Effects of Lactiplantibacillus plantarum CCFM1214 and Ligilactobacillus salivarius CCFM1215 on halitosis: a double-blind, randomized controlled trial.

The purpose of this study was to evaluate the effects of known probiotic species Lactiplantibacillus plantarum CCFM1214 and Ligilactobacillus salivarius CCFM1215 on halitosis, the oral status, and the oral microbiome. In a double-blind, randomized controlled trial that lasted for five weeks, 43 participants were divided into an oral probiotics group and a control group and given probiotics or control powder for the first four weeks, with the fifth week being the discontinuation period. 33 participants (probiotics group = 21, control group = 12) completed the entire experiment in the end. Oral samples were taken as part of oral health examinations during the baseline period (day 0) and four weeks after (day 28). The nucleotide sequence of the V3-V4 region of 16S rRNA was determined to examine the impact of intervention and time on the oral microbiome. The effects of L. plantarum CCFM1214 and L. salivarius CCFM1215 on the number of Fusobacterium nucleatum in gingival crevicular fluid (GCF) samples of participants were detected by quantitative PCR. After the intervention, L. plantarum CCFM1214 and L. salivarius CCFM1215 significantly reduced the levels of volatile sulfur compounds (VSCs) and the quantity of F. nucleatum in GCF samples, where the average DNA copy number per ng (log) of F. nucleatum decreased from 7.12 ± 0.04 to 6.01 ± 0.09. The ß diversity of the probiotics group, on the whole, tended to be more concentrated and stable after the intervention. In addition, after probiotic intervention, the abundance of Lactobacillus and Bifidobacterium increased, while the abundance of Fusobacterium, Acinetobacter, Porphyromonas, and Aggregatibacter decreased significantly. In general, L. plantarum CCFM1214 and L. salivarius CCFM1215 can alleviate halitosis and considerably lower the value of VSCs and improve the oral microbiota in participants with halitosis.

Imaging Mass Spectrometry and Genome Mining Reveal Antimicrobial Peptides of Novel Pediococcus acidilactici CCFM18.

The mechanism of metabolites produced by lactic acid bacteria in mediating microbial interactions has been difficult to ascertain. This study comparatively evaluated the antimicrobial effect of the novel bacterium Pediococcus acidilactici CCFM18 and explored the global chemical view of its interactions with indicator bacteria. P. acidilactici CCFM18 had sufficiently strong antimicrobial activity to effectively inhibit the growth of the indicator bacteria and enhance their intracellular reactive oxygen species (ROS) level. The emerging technique of matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) imaging mass spectrometry indicated that P. acidilactici CCFM18 increased the production of pediocin PA-1 and the penocin A profile during its interaction with the indicator bacteria, thus differing from P. acidilactici CCFM28 (a commonly used laboratory strain). Strikingly, the production of coagulin A was triggered only by signaling molecules made by the competing strain L. thermophilus, suggesting an idiosyncratic response from P. acidilactici CCFM18. Bioinformatic mining of the P. acidilactici CCFM18 draft genome sequence revealed gene loci that code for the complex secondary metabolites analyzed via MSI. Taken together, these results illustrate that chemical interactions between P. acidilactici CCFM18 and indicator bacteria exhibit high complexity and specificity and can drive P. acidilactici CCFM18 to produce different secondary metabolites.

Tracking Childhood Lead Exposure in Early Industrial Romanians.

Childhood lead exposure has been linked to severe adverse health outcomes throughout life. Measurements of lead in teeth have established that individuals living in contaminated environments show higher levels compared to individuals living further away, although less is known about when individuals are most susceptible to these exposures. We examined lead (Pb208) concentrations (ppm) in teeth over the first 2.5 years of life in 16 children born in the late 19th to early 20th century throughout Romania. This period of intense industrialization was characterized by increases in mining, coal burning, and oil refining-activities that contaminate air, water, and food with Pb. We hypothesized the distance from an operational mine or oil refinery, or being born in a city, would be positively associated with cumulative dentine Pb exposure (CDPE). We also predicted that Pb exposures would peak in the first six months of life when gastrointestinal (GI) absorption of Pb is likely highest. Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) of sectioned tooth dentine followed by Bayesian statistical analyses revealed that living 30 km or more from a mine or oil refinery did not explain CDPE. However, being born in a city explained 42% of CDPE. All individuals showed maximum Pb exposures after six months of age, likely due to contaminated solid food and/or non-milk liquids. This research demonstrates how tooth formation can be coupled with comprehensive elemental mapping to analyse the context and timing of early-life neurotoxicant exposures, which may be extended to well-preserved teeth from clinical and historic populations.

