Gut microbiota: A key role for human milk oligosaccharides in regulating host health early in life.

Human milk oligosaccharides (HMOs) are an evolutionarily significant advantage bestowed by mothers for facilitating the development of the infant's gut microbiota. They can avoid absorption in the stomach and small intestine, reaching the colon successfully, where they engage in close interactions with gut microbes. This process also enables HMOs to exert additional prebiotic effects, including regulating the mucus layer, promoting physical growth and brain development, as well as preventing and mitigating conditions such as NEC, allergies, and diarrhea. Here, we comprehensively review the primary ways by which gut microbiota, including Bifidobacteria and other genera, utilize HMOs, and we classify them into five central pathways. Furthermore, we emphasize the metabolic benefits of bacteria consuming HMOs, particularly the recently identified intrinsic link between HMOs and the metabolic conversion of tryptophan to indole and its derivatives. We also examine the extensive probiotic roles of HMOs and their recent research advancements, specifically concentrating on the unsummarized role of HMOs in regulating the mucus layer, where their interaction with the gut microbiota becomes crucial. Additionally, we delve into the principal tools used for functional mining of new HMOs. In conclusion, our study presents a thorough analysis of the interaction mechanism between HMOs and gut microbiota, emphasizing the cooperative utilization of HMOs by gut microbiota, and provides an overview of the subsequent probiotic effects of this interaction. This review provides new insights into the interaction of HMOs with the gut microbiota, which will inform the mechanisms by which HMOs function.

B cell-related gene signature and cancer immunotherapy response.

BACKGROUND: B lymphocytes have multifaceted functions in the tumour microenvironment, and their prognostic role in human cancers is controversial. Here we aimed to identify tumour microenvironmental factors that influence the prognostic effects of B cells. METHODS: We conducted a gene expression analysis of 3585 patients for whom the clinical outcome information was available. We further investigated the clinical relevance for predicting immunotherapy response. RESULTS: We identified a novel B cell-related gene (BCR) signature consisting of nine cytokine signalling genes whose high expression could diminish the beneficial impact of B cells on patient prognosis. In triple-negative breast cancer, higher B cell abundance was associated with favourable survival only when the BCR signature was low (HR = 0.68, p = 0.0046). By contrast, B cell abundance had no impact on prognosis when the BCR signature was high (HR = 0.93, p = 0.80). This pattern was consistently observed across multiple cancer types including lung, colorectal, and melanoma. Further, the BCR signature predicted response to immune checkpoint blockade in metastatic melanoma and compared favourably with the established markers. CONCLUSIONS: The prognostic impact of tumour-infiltrating B cells depends on the status of cytokine signalling genes, which together could predict response to cancer immunotherapy.

Co-fermented cow milk protein by Lactobacillus helveticus KLDS 1.8701 and Lactobacillus plantarum KLDS 1.0386 attenuates its allergic immune response in Balb/c mice.

Milk protein is one of the major food allergens. As an effective processing method, fermentation may reduce the potential allergenicity of allergens. This study aimed to evaluate the therapeutic potential of co-fermented milk protein using Lactobacillus helveticus KLDS 1.8701 and Lactobacillus plantarum KLDS 1.0386 in cow milk protein allergy (CMPA) management. This study determined the secondary and tertiary structures of the fermented versus unfermented proteins by Fourier-transform infrared spectroscopy and surface hydrophobicity to evaluate its conformational changes. Our results showed that different fermentation methods have significantly altered the conformational structures of the cow milk protein, especially the tertiary structure. Further, the potential allergenicity of the fermented cow milk protein was assessed in Balb/c mice, and mice treated with the unfermented milk and phosphate-buffered saline were used as a control. We observed a significant reduction in allergenicity via the results of the spleen index, serum total IgE, specific IgE, histamine, and mouse mast cell protease 1 in the mice treated with the co-fermented milk protein. In addition, we analyzed the cytokines and transcription factors expression levels of spleen and jejunum and confirmed that co-fermentation could effectively reduce the sensitization of cow milk protein by regulating the imbalance of T helper (Th1/Th2 and Treg/Th17). This study suggested that changes of conformational structure could reduce the potential sensitization of cow milk protein; thus, fermentation may be a promising strategy for developing a method of hypoallergenic dairy products.

