Jae-Hwan Lee

Alcohol-associated liver disease (ALD) contributes substantially to the global burden of chronic liver disease, yet few effective pharmacological treatments are currently available. The hepatoprotective potential of Lactobacillus helveticus HY7804 was evaluated in ethanol-exposed HepG2 cells and in a modified chronic-binge ethanol-fed mouse model adapted from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) paradigm. Ethanol-induced cytotoxicity in HepG2 cells was attenuated by HY7804, as demonstrated by the recovery of cell viability and the reduction in lactate dehydrogenase release. HY7804 also decreased ethanol-induced inflammatory cytokine production, including IL-6, TNF-α, IL-1β, and IL-8, and modulated apoptosis-related gene expression. In chronic-binge ethanol-fed mice, HY7804 reduced serum AST from 183.4 ± 34.1 to 129.4 ± 16.4 U/L (p < 0.01) and ALT from 67.5 ± 4.5 to 52.1 ± 4.7 U/L (p < 0.05). Hepatic lipid accumulation was also significantly reduced by HY7804 treatment compared with the EtOH group, as indicated by the decreased Oil Red O-positive area (p < 0.01). Hepatic MDA levels decreased from 46.01 ± 3.38 to 30.58 ± 6.38 nmol/mg tissue (p < 0.01). In addition, HY7804 modulated hepatic inflammatory cytokine profiles, antioxidant-related responses, and the Bax/Bcl-2 expression ratio. These findings suggest that HY7804 mitigates ethanol-induced hepatic injury, with associated changes in inflammatory responses, antioxidant-related markers, lipid peroxidation, and apoptosis-related gene expression.

Dong-Ki Hong, Soomin Jeon, Man Young Jo, Soo-Dong Park, Il-Dong Choi, Jae-Jung Shim, Do Yup Lee, and Jae-Hwan Lee. J. Microbiol. Biotechnol. 2026;36:1-12. https://doi.org/10.4014/jmb.2604.04018

Background/Objectives: Hypertriglyceridemia is a critical cardiovascular risk factor, and the probiotic combination of Latilactobacillus curvatus HY7601 and Lactiplantibacillus plantarum KY1032 (HY+KY) has emerged as a potential therapeutic strategy, though clinical validation in adults with mild hypertriglyceridemia (HTG) is needed. Methods: In this randomized, double-blind, placebo-controlled, 12-week trial, a total of 100 overweight participants with mild HTG were randomized (n = 50 per group). Ultimately, 80 participants completed the study without major protocol violations and were evaluated in the Per-Protocol Set (probiotics group: n = 41; placebo group: n = 39). Primary outcomes included changes in serum lipid profiles such as triglycerides (TG) and LDL cholesterol (LDL), metabolic biomarkers, and gut microbiota composition analyzed via 16S rRNA gene sequencing. Results: HY+KY supplementation led to significant reductions in serum TG (158.61 ± 23.17 to 139.54 ± 54.31 mg/dL, p = 0.009) and LDL (129.22 ± 28.45 to 111.34 ± 21.03 mg/dL, p = 0.005) compared to baseline, while the placebo group showed no significant changes. Furthermore, the HY+KY group exhibited a significant increase in Apolipoprotein CII (ApoC2, p = 0.034) and a reduction in fasting glucose levels (p = 0.021). Microbiome analysis revealed that HY+KY significantly increased alpha diversity (Shannon index, p = 0.012) and significantly altered the microbial community structure (beta diversity, p = 0.015). Co-occurrence network analysis identified Lactiplantibacillus as a highly connected central node that is strongly associated with the favorable shifts in clinical biomarkers. Conclusions: HY+KY supplementation was associated with improved fasting TG and LDL profiles in adults with mild HTG, alongside coordinated changes in ApoC2, fasting glucose, and gut microbiota structure. These findings support the potential of probiotic supplementation as a preventive nutritional approach in borderline HTG.

Chronic kidney disease (CKD), a progressive disorder leading to renal dysfunction, remains a significant global health issue. This study investigated whether Lactiplantibacillus plantarum HY7718 modulates gut–kidney axis-associated inflammatory, gastrointestinal, and microbial alterations in a mouse model of adenine-induced chronic kidney disease. We examined fibrosis- and inflammation-related gene expression in mouse tissues and analyzed the gut microbiota via next-generation sequencing. HY7718 supplementation was associated with reduced expression of genes related to renal fibrosis (Col1a1, Acta2) and vascular inflammation (Icam-1, Vcam-1). Further, HY7718 suppressed intestinal inflammatory responses, including downregulation of pro-inflammatory cytokines (Tnf, Il-1β, Il-6) and TLR4/MyD88/NF-κB signaling pathway genes in the colon tissues. Gastrointestinal function was also improved, with significant upregulation of gastric motility-related genes and increased digestive enzyme activity. The gut microbiota composition was altered by HY7718, with reduced abundance of pro-inflammatory taxa such as Mucispirillum and Deferribacterota, whereas beneficial genera like Lactiplantibacillus were enriched. These microbial shifts were associated with reduced intestinal inflammatory and renal fibrosis-related markers. Overall, the findings indicate that HY7718 supplementation modulates gut–kidney axis-associated inflammatory, gastrointestinal, and microbial alterations in adenine-induced CKD mice and supports further investigation of this strain in CKD-related settings.

Lactiplantibacillus plantarum HY7715, isolated from Korean kimchi, has been previously reported to overproduce riboflavin in vitro and in vivo, indicating its functional potential as a probiotic candidate. Given this characteristic, a comprehensive safety and genomic evaluation is required prior to application. In this study, we assessed the safety, genomic stability, and probiotic–related properties of HY7715 through whole–genome sequencing, comparative genomics, and phenotypic analyses. The genome (3,348,486 bp; 44.29% GC content) was assembled into seven contigs and encoded 3,224 protein–coding sequences, of which 2,933 functionally annotated. No virulence factors or acquired antimicrobial resistance genes were detected, and mobile genetic elements did not harbor undesirable determinants. Although phenotypic resistance to kanamycin was observed, the absence of corresponding resistance genes indicates intrinsic resistance. HY7715 also exhibited γ-hemolysis and lacked genes associated with cytotoxic secondary metabolites or biogenic amine production. The rib operon was identified in the genome, and in silico analysis of the FMN riboswitch region revealed a unique nucleotide substitution potentially affecting regulatory conformation, which may contribute to the riboflavin–overproducing phenotype. Comparative pangenome analysis of 60 L. plantarum genomes revealed that HY7715 shares a conserved genomic backbone dominated by core and soft–core genes. Genes associated with stress tolerance, adhesion, carbohydrate utilization, and bacteriocin production were identified, consistent with probiotic–related traits. Collectively, these findings indicate that HY7715 is a genomically stable and safe strain with regulatory features supporting its functional probiotic potential.

Inflammatory bowel disease (IBD) involves chronic inflammation and disruption of the intestinal barrier, often accompanied by alterations in gut microbiota composition. This study examined the protective potential of a prebiotic mixture extract (PME) prepared from Vigna radiata (mung bean), Vigna angularis (red bean), and Foeniculum vulgare (fennel) using the HT-29 cell and colitis animal model. PME exhibited concentration-dependent antioxidant activity, with greater radical-scavenging capacity in the ABTS assay than in the DPPH assay. In LPS-stimulated HT-29 epithelial cells, PME reduced the mRNA expression of inflammation-associated genes (TNF-α, IL-1β, NF-κB) and upregulated tight junction markers (CLDN1 and OCLN), demonstrating its anti-inflammatory and supportive effects on the intestinal barrier. Vitexin, a C-glycosylated flavonoid, was detected in PME and is expected to mediate these protective effects. In a DSS-induced colitis mouse model, PME administration alleviated disease severity by increasing colon length, reducing serum levels of inflammatory cytokines and COX-2/PGE2, and restoring intestinal permeability. Furthermore, PME modulated the gut microbiota by enhancing beneficial bacteria such as Bifidobacterium and Faecalibaculum while suppressing inflammation-associated taxa, including Escherichia, Bacteroides, and Mucispirillum. These improvements collectively suggest that PME reinforces epithelial barrier integrity and promotes intestinal homeostasis through both anti-inflammatory and microbiota-regulating actions.

This study investigated the therapeutic potential of Codonopsis lanceolata peel extract (CPE) for premenstrual syndrome (PMS). The focus was on hormonal, immune, and microbial pathways. In vitro, CPE reduced nitric oxide production and suppressed IL-6 and TNF-α expression in LPS-stimulated macrophages. In pituitary GH3 cells stimulated with estradiol, CPE inhibited prolactin secretion. In a metoclopramide (MCP)-induced hyperprolactinemia mouse model, CPE decreased serum prolactin, PGE2, and inflammatory cytokines, while increasing PGE1 and FSH levels. Microbiome analysis showed that CPE enriched beneficial genera such as Lactobacillus and Bifidobacterium and reduced pro-inflammatory taxa including Oscillibacter and Desulfovibrionaceae . These microbial shifts were associated with improved inflammatory and hormonal markers. Overall, these findings suggest that CPE alleviates PMS symptoms by modulating endocrine function and regulating gut microbiota.