The therapeutic effect of levosimendan in patients with prolonged ventilator weaning and cardiac dysfunction.

OBJECTIVE: To explore the therapeutic effect of levosimendan in patients with prolonged ventilator weaning and cardiac dysfunction. METHOD: Patients with prolonged ventilator weaning and cardiac dysfunction were randomly allocated to receive conventional treatment (control group) or intravenous infusion of levosimendan for 24 h based on conventional treatment (levosimendan group). Weaning success rates were then compared between the two groups. The study was retrospectively registered with Research Registry (ID No. researchregistry10304). RESULTS: A total of 40 patients were included (20 per group). Within 3 days after initiation of treatment, significantly more cases were successfully weaned in the levosimendan group versus control group (eight versus four cases, respectively). Among the eight patients who underwent pulse indicator continuous cardiac output monitoring in the levosimendan group, the global ejection fraction increased 24 h after treatment, and the cardiac function index and cardiac index increased 72 h after treatment. CONCLUSION: For patients requiring prolonged mechanical ventilation who have concomitant cardiac dysfunction, levosimendan may be considered to increase the probability of weaning success.

Bifidobacterium longum subsp. infantis regulates Th1/Th2 balance through the JAK-STAT pathway in growing mice.

Objectives: Bifidobacterium longum subsp. infantis is a dominant bacterium in infant gut, which plays a critical role in maintaining the health and development of infants. This study investigated the abilities of eight different strains of B. longum subsp. infantis to regulate the T helper (Th)1/Th2 balance. Methods: Eight B. longum subsp. infantis strains, including I2MI (FJSWXI2MIM1), I4MI [FJSWXI4MI (CCFM1270)], I4MNI (FJSWXI4MNIM1), I5TI (FJSWXI5TIM1), I6TI (FJSWXI6TIM1), I8TI [FJSWXI8TI (CCFM1271)], I10TI [FJSWXI10TI (CCFM1272)], and B6MNI [BJSWXB6MNIM1 (CCFM1269)], were gavaged to BALB/C pups in both female (n = 8) and male (n = 8) mice starting from 1 to 3 weeks old (1 × 109 CFU/day/mice). Selected immune cells were assessed by immunofluorescence and flow cytometry. Cytokines and immunoglobulins were determined by ELISA. Bacterial and bifidobacterial communities were determined by 16S rRNA gene sequencing and bifidobacterial groEL sequencing. Results: B. longum subsp. infantis I4MI and I8TI were shown to increase the ration of colonic IgG2a/IgE in male mice (P < 0.05). B6MNI was demonstrated to significantly increase the levels of colonic IFN-γ and IgG2a, as well as the ratio of IgG2a/IgE in female mice (P < 0.05). It was also shown to significantly increase the ratio of colonic IgG2a/IgE (P < 0.05) and reduce the level of colonic IL-4 in male mice (P < 0.05). Furthermore, B6MNI was demonstrated to regulate colonic JAK/STAT pathway in both male and female mice. I4MI, I5TI, and B6MNI were shown to increase the relative abundance of Bifidobacterium and B. longum subsp. infantis in both male and female mice, whereas I8TI was only shown to increase the relative abundance of Bifidobacterium and B. longum subsp. infantis in male mice (P < 0.05). Conclusion: These results indicated supplementation with B. longum subsp. infantis in early infancy may regulate the Th1/Th2 immune balance, which may prevent the development of related diseases.

Metabolomic analysis reveals Ligilactobacillus salivarius CCFM 1266 fermentation improves dairy product quality.

