Oral administration of Lactobacillus delbrueckii subsp. lactis LDL557 attenuates airway inflammation and changes the gut microbiota in a Der p-sensitized mouse model of allergic asthma.

BACKGROUND: Lactic acid bacteria may be used as probiotics to prevent or treat various diseases, and Lactobacillus delbrueckii has an inhibitory effect on the development of atopic diseases. OBJECTIVE: This study explored the effects of L. delbrueckii subsp. lactis strain LDL557 administration on a mouse asthma model resulting from Dermatophoides pteronyssinus (Der p) sensitization and investigated the associated gut microbiota. METHODS: Der p-sensitized and challenged BALB/c mice were orally administered with three different doses of live (low, 107 colony-forming units (CFU); medium, 108 CFU; high, 109 CFU) and heat-killed (109 cells) LDL557 in 200 µL of PBS daily, starting 2 weeks before Der p sensitization and lasting 4 weeks. After the allergen challenge, airway responsiveness to methacholine and the influx of inflammatory cells to the lungs were assessed. The gut microbiome was obtained by sequencing the V3-V4 region of the 16S rRNA gene from mice stool samples. RESULTS: LDL557 in the live (109 CFU) and heat-killed (109 cells) conditions reduced the airway hyper-responsiveness after stimulation with methacholine, inflammatory cell infiltration, and mucus production. These effects were similar to those in groups treated with dexamethasone. No significant change in the gut microbiota was observed after LDL557 treatment, except for the tendency of heat-killed LDL557 to change the gut microbial profile to a greater extent than live LDL557. CONCLUSION: In summary, we found that live and heat-killed LDL557 had the beneficial effect of preventing Der p-induced allergic inflammation in a mouse model of asthma.

Effects of heat-killed Lactiplantibacillus plantarum TWK10 on exercise performance, fatigue, and muscle growth in healthy male adults.

Consumption of Lactiplantibacillus plantarum TWK10 (TWK10) has beneficial probiotic effects, improves exercise endurance performance, regulates body composition, and mitigates aging-related problems in mice and humans. Here, we investigated the effects of heat-killed TWK10 on exercise endurance performance, muscle weight and strength, fatigue, and body composition in a double-blind, placebo-controlled clinical trial. Thirty healthy males aged 20-40 years were assigned to the Control group or heat-killed TWK10 group (TWK10-HK) in a balanced order according to each individual's initial maximal oxygen uptake. After 6-week administration, the exercise endurance time in the TWK10-HK was significantly increased (p = 0.0028) compared with that in the Control group. The grip strength on the right and left hands of the subjects was significantly increased (p = 0.0002 and p = 0.0140, respectively) in the TWK10-HK compared with that in the Control group. Administration of heat-killed TWK10 resulted in a significant increase (p = 0.0275) in muscle weight. After 6-week administration, serum lactate, and ammonia levels were significantly lower in the TWK10-HK group than in the Control group during the exercise and recovery periods. These findings demonstrate that heat-killed TWK10 has significant potential to be used as a postbiotic for humans.

Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease.

Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.

Safety Assessment of Lactiplantibacillus plantarum TWK10 Based on Whole-Genome Sequencing, Phenotypic, and Oral Toxicity Analysis.

Lactiplantibacillus plantarum TWK10 (TWK10), isolated from Taiwanese pickled cabbage, has been demonstrated to exert beneficial probiotic effects in both mice and humans. Here, we comprehensively assessed the safety of TWK10 using both in vivo and in vitro approaches, including whole-genome sequence analysis, an assessment of hemolytic activity, and performing an antimicrobial susceptibility test, the Ames bacterial reverse mutation assay, the chromosomal aberration test, a rodent peripheral blood micronucleus test, and the 28-day subacute oral toxicity assay. