Buddhiman Tamang

Toddy , a naturally fermented traditional beverage, is increasingly recognized not only as a cultural staple but also as a reservoir of diverse bioactive metabolites. However, the molecular mechanisms by which these compounds interact with host proteins involved in inflammation remain unclear. Earlier studies largely focused on metabolite profiling or basic in vitro assays, leaving a gap in structure‐based validation, molecular dynamics analysis, and pharmacokinetic assessment. To address this, the present study employed an integrated in silico approach combining molecular docking, long‐timescale molecular dynamics simulations, and ADMET prediction to evaluate the potential interactions of toddy ‐derived metabolites with inflammation‐associated protein targets relevant to gut inflammation. Using untargeted LC–MS/MS data, 520 metabolites were screened against 22 inflammation‐associated proteins known to be upregulated. Pfaffic acid emerged as a leading candidate and exhibited a favorable predicted binding affinity toward SerpinB4 (−10.0 kcal/mol), which was lower than that predicted for the reference drug etrasimod (−9.4 kcal/mol) under the computational conditions used. Interaction analysis revealed extensive hydrogen bonding, hydrophobic interactions, π–π stacking, and halogen contacts within the SerpinB4 binding pocket. These results were supported by 200 ns molecular dynamics simulations, demonstrating improved structural stability, reduced residue flexibility, enhanced compactness, and more favorable binding free energy.

Lactiplantibacillus plantarum is widely recognized for its probiotic and technological applications in fermented foods. This study comprehensively evaluated traditionally fermented bamboo shoot products from Tripura, India, as a source of functional lactic acid bacteria through safety assessment, in vitro probiotic characterization, antimicrobial activity, and whole-genome sequencing. A total of 160 bacterial isolates were obtained, among which eight exhibited high β-glucosidase activity. Among these, strain MP49 demonstrated the highest functional potential and was selected for detailed characterization. The strain showed tolerance to acidic conditions (pH 3) and bile salts (1%), along with auto-aggregation (77.55 ± 2.28%), co-aggregation (> 95%), and cell surface hydrophobicity (> 96%), indicating strong probiotic attributes. MP49 exhibited broad antimicrobial activity against Escherichia coli, Bacillus cereus, and Staphylococcus aureus, with inhibition zones up to 25 mm. Whole-genome analysis revealed probiotic-related genes for stress tolerance, adhesion, bacteriocin production, and diverse carbohydrate metabolism pathways supporting functional potential. Importantly, no virulence determinants or known transferable antimicrobial resistance genes were identified in the genome. Although mobile genetic element-related genes and insertion sequence families were detected, these findings are common in lactic acid bacteria and do not necessarily indicate safety risks. Therefore, the strain is considered to exhibit a favorable predicted safety profile based on the available genomic evidence. Lactiplantibacillus plantarum MP49 represents a functionally promising probiotic candidate from fermented bamboo shoots with potential for future application in functional food development, subject to further validation in host-cell, animal, and clinical studies.

Traditional fermented rice beverages are produced through complex microbial fermentation processes that influence their physicochemical characteristics and metabolite composition. In this study, metagenomic sequencing and GC-MS/MS-based metabolomics were integrated to characterize four indigenous rice beverages: Black Rohi Modh (BR), Rohi Modh (RH), Jou Bidwi (JOU), and Sai Mod (SM). All beverages were mildly acidic, with pH values ranging from 4.1 to 4.5 and titratable acidity between 0.58 and 0.72% lactic acid. Ethanol content varied among samples, with BR showing the highest concentration (8.13% v/v), followed by JOU and RH (approximately 5.5% v/v), while SM exhibited the lowest level (4.28% v/v). Antioxidant activity differed across beverages, with RH and BR demonstrating higher DPPH radical scavenging activity and SM showing the highest ferric reducing antioxidant power (96.93 µmol/mL). Metagenomic analysis generated 57.69 Mb of assembled sequences, identifying 48 microbial phyla and 1,785 species, with Eukarya accounting for 66.12% of the total community. Ascomycota predominated in BR and JOU, whereas Bacillota was more abundant in RH. The genus Saccharomyces was consistently dominant across samples. Functional annotation indicated enrichment in metabolic pathways related to carbohydrate and amino acid metabolism, as well as genes associated with ethanol biosynthesis and retinol metabolism pathways, reflecting microbial metabolic potential rather than direct vitamin production. Metabolomic profiling identified 113-167 metabolites per beverage, with 93 compounds shared among all samples. Correlation analysis revealed significant associations between Saccharomyces cerevisiae and short-chain fatty acids (ρ = 0.62-0.71, FDR < 0.05), indicating a strong positive relationship between microbial abundance and metabolite production.

This study presents a comprehensive metagenomic and computational investigation of seven high‐quality metagenome‐assembled genomes (MAGs) from gundruk , focusing on their taxonomic, functional, and enzymatic profiles. Among these, five MAGs harbor the bglA gene encoding 6‐phospho‐beta‐glucosidase, notably from Lactiplantibacillus plantarum TG15‐2, which exhibits strong myrosinase‐like activity in sinigrin degradation. Molecular docking revealed superior binding affinity of bglA (‐7.3 kcal/mol) compared to classical plant myrosinase (‐6.7 kcal/mol). Molecular dynamics simulations over 200 ns demonstrated enhanced stability, compactness, and consistent hydrogen bonding in the bglA ‐sinigrin complex, confirmed by lower RMSD and RMSF values and favorable binding free energies (−158.42 kJ/mol) via MM‐PBSA analysis. Functional annotations highlighted the presence of key probiotic and metabolic genes supporting bacterial resilience and fermentation adaptability. This integrated approach elucidates the microbial potential for glucosinolate biotransformation, paving the way for biotechnological exploitation in functional food design and nutraceutical development.