Previous studies have demonstrated that Ligilactobacillus salivarius CCFM 1266 exhibits anti-inflammatory properties and the capability to synthesize niacin. This study aimed to investigate the fermentative abilities of L. salivarius CCFM 1266 in fermented milk. Metabonomic analysis revealed that fermentation by L. salivarius CCFM 1266 altered volatile flavor compounds and metabolite profiles, including heptanal, nonanal, and increased niacin production. Genomic investigations confirmed that L. salivarius CCFM 1266 possess essential genes for the metabolism of fructose and mannose, affirming its proficiency in utilizing fructooligosaccharides and mannan oligosaccharides. The addition of fructooligosaccharides and mannan oligosaccharides during the fermentation process significantly facilitated the proliferation of L. salivarius CCFM 1266 in fermented milk, with growth exceeding 107 colony-forming units (CFU)/mL. This intervention not only augmented the microbial density but also modified the metabolite composition of fermented milk, resulting in an elevated presence of advantageous flavor compounds such as nonanal, 2,3-pentanedione, and 3-methyl-2-butanone. However, its influence on improving the texture of fermented milk was observed to be minimal. Co-fermentation of L. salivarius CCFM 1266 with commercial fermentation starters indicated that L. salivarius CCFM 1266 was compatible, similarly altering metabolite composition and increasing niacin content in fermented milk. In summary, the findings suggest that L. salivarius CCFM 1266 holds substantial promise as an adjunctive fermentation starter, capable of enhancing the nutritional diversity of fermented milk products.

O-glycosylation in viruses: A sweet tango.

O-glycosylation is an ancient yet underappreciated protein posttranslational modification, on which many bacteria and viruses heavily rely to perform critical biological functions involved in numerous infectious diseases or even cancer. But due to the innate complexity of O-glycosylation, research techniques have been limited to study its exact role in viral attachment and entry, assembly and exit, spreading in the host cells, and the innate and adaptive immunity of the host. Recently, the advent of many newly developed methodologies (e.g., mass spectrometry, chemical biology tools, and molecular dynamics simulations) has renewed and rekindled the interest in viral-related O-glycosylation in both viral proteins and host cells, which is further fueled by the COVID-19 pandemic. In this review, we summarize recent advances in viral-related O-glycosylation, with a particular emphasis on the mucin-type O-linked α-N-acetylgalactosamine (O-GalNAc) on viral proteins and the intracellular O-linked ß-N-acetylglucosamine (O-GlcNAc) modifications on host proteins. We hope to provide valuable insights into the development of antiviral reagents or vaccines for better prevention or treatment of infectious diseases.

Cross-feeding of bifidobacteria promotes intestinal homeostasis: a lifelong perspective on the host health.

Throughout the life span of a host, bifidobacteria have shown superior colonization and glycan abilities. Complex glycans, such as human milk oligosaccharides and plant glycans, that reach the colon are directly internalized by the transport system of bifidobacteria, cleaved into simple structures by extracellular glycosyl hydrolase, and transported to cells for fermentation. The glycan utilization of bifidobacteria introduces cross-feeding activities between bifidobacterial strains and other microbiota, which are influenced by host nutrition and regulate gut homeostasis. This review discusses bifidobacterial glycan utilization strategies, focusing on the cross-feeding involved in bifidobacteria and its potential health benefits. Furthermore, the impact of cross-feeding on the gut trophic niche of bifidobacteria and host health is also highlighted. This review provides novel insights into the interactions between microbe-microbe and host-microbe.

Comparison of the hepatoprotection of intragastric and intravenous cyanidin-3-glucoside administration: focus on the key metabolites and gut microbiota modulation.

Liver injury is a life-threatening condition, and the hepatoprotective potential of cyanidin-3-glucoside (C3G) has been previously demonstrated. However, due to the low bioavailability, it has been doubtful that relatively low concentrations of intact C3G in vivo could account for these bioactivities. In this study, the hepatoprotective effects of intragastric and intravenous administration of C3G were investigated in a CCl4 induced liver injury model. Intragastric C3G administration was more effective than intravenous C3G injection in reducing serum damage biomarkers, oxidative stress, and inflammatory responses, indicating that absorption of C3G into the bloodstream does not fully account for its observed benefits in vivo. Furthermore, intragastric C3G administration modulated the gut microbiota structure and increased the contents of five metabolites in the feces and serum with high inter-individual variation, indicating the key role of the interaction between C3G and the gut microbiota. At equivalent doses, the metabolites cyanidin and protocatechuic acid exhibited greater efficacy than C3G in reducing apoptosis and ROS production by activating the Nrf2 pathway in an AAPH-induced oxidative stress model. To achieve the desired health effects via C3G-rich food intake, more attention should be paid to microbially derived catabolites. Screening of specific metabolite-producing strains will help overcome individual differences and enhance the health-promoting effects of C3G.

Gut microbiota: a superior operator for dietary phytochemicals to improve atherosclerosis.

Mounting evidence implicates the gut microbiota as a possible key susceptibility factor for atherosclerosis (AS). The employment of dietary phytochemicals that strive to target the gut microbiota has gained scientific support for treating AS. This study conducted a general overview of the links between the gut microbiota and AS, and summarized available evidence that dietary phytochemicals improve AS via manipulating gut microbiota. Then, the microbial metabolism of several dietary phytochemicals was summarized, along with a discussion on the metabolites formed and the biotransformation pathways involving key gut bacteria and enzymes. This study additionally focused on the anti-atherosclerotic potential of representative metabolites from dietary phytochemicals, and investigated their underlying molecular mechanisms. In summary, microbiota-dependent dietary phytochemical therapy is a promising strategy for AS management, and knowledge of "phytochemical-microbiota-biotransformation" may be a breakthrough in the search for novel anti-atherogenic agents.

Lactobacillus delbrueckii subsp. bulgaricus Alleviates Acute Injury in Hypoxic Mice.

Acute mountain sickness (AMS) is a common ailment in high-altitude areas caused by the body's inadequate adaptation to low-pressure, low-oxygen environments, leading to organ edema, oxidative stress, and impaired intestinal barrier function. The gastrointestinal tract, being the first to be affected by ischemia and hypoxia, is highly susceptible to injury. This study investigates the role of Lactobacillus delbrueckii subsp. bulgaricus in alleviating acute hypoxic-induced intestinal and tissue damage from the perspective of daily consumed lactic acid bacteria. An acute hypoxia mouse model was established to evaluate tissue injury, oxidative stress, inflammatory responses, and intestinal barrier function in various groups of mice. The results indicate that strain 4L3 significantly mitigated brain and lung edema caused by hypoxia, improved colonic tissue damage, and effectively increased the content of tight junction proteins in the ileum, reducing ileal permeability and alleviating mechanical barrier damage in the intestines due to acute hypoxia. Additionally, 4L3 helped to rebalance the intestinal microbiota. In summary, this study found that Lactobacillus delbrueckii subsp. bulgaricus strain 4L3 could alleviate acute intestinal damage caused by hypoxia, thereby reducing hypoxic stress. This suggests that probiotic lactic acid bacteria that exert beneficial effects in the intestines may alleviate acute injury under hypoxic conditions in mice, offering new insights for the prevention and treatment of AMS.

Gut microbial genomes with paired isolates from China illustrate probiotic and cardiometabolic effects.

The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we present the Chinese Gut Microbial Reference (CGMR) set, comprising 101,060 high-quality metagenomic assembled genomes (MAGs) of 3,707 nonredundant species from 3,234 fecal samples across primarily rural Chinese locations, 1,376 live isolates mainly from lactic acid bacteria, and 987 novel species relative to worldwide databases. We observed region-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. Preliminary mouse experiments suggest a probiotic effect of two Faecalibacillus intestinalis isolates in alleviating constipation, cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and isolates from the genera Parabacteroides and Lactobacillus in host lipid metabolism. Our study expands the current microbial genomes with paired isolates and demonstrates potential host effects, contributing to the mechanistic understanding of host-microbe interactions.

Isolation and Characterisation of Streptococcus spp. with Human Milk Oligosaccharides Utilization Capacity from Human Milk.

