Mon-Chien Lee

Live and heat-treated microbial preparations are candidate nutritional ingredients for supporting function during aging. This study evaluated Lacticaseibacillus paracasei NB23 in naturally aged male C57BL/6NCrl mice. Ten young mice served as a reference group, and forty aged mice received vehicle, live NB23 at 2.05 × 10⁹ or 6.15 × 10⁹ colony-forming units (CFU)/kg/day, or heat-treated NB23 at 6.15 × 10⁹ cell equivalents/kg/day for 12 weeks. Relative to aged controls, NB23-treated mice had shorter water-maze acquisition latency, longer treadmill endurance, higher hepatic antioxidant enzyme activities and glycogen, and lower selected whole-brain oxidative-damage markers. High-dose live and heat-treated NB23 also increased grip strength and muscle glycogen. Gastrocnemius myofiber area and selected femoral microarchitectural outcomes improved, whereas rotarod performance and tibialis anterior myofiber area did not. Exploratory analyses of brain and intestinal transcripts, fecal metabolites, and microbiota–host associations did not establish a gut-mediated mechanism. Among 325 taxon–outcome pairs in the exploratory microbiome–host screen, 49 met nominal p < 0.05, but none survived Benjamini–Hochberg correction (minimum adjusted p = 0.08967). Assay-specific subsets comprised four mice per group for micro-CT and five per group for qPCR, fecal metabolites, and microbiome sequencing, with two gene-specific qPCR exclusions. These findings support further evaluation of NB23 as a functional food ingredient, while the small, male-only animal study does not establish clinical anti-aging efficacy or equivalence of the live and heat-treated preparations.

Background: Exercise-induced fatigue (EIF) and exercise-induced muscle damage (EIMD) impair neuromuscular performance and delay post-exercise recovery. However, human evidence regarding the structural and functional recovery kinetics following Lactiplantibacillus plantarum GKK1 supplementation remains limited. Objective: This randomized, double-blind, placebo-controlled trial investigated whether 4 weeks of L. plantarum GKK1 supplementation improves functional recovery and modulates biochemical responses after an EIMD protocol in healthy men. Methods: Forty-eight healthy men with no regular exercise habits were randomly assigned to receive either placebo (n = 24) or L. plantarum GKK1 (two capsules daily, totaling 1.0 × 10¹¹ CFU; n = 24) for 28 consecutive days. The trial was registered at ClinicalTrials.gov (NCT06893549). After supplementation, participants completed 100 maximal plyometric jumps. Countermovement jump (CMJ), isometric mid-thigh pull (IMTP), and Wingate anaerobic performance were assessed before EIMD and at 3, 24, and 48 h post-EIMD. Blood biomarkers of muscle damage, inflammation, oxidative stress, endocrine response, and sympathoadrenal activity were analyzed, and urinary 3-methylhistidine and creatinine were measured. Results: Compared with placebo, GKK1 supplementation was associated with smaller post-exercise decrements in the CMJ rate of force development, relative peak force, jump height, IMTP relative peak force and peak RFD, and Wingate anaerobic performance (p < 0.05). GKK1 also attenuated post-exercise increases in CK, myoglobin, hs-CRP, and TBARS, and was associated with more favorable testosterone, HGH, catecholamine, and dopamine responses. At 24 h post-EIMD, urinary 3-methylhistidine and the 3-methylhistidine/urinary creatinine ratio were lower in the GKK1 group than in the placebo group. No adverse changes were observed in clinical safety biomarkers. Conclusion: These findings suggest that GKK1 may be a safe nutritional strategy to facilitate functional recovery, attenuate secondary inflammatory responses and modulate urinary markers associated with muscle breakdown following muscle-damaging exercise in healthy young men.

While high-intensity interval training (HIIT) enhances physical conditioning, its specific impact on the TMG-derived mechanical properties of rowing-related muscles and sport-specific performance remains underexplored. This study investigated the effects of a 4-week rowing ergometer-based HIIT intervention on 2000-m rowing performance and muscle mechanical properties, evaluated via tensiomyography (TMG). Seventeen rowers were randomized into the HIIT group (n = 9) or the control group (CON, n = 8). Over four weeks, the HIIT group completed two weekly rowing ergometer HIIT sessions (ten 60-s all-out sprints, 30-s recovery), while the CON group continued regular training without additional HIIT. Pre- and post-intervention, participants underwent a 2000-m ergometer trial and TMG assessments across five rowing-related muscles. The HIIT group demonstrated a 3.1% reduction in 2000-m completion time, together with increases in mean power output (7.7%) and stroke rate (6.5%) (group × time interaction η²p = 0.53, 0.39, and 0.27, respectively; p < 0.05). TMG analysis showed shortened delay time (Td) and half-relaxation time (Tr) across all targeted muscles after false discovery rate correction. Contraction time (Tc) was shortened in the tibialis anterior and vastus medialis, while the erector spinae showed a nominal uncorrected change that should be interpreted cautiously. Maximal displacement (Dm) and sustain time (Ts) remained unchanged. These findings suggest that short-term rowing-specific HIIT is associated with improved 2000-m performance and TMG-derived peripheral temporal properties; however, unchanged Dm should be interpreted only as no detectable change in radial displacement under the present TMG conditions rather than definitive evidence of unchanged muscle stiffness. Because of the small sample size, unbalanced total training load between groups, and the absence of direct physiological or biomechanical measurements such as VO₂max, lactate, electromyography, and stroke biomechanics, these findings should be interpreted as preliminary.

Background: Insomnia is prevalent and difficult to treat safely over the long term. Given the role of the microbiota–gut–brain axis in melatonin and hypothalamic–pituitary–adrenal (HPA) regulation, and preclinical evidence for Limosilactobacillus fermentum PS150, we evaluated whether a heat-treated formulation (HT-PS150) could improve sleep and modulate endocrine/circadian markers in adults with poor sleep. Methods: In a randomized, double-blind, placebo-controlled trial, 84 adults aged 20–60 years with PSQI ≥ 5 and ISI < 22 were assigned to receive either placebo or HT-PS150 for eight weeks. Outcomes included patient-reported sleep (PSQI, ISI), anxiety/depression (GAD-7, PHQ-9), quality of life (QLESQ-SF), gastrointestinal symptoms (VAS-GI), wrist actigraphy (Fitbit Inspire 3), and sleep-relevant biomarkers measured from urine, saliva, and/or blood samples (melatonin, cortisol, orexin, serotonin, GABA, and/or norepinephrine). Repeated measures were analyzed using generalized estimating equations. An exploratory proportional regulation analysis classified individual biomarker changes as up- or down-regulated and compared proportions between study arms. Per-protocol analyses required ≥80% compliance. Results: Improvements in the primary outcomes, PSQI and ISI, were observed over time in both groups, while no significant group × time interactions were detected. In exploratory proportional analyses, a higher proportion of participants in the HT-PS150 group exhibited up-regulated nocturnal melatonin secretion and improved daytime plasma orexin levels, as well as a tendency toward greater reductions in nocturnal salivary cortisol compared with placebo. In subgroup analyses with higher baseline insomnia severity (ISI ≥ 8), HT-PS150 was associated with greater improvements in PSQI (notably sleep duration and efficiency) and reduction in anxiety (GAD-7) upon post hoc testing. Conclusions: Although group mean scores on sleep symptom scales did not differ significantly in the full cohort, HT-PS150 appeared to modulate sleep–wake regulation by enhancing nocturnal melatonin secretion, attenuating HPA-axis activity, and stabilizing wakefulness. Clinical benefits were most evident among participants with greater baseline symptom burden, suggesting potential utility in more symptomatic populations.

Chronic psychological stress impairs neuroendocrine balance and increases the risk of mental health disturbances, including anxiety, sleep disruption, and low mood. The gut–brain axis has emerged as a promising target for stress modulation, particularly through psychobiotic interventions. This randomized, double-blind, placebo-controlled trial evaluated the effects of a combined psychobiotic formulation (Neuralli Mood), comprising live Lactiplantibacillus plantarum PS128 (PS128) and heat-treated Lacticaseibacillus paracasei PS23 (HT-PS23), on the psychological and physiological stress responses in a high-stress occupational population. A total of 116 healthy participants with elevated perceived stress (PSS ≥ 14), primarily firefighters, were randomly assigned to receive the dual-strain supplement or placebo for 8 weeks. Stress-related outcomes were assessed by using validated psychological scales and serum biomarkers. Compared with placebo, the psychobiotics group showed significantly greater reductions in overall job stress perception (JSS), state anxiety (STAI), and insomnia severity (ISI) (all p < 0.05). Additionally, serum adrenocorticotropic hormone (ACTH) and norepinephrine levels were significantly reduced post-intervention, whereas cortisol levels remained unchanged. These findings suggested that combining live and heat-treated psychobiotic strains may provide a safe and effective strategy for alleviating psychological stress and regulating neuroendocrine function in high-risk populations.

Background/Objectives: Aging is characterized by progressive physiological and metabolic decline. Aerobic exercise mitigates age-related impairments, and nicotinamide mononucleotide (NMN), a precursor in the NAD⁺ salvage pathway, has emerged as a nutritional intervention to promote healthy aging. This study investigated whether NMN supplementation combined with aerobic exercise provides synergistic benefits on physical performance and metabolic regulation in aged mice. Methods: Forty male C57BL/6J mice, including eight young (8 weeks) and thirty-two aged (85 weeks) mice, were randomly assigned to five groups: young sedentary (YS), aged sedentary (AS), aged with exercise (AE), aged with NMN (ASNMN; 300 mg/kg/day), and aged with combined NMN and exercise (AENMN). Interventions lasted six weeks. Assessments included grip strength, muscle endurance, aerobic capacity, oral glucose tolerance test (OGTT), and indirect calorimetry, followed by biochemical and molecular analyses of NAMPT and SirT1 expression. Results: The AENMN group demonstrated significant improvements in maximal strength and aerobic endurance compared with the AS group (p < 0.05). Both NMN and exercise interventions increased blood NAMPT concentrations, with the highest levels observed in the AENMN group (p < 0.05). SirT1 expression was elevated in the ASNMN and AENMN groups relative to YS (p < 0.05). Glucose tolerance improved in the ASNMN and AENMN groups (p < 0.05). Enhanced energy metabolism in the AENMN group was indicated by increased oxygen consumption, elevated energy expenditure, and reduced respiratory quotient. Conclusions: NMN supplementation, particularly when combined with aerobic exercise, effectively improved aerobic performance, glucose regulation, and systemic energy metabolism in aged mice. These findings suggest that NMN, in synergy with exercise, may serve as a promising nutritional strategy to counteract age-associated metabolic and functional decline.

Background: Exercise-induced fatigue arises primarily from energy substrate depletion and the accumulation of metabolites such as lactate and ammonia, which impair performance and delay recovery. Emerging evidence implicates gut microbiota modulation—particularly via probiotics—as a means to optimize host energy metabolism and accelerate clearance of fatigue-associated by-products. Objective: This study aimed to determine whether live or heat-inactivated Lacticaseibacillus paracasei NB23 can enhance exercise endurance and attenuate fatigue biomarkers in a murine model. Methods: Forty male Institute of Cancer Research (ICR) mice were randomized into four groups (n = 10 each) receiving daily gavage for six weeks with vehicle, heat-killed NB23 (3 × 10¹⁰ cells/human/day), low-dose live NB23 (1 × 10¹⁰ CFUs/human/day), or high-dose live NB23 (3 × 10¹⁰ CFUs/human/day). Forelimb grip strength and weight-loaded swim-to-exhaustion tests assessed performance. Blood was collected post-exercise to measure serum lactate, ammonia, blood urea nitrogen (BUN), and creatine kinase (CK). Liver and muscle glycogen content was also quantified, and safety was confirmed by clinical-chemistry panels and histological examination. Results: NB23 treatment produced dose-dependent improvements in grip strength (p < 0.01) and swim endurance (p < 0.001). All NB23 groups exhibited significant reductions in post-exercise lactate (p < 0.0001), ammonia (p < 0.001), BUN (p < 0.001), and CK (p < 0.0001). Hepatic and muscle glycogen stores rose by 41–59% and 65–142%, respectively (p < 0.001). No changes in food or water intake, serum clinical-chemistry parameters, or tissue histology were observed. Conclusions: Our findings suggest that both live and heat-treated L. paracasei NB23 may contribute to improved endurance performance, increased energy reserves, and faster clearance of fatigue-related metabolites in our experimental model. However, these results should be interpreted cautiously given the exploratory nature and limitations of our study.

Background: As individuals age, there is a gradual loss of muscle mass and strength, which not only impairs physical functionality but also heightens the risk of falls and diminishes independence among older adults. Probiotics have emerged as a focus of recent research due to their potential role in enhancing muscle health via the gut–muscle axis. This study evaluates the effects of live and heat-treated Lacticaseibacillus paracasei PS23 (PS23) supplementation on muscle strength and mass in the elderly. Methods: This study recruited 119 participants, aged 65–85 years, and randomly assigned them to receive a placebo (0 × 10¹⁰ CFU/day), L-PS23 (live PS23, 2 × 10¹⁰ CFU/day), or HT-PS23 (heat-treated PS23, 2 × 10¹⁰ cells/day) for a duration of 12 weeks. Assessments of blood pressure, body composition, muscle strength, functional physical fitness, and biochemical parameters were conducted at baseline, 6 weeks, and 12 weeks. Results: Among the 100 subjects who completed the trial, supplementation with both L-PS23 and HT-PS23 significantly enhanced lower limb muscle strength and endurance compared to the placebo (p < 0.05), although no significant differences were observed in muscle mass or upper limb muscle strength across the groups. Additionally, while most muscle anabolism-related markers showed no significant changes, both supplements effectively decreased inflammatory markers related to aging—C-reactive protein (CRP: L-PS23, p = 0.016; HT-PS23, p = 0.013) and interleukin-6 (IL-6: L-PS23, p = 0.003; HT-PS23, p < 0.001)—and increased interleukin-10 levels (L-PS23, p = 0.014; HT-PS23, p = 0.005). Notably, only the HT-PS23 group demonstrated a significant increase in testosterone levels (p = 0.029). Conclusions: 12 weeks of supplementation with L-PS23 and HT-PS23 improved lower limb muscle strength and endurance but did not significantly enhance muscle mass in older adults. Both supplements also proved effective in reducing inflammatory markers and elevating testosterone levels. HT-PS23, administered as a heat-treated probiotic, provided more pronounced benefits to the elderly compared with its probiotic counterpart, L-PS23.

Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO_2max), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion (p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage (p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 (p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.