“Miyamikhri,” a traditionally fermented bamboo shoot consumed by the Dimasa tribe of Assam, was investigated using a multi-omics approach integrating metagenomics, functional prediction, molecular docking, and probiotic evaluation. Samples (M1, M2, M3; pH: 4.03–4.52) showed Bacillota dominance (50.04–100%), with notable abundance of Cyanobacteria (M1: 32.72%) and Proteobacteria (M2: 28.85%). At the genus level, Lactobacillus (38.75–60.86%), Weissella, and Pediococcus were predominant. Diversity indices indicated M3 had the highest diversity species (Simpson: 0.7099; Evenness: 0.9199), while M1 showed the highest richness (Chao-1 = 6). Functionally, predictive KEGG analysis identified enrichment in metabolism (29.72%) and disease-related pathways (23.27%). Genes related to dopaminergic synapse (mao, comt, ddc, th), cyanoamino acid metabolism (bgl) and glycerolipid metabolism (mgll, gk, agpat1, lpin1) were detected. From 51 LAB isolates, eight showed high β-D-glucosidases activity (> 0.7 µg/mL pNP); Levilactobacillus brevis M12 exhibited the highest activity under optimal conditions (pH 5, 30 °C, 7% NaCl). Molecular docking revealed highest affinity of − 8.049 kcal/mol (M12) with taxiphyllin. MD simulations (100 ns) confirmed complex stability (RMSD: 0.27 ± 0.04 nm, avg. H-bonds: 6.86), and MM-PBSA calculations showed stronger binding for M12 (–190.28 kJ/mol) over L. plantarum WCFS1 (–49.16 kJ/mol).

Fermented bamboo shoot (FBS) products are widely consumed traditional foods across the Northeast region (NER) of India, yet their microbiome structure, functional capacity, biosynthetic potential, and safety attributes remain insufficiently explored. Here, comparative shotgun metagenomics of ten traditional FBS products from six NER states was used to address these gaps integrating previously generated metagenomic data from Tripura with newly generated datasets from Manipur, Meghalaya, Arunachal Pradesh, Nagaland, and Sikkim thereby bringing the total number of samples to 24. Taxonomic profiling revealed a predominance of lactic acid bacteria, primarily members of Lactiplantibacillus, Levilactobacillus, Lactobacillus, Lactococcus, and Pediococcus, with pronounced product- and region-specific community signatures. Functional annotation demonstrated predominance of genes involved in carbohydrate metabolism, stress response, quorum sensing, ABC transporters, vitamin biosynthesis, and energy metabolism, supporting strong probiotic-associated functional potential across FBS types. AntiSMASH analysis enabled the identification of diverse biosynthetic gene clusters (BGCs) responsible for the production of various secondary metabolites, including bacteriocins, non-ribosomal peptides, terpenes, and siderophores, with higher biosynthetic diversity observed in Mesu (Sikkim), Tuaithar (Manipur), Lung-Seij (Meghalaya), and Bastenga (Nagaland). Antimicrobial resistance (AMR) profiling revealed a generally low resistome burden, dominated by intrinsic resistance determinants, with FBS Sikkim and Tripura exhibiting the lowest AMR prevalence among all products. High-quality metagenome-assembled genomes affiliated with Lactiplantibacillus plantarum, Lactobacillus acetotolerans, and Pediococcus pentosaceus exhibited conserved probiotic traits, carbohydrate-active enzymes, biosynthetic pathways, and a limited presence of mobile genetic elements. Overall, the microbiome-based comparative analysis provides a framework for understanding the microbial community structure and functional potential across the NER, demonstrating broad probiotic potential and biosynthetic richness, with mesu samples from Sikkim showed a comparatively consistent distribution of functional pathways, biosynthetic gene clusters, and AMR-related features relative to the other FBS samples analysed.

This study explores the therapeutic potential of metabolites derived from fermented bamboo shoots (FBS) ekung , hirring , and mesu with a focus on their interaction with cancer‐associated protein targets. LC‐MS/MS‐based metabolomic profiling identified 138–161 unique metabolites across FBS samples, with butin consistently upregulated. Reverse docking of 81 metabolites against 21 cancer‐associated proteins revealed that butin exhibited the highest binding affinity with GTPase HRAS (PDB ID: 6ZL3; −9.41 kcal/mol), outperforming the FDA‐approved inhibitor tipifarnib (−7.5 kcal/mol). Protein–ligand interaction analysis showed that butin formed seven hydrogen bonds and π‐stacking, while tipifarnib lacked hydrogen bonding. ADMET profiling indicated butin had superior drug‐likeness (QED: 0.694), favorable permeability, no hERG cardiotoxicity risk, and P‐glycoprotein inhibitory activity. Molecular dynamics (MD) simulations over 200 ns further validated these findings. Butin–HRAS complexes showed greater structural stability (RMSD: 0.339 ± 0.045 nm), lower atomic fluctuations (RMSF: 0.223 ± 0.14 nm), and higher protein compactness (Rg: 1.651 ± 0.032 nm) compared to tipifarnib. Butin also maintained 0–8 stable hydrogen bonds, a consistent binding pose, and a more compact free energy landscape. MM‐PBSA calculations confirmed favorable binding energetics. Overall, butin represents a promising HRAS‐targeted anticancer agent derived from traditional FBS fermentation.