Infant formula supplemented with 1,3-olein-2-palmitin regulated the immunity, gut microbiota, and metabolites of mice colonized by feces from healthy infants.

Infant formula is currently an important food to cope with insufficient breastfeeding. Although 1,3-olein-2-palmitin (OPO) has been used in infant formula, its effects on the immune system, gut microbiota, and metabolites for infants remain unclear. This study constructed a mouse model of colonizing healthy infant feces using antibiotic treatment and fecal microbial transplantation. Thus, the gap between the infant formula supplemented with OPO and human milk in mouse serum biochemistry, immune system, intestinal microbiota, short-chain fatty acid production, and metabolites was evaluated. Our results showed that regarding IL-9, IL-10 levels, fecal secretory IgA, and endotoxin, formula supplemented with OPO and human milk types had comparable levels. Additionally, OPO slightly increased the content of short-chain fatty acids. The 16S rRNA gene sequence analysis and metabonomics analysis demonstrated that feeding different foods affects the gut microbiota of mice; in particular, supplementing formula feeding with OPO enriched the abundance of bifidobacteria. Furthermore, feeding different foods leads to unique intestinal content of metabolites, and the gut microbiota regulates the metabolites' differences. Our results reveal a brand new perspective of OPO regarding gut microbiota and metabolites.

Analysis of the complete genome sequence of Lactobacillus delbrueckii ssp. bulgaricus with post-acidification capacity and its influence on yogurt in storage.

In recent years, yogurt has been one of the most popular fermented dairy products and is sold worldwide. In this study, pH and titrated acid changes of 4 strains of Lactobacillus delbrueckii ssp. bulgaricus fermented milk during storage were detected. The difference between L. bulgaricus KLDS1.1011 and KLDS1.0207 was significant, with the latter exhibiting reduced acidity levels. Therefore, we determined the complete genome sequence of the 2 strains. Then the expression of specific genes and common genes related to glucose metabolism and proteolysis of L. bulgaricus KLDS1.1011 and KLDS1.0207 were detected by quantitative real-time reverse-transcription PCR. Analysis indicated that the key enzymes in glycometabolism and proteolysis of L. bulgaricus KLDS1.1011 were significantly different than those of L. bulgaricus KLDS1.0207. The contents of lactose and glucose decreased during storage of L. bulgaricus fermented milk, as determined by HPLC, and the contents of lactic acid and galactose increased, with L. bulgaricus KLDS1.1011 increasing less. With skim milk as a raw material, L. bulgaricus KLDS1.1011, KLDS1.0207, and Streptococcus thermophilus S1 were used as fermentation strains to yield yogurt at 42°C, and sensory evaluation was compared with yogurt fermented by commercial starter cultures. Yogurt from L. bulgaricus KLDS1.1011 was the highest-rated. Therefore, the study may provide guidelines for the development of yogurt starters.

Proteolytic activities of combined fermentation with Lactobacillus helveticus KLDS 1.8701 and Lactobacillus plantarum KLDS 1.0386 reduce antigenic response to cow milk proteins.

Cow milk protein is one of the leading food allergens. This study aimed to develop an effective method for reducing milk sensitization by evaluating antigenicity of fermented skim milk protein using Lactobacillus helveticus KLDS 1.8701, Lactobacillus plantarum KLDS 1.0386, and a combination of both strains. The proteolytic systems of strains in terms of genotype and phenotype are characterized by complete genome sequence, and evaluation the antigenicity of skim milk proteins was determined by ELISA and liquid chromatography with tandem mass spectrometry. Our results showed that the genomes encoded a variety of peptidase genes. For fermented skim milk, the degree of hydrolysis of the combined strains was higher than that of individual strain. Electrophoresis showed that the band color density of α-casein (α-CN) by fermentation of the combined strains was reduced when compared with control group. The fermentation process of the combined strains inhibited α-CN, ß-lactoglobulin, and α-lactalbumin antigenicity by 69.13, 36.10, and 20.92, respectively. Major allergic epitopes of α-CN and ß-lactoglobulin were cleaved by abundant proteases of combined strains. In all, this study showed that the fermentation process involving both L. helveticus and L. plantarum strains could reduce cow milk protein allergenicity through the combination of cell-envelope proteinase and peptidase on α-CN.

Prognostic value and molecular correlates of a CT image-based quantitative pleural contact index in early stage NSCLC.

PURPOSE: To evaluate the prognostic value and molecular basis of a CT-derived pleural contact index (PCI) in early stage non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: We retrospectively analysed seven NSCLC cohorts. A quantitative PCI was defined on CT as the length of tumour-pleura interface normalised by tumour diameter. We evaluated the prognostic value of PCI in a discovery cohort (n = 117) and tested in an external cohort (n = 88) of stage I NSCLC. Additionally, we identified the molecular correlates and built a gene expression-based surrogate of PCI using another cohort of 89 patients. To further evaluate the prognostic relevance, we used four datasets totalling 775 stage I patients with publically available gene expression data and linked survival information. RESULTS: At a cutoff of 0.8, PCI stratified patients for overall survival in both imaging cohorts (log-rank p = 0.0076, 0.0304). Extracellular matrix (ECM) remodelling was enriched among genes associated with PCI (p = 0.0003). The genomic surrogate of PCI remained an independent predictor of overall survival in the gene expression cohorts (hazard ratio: 1.46, p = 0.0007) adjusting for age, gender, and tumour stage. CONCLUSIONS: CT-derived pleural contact index is associated with ECM remodelling and may serve as a noninvasive prognostic marker in early stage NSCLC. KEY POINTS: • A quantitative pleural contact index (PCI) predicts survival in early stage NSCLC. • PCI is associated with extracellular matrix organisation and collagen catabolic process. • A multi-gene surrogate of PCI is an independent predictor of survival. • PCI can be used to noninvasively identify patients with poor prognosis.

Short communication: Genomic and phenotypic analyses of exopolysaccharides produced by Streptococcus thermophilus KLDS SM.

Streptococcus thermophilus plays important roles in the dairy industry. Streptococcus thermophilus KLDS SM could produce a high amount of exopolysaccharides (EPS). To understand the possible link between the genotype and the phenotype regarding EPS, the complete genome of S. thermophilus KLDS SM was sequenced and investigated in silico for genes related to carbohydrate fermentation, nucleotide sugars synthesis, and EPS gene cluster. We found that S. thermophilus KLDS SM is able to ferment sucrose, mannose, glucose, galactose, and lactose from the genomic research, which was confirmed by API 50 CH (bioMérieux, Marcy l'Etoile, France). The genetic analysis of nucleotide sugars and EPS cluster revealed that the EPS produced by this strain are composed of galactose and glucose, in accordance with the biochemical result. Furthermore, differences in the molecular mass of EPS from S. thermophilus KLDS SM cultivated under different carbon sources were correlated with the transcription levels of the genes encoding chain length determination protein and glycosyltransferase. Our findings provide a better understanding of the link between the genetic elements and the chemical conformation of EPS and a theoretical basis for producing tailor-made EPS through genetic and metabolic engineering approaches.

Technological and Genomic Analysis of Roles of the Cell-Envelope Protease PrtS in Yoghurt Starter Development.

The cell-envelope protease PrtS was proved to be efficient in optimal bacterial growth and fast acidification in pure culture, while its positive effect on the performance of mixed-cultures in milk fermentation was not defined. The aim was to analyze effects of the PrtS on the symbiosis between strains during yoghurt production and cold storage. Two Streptococcus thermophilus strains, KLDS3.1012 and KLDS SM, and two different proteolytic strains of Lactobacillus delbrueckii subsp. Bulgaricus, L7 and L12, were used. Technological properties (viability, acid production, and proteolysis) were determined. Comparative genomics was used to analyze the proteolytic system (cell-envelope protease, transport system, intracellular peptidase) of Streptococcus thermophilus strains. S. thermophilus KLDS SM possesses an intact gene encoding PrtS (A9497_00420), which was not found in the genome of S. thermophilus KLDS3.1012. This gene is the main difference in the proteolytic system between the two genomes. PrtS endowed KLDS SM high levels of viability during fermentation and cold storage. When combined with a weaker lactobacillus strain during fermentation, the acceleration of acid production of mixed-culture by KLDS SM would start at an earlier time. KLDS SM increased the post-acidification of yoghurts during cold storage, but the pH was steadily maintained during 14-28 days. Results suggest that strains of Streptococcus thermophilus with strong proteolytic ability could be used in a wide range of dairy production. The present study provided data for yoghurt starter development from the point of view of proteolysis.