Human milk oligosaccharides (HMO) that promote the growth of beneficial gut microbes in infants are abundant in human milk. Streptococcus, one of the dominant genera in human milk microbiota, is also highly prevalent in the infant gut microbiota, possibly due to its adeptness at utilizing HMOs. While previous studies have mainly focused on HMO interactions with gut bacteria like Bifidobacterium and Bacteroides spp., the interaction with Streptococcus spp. has not been fully explored. In this study, Streptococcus spp. was isolated from human milk and identified to exhibit extensive capabilities in utilizing HMOs. Their consumption rates of 2'-fucosyllactose (2'-FL), 6'-sialyllactose (6'-SL), and lacto-N-tetraose (LNT) closely matched those of Bifidobacterium longum subsp. infantis ATCC 15697. Furthermore, we assessed the safety-related genes in the genomes of the Streptococcus species capable of utilizing HMOs, revealing potential virulence and resistance genes. In addition, no haemolytic activity was observed. These findings expand the knowledge of metabolic interactions and networks within the microbiota of human milk and the early life human gut.

Gut Microbiota-Derived Tryptophan Metabolites Alleviate Allergic Asthma Inflammation in Ovalbumin-Induced Mice.

Asthma is a prevalent respiratory disease. The present study is designed to determine whether gut microbiota-derived tryptophan metabolites alleviate allergic asthma inflammation in ovalbumin (OVA)-induced mice and explore the effect and potential mechanism therein. Asthma model mice were constructed by OVA treatment, and kynurenine (KYN), indole-3-lactic acid (ILA), in-dole-3-carbaldehyde (I3C), and indole acetic acid (IAA) were administered by intraperitoneal injection. The percent survival, weight and asthma symptom score of mice were recorded. The total immunoglobulin E and OVA-specific (s)IgE in the serum and the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) were detected by the corresponding ELISA kits. The composition of the gut microbiota and tryptophan-targeted metabolism in mouse feces were analyzed using 16S rRNA gene sequencing and targeted metabolomics, respectively. The four tryptophan metabolites improved the percent survival, weight and asthma symptoms of mice, and reduced the inflammatory cells in lung tissues, especially I3C. I3C and IAA significantly (p < 0.05) downregulated the levels of OVA-IgE and inflammatory cytokines. KYN was observed to help restore gut microbiota diversity. Additionally, I3C, KYN, and ILA increased the relative abundance of Anaeroplasma, Akkermansia, and Ruminococcus_1, respectively, which were connected with tryptophan metabolic pathways. IAA also enhanced capability of tryptophan metabolism by the gut microbiota, restoring tryptophan metabolism and increasing production of other tryptophan metabolites. These findings suggest that tryptophan metabolites may modulate asthma through the gut microbiota, offering potential benefits for clinical asthma management.

Biotransformation of Cacumen platycladi Extract by Lactiplantibacillus plantarum CCFM1348 Promotes Hair Growth in Mice.

Cacumen platycladi (CP) is a frequently used traditional Chinese medicine to treat hair loss. In this study, CP fermented by Lactiplantibacillus plantarum CCFM1348 increased the proliferation of human dermal papilla cells. In an in vivo assay, compared to nonfermented CP, postbiotics (fermented CP) and synbiotics (live bacteria with nonfermented CP) promoted hair growth in mice. The Wnt/ß-catenin signaling pathway plays crucial roles in the development of hair follicles, including growth cycle restart and maintenance. Both postbiotics and synbiotics upregulated ß-catenin, a major factor of the Wnt/ß-catenin signaling pathway. Postbiotics and synbiotics also increased the vascular endothelial growth factor expression and decreased the BAX/Bcl2 ratio in the dorsal skin of mice. These results suggest that fermented CP by L. plantarum CCFM1348 may promote hair growth through regulating the Wnt/ß-catenin signaling pathway, promoting the expression of growth factors and reducing apoptosis.

Biomolecular investigations into BBI reveal an enzymatic mechanism for PUFA isomerisation in bifidobacterium CFA bioconversion strains.

