The compartment-specific manipulation of the NAD+/NADH ratio affects the metabolome and the function of glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive type of cancer in the brain and has an inferior prognosis because of the lack of suitable medicine, largely due to its tremendous invasion. GBM has selfish metabolic pathways to promote migration, invasion, and proliferation compared to normal cells. Among various metabolic pathways, NAD (nicotinamide adenine dinucleotide) is essential in generating ATP and is used as a resource for cancer cells. LbNOX (Lactobacillus brevis NADH oxidase) is an enzyme that can directly manipulate the NAD+/NADH ratio. In this study, we found that an increased NAD+/NADH ratio by LbNOX or mitoLbNOX reduced intracellular glutamate and calcium responses and reduced invasion capacity in GBM. However, the invasion was not affected in GBM by rotenone, an ETC (Electron Transport Chain) complex I inhibitor, or nicotinamide riboside, a NAD+ precursor, suggesting that the crucial factor is the NAD+/NADH ratio rather than the absolute quantity of ATP or NAD+ for the invasion of GBM. To develop a more accurate and effective GBM treatment, our findings highlight the importance of developing a new medicine that targets the regulation of the NAD+/NADH ratio, given the current lack of effective treatment options for this brain cancer.

Levilactobacillus brevis IBARAKI-TS3 Isolated From Pickles Promotes Production of Interleukin-10 via Toll-Like Receptor 2 in Human M2 Macrophages.

M2 macrophages play an important role in food allergy. Several studies have reported that lactic acid bacteria isolated from pickles exert antiallergic effects. We investigated the effects of several strains of lactic acid bacteria on the immune function of M2 macrophages. M2 macrophages differentiated from THP-1 cell line by interleukin-4 (IL-4) and IL-13 strongly expressed CD163, CD206, and HMOX1 mRNA. Levilactobacillus brevis IBARAKI-TS3 (IBARAKI-TS3) isolated from pickles was identified as a lactic acid bacterium that enhances the expressions of IL-10 and EBI3 mRNA in M2 macrophages. IBARAKI-TS3 induced the expression of genes involved in Toll-like receptor (TLR) signaling, such as IRAK, mitogen-activated protein kinases (MAPKs), and NF-κB mRNA. IBARAKI-TS3-induced IL-10 production was suppressed by anti-TLR2-neutralizing antibodies. Furthermore, the IBARAKI-TS3-induced increase in IL-10 levels was significantly reduced in TLR2-knockdown M2 macrophages compared to M2 macrophages. These results suggest that IBARAKI-TS3 promotes of IL-10 production via TLR2 in M2 macrophages.

Gaba-producing lactobacilli boost cognitive reactivity to negative mood without improving cognitive performance: A human Double-Blind Placebo-Controlled Cross-Over study.

BACKGROUND: Psychobiotic bacteria are probiotics able to influence stress-related behavior, sleep, and cognitive outcomes. Several in vitro and human studies were performed to assess their physiological potential, to find strains having psychotropic activity in humans, and to elucidate the metabolic pathways involved. In our previous in vitro study, we identified two strains Levilactobacillus brevis P30021 and Lactiplantibacillus plantarum P30025, able to produce GABA and acetylcholine, being promising candidates to provide an effect on mood and cognitive performance. AIM: To investigate the effects of probiotics in the alleviation on the cognitive performance of moderately stressed healthy adults. Secondary outcomes were related to mood improvement, production of GABA, glutamate, acetylcholine, and choline and modification of the microbiota composition. METHODS: A 12-week randomized, double-blind, placebo-controlled, cross-over study investigated the effects of a probiotic formulation (Levilactobacillus brevis P30021 and Lactiplantibacillus plantarum P30025) on psychological, memory, and cognition parameters in 44 (Probiotic = 44, Placebo = 43) adults with a mean age of 29 ± 5.7 years old by CogState Battery test. Subjects-inclusion criteria was a mild-moderate (18.7 ± 4.06) stress upon diagnosis using the DASS-42 questionnaire. RESULTS: Probiotic treatment had no effect on subjective stress measures. The probiotic formulation showed a significant beneficial effect on depressive symptoms by reducing cognitive reactivity to sad mood (p = 0.034). Rumination significantly improved after intake of the probiotic (p = 0.006), suggesting a potential benefit in reducing the negative cognitive effects associated with depression and improving overall mental health. When stratifying the treated subjects according to the response, we found an increase in the abundance of the probiotic genera in the gut microbiota of positive responders (p = 0.009 for Lactiplantibacillus and p = 0.004 for L.brevis). No relevant correlations were observed between the neurotransmitter concentration in the faecal sample, scores of LEIDS, DASS-42, and cognitive tests. CONCLUSION: We highlight the potential of this probiotic preparation to act as psycobiotics for the relief of negative mood feelings. The assessment of the psychotropic effects of dietary interventions in human participants has many challenges. Further interventional studies investigating the effect of these psychobiotic bacteria in populations with stressed-related disorders are required including longer period of intervention and larger sample size in order to verify the effects of the treatment on further stress-related indicators.

Impact of Different Carbon Sources on Volatile Organic Compounds (VOCs) Produced during Fermentation by Levilactobacillus brevis WLP672 Measured Using Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS).

Bacterial fermentation is considered to be a cost-effective means of generating desired flavour compounds from plant-based substrates. However, the wide range of substrates present in plants makes it challenging to understand how individual components impact on flavour volatile organic compound (VOC) production. To simplify this, a defined medium can be used to better understand VOCs production with regard to individual compounds. In the current study, the VOCs produced by the lactic acid bacterium, Levilactobacillus brevis WLP672, growing in a defined medium containing different carbon sources (either glucose (DM), fructose (DMFr) or citrate (DMCi)) under a range of fermentation conditions (time: 0, 7, and 14 days; and temperature: 25 and 35 °C) were assessed using proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS). Among the detected mass peaks (m/z), after 7 days of fermentation, the concentrations of m/z 45.033 (t.i. acetaldehyde), m/z 49.011 (t.i. methanethiol), and m/z 89.060 (t.i. ethyl acetate) were significantly (p < 0.05) higher in DM at 35 °C than all other treatments at either temperature. The knowledge obtained will help to produce desirable LAB fermentation flavour VOCs or VOC mixtures that could be used in developing plant-based analogues with acceptable sensory properties.

Changes in microbial dynamics and fermentation characteristics of alfalfa silage: A potent approach to mitigate greenhouse gas emission through high-quality forage silage.

Feeding ruminants with high-quality forage can enhance digestibility and reduce methane production. Development of high-quality silage from leguminous plants with lactic acid bacteria can improve digestibility and it mitigate the greenhouse gas emissions. In this study, we developed a high-quality alfalfa silage with improved fermentation index and microbial dynamics using Levilactobacillus brevis-KCC-44 at low or high moisture (LM/HM) conditions and preserved it for 75 or 150 days. Alfalfa fermentation with L. brevis enhances acidification and fermentation characteristics primarily due to the dominance of lactic acid bacteria (LAB) L. brevis (>95%) compared to alfalfa fermented with epiphytic LAB. The inoculant L. brevis improved the anaerobic fermentation indexes resulting in a higher level of lactic acid in both high (10.0 ± 0.12 & 8.90 ± 0.31%DM) and low moisture (0.55 ± 0.08 & 0.39 ± 0.0 %DM) in 75 and 150 days respectively, compared to control silage. In addition, the marginal amount of acetic acid (range from 0.23 ± 0.07 to 2.04 ± 0.27 %DM) and a reduced level of butyric acid (range between 0.03 ± 0.0 to 0.13 ± 02 %DM) was noted in silage treated with LAB than the control. The LAB count and abundance of Levilactobacillus were higher in alfalfa silage fermented with L. brevis. Microbial richness and diversity were reduced in alfalfa silage treated with L. brevis which prompted lactic acid production at a higher level even for a prolonged period of time. Therefore, this L.brevis is an effective inoculant for producing high-quality alfalfa silage since it improves fermentation indexes and provides reproducible ensiling properties.

Pasteurized form of a potential probiotic lactobacillus brevis IBRC-M10790 exerts anti-inflammatory effects on inflammatory bowel disease in vitro.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal system. So far, no treatment has been identified that can completely cure IBD. Lactobacillus brevis is hypothesized to be beneficial in preventing inflammation. This study aimed to evaluate the potential probiotic effects of live and pasteurized L. brevis IBRC-M10790 on the in vitro cell co-culture model of IBD. METHODS: An in vitro intestinal model was established using a transwell co-culture system of Caco-2 intestinal epithelial cells and RAW264.7 macrophages. Inflammatory conditions were induced in RAW264.7 cells using lipopolysaccharide. The effects of live and pasteurized L. brevis IBRC-M10790 on inflammatory mediators and epithelial barrier markers were investigated. RESULTS: L. brevis IBRC-M10790 was able to significantly decrease the proinflammatory cytokines (IL-6, IL-1ß, and TNF-α) and increase the anti-inflammatory cytokine (IL-10) in the in vitro co-culture system. In addition, L. brevis increased adherens and tight junction (TJ) markers (ZO-1, E-cadherin, and Occludin) in Caco-2 intestinal epithelial cells. Based on the results, pasteurized L. brevis showed a higher protective effect than live L. brevis. CONCLUSIONS: Our findings suggest that live and pasteurized forms of L. brevis possess probiotic properties and can mitigate inflammatory conditions in IBD.

A protective mechanism of heat inactivation to enhance Levilactobacillus brevis PDD-2 against alcohol-induced chronic liver disease based on proteomic analysis.

A proteomics-based analysis of the effect of heat inactivation on the alleviation of alcoholic liver disease (ALD) using Levilactobacillus brevis PDD-2 is presented, aimed at exploring the potential and mechanisms of postbiotic elements prepared through heat inactivation in the treatment of ALD. It was found that L. brevis PDD-2 and its postbiotic (heat-inactivated L. brevis PDD-2) alleviate chronic ALD via the gut-liver axis. In particular, heat-inactivated L. brevis PDD-2 significantly increased the relative abundance of Erysipelotrichaceae and better facilitated the oxidative stress balance in the liver. The tandem mass tag (TMT)-based quantitative proteomics technique analyses revealed that heat-inactivated L. brevis PDD-2 was associated with up-regulated expression levels of proteins related to the redox system, cellular metabolism, amino acid and oligopeptide transport, and surface proteins with immunomodulatory capacity. These findings provide a theoretical basis for developing novel therapeutic strategies and lay a solid foundation for further revealing its exhaustive mechanisms.

Kimchi Lactic Acid Bacteria Starter Culture: Impact on Fermented Malt Beverage Volatile Profile, Sensory Analysis, and Physicochemical Traits.

Starter cultures used during the fermentation of malt wort can increase the sensory characteristics of the resulting beverages. This study aimed to explore the aroma composition and flavor recognition of malt wort beverages fermented with lactic acid bacteria (Levilactobacillus brevis WiKim0194) isolated from kimchi, using metabolomic profiling and electronic tongue and nose technologies. Four sugars and five organic acids were detected using high-performance liquid chromatography, with maltose and lactic acid present in the highest amounts. Additionally, e-tongue measurements showed a significant increase in the sourness (AHS), sweetness (ANS), and umami (NMS) sensors, whereas bitterness (SCS) significantly decreased. Furthermore, 20 key aroma compounds were identified using gas chromatography-mass spectrometry and 15 key aroma flavors were detected using an electronic nose. Vanillin, citronellol, and ß-damascenone exhibited significant differences in the flavor profile of the beverage fermented by WiKim0194, which correlated with floral, fruity, and sweet notes. Therefore, we suggest that an appropriate starter culture can improve sensory characteristics and predict flavor development in malt wort beverages.

Optimisation ofLevilactobacillus brevis-fermented finger millet (Eleusine coracana) and evaluation of its effects on cancer cells (HCT116 and MDA-MB-231).

The objective of this study was to optimise the millet formulation using Levilactobacillus brevis and to evaluate its anticarcinogenic potential in vitro. The formula was developed in the course of the fermentation of finger millet (Eleusine coracana) using L. brevis MTTC 4460 and optimised by response surface methodology and validation by artificial neural networking (ANN). The optimised millet formulation could be obtained using 2 % of bacterial inoculum, 2 % of glucose, and a fermentation duration of 3.3 days with a yield of 5.98 mg/mL lactic acid and 3.38 log10 (CFU/mL) viable L. brevis with overall desirability value of 1. The fermented millet formulation exhibited antiproliferative and antimigratory effects on MDA-MB-231 and HCT116 cancer cell lines. In addition, the outcomes observed in western blot analysis revealed that the formulation elicited apoptotic responses mediated by the Bcl-2 family of proteins in MDA-MB-231 and HCT116 cell lines while demonstrating no discernible impact on HEK293 normal cells.

Protective Effects of the Postbiotic Levilactobacillus brevis BK3 against H2O2-Induced Oxidative Damage in Skin Cells.

Postbiotics have various functional effects, such as antioxidant, anti-inflammatory, and anti-obesity. Levilactobacillus brevis BK3, the subject of this study, was derived from lactic acid bacteria isolated from Kimchi, a traditional Korean fermented food. The antioxidant activity of BK3 was confirmed through the measurements of 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and total antioxidant capacity (TAC). The wrinkle improvement effect was validated by assessing elastase inhibitory activity and collagenase inhibitory activity. The intracellular activity was confirmed using human keratinocytes (HaCaT) and human fibroblasts (HFF-1). BK3 protects skin cells from oxidative stress induced by H2O2 and reduces intracellular reactive oxygen species (ROS) production. In addition, the expressions of the antioxidant genes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were upregulated. Meanwhile, matrix metalloproteinase-1 (MMP-1) and collagen type I alpha 1 (COL1A1), involved in collagen degradation and synthesis, were significantly regulated. These results suggest the possibility of utilizing BK3 as a functional ingredient with antioxidant and wrinkle-improving effects.

Whole-genome analysis, evaluation and regulation of in vitro and in vivo GABA production from Levilactobacillus brevis YSJ3.

Gamma-aminobutyric acid (GABA) produced by lactic acid bacteria (LAB) is safe and has several health benefits. Levilactobacillus brevis YSJ3 was selected from 110 LAB. It exhibited the highest in vitro GABA production level of 970.10 µg/mL. Whole-genome analysis revealed that L. brevis YSJ3 contained gadR, gadC, gadB and gadA. Furthermore, the Luedeking-Piret model was fitted, which indicated that GABA production was divided into three stages. The gadR 0079, gadC 0080, and gadB 0081 were confirmed to promote GABA synthesis. Moreover, 55 metabolites, particularly those involved in arginine metabolism, were significantly different at 6 and 20 h of cultivation. Notably, L. brevis YSJ3 significantly improved sleep in mice and increased GABA levels in the mice's gut compared with the control group. This suggests that the oral administration of L. brevis YSJ3 improves sleep quality, probably by increasing intestinal GABA levels. Overall, L. brevis YSJ3 was confirmed as a GABA-producing strain in vitro and in vivo, making it a promising probiotic candidate for its application in food and medicine.

Evolution-aided improvement of the acid tolerance of Levilactobacillus brevis and its application in sourdough fermentation.

Levilactobacillus brevis is crucial in food fermentation, particularly in sourdough production. However, the cultivation of L. brevis faces a challenge with accumulation of lactic acid, a major inhibitor. We aimed to increase the acid tolerance of L. brevis, an industrial strain for sourdough fermentation. We used the adaptive laboratory evolution (ALE) to obtain lactic acid tolerant strains. The evolved strain's fermentation and metabolite profiles, alongside sensory evaluation, were compared with the parental strain by using various analytical techniques. The ALE approach increased lactic acid tolerance in the evolved strain showing an increased growth rate by 1.1 and 1.9 times higher than the parental strain at pH 4.1 and 6.5, respectively. Comprehensive analyses demonstrated its potential application in sourdough fermentation, promising reduced downstream costs. The evolved strain, free from genetically modified organisms concerns, has great potential for industrial use by exhibiting enhanced growth in acidic conditions without affecting consumers' bread preferences.

Levilactobacillus brevis SG031 modulates mood-related behaviors and attenuates stress-related sleep disturbance and autonomic dysfunction via gut microbiota modulation in Wistar-Kyoto rats.

AIMS: The probiotic bacterium Levilactobacillus brevis (L. brevis) has been proposed as a potential solution to manage mood disorders and alleviate stress-related sleep disturbances. However, the underlying mechanisms of its effects have not been fully elucidated. The aim of this study was to explore the impact and potential mechanisms of L. brevis SG031 supplementation on anxiety/depression-like behaviors and stress-induced changes in sleep patterns and sleep-related autonomic function. MAIN METHODS: Male Wistar-Kyoto rats were administered low, medium, or high doses of L. brevis SG031 or a vehicle for 4 weeks, followed by behavioral tests to evaluate anxiety and depression. After an additional 2 weeks of SG031 or vehicle administration, a cage-exchange paradigm was performed with 24-hour physiological signal measurements under different stress conditions. Fecal samples were collected to construct a 16S rRNA library and assess fecal short-chain fatty acids (SCFAs). KEY FINDINGS: High-dose SG031 administration yielded reduced depression-like responses and enhanced social interaction in behavioral tests. It also exhibited a protective effect against stress-induced sleep disturbance characterized by decreased sleep time, increased awake time, and autonomic dysfunction during sleep. Fecal examination indicated that high-dose SG031 administration exerted beneficial effects on gut health by maintaining the gut microbial abundance, preserving stability of the microbial composition, and enriching the gut with SCFAs, which were associated with improvements in sleep and autonomic function. SIGNIFICANCE: These findings collectively underscore the multifaceted potential of SG031 in addressing mental health and stress-related sleep challenges through the modulation of the gut microbiota.

Ethanolamine enhances adhesion, promotes microcompartment formation, and modulates gene expression in Levilactobacillus brevis ATCC 14869.

Ethanolamine is an abundant compound in the gastrointestinal tract and a valuable source of carbon and nitrogen for pathogenic bacteria harboring ethanolamine utilization (eut) genes. Eut-positive pathogens can consume free ethanolamine to outcompete commensal microbes, which often lack eut genes, and establish infection. Ethanolamine can also act as a host recognition signal for eut-positive pathogens to upregulate virulence genes during colonization. Therefore, reducing free ethanolamine titers may represent a novel approach to preventing infection by eut-positive pathogens. Interestingly, the commensal microorganism Levilactobacillus brevis ATCC 14869 was found to encode over 18 eut genes within its genome. This led us to hypothesize that L. brevis can compete with eut-positive pathogens by clearing free ethanolamine from the environment. Our results demonstrate that despite being unable to metabolize ethanolamine under most conditions, L. brevis ATCC 14869 responds to the compound by increasing the expression of genes encoding proteins involved in microcompartment formation and adhesion to the intestinal epithelial barrier. The improved intestinal adhesion of L. brevis in the presence of ethanolamine also enhanced the exclusion of eut-positive pathogens from adhering to intestinal epithelial cells. These findings support further studies to test whether L. brevis ATCC 14869 can counter enteric pathogens and prevent or reduce the severity of infections. Overall, the metabolic capabilities of L. brevis ATCC 14869 offer a unique opportunity to add to the armamentarium of antimicrobial therapies as well as our understanding of the mechanisms used by beneficial microbes to sense and adapt to host microenvironments.

Directed Evolution and Immobilization of Lactobacillus brevis Alcohol Dehydrogenase for Chemo-Enzymatic Synthesis of Rivastigmine.

Rivastigmine is one of the several pharmaceuticals widely prescribed for the treatment of Alzheimer's disease. However, its practical synthesis still faces many issues, such as the involvement of toxic metals and harsh reaction conditions. Herein, we report a chemo-enzymatic synthesis of Rivastigmine. The key chiral intermediate was synthesized by an engineered alcohol dehydrogenase from Lactobacillus brevis (LbADH). A semi-rational approach was employed to improve its catalytic activity and thermal stability. Several LbADH variants were obtained with a remarkable increase in activity and melting temperature. Exploration of the substrate scope of these variants demonstrated improved activities toward various ketones, especially acetophenone analogs. To further recycle and reuse the biocatalyst, one LbADH variant and glucose dehydrogenase were co-immobilized on nanoparticles. By integrating enzymatic and chemical steps, Rivastigmine was successfully synthesized with an overall yield of 66 %. This study offers an efficient chemo-enzymatic route for Rivastigmine and provides several efficient LbADH variants with a broad range of potential applications.

Postbiotic properties of exopolysaccharide produced by Levilactobacillus brevis M-10 isolated from natural fermented sour porridge through in vitro simulated digestion and fermentation.

The simulated digestion and fermentation characteristics in vitro of exopolysaccharide (EPS) of Levilactobacillus brevis M-10 were studied to evaluate its postbiotic properties. The simulated digestion results showed that EPS could not be degraded in saliva but could be very slightly degraded in gastric juice and could be degraded in intestinal juice. The results of simulated fermentation demonstrated that EPS could lower the intestine pH and be utilized by gut microbes to produce short-chain fatty acids such as propionic acid and butyric acid. Meanwhile, EPS significantly raised the diversity of human gut microbiota, and the relative abundances of Phascolarctobacterium were significantly increased, whereas Fusobacterium and Morganella significantly decreased. In conclusion, EPS from L. brevis M-10 was a good postbiotic as inulin. This was the first report about EPS as the postbiotic of L. brevis M-10 screened from broomcorn millet sour porridge in northwestern Shanxi Province, China.

Recombinant Arginine Deiminase from Levilactobacillus brevis Inhibits the Growth of Stomach Cancer Cells, Possibly by Activating the Intrinsic Apoptosis Pathway.

The anticancer potential of Levilactobacillus brevis KU15176 against the stomach cancer cell line AGS has been reported previously. In this study, we aimed to analyze the genome of L. brevis KU15176 and identify key genes that may have potential anticancer properties. Among potential anticancer molecules, the role of arginine deiminase (ADI) in conferring an antiproliferative functionality was confirmed. In vitro assay against AGS cell line confirmed that recombinant ADI from L. brevis KU15176 (ADI_br, 5 µg/mL), overexpressed in E. coli BL21 (DE3), exerted an inhibitory effect on AGS cell growth, resulting in a 65.32% reduction in cell viability. Moreover, the expression of apoptosis-related genes, such as bax, bad, caspase-7, and caspase-3, as well as the activity of caspase-9 in ADI_br-treated AGS cells, was higher than those in untreated (culture medium-only) cells. The cell-scattering behavior of ADI_br-treated cells showed characteristics of apoptosis. Flow cytometry analyses of AGS cells treated with ADI_br for 24 and 28 h revealed apoptotic rates of 11.87 and 24.09, respectively, indicating the progression of apoptosis in AGS cells after ADI_br treatment. This study highlights the potential of ADI_br as an effective enzyme for anticancer applications.

A Novel Lactobacillus brevis Fermented with a Vegetable Substrate (AL0035) Counteracts TNBS-Induced Colitis by Modulating the Gut Microbiota Composition and Intestinal Barrier.