Heterogeneous Enhancement Patterns of Tumor-adjacent Parenchyma at MR Imaging Are Associated with Dysregulated Signaling Pathways and Poor Survival in Breast Cancer.

Purpose To identify the molecular basis of quantitative imaging characteristics of tumor-adjacent parenchyma at dynamic contrast material-enhanced magnetic resonance (MR) imaging and to evaluate their prognostic value in breast cancer. Materials and Methods In this institutional review board-approved, HIPAA-compliant study, 10 quantitative imaging features depicting tumor-adjacent parenchymal enhancement patterns were extracted and screened for prognostic features in a discovery cohort of 60 patients. By using data from The Cancer Genome Atlas (TCGA), a radiogenomic map for the tumor-adjacent parenchymal tissue was created and molecular pathways associated with prognostic parenchymal imaging features were identified. Furthermore, a multigene signature of the parenchymal imaging feature was built in a training cohort (n = 126), and its prognostic relevance was evaluated in two independent cohorts (n = 879 and 159). Results One image feature measuring heterogeneity (ie, information measure of correlation) was significantly associated with prognosis (false-discovery rate < 0.1), and at a cutoff of 0.57 stratified patients into two groups with different recurrence-free survival rates (log-rank P = .024). The tumor necrosis factor signaling pathway was identified as the top enriched pathway (hypergeometric P < .0001) among genes associated with the image feature. A 73-gene signature based on the tumor profiles in TCGA achieved good association with the tumor-adjacent parenchymal image feature (R2 = 0.873), which stratified patients into groups regarding recurrence-free survival (log-rank P = .029) and overall survival (log-rank P = .042) in an independent TCGA cohort. The prognostic value was confirmed in another independent cohort (Gene Expression Omnibus GSE 1456), with log-rank P = .00058 for recurrence-free survival and log-rank P = .0026 for overall survival. Conclusion Heterogeneous enhancement patterns of tumor-adjacent parenchyma at MR imaging are associated with the tumor necrosis signaling pathway and poor survival in breast cancer. © RSNA, 2017 Online supplemental material is available for this article.

[Detection of CRSPR-Cas system in Streptococcus thermophiles].

Objective: We aimed to detect the CRSPR-Cas system of six Streptococcus thermophilus. Methods: Bioinformatics method was used to predict CRSPR-Cas system of nine S. thermophilus that published in National Center for Biotechnology Information. Four primers were designed according to the flanking sequences of standard strains and the CRISPR-Cas system of six S. thermophilus have been detected by PCR method. Results: S. thermophilus S4 had a Cas9 gene, others all had Cas9 gene, Cas10 gene and Cas9* gene. In addition, 79 and KLDS3.0207 still had Cas3 gene. Conclusion: Signature genes amplification of CRSPR-Cas system could predict the type of CRSPR-Cas system in unsequenced strains, these findings will help establish the foundation for the study of CRSPR-Cas system in lactic acid bacteria.

Complete genome sequence of Lactococcus lactis subsp. lactis KLDS4. 0325, a bacterium newly isolated from Koumiss in Xinjiang, China.

OBJECTIVE: Aim to study the physiology and functionally important genes of Lactobacillus lactis KLDS4. 0325. METHODS: We sequenced the complete genome of L. lactis KLDS4. 0325, drew the genomic map, and performed functional annotation and analysis in metabolism and probiotic. RESULTS: L. lactis KLDS4. 0325 contains a chromosome of 2589261 bp, GC content is 35.4%, with 2662 predicted ORFs, of which 1310 are functionally classified. L. lactis KLDS4. 0325 can carry out hydrolysis of extracellular proteins effectively, has the potential to degrade bitter peptides and produce a series of peptides of inhibiting angiotensin converting enzyme. L. lactis KLDS4. 0325 has complete enzyme system for transamination pathway, which can catalyze relevant amino acids to flavor compounds. More key enzyme-coding genes involved in transport and metabolizing of sugars, and L-lactic acid synthesis, are exist in L. lactis KLDS4. 0325 genome. L. lactis KLDS4. 0325 has a set of more complete encoding genes in the biosynthetic pathways of folate and riboflavin. In addition, gene cluster for Lactococcin and 2 cold stress protein (cspD and cspE) were identified. CONCLUSION: The presence of these genes encoding desirable traits provides the theoretical basis for the strain in industrial fermentation, and relevant further research.

