centers for Disease Control (CDC), salmonella causes about 1.2 million illnesses, 23,000 hospitalizations, and 450 deaths in US every year. S. heidelberg is a multidrug-resistant strain that has been associated with high risk of hospitalizations. Probiotics produce organic acids that lower pH of intestines thus inhibiting pathogenic microorganisms. Probiotics may be utilized in livestock feed to reduce the chance of any contamination before the materials undergo processing, thereby developing sustainable food products that are safe from farm to fork. Funding Sources USDA-NIFA. Supporting Tables, Images and/or Graphs
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Yeung, Nicolas, and Arthur C. Ouwehand. "Comparison of qRT-PCR and ddPCR for multi-strain probiotic detection after a randomized human clinical trial." Frontiers in Microbiology 16 (April 28, 2025). https://doi.org/10.3389/fmicb.2025.1579797.
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The ability to detect probiotic consumption during a human clinical trial is crucial to verify and validate placebo and verum groups in post hoc analysis. While bacterial plating is still a common method for detecting and counting bacteria, when dealing with complex matrices like fecal samples, and given that most probiotics share genera or even species with commensal bacteria, plate counting is not a precise or accurate enough method. Species-specific quantitative real-time polymerase chain reaction (qRT-PCR) has been the most cited method in the literature and when properly validated and optimized remains the high watermark for detecting probiotics from fecal samples. Recent advancements in PCR technology have given rise to a parallel platform, droplet digital PCR (ddPCR). In this work we aimed to detect the components of a multi-strain probiotic product from a human clinical trial and compare both methods. This work dually demonstrates a process for determining multi-strain detection criteria as well as directly comparing the methods through the lens of sensitivity and specificity or the ability to properly discern true positives and true negatives. We described the optimization and validation of three assays for use in our detection panel and observed that, between qRT-PCR and ddPCR. The two methods were found to be quite congruent with ddPCR demonstrating a 10–100 fold lower limit of detection. Moreover, we discovered that most of the sensitivity and specificity had come from a single assay alone (Bifidobacterium animalis subsp. lactis Bl-04). This is despite all three assays performing well in optimization and validation. This suggests that more work needs to be done in the validation stage when developing novel probiotic detection assays. Taken together we can recommend ddPCR as a method for detecting probiotics from human clinical trials, but that qRT-PCR still performs well and comparably to ddPCR, when properly optimized and validated. However, when novel assays or those with unknown performance in a given biological matrix are needed, employing a strategy that combines multiple assays in a layered discrimination approach can help mitigate the potential underperformance of any single assay.