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Bacteriocins are antimicrobial peptides produced by bacteria, and their production is regarded as a desirable probiotic trait. We found that Lactobacillus gasseri LM19, a strain isolated from human milk, produces several bacteriocins, including a novel bacteriocin, gassericin M. These bacteriocins were purified from culture and synthesised to investigate their activity and potential synergy. L. gasseri LM19 was tested in a complex environment mimicking human colon conditions; it not only survived, but expressed the seven bacteriocin genes and produced short-chain fatty acids. Metagenomic analysis of these in vitro colon cultures showed that co-inoculation of L. gasseri LM19 with Clostridium perfringens gave 16S ribosomal RNA metagenomic profiles with more similarity to controls than to vessels inoculated with C. perfringens alone. These results indicate that L. gasseri LM19 could be an interesting candidate for maintaining homeostasis in the gut environment.

Excessive expression of interleukin (IL)-1β in the brain causes depression and cognitive dysfunction. Herein, we investigated the effect of Lactobacillus gasseri NK109, which suppressed IL-1β expression in activated macrophages, on Escherichia coli K1-induced cognitive impairment and depression in mice. Germ-free and specific pathogen-free mice with neuropsychiatric disorders were prepared by oral gavage of K1. NK109 alleviated K1-induced cognition-impaired and depressive behaviors, decreased the expression of IL-1β and populations of NF-κB+/Iba1+ and IL-1R+ cells, and increased the K1-suppressed population of BDNF+/NeuN+ cells in the hippocampus. However, its effects were partially attenuated by celiac vagotomy. NK109 treatment mitigated K1-induced colitis and gut dysbiosis. Tyndallized NK109, even if lysed, alleviated cognitive impairment and depression. In conclusion, NK109 alleviated neuropsychiatric disorders and colitis by modulating IL-1β expression, gut microbiota, and vagus nerve-mediated gut–brain signaling.

Summary Lactic-acid bacteria are widely recognized beneficial host associated groups of the microbiota of humans and animals. Some lactic-acid bacteria have the ability to extend the lifespan of the model animals. The mechanisms behind the probiotic effects of bacteria are not entirely understood. Recently, we reported the benefit effects of Lactobacillus gasseriSBT2055 (LG2055) on animal and human health, such as preventing influenza A virus, and augmentation of IgA production. Therefore, it was preconceived that LG2055 has the beneficial effects on longevity and/or aging. We examined the effects of LG2055 on lifespan and aging of Caenorhabditis elegans and analyzed the mechanism of prolongevity. Our results demonstrated that LG2055 has the beneficial effects on longevity and anti-aging of C. elegans. Feeding with LG2055 upregulated the expression of the skn-1 gene and the target genes of SKN-1, encoding the antioxidant proteins enhancing antioxidant defense responses. We found that feeding with LG2055 directly activated SKN-1 activity via p38 MAPK pathway signaling. The oxidative stress response is elicited by mitochondrial dysfunction in aging, and we examined the influence of LG2055 feeding on the membrane potential of mitochondria. Here, the amounts of mitochondria were significantly increased by LG2055 feeding in comparison with the control. Our result suggests that feeding with LG2055 is effective to the extend lifespan in C. elegans by a strengthening of the resistance to oxidative stress and by stimulating the innate immune response signaling including p38MAPK signaling pathway and others.

Previous studies showed that the female genital tract microbiome plays a crucial role in regulating the host’s immune defense mechanisms. Our previous research has shown that Lactobacillus gasseri LGV03 ( L. gasseri LGV03) isolated from cervico-vagina of HPV-cleared women contributes to clearance of HPV infection and beneficially regulate immune response. However, the mechanisms behind the regulation of L. gasseri LGV03 in immune response remain unclear. To better understand the interaction between female genital tract microbiome and immune function, the immunomodulatory activities of L. gasseri LGV03 were investigated in zebrafish models of neutropenia, macrophage and T cells deficiency. L. gasseri LGV03 showed higher potent activities in ameliorating vinorelbine-induced neutropenia, macrophage and T cells deficiency, and significantly enhanced mRNA expressions of cytokines TNF-α, TNF-β and IFN-α. Moreover, the transcriptome sequencing results indicated L. gasseri LGV03 might alleviate vinorelbine-induced immunosuppression in zebrafish. Non-targeted detection and analysis revealed that indole derivatives including phenylacetaldehyde, 3-phenyllactic acid, N-acetylserotonin and indole-3-lactic acid were significantly increased in the lysate and supernatant of L. gasseri LGV03. Meanwhile, L. gasseri LGV03 supernatant and indole-3-lactic acid ameliorated the vinorelbine-induced reduction in abundance of macrophages, neutrophils and T cells. However, the alleviating effects of L. gasseri LGV03 supernatant or indole-3-lactic acid were eliminated by aryl hydrocarbon receptor (AHR) antagonist CH-223,191. Furthermore, L. gasseri LGV03 supernatant and indole-3-lactic acid significantly increased the secretion of IFN-α, IFN-β and chemokines (MIP-1α, MIP-1β) in Ect1/E6E7 cells, meanwhile, these benefits were eliminated by CH-223,191 treatment. In summary, L. gasseri LGV03-derived indole-3-lactic acid can activate AHR-mediated immune response.

Carrot juice (straight, 8.5 Brix and concentrated, 15.2 Brix) was fermented by lactic acid bacteria (Lactobacillus gasseri strain DSM 20604 or DSM 20077). Fermentation enhanced the nutritional profile of carrot juice. There was a greater sugar reduction (27%) in fermented straight carrot juices than in the fermented concentrated juices (15%). The sugar reduction was independent of the strain used for fermentation. The two L. gasseri strains synthesised fructosyltransferase enzymes during fermentation of carrot juice samples that enabled conversion of simple sugars primarily into polysaccharides. The level of conversion to polysaccharides was dependent on the L. gasseri strain and juice concentration. Fermentation of carrot juice by L. gasseri enables the production of a nutritionally-enhanced beverage with reduced calorie and prebiotic potential. An additional benefit is the increased carotenoid content observed in straight and concentrated juices fermented by Lactobacillus gasseri DSM 20077 and the concentrated juice fermented by Lactobacillus gasseri DSM 20604.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease, and the intestinal barrier is an important line of defense against intestinal disease. Herein, we investigated the effect of Lactobacillus gasseri JM1 at different doses (1 × 106, 1 × 107, 1 × 108 CFU/day) on colitis mice and explored the possible mechanism. The results showed that L. gasseri JM1 alleviated DSS-induced colitis in mice, with reductions in disease activity index (DAI), histological scores and myeloperoxidase activity as well as alleviation of colonic shortening. Furthermore, L. gasseri JM1 regulated the levels of inflammatory cytokines TNF-α, IL-6, IL-1β, and IL-10; restored the expression of Claudin-3, Occludin, ZO-1, and MUC2; and increased the number of goblet cells and acidic mucin. The 16S rDNA sequencing results indicated that intervention with L. gasseri JM1 balanced the gut microbiota structure by elevating the abundance of beneficial bacteria (Oscillospira, Clostridium and Ruminococcus) and decreasing that of harmful bacteria (Shigella and Turicibacter). Meanwhile, the contents of short-chain fatty acids (SCFAs) increased. In conclusion, L. gasseri JM1 could alleviate intestinal barrier damage in colitis mice by modulating the tight junction structures, intestinal mucus layer, inflammatory cytokines, gut microbiota, and SCFAs. It can be considered a potential preventive strategy to alleviate colitis injury.

Short-term administration of Lactobacillus gasseri CP2305 improves stress-associated symptoms and clinical symptoms in healthy young adults and in patients with irritable bowel syndrome, respectively. We evaluated the efficacy and health benefits of the long-term use of a tablet containing heat-inactivated, washed Lactobacillus gasseri CP2305 (CP2305) in healthy young adults. Sixty Japanese medical students (41 men and 19 women) preparing for the national examination for medical practitioners ingested CP2305-containing or placebo tablets once daily for 24 weeks. Intake of the CP2305 tablet significantly reduced anxiety and sleep disturbance relative to placebo, as quantitated by the Spielberger State-Trait Anxiety Inventory and the Pittsburgh Sleep Quality Index. Single-channel sleep electroencephalograms show that CP2305 significantly shortened sleep latency and wake time after sleep onset and increased the delta power ratio in the first sleep cycle. CP2305 also significantly lowered salivary chromogranin A levels compared with placebo. Furthermore, 16S rRNA gene sequencing of participant feces demonstrated that CP2305 administration attenuated the stress-induced decline of Bifidobacterium spp. and the stress-induced elevation of Streptococcus spp. We conclude that the long-term use of CP2305-containing tablets may improve the mental state, sleep quality, and gut microbiota of healthy adults under stressful conditions.