Crohn's and ulcerative colitis are common conditions associated with inflammatory bowel disease as well as intestinal flora and epithelial barrier dysfunction. A novel fermented Lactobacillus brevis (AL0035) herein assayed in a trinitro benzene sulfonic acid (TNBS)-induced colitis mice model after oral administration significantly counteracted the body weight loss and improves the disease activity index and histological injury scores. AL0035 significantly decreased the mRNA and protein expression of different pro-inflammatory cytokines (TNFalpha, IL-1beta, IL-6, IL-12, IFN-gamma) and enhanced the expression of IL-10. In addition, the probiotic promoted the expression of tight junction proteins, such as ZO-1, keeping the intestinal mucosal barrier function to attenuate colitis symptoms in mice. Markers of inflammation cascade such as myeloperoxidase (MPO) and PPAR-gamma measured in the colon were also modified by AL0035 treatment. AL0035 was also able to reduce different lymphocyte markers' infiltration in the colon (GATA-3, T-Bet, NK1.1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), a key chemokine involved in the migration and infiltration of monocytes/macrophages in the immunological surveillance of tissues and inflammation. In colonic microbiota profile analysis through 16S rRNA sequencing, AL0035 increased the microbial diversity depleted by TNBS administration and the relative abundance of the Lactobacillaceae and Lachnospiraceae families, whereas it decreased the abundance of Proteobacteria. Altogether, these data indicated that AL0035 could lower the severity of colitis induced by TNBS by regulating inflammatory cytokines, increasing the expression of tight junction proteins and modulating intestinal microbiota, thus preventing tissue damage induced by colitis.

Lactobacillus brevis-Fermented Gamma-Aminobutyric Acid Ameliorates Depression- and Anxiety-Like Behaviors by Activating the Brain-Derived Neurotrophic Factor-Tropomyosin Receptor Kinase B Signaling Pathway in BALB/C Mice.

This study investigated the effects of Lactobacillus brevis-fermented gamma-aminobutyric acid (LB-GABA) on depressive and anxiety-like behaviors with the underlying molecular mechanism in a chronic stress model of BALB/c mice. LB-GABA attenuates both neuronal cell death and the increase of monoamine oxidase activity induced by hydrogen peroxide. Behavioral tests revealed that GABA significantly increased sucrose preference and reduced immobility time in both tail suspension and forced swimming tests. LB-GABA increased exploration of the open arms in the elevated plus maze and restored activity in the open field. Moreover, LB-GABA lowered stress hormone and inflammatory mediator levels. Mechanistically, LB-GABA increased protein levels of BDNF and TrkB, activating downstream targets (AKT, ERK, and CREB), crucial for neuronal survival and plasticity. Furthermore, LB-GABA protected hippocampal neurons from stress-induced cell death and increased serotonin and dopamine levels. Overall, LB-GABA has the potential to alleviate stress-induced depression and anxiety-like symptoms and neuroinflammation by activating the BDNF-TrkB signaling pathway.

Volatile Organic Compounds (VOCs) Produced by Levilactobacillus brevis WLP672 Fermentation in Defined Media Supplemented with Different Amino Acids.

Fermentation by lactic acid bacteria (LAB) is a promising approach to meet the increasing demand for meat or dairy plant-based analogues with realistic flavours. However, a detailed understanding of the impact of the substrate, fermentation conditions, and bacterial strains on the volatile organic compounds (VOCs) produced during fermentation is lacking. As a first step, the current study used a defined medium (DM) supplemented with the amino acids L-leucine (Leu), L-isoleucine (Ile), L-phenylalanine (Phe), L-threonine (Thr), L-methionine (Met), or L-glutamic acid (Glu) separately or combined to determine their impact on the VOCs produced by Levilactobacillus brevis WLP672 (LB672). VOCs were measured using headspace solid-phase microextraction (HS-SPME) gas chromatography-mass spectrometry (GC-MS). VOCs associated with the specific amino acids added included: benzaldehyde, phenylethyl alcohol, and benzyl alcohol with added Phe; methanethiol, methional, and dimethyl disulphide with added Met; 3-methyl butanol with added Leu; and 2-methyl butanol with added Ile. This research demonstrated that fermentation by LB672 of a DM supplemented with different amino acids separately or combined resulted in the formation of a range of dairy- and meat-related VOCs and provides information on how plant-based fermentations could be manipulated to generate desirable flavours.