Double-layer microcapsules based on shellac for enhancing probiotic survival during freeze drying, storage, and simulated gastrointestinal digestion.

Probiotics are susceptible to diverse conditions during processing, storage, and digestion. Here, shellac (SC), sodium alginate (SA), coconut oil (CO), soybean oil (SO), and trehalose (AL) were used to prepare microcapsules aiming to improve the survival of Lactiplantibacillus plantarum KLDS1.0318 during freeze-drying, storage process, and gastrointestinal digestion. The results showed that for SA/AL/SC/CO and SA/AL/SC/SO, the survival loss decreased by 51.2 % and 51.0 % after a freeze-drying process compared with microcapsules embedded by SA; the viable bacteria count loss decreased by 4.36 and 4.24 log CFU/mL compared with free cell (CON) during storage for 28 d under 33%RH at 25 °C, respectively; while for simulating digestion in vitro, the survival loss decreased by 3.05 and 2.70 log CFU/mL, 0.63 and 0.55 log CFU/mL after digestion at simulated gastric fluid for 120 min and small intestine fluid for 180 min, respectively (P < 0.05). After microcapsules were added to fermented dairy stored at 4 °C for 21 d, the viable bacteria count of SA/AL/SC/CO and SA/AL/SC/SO significantly increased by 2.10 and 1.70 log CFU/mL compared with CON, respectively (P < 0.05). In conclusion, the current study indicated that shellac-based probiotic microcapsules have superior potential to protect and deliver probiotics in food systems.

Effect of Lactobacillus helveticus exopolysaccharides molecular weight on yogurt gel properties and its internal mechanism.

The processing characteristics of yogurt are closely related to the composition and arrangement of exopolysaccharides (EPS) in lactic acid bacteria (LAB). To fully understand and develop the functional properties of EPS and to study the effect of EPS molecular weight on yogurt and its mechanism, the physicochemical properties of high molecular weight EPS-LH43, medium molecular weight EPS-LH13, and low molecular weight EPS-LH23, as well as the gel properties and protein conformation of yogurt, were determined and analyzed in this experiment. The results indicate that EPS-LH43 and EPS-LH13 are both composed of mannose, rhamnose, galacturonic acid, glucose, and galactose. EPS-LH23 is composed of mannose, galacturonic acid, glucose, and galactose. Their Number-average Molecular Weight is 5.21 × 106 Da, 2.39 × 106 Da and 3.76 × 105 Da, respectively. In addition, all three types of EPS have good thermal stability and can improve the stability of casein. In addition, the analysis of the texture, particle size, potential, water holding capacity, rheology, low field nuclear magnetic resonance, microstructure, and flavor characteristics of yogurt confirmed the relationship between the molecular weight of LAB EPS and the gel properties of yogurt. Fluorescence spectrophotometer and circular dichroism analysis indicate that the different molecular weights of LAB EPS have different effects on protein structure, which is an intrinsic factor leading to significant differences in the gel properties of the three types of fermented milk. These findings provide new references for enhancing the understanding of the structure-activity relationship of EPS and indicate that EPS-LH43 can be used to improve the gel properties of dairy products.

Exopolysaccharides of lactic acid bacteria: Structure, biological activity, structure-activity relationship, and application in the food industry: A review.

