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At least 19 recordsLinked to original sources
PubMed2025

Targeting MondoA-TXNIP restores antitumour immunity in lactic-acid-induced immunosuppressive microenvironment.

In the tumour microenvironment, accumulated lactic acid (LA) promotes tumour immune evasion by facilitating regulatory T cell (Treg) immunosuppressive function and restraining CD8+ T cell cytotoxicity, but the underlying mechanism remains elusive. Here we report that transcriptional factor MondoA-induced thioredoxin interacting protein (TXNIP) transcription is a common feature of both Treg and CD8+ T cells in response to lactic acid. In contrast to reduction in immunosuppressive capacity in MondoA-deficient Treg cells, loss of MondoA enhanced CD8+ T cell cytotoxic function in the lactic-acid-induced immunosuppressive microenvironment, by restoring glucose uptake and glycolysis. Mechanistically, lactic acid relied on sentrin/SUMO-specific protease 1 (SENP1) to stimulate the MondoA-TXNIP axis, which impaired TCR/CD28-signal-induced CD8+ T cell activation. Importantly, targeting the MondoA-TXNIP axis potentiated antitumour immunity in multiple cancer types and synergized with anti-PD-1 therapy to promote effective T cell responses in colorectal cancer. Our results demonstrate that the MondoA-TXNIP axis is a promising therapeutic target for improving cancer immunotherapy.

Tumor Microenvironment↗
PubMed2026

Fructophilic lactic acid bacteria as a window into multi-scale convergent evolution.

Fructophilic lactic acid bacteria (FLAB) are a group of lactic acid bacteria with unique growth characteristics, that is, poor growth on glucose. Their growth is enhanced in the presence of fructose or external electron acceptors. These organisms inhabit fructose-rich environments such as flowers, fruits, and pollinating insects, particularly honey bees. Apilactobacillus spp. and Fructobacillus spp. are representatives of FLAB, although they belong to phylogenetically distant clades. These organisms commonly possess markedly small genomes with a low number of coding DNA sequences. Furthermore, their genomes are characterized by a markedly reduced number of genes involved in carbohydrate transport and metabolism. Genome reduction in FLAB reflects convergent adaptation to fructose-rich environments rather than general genome streamlining. The two distinct FLAB genera, Fructobacillus and Apilactobacillus, independently lost more than 100 genes in statistically similar orders. In contrast, genes involved in carbohydrate and amino acid metabolism exhibited reversed orders of loss between the two genera. Furthermore, FLAB genomes lack an intact bifunctional alcohol/aldehyde dehydrogenase gene (adhE), which causes their poor growth on glucose. A comparative genomic study suggested the evolutionary process underlying adhE gene decay during adaptation to the fructose-rich environments, including pollinating insects. In conclusion, FLAB represent a unique example of habitat-driven convergent reductive evolution that can be investigated across multiple biological scales - from individual genes to whole genomes - in the diverse LAB group with a wide range of habitats, and partially share the fructophilic evolution with eukaryotic yeasts found in fructose-rich habitats.

Fructose↗
PubMed2026

Genomic determinants underlying biogenic amine detoxification phenotypes in food-associated lactic acid bacteria: Mechanism, evolutionary origin, and relevance to fermented food safety.