Multiple species of Bifidobacterium exhibit the ability to bioconvert conjugated fatty acids (CFAs), which is considered an important pathway for these strains to promote host health. However, there has been limited progress in understanding the enzymatic mechanism of CFA bioconversion by bifidobacteria, despite the increasing number of studies identifying CFA-producing strains. The protein responsible for polyunsaturated fatty acid (PUFA) isomerization in B. breve CCFM683 has recently been discovered and named BBI, providing a starting point for exploring Bifidobacterium isomerases (BIs). This study presents the sequence classification of membrane-bound isomerases from four common Bifidobacterium species that produce CFA. Heterologous expression, purification, and enzymatic studies of the typical sequences revealed that all possess a single c9, t11 isomer as the product and share common features in terms of enzymatic properties and catalytic kinetics. Using molecular docking and alanine scanning, Lys84, Tyr198, Asn202, and Leu245 located in the binding pocket were identified as critical to the catalytic activity, a finding further confirmed by site-directed mutagenesis-based screening assays. Overall, these findings provide insightful knowledge concerning the molecular mechanisms of BIs. This will open up additional opportunities for the use of bifidobacteria and CFAs in probiotic foods and precision nutrition.

In vitro batch fermentation demonstrates variations in the regulation of gut microbiota and metabolic functions by ß-glucans of differing structures.

The gut microbiota is widely acknowledged as a crucial factor in regulating host health. The structure of dietary fibers determines changes in the gut microbiota and metabolic differences resulting from their fermentation, which in turn affect gut microbe-related health effects. ß-Glucan (BG) is a widely accessible dietary fiber to humans, and its structural characteristics vary depending on the source. However, the interactions between different structural BGs and gut microbiota remain unclear. This study used an in vitro fermentation model to investigate the effects of BG on gut microbiota, and microbiomics and metabolomics techniques to explore the relationship between the structure of BG, bacterial communities, and metabolic profiles. The four sources of BG (barley, yeast, algae, and microbial fermentation) contained different types and proportions of glycosidic bonds, which differentially altered the bacterial community. The BG from algal sources, which contained only ß(1 â†’ 4) glycosidic bonds, was the least metabolized by the gut microbiota and caused limited metabolic changes. The other three BGs contain more diverse glycosidic bonds and can be degraded by bacteria from multiple genera, causing a wider range of metabolic changes. This work also suggested potential synergistic degradation relationships between gut bacteria based on BG. Overall, this study deepens the structural characterization-microbial-functional understanding of BGs and provides theoretical support for the development of gut microbiota-targeted foods.

Probiotic intervention improves metabolic outcomes in gestational diabetes mellitus: A meta-analysis of randomized controlled trials.

AIMS: To conduct a randomized controlled trial meta-analysis and provide concise and specific recommendations for clinical practice optimization of gestational diabetes for probiotics. METHODS: Up until May 2023, we conducted a thorough, systematic search of PubMed, Cochrane Central Controlled Trials, and Embase. Stata software was used to merge the resulting data from the original studies. Cochran's Q and the I2 statistics were used to evaluate and quantify heterogeneity. The GRADE method was used to evaluate the overall quality of the evidence. Sources of heterogeneity were analyzed through a leave-one-out meta-analysis, a Galbraith plot, and a subgroup analysis. RESULTS: A meta-analysis of 11 randomized controlled trials with a total of 713 participants was finally conducted. Our findings indicated the administration of probiotics at a median dosage of 6 × 109 CFU/day led to a substantial improvement in fasting glucose levels (MD: -4.16 mg/dL [95% CI: -6.78, -1.54]; P < 0.001), fasting insulin levels (MD: -3.33 µIU/ml [95% CI: -4.92, -1.74]; P < 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) (MD: -0.71 [95% CI: -0.97, -0.45]; P < 0.001), and quantitative insulin sensitivity check index (QUICKI) (MD: 0.01 [95% CI: 0.01, 0.02]; P < 0.001). Subgroup analysis indicated that probiotic intervention exerted a more significant reduction in fasting blood glucose in patients with higher baseline BMI and glucose levels, and reduced fasting insulin more markedly in those with elevated baseline insulin. According to the GRADE assessment, the quality of evidence for fasting blood glucose and QUICKI was rated as "high", while the quality for fasting insulin and HOMA-IR was rated as "moderate". CONCLUSIONS: Probiotic intervention has been shown to significantly decrease levels of fasting blood glucose, fasting insulin, and HOMA-IR, while elevating QUICKI levels in patients with GDM, underscoring the potential utility of probiotics in the adjunctive management of GDM.