Chronic kidney disease (CKD) causes a variety of health problems including renal dysfunction and cardiovascular disease. This study aimed to investigate whether the probiotic strain Lactiplantibacillus plantarum HY7718 (HY7718) can protect against CKD using HK2 cells and a CKD mouse model, generated by feeding mice a diet containing 0.15% adenine. In vitro tests showed that HY7718 was anti-inflammatory in H₂O₂-treated HK2 cells and reduced apoptosis of tumor necrosis factor-α/cycloheximide-induced HK2 cells. In the adenine-induced CKD model, markers of renal dysfunction (blood urea nitrogen (BUN) and creatinine (Crea)) and inorganic calcium and phosphorus were markedly increased. However, oral administration of HY7718 (10⁸ colony-forming units/kg/day) significantly attenuated these increases. HY7718 also reduced the kidney histopathological score, including tubular necrosis, cast formation, and tubular dilatation, as well as the mononuclear cell infiltration score in kidney tissue, suggesting that it could reverse the progression of CKD. Additionally, HY7718 downregulated the renal expression of pro-inflammatory cytokine genes and members of the TLR/NF-κB signaling pathway. Furthermore, HY7718 reduced tubule apoptotic cells and expression of apoptosis-related genes, indicating that it is potentially renoprotective. These results demonstrate that supplementation with the probiotic HY7718 can ameliorate CKD symptoms by improving renal function and reducing kidney injury.

Anxiety disorders are closely associated with oxidative stress-mediated neuronal damage, mitochondrial dysfunction, and apoptosis. In this study, we investigated the neuroprotective effects of Lactiplantibacillus plantarum HY7715 in a mouse model of restraint stress-induced anxiety, and in neuronal cell models (HT-22 mouse hippocampal neuroblast cell and SH-SY5Y human neuroblastoma cells). Oral administration of HY7715 (1 × 10⁹ CFU/kg/day) alleviated anxiety-like behaviors significantly, as shown by increased central exploration in the open field test and prolonged open-arm activity in the elevated plus maze. HY7715 reduced serum norepinephrine levels elevated by stress, and restored hippocampal expression of brain-derived neurotrophic factor, while suppressing pro-inflammatory (NF-κB, IL-6) and pro-apoptotic (BAX, caspase-3) markers. It also increased expression of mitochondrial regulatory genes (SIRT1, mTOR), and decreased that of cytochrome c, in brain tissue. Histological analysis revealed that HY7715 preserved neuronal integrity in the CA1 and CA3 hippocampal regions. In vitro, HY7715 attenuated oxidative stress-induced cytotoxicity, decreased intracellular ROS accumulation, maintained mitochondrial activity, and inhibited apoptosis of both neuronal cell types, showing greater efficacy than the strain type L. plantarum KCTC3108. These findings suggest that HY7715 exerts neuroprotective effects by modulating oxidative stress/apoptosis/mitochondrial pathways, and highlight its potential as a psychobiotic for stress-related neuropsychiatric disorders.

Stress is a major factor that threatens the body’s homeostasis or well-being. Excessive stress causes psychological anxiety and tension, which disrupts the balance of the autonomic nervous system that maintains the body’s balance, resulting in hormonal imbalance and brain changes. In this study, we investigated the effects of Withania somnifera (Ashwagandha) extract on depression, neurobehavior, and hippocampal changes in model mice exposed to stress. Using an excessive restraint stress-induced depression model, we measured the behavioral changes and the levels of brain-derived neurotrophic factor (BDNF) and antioxidant genes in five groups: control, stress, low-dose W. somniferous extract (20 mg/kg/day), high-dose W. somniferous extract (40 mg/kg/day), and L-theanine (50 mg/kg/day, positive control). Stressed mice showed poorer performance in the open field and elevated plus maze tests compared with the control group. The impaired performance was restored following W. somniferous extract administration. In addition, W. somniferous extract restored the decreased expression of BDNF in the hippocampus caused by restraint stress, improved the balance of stress hormones (i.e., cortisol, dopamine, and norepinephrine), and also regulated BDNF, inflammatory genes, and antioxidant genes in brain tissue. Therefore, W. somniferous extract can induce antidepressant and anti-stress effects by maintaining brain BDNF expression and preventing hippocampal tissue alterations caused by restraint stress.