Biogenic amines (BAs) are toxic metabolites that accumulate in fermented foods and pose significant food safety concerns. Although several lactic acid bacteria (LAB) have previously been reported to exhibit strain-specific BA-degrading phenotypes, the genetic determinants underlying these activities have remained largely uncharacterized. Here, we analyzed 8251 LAB genomes to validate BA-degrading phenotypes. We predicted five BA-associated genes, including two direct biogenic amine-degrading genes (BADGs), mco and patA, and three polyamine-modifying genes (PMGs), speG, paiA, and bltD. Among BADGs, mco was broadly distributed across LAB and strongly enriched across food-associated niches. patA, organized within a conserved potD-glnB-potABC-patA cassette, is a putative, functionally distinct BADG in LAB, revealing a nitrogen-responsive polyamine uptake-catabolism module. Phylogenomics, phylogenetic reconciliation, and synteny analysis established that all five genes entered the LAB through episodic horizontal gene transfer followed by lineage-specific fixation. GC compositional bias and mobile genetic element association further corroborated the horizontal origin of the two BADGs. Structural analysis confirmed the conservation of catalytic core residues of BADGs across LAB, indicating strong purifying selection. Phenotype-to-genotype correlation with experimentally reported LAB suggested mco as a reliable genomic predictor of degrading phenotype. Integration of degradation and biosynthetic profiles predicted multiple LAB species capable of both synthesizing and degrading BA, along with 1823 genomes with degradation potential but lacking detectable BA biosynthesis genes. This study provides the first large-scale genome framework linking BA-degrading phenotypes with their genetic determinants in LAB and offers a rational basis for selecting BA-detoxifying strains for fermented food applications.

Biogenic Amines↗
PubMed2026

Whole-genome sequencing reveals hidden antimicrobial resistance genes in phenotypically susceptible probiotic candidate lactic acid bacteria.

Phenotypic assays commonly used to evaluate probiotic safety may fail to detect clinically relevant antimicrobial resistance (AMR), potentially allowing genetically concerning strains to appear acceptable based on MIC testing alone. To explore this issue, we applied whole-genome sequencing (WGS) to three lactic acid bacteria (LAB) isolates previously identified as probiotic candidates based on acid and bile tolerance, antagonism against enteric pathogens, and biofilm formation in vitro: Lactiplantibacillus plantarum L25F and L22F (from pigs) and Ligilactobacillus salivarius AF2319 (from a chicken). Genome annotation identified extensive repertoires of probiotic-associated genes (46-47 per strain) linked to stress tolerance, adhesion, immunomodulation, and quorum sensing, supporting functional potential. The two L. plantarum strains exhibited broader predicted metabolic capacities than L. salivarius AF2319. However, genomic analysis revealed acquired AMR genes with complex genotype-phenotype relationships not fully apparent from phenotypic testing. The L. plantarum strains harbored lnu(A) (99.79% identity) on extrachromosomal DNA, conferring the L-phenotype (lincomycin resistance, clindamycin susceptibility); clindamycin MICs (1 mg/L) were concordant with this genotype, though lincomycin MICs were not determined. L. salivarius AF2319 carried tet(M), tet(L), and erm(C) (99.48%, 99.49%, and 99.45% identity by ResFinder, respectively) on extrachromosomal DNA; notably, the erythromycin MIC (1 mg/L) was precisely at the EFSA breakpoint (≤ 1 mg/L), representing borderline genotype-phenotype discordance potentially due to silent gene expression. Under current EFSA QPS criteria, these acquired ARGs would preclude all three strains from approval as probiotic feed additives despite favorable functional profiles, underscoring the indispensable role of WGS-based AMR gene detection in modern probiotic safety evaluation.

Probiotics↗
PubMed2026

Directed evolution of Lactiplantibacillus plantarum for utilizing ethanol to produce postbiotics.

Alcohol is a recognized carcinogen worldwide. In this study, we aimed to utilize probiotics to metabolize ethanol and produce postbiotics. Initially, we identified a lactic acid bacteria community in kimchi with excellent probiotic activity. By employing our previously developed directed evolution techniques, a Lactiplantibacillus plantarum mutant with safe characteristics and an ethanol utilization capacity of 40 g/L and 0.15 g/L/OD was obtained. Genome sequencing and RT-qPCR analysis revealed the up-regulated expression of alcohol dehydrogenase and aldehyde dehydrogenase genes greatly contributed to ethanol utilization. Furthermore, the mutant strain demonstrated marked superiority in producing postbiotics, including antimicrobial peptides and beneficial organic acids such as lactic acid, phenyllactic acid, succinic acid, and indole-3-lactic acid. In the ethanol-fed fermentation process, the mutant strain achieved a lactic acid yield of 8.47 g/L and a carbon conversion rate of 21.8%. In vivo testing further validated its safety and ability to assist alcohol metabolism.

Adaptive laboratory evolution↗
PubMed2025

Structural properties of short-chain carboxylic acids and alcohols relate to the molecular and physiological response of Salmonella enterica in an acidic environment.

Short-chain carboxylic acids (SCCA) and short-chain alcohols (SCALC) are naturally occurring antimicrobials that contribute to the biopreservation of food fermentations. This study investigated the effect of structurally different SCCA/SCALC with two-carbon (acetic acid; phenylacetic acid; 2-phenylethanol), three-carbon (propionic acid; 3-phenylpropionic acid; 3-phenylpropanol), and three-carbon chain with an additional hydroxyl group (lactic acid; 3-phenyllactic acid; 1-phenylpropanol) on the fitness, metabolic activity and gene expression of the pathogen Salmonella enterica at pH 4.5. SCCA inhibited Salmonella at lower concentrations than SCALC with the exception of lactic acid, which was partly consumed. The presence of a phenyl group enhanced antimicrobial activity. SCCA but not SCALC increased the lag phase of S. enterica, and in general, acetate was formed when cell growth was reduced by 20% suggesting a negative impact on bacteria fitness. Principal component analysis and hierarchical clustering indicated distinct gene expression profiles of S. enterica in response to SCCA or SCALC. In the presence of certain SCCA/SCALC, Salmonella activated pathways related to cellular pH control, and 1,2-propanediol, propionic acid and ethanolamine metabolism that involved the formation of metabolosomes. Genes related to flagellar assembly were less expressed and mobility was lower in the presence of lactic and 3-phenyllactic acid compared to controls suggesting a compound-specific response. KEY POINTS: • Differences in response among structurally different SCCA/SCALC at acidic condition. • SCCA/SCALC stress interfered with cell growth and metabolism of acetic and propionic acid. • Lactic acid prolonged the lag phase and reduced motility of Salmonella.

Salmonella enterica↗
PubMed2026

Multiomic insights into fungal polylactic acid degradation: Metabolic adaptation and hydrolytic mechanisms of Sporobolomyces pararoseus.

Polylactic acid (PLA), a biodegradable polyester from renewable resources, is a sustainable alternative to petrochemical plastics. However, its environmental degradation is inefficient naturally, requiring specific microbial activities. While bacterial PLA-degrading mechanisms are well documented, fungal degrading systems-particularly their molecular mechanisms-are underexplored.We isolated Sporobolomyces pararoseus ZRQ01 from the gut microbiota of PLA-fed mealworms. This fungal strain noticeably degraded PLA in PLA-containing medium supplemented with 2% glucose. Biodegradation assays revealed 22.8% loss of the PLA film weight after 35 days of incubation, and scanning electron microscopy confirmed extensive surface erosion and pore formation. Integrated transcriptomic and proteomic analyses, together with the reference genome of S. pararoseus ZRQ01, revealed that S. pararoseus ZRQ01 upregulates hydrolytic enzymes at both transcript and protein levels to cleave PLA into lactic acid. After lactic acid is transferred into S. pararoseus ZRQ01 cells by monocarboxylate transporters with increased abundance, it is assimilated by pathways of pyruvate metabolism and the TCA cycle with increased protein abundance. Intriguingly, upregulation of genes in autophagy-related and MAPK signaling pathways underscores an adaptive stress response potentially supporting cellular homeostasis and degradation-related gene expression. Our results highlight S. pararoseus ZRQ01's metabolic potential for bioremediation and offer insights into fungal bioplastic degradation pathways.