Inflammatory bowel disease (IBD) is an immune system disorder primarily characterized by colitis, the exact etiology of which remains unclear. Traditional treatment approaches currently yield limited efficacy and are associated with significant side effects. Extensive research has indicated the potent therapeutic effects of probiotics, particularly Lactobacillus strains, in managing colitis. However, the mechanisms through which Lactobacillus strains ameliorate colitis require further exploration. In our study, we selected Lactobacillus gasseri ATCC33323 from the intestinal microbiota to elucidate the specific mechanisms involved in modulation of colitis. Experimental findings in a DSS-induced colitis mouse model revealed that L . gasseri ATCC33323 significantly improved physiological damage in colitic mice, reduced the severity of colonic inflammation, decreased the production of inflammatory factors, and preserved the integrity of the intestinal epithelial structure and function. It also maintained the expression and localization of adhesive proteins while improving intestinal barrier permeability and restoring dysbiosis in the gut microbiota. E-cadherin, a critical adhesive protein, plays a pivotal role in this protective mechanism. Knocking down E-cadherin expression within the mouse intestinal tract significantly attenuated the ability of L . gasseri ATCC33323 to regulate colitis, thus confirming its protective role through E-cadherin. Finally, transcriptional analysis and in vitro experiments revealed that L . gasseri ATCC33323 regulates CDH1 transcription by affecting NR1I3, thereby promoting E-cadherin expression. These findings contribute to a better understanding of the specific mechanisms by which Lactobacillus strains alleviate colitis, offering new insights for the potential use of L . gasseri as an alternative therapy for IBD, particularly in dietary supplementation.

Lactobacillus gasseri SBT2055 (LG2055) is a probiotic lactic acid bacterium with multifunctional effects, including the prevention of influenza A virus infection in mice, reduction of adipocyte size in mice, and increased lifespan in C. elegans . We investigated whether LG2055 exhibits antiviral activity against respiratory syncytial virus (RSV), a global pathogen for which a preventive strategy is required. Following oral administration of LG2055 in mice, the RSV titre in the lung was significantly decreased, while body weight was not decreased after virus infection. Additionally, the elevated expression of pro-inflammatory cytokines in the lung upon RSV infection decreased after LG2055 administration. Moreover, interferon and interferon stimulated genes were upregulated by LG2055 treatment. Comparative cellular proteomic analysis revealed that SWI2/SNF2-related CREB-binding protein activator protein (SRCAP) was a candidate for the antiviral activity of LG2055 against RSV. There was a positive correlation between the inhibition of RSV replication and the suppression of SRCAP expression and RSV replication was suppressed by SRCAP silencing. Since SRCAP is a scaffold protein to which viral non-structural proteins bind, the downregulation of SRCAP induced by LG2055 could provide new insights about the inhibition of RSV replication. In summary, our study demonstrated that LG2055 has prophylactic potential against RSV infection.

Oxalate, a ubiquitous compound in many plant-based foods, is absorbed through the intestine and precipitates with calcium in the kidneys to form stones. Over 80% of diagnosed kidney stones are found to be calcium oxalate. People who form these stones often experience a high rate of recurrence and treatment options remain limited despite decades of dedicated research. Recently, the intestinal microbiome has become a new focus for novel therapies. Studies have shown that select species of Lactobacillus, the most commonly included genus in modern probiotic supplements, can degrade oxalate in vitro and even decrease urinary oxalate in animal models of Primary Hyperoxaluria. Although the purported health benefits of Lactobacillus probiotics vary significantly between species, there is supporting evidence for their potential use as probiotics for oxalate diseases. Defining the unique metabolic properties of Lactobacillus is essential to define how these bacteria interact with the host intestine and influence overall health. We addressed this need by characterizing and comparing the metabolome and lipidome of the oxalate-degrading Lactobacillus acidophilus and Lactobacillus gasseri using ultra-high-performance liquid chromatography-high resolution mass spectrometry. We report many species-specific differences in the metabolic profiles of these Lactobacillus species and discuss potential probiotic relevance and function resulting from their differential expression. Also described is our validation of the oxalate-degrading ability of Lactobacillus acidophilus and Lactobacillus gasseri, even in the presence of other preferred carbon sources, measuring in vitro 14C-oxalate consumption via liquid scintillation counting.