Over the past few decades, researchers have discovered that probiotics play an important role in our daily lives. With the further deepening of research, more and more evidence show that bacterial metabolites have an important role in food and human health, which opens up a new direction for the research of lactic acid bacteria (LAB) in the food and pharmaceutical industry. Many LAB have been widely studied because of the ability of exopolysaccharides (EPS). Lactic acid bacteria exopolysaccharides (LAB EPS) not only have great potential in the treatment of human diseases but also can become natural ingredients in the food industry to provide special qualitative structure and flavor. This paper has organized and summarized the biosynthesis, strain selection, production process parameters, structure, and biological activity of LAB EPS, filling in the monotony and incompleteness of previous articles' descriptions of LAB EPS. Therefore, this paper focuses on the general biosynthetic pathway, structural characterization, structure-activity relationship, biological activity of LAB EPS, and their application in the food industry, which will help to deepen people's understanding of LAB EPS and develop new active drugs from LAB EPS. Although the research results are relatively affluent, the low yield, complex structure, and few clinical trials of EPS are still the reasons that hinder its development. Therefore, future knowledge expansion should focus on the regulation of structure, physicochemical properties, function, higher production of EPS, and clinical trial applications, which can further increase the commercial significance and value of EPS. Furthermore, better understanding the structure-function relationship of EPS in food remains a challenge to date.

Milk-derived Lactobacillus with high production of short-chain fatty acids relieves antibiotic-induced diarrhea in mice.

Antibiotic-associated diarrhea (AAD) is a common side effect during antibiotic treatment, and this has warranted research into alternative protocols. In this study, we investigated the potential therapeutic effects of three cohorts, Lactobacillus plantarum KLDS 1.0386, Lactobacillus acidophilus KLDS 1.0901 and a mixed strain of both, on intestinal inflammation, the intestinal mucosal barrier, and microbial community in mice with ampicillin-induced diarrhea. The results showed that Lactobacillus inhibited the activation of the TLR4/NF-κB signaling pathway, decreased the expression of pro-inflammatory cytokines, increased the expression of anti-inflammatory cytokines in the murine intestine, and alleviated the intestinal barrier damage and inflammation induced by ampicillin. In addition, Lactobacillus ameliorates intestinal epithelial barrier damage by increasing the expression of tight junction proteins and aquaporins. After Lactobacillus treatment, the diversity of gut microbiota increased significantly, and the composition and function of gut microbiota gradually recovered. In the gut microbiota, Bacteroidetes and Escherichia Shigella related to the synthesis of short-chain fatty acids (SCFAs) were significantly affected by ampicillin, while Lactobacillus regulates the cascade of the microbial-SCFA signaling pathway, which greatly promoted the generation of SCFAs. Collectively, Lactobacillus showed better results in treating AAD, especially in mixed strains.

Effect of exopolysaccharides yield and addition concentration of Lactobacillus helveticus on the processing characteristics of fermented milk and its mechanism.

Exopolysaccharides (EPS) yield and added concentration of lactic acid bacteria can greatly affect the processing characteristics of fermented milk. In order to investigate the effects and mechanisms of EPS yield and added concentration on fermented milk, researchers extracted EPS from 50 strains of Lactobacillus helvedicus (L. helvedicus) and selected the two strains with the largest difference in EPS yield (L. helvedicus LH18 and L. helvetigus LH33) for subsequent experiments. The physicochemical properties of EPS-LH18 and EPS-LH33 were analyzed. The gel characteristics and protein conformation of fermented milk were studied by means of texture analyzer, rheometer, scanning electron microscopy, nuclear magnetic resonance machine, fluorescence spectrophotometer and circular dichroism. The results indicate that the monosaccharide compositions of EPS-LH18 and EPS-LH33 are the same and have good thermal stability. The texture and rheological properties of L. helveticus LH18 fermented milk are significantly superior to other fermented milk. The reason is that L. helveticus LH18 EPS has the highest yield, which leads to a denser gel structure, lower surface hydrophobicity and free sulfhydryl content of its fermented milk. According to circular dichroism analysis, ß- sheet and random coil are the internal factors leading to the difference in fermented milk gel. In addition, the fermented milk improved even more favorably as the concentration of the two EPS additions increased. As described above, L. helveticus LH18 has the potential to be an excellent yogurt starter, and both of the above EPS can be used as probiotic stabilizer alternatives for fermented dairy products.

Enhancing immune regulation in vitro: the synergistic impact of 3'-sialyllactose and osteopontin in a nutrient blend following influenza virus infection.

Natural components of breast milk, human milk oligosaccharides (HMOs) and osteopontin (OPN) have been shown to have a variety of functional activities and are widely used in infant formulas. However, the preventive and therapeutic effects of both on influenza viruses are not known. In this study, antiviral assays using a human laryngeal carcinoma cell line (HEP-2) showed that 3'-sialyllactose (3'-SL) and OPN had the best antiviral ability with IC50 values of 33.46 µM and 1.65 µM, respectively. 3'-SL (10 µM) and OPN (4 µM) were used in combination to achieve 75% inhibition. Further studies found that the combination of 200 µg/mL of 3'-SL with 500 µg/mL of OPN exerted the best antiviral ability. The reason for this was related to reduced levels of the cytokines TNF-α, IL-6, and iNOS in relation to mRNA expression. Plaque assay and TCID50 assay found the same results and verified synergistic effects. Our research indicates that a combination of 3'-SL and OPN can effectively reduce inflammatory storms and exhibit anti-influenza virus effects through synergistic action.

Lactobacillus delbrueckii subsp. bulgaricus 1.0207 Exopolysaccharides Attenuate Hydrogen Peroxide-Induced Oxidative Stress Damage in IPEC-J2 Cells through the Keap1/Nrf2 Pathway.

Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) is one of the most commonly employed Lactobacillus in the food industry. Exopolysaccharides (EPS) of Lactobacillus, which are known to exhibit probiotic properties, are secondary metabolites produced during the growth of Lactobacillus. This study identified the structure of the EPS produced by L. bulgaricus 1.0207 and investigated the mitigation of L. bulgaricus 1.0207 EPS on H2O2-induced oxidative stress in IPEC-J2 cells. L. bulgaricus 1.0207 EPS consisted of glucose and galactose and possessed a molecular weight of 4.06 × 104 Da. L. bulgaricus 1.0207 EPS exhibited notable scavenging capacity against DPPH, hydroxyl radicals, superoxide anions, and ABTS radicals. Additionally, L. bulgaricus 1.0207 EPS enhanced cell proliferation, reduced intracellular reactive oxygen species (ROS) accumulation, increased activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC) elevated the relative expression of CAT, SOD, HO-1, NQO1, ZO-1, and Occludin genes. Moreover, L. bulgaricus 1.0207 EPS improved the expression of Nrf2, pNrf2, pNrf2/Nrf2, and Bcl-2 proteins, while decreasing the expression of Keap1, Caspase3, and Bax proteins, with the best effect at a concentration of 100 µg/mL. L. bulgaricus 1.0207 EPS mitigated H2O2-induced oxidative stress injury in IPEC-J2 cells by activating the Keap1/Nrf2 pathway. Meanwhile, L. bulgaricus 1.0207 EPS exhibited the potential to decrease apoptosis and restore the integrity of the gut barrier. The findings establish a theoretical foundation for the development and application of L.bulgaricus 1.0207 and its EPS.

Potential Probiotic Weizmannia coagulans WC10 Improved Antibiotic-Associated Diarrhea in Mice by Regulating the Gut Microbiota and Metabolic Homeostasis.

Antibiotic-associated diarrhea (AAD) is a common side effect of long-term and heavy antibiotic therapy. Weizmannia coagulans (W. coagulans) is an ideal probiotic because of its high viability, stability, and numerous health benefits to the host. In this study, the strains were first screened for W. coagulans WC10 (WC10) with a high combined ability based on their biological properties of gastrointestinal tolerance, adhesion, and short-chain fatty acid production ability. The effect of WC10 on mice with AAD was further evaluated. The results showed that WC10 was effective in improving the symptoms of AAD, effectively restoring antibiotic-induced weight loss, and reducing diarrhea status score and fecal water content. In addition, WC10 decreased the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines, alleviated intestinal tissue damage and inflammation, and improved intestinal epithelial barrier function by decreasing serum levels of enterotoxin, DAO, and D-lactic acid, and by increasing the expression of the intestinal mucosal immune factors sIgA and occludin. Importantly, the composition and function of the gut microbiota gradually recovered after WC10 treatment, increasing the number of SCFAs-producing Bifidobacterium and Roseburia. Subsequently, the short-chain fatty acid (SCFA) content was examined and WC10 significantly increased acetate, propionate, and butyrate production. Additionally, metabolomic analysis also showed that WC10 reversed the antibiotic interference with major metabolic pathways. These findings provide a solid scientific basis for the future application of W. coagulans WC10 in the treatment of AAD.