Polyesters↗
PubMed2026

Single-cell transcriptomics reveals heterogeneous stress responses and Mg2+-mediated survival mechanisms in Lactobacillus delbrueckii subsp. bulgaricus during freeze-drying and storage.

Maintaining the viability of lactic acid bacteria during dehydration and subsequent storage remains a significant challenge. Here, we employed single-cell RNA sequencing to reveal the heterogeneous stress responses of Lactobacillus delbrueckii subsp. bulgaricus, identifying seven distinct transcriptional clusters across the liquid culture, freeze-drying, and storage phases. The dominant clusters in the freeze-drying and storage were not completely consistent, showing significant functional differentiation. Genomic stability may be important for survival during freeze-drying and storage, while intracellular energy homeostasis appears important for viability during storage. The magnesium transporter mgtB was highly expressed in clusters tolerant to freeze-drying and storage, suggesting a critical role for Mg2+ homeostasis. Further experimental validation confirmed that Mg2+ treatment significantly bolstered stress resistance, increasing immediate post-freeze-drying survival by over 2-fold (up to 92.90%) and post-storage survival by over 5-fold (up to 5.98%). Proteomic data indicated that Mg2+ supplementation correlated with the maintenance of several biological functions potentially relevant to bacterial survival during freeze-drying and storage, including DNA repair, translation, and central carbon metabolism. These findings provide a map of microbial stress resistance through population heterogeneity and offer a potential strategy that may be adapted for enhancing the stability of other industrial lactic acid bacteria products.

Freeze Drying↗
PubMed2026

Hybrid genome assembly and phenotypic assays reveal carbohydrate metabolism diversity in Lacticaseibacillus strains.

Investigation of carbohydrate metabolism in lactic acid bacteria is essential for the rational selection of strains for fermentation processes, particularly in emerging applications involving non-conventional substrates or building of synthetic microbial consortia. However, establishing robust genotype-phenotype relationships remains challenging, as gene presence alone often fails to explain observed metabolic traits without considering the genomic context and regulatory architecture. In the present study, we combined hybrid genome assembly (Illumina and Oxford Nanopore) with high-throughput phenotype profiling (Biolog GENIII and PM2A) to investigate carbohydrate utilization in five Lacticaseibacillus strains. Phenotypic assays revealed clear intra- and inter-specific variability in substrate utilization. We therefore investigated whether such differences could be attributed to the organization and regulatory context of carbohydrate-associated loci, rather than to gene presence alone. Functional annotation based on COG and CAZyme databases revealed candidate genomic regions potentially involved in carbohydrate metabolism. Comparative analysis between predicted and experimentally observed substrate usage highlighted specific loci associated with carbohydrate utilization profile. The trehalose (tre) operon was conserved across all strains, while at least two distinct cellobiose-associated loci were detected in each genome. Despite the presence of these loci, L. paracasei strains were unable to metabolize cellobiose, a phenotype likely linked to the presence of a downstream TetR-type transcriptional repressor within the cellobiose (cel) operon. Additionally, a genomic region uniquely found in L. rhamnosus strains was associated with gentiobiose utilization, consistent with phenotypic observations. Overall, these findings highlight the importance of integrating phenotypic validation with complete genome context to support the identification of candidate structural and regulatory determinants of carbohydrate utilization in lactic acid bacteria. KEY POINTS: • Phenotype microarrays reveal metabolic traits of interest in isolated strains. • Regulatory context is key to understanding carbohydrate metabolism differences. • Basis of subspecies-dependent cellobiose metabolism in L. paracasei is provided.

Carbohydrate Metabolism↗
PubMed2026

Screening, Physiological Characterization, Genomic Analysis and Optimization by Conjugated Linoleic Acid Bioconversion of Two Lactiplantibacillus plantarum Strains.

Conjugated linoleic acid (CLA) comprises a group of C18 fatty acids containing conjugated double bonds and has been associated with potential anti-obesity and antitumor effects. In this study, 116 presumptive lactic acid bacteria (LAB) isolates were recovered from homemade Sichuan pickles. Primary screening identified 28 CLA-producing isolates, among which strains 7# and 31# showed the highest absorbance at 233 nm (A233). CLA production by both strains was subsequently optimized and quantified using gas chromatography-quadrupole time-of-flight mass spectrometry (GC-Q-TOF). Under the optimized conditions, strain 31# produced 66.50 ± 3.80 μg/mL total CLA, including 52.70 ± 3.29 μg/mL c9,t11-CLA and 13.80 ± 0.51 μg/mL t10,c12-CLA. Strain 7# produced 26.79 ± 1.09 μg/mL total CLA, including 14.05 ± 0.49 μg/mL c9,t11-CLA and 12.74 ± 0.60 μg/mL t10,c12-CLA. Physiological, biochemical, and safety assessments showed that strain 31# outperformed strain 7# overall, supporting its use in further product development and mechanistic studies. Functional annotation using the COG database and pathway mapping with KEGG identified candidate genes encoding an enzyme associated with linoleic acid isomerization in both strains. Potential mechanisms underlying their different CLA-producing capacities were also examined, providing a basis for the selection and development of high-CLA-producing strains.

conjugated linoleic acid↗
PubMed2026

Lpb. plantarum inhalation powders for the reduction of lung inflammation and S. aureus growth control in non-CF bronchiectasis.

INTRODUCTION: The reduced diversity of the lung microbiome in respiratory conditions, including bronchiectasis, promotes bacterial infection and inflammation, contributing to worsening clinical outcomes. Traditional treatments often fail to address both infection and inflammation. Because of their potential dual-action, lactic acid bacteria (LAB) directly administered to the lungs could represent an innovative therapeutic approach for these diseases. RESEARCH DESIGN AND METHODS: Two powders for inhalation containing Lpb. plantarum, lactose, l-leucine with and without raffinose, a prebiotic, were produced by spray drying and in vitro tested. The focus was on investigating their potential in vitro anti-inflammatory and anti-microbial activities against S. aureus. RESULTS: The powders showed a fine particle fraction (<5&#x2009;&#xb5;m) of >40% and allowed the maintenance of anti -inflammatory activity in vitro for both treatment and prevention. Moreover, both powders led to a significant reduction in S. aureus growth. The stability study of the powders in capsules at different storage conditions showed the preservation of the LAB up to 90&#x2009;days in refrigerated conditions (4&#xb0;C/-20&#xb0;C). CONCLUSIONS: This proof-of-concept study shows that inhalable spray-dried live LABs retain biological activity and are suitable for pulmonary delivery, supporting their potential as a microbiota-modulating therapy, which, however, requires further preclinical validation.

Inhalation↗
PubMed2026

Screening, isolation, and identification of Latilactobacillus sakei strains from kimchi with potential probiotic properties.

UNLABELLED: The study aimed to screen 40 lactic acid bacterial isolates from kimchi types to isolate Latilactobacillus (L.) sakei strains for their probiotic potential. Based on random amplified polymorphic DNA-based initial screening, 16&#xa0;S rRNA-based phylogeny, and species-specific PCR, three sakei strains (RKA, RKC, and TAB) were selected for evaluating their probiotic and functional attributes. The selected strains demonstrated probiotic characteristics, including acid tolerance (33-85%), bile salt tolerance (49-68%), cell surface hydrophobicity with ethyl acetate (11.5-25.6%) and hexane (21.0-47.4%), and auto-aggregation (12.6-44.0%). The safety of strains was assessed by &#x3b3;-hemolytic activity and susceptibility to most tested antibiotics, including carbenicillin, clindamycin, chloramphenicol, ampicillin, erythromycin, and tetracycline, with resistance to cefoxitin and metronidazole. Both crude and cell-free supernatants (CFSs) of selected strains were tested for antimicrobial and antioxidant activities, as well as for cytotoxic effects against human colon adenocarcinoma (Caco-2) cells. CFSs displayed DPPH and ABTS radical scavenging activities of 34.1-37.9% and 41.6-43.1%, whereas the crude ranged from 3.9 to 8.7% and 11.0-17.3%, respectively, supported by the presence of the sod and katA genes. All strains showed good resistance to hydrogen peroxide at various concentrations. Notably, RKC showed superior antimicrobial activity against Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans, compared to RKA and TAB. No significant cytotoxicity was observed in Caco-2 cells. In summary, these findings indicate the probiotic potential of L. sakei isolates and the preliminary functional properties of their CFSs; further genome-based characterization of selected strains is warranted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-04978-7.

Antimicrobial↗
PubMed2026

Bioactive macromolecules in LAB-fermented cereals: Mechanisms of formation, functional properties, and health benefits.

Cereal and pseudo-cereal based fermented food products represent a substantial segment of global diet, nutrition as well as food security. Fermentation, especially by Lactic Acid Bacteria (LAB) increases the nutritional and functional values of foods by increasing palatability, bioavailability and minimizing antinutritional factors. LAB plays a pivotal role in synthesizing bioactive peptides, vitamins, minerals and reducing anti-nutrients parallelly. This review elucidates the mechanism through which LAB revamping nutritional macromolecules, such as peptides and polysaccharides, during fermentation and their role in the development of traditional as well as modern fermented foods. Additionally, these fermented foods have been associated with several health benefits. Recent advancement in biotechnology such as genome sequencing, functional genomics, and AI-assisted bioinformatics, have significantly enhanced our understanding of the diversity of LAB, the metabolism, and adaptation mechanisms. The combination of in silico and experimental methods has enabled the development of novel food enzymes as well as highly precise fermentation processes. Together with new innovations, growing demands for quality, consistency, safety as well as health benefits point out the significance of continued research. More studies employing both conventional and modern methods are necessary to explore these food groups completely and achieve better food quality, increased nutrition, more health benefits and comprehensive socioeconomic advantages.

Bioactive macromolecules↗
PubMed2026

From bioactive compounds to volatile profiles: a multidimensional characterization of Indonesian stingless bee honeys.

BACKGROUND: Stingless bee honeys are drawing increasing attention as ingredients for functional foods and health-oriented products because of their distinctive sensory characteristics and bioactive potential. In this study, honeys collected from nine stingless bee species reared in West Sumatra, Indonesia, were comprehensively characterized using physicochemical indices, antioxidant assays [DPPH (i.e. 2,2-diphenyl-1-picrylhydrazyl) and ferric reducing antioxidant power], microbiological screening, volatile profiling [gas chromatography-mass spectrometry (GC-MS)] and Fourier transform infrared (FTIR) fingerprinting. RESULTS: Marked between-sample variability was observed across key quality attributes, including pH (2.80-3.68), Brix (49.83-61.25), viscosity (23.36-175.22&#x2009;cP) and color parameters. FTIR spectra were consistent with carbohydrate-rich matrices and exhibited carbonyl-related bands. GC-MS profiling identified linalool oxide isomers and junenol among the predominant volatiles. To the best of our knowledge, junenol has not previously been reported in stingless bee honey and may represent a potential regional chemical marker for Indonesian stingless bee honeys. Lactic acid bacteria were detected in selected samples, whereas yeast and mold were not detected. Antioxidant activities were comparatively low, which may reflect local environmental and ecosystem-related factors. CONCLUSION: The results provide a multi-parameter baseline for stingless bee honeys produced within a shared ecosystem in West Sumatra and demonstrate the value of integrating conventional chemical indices with FTIR and volatile fingerprints for quality assessment. This combined approach may also support future authentication and origin-tracing frameworks for Indonesian stingless bee honeys. &#xa9; 2026 Society of Chemical Industry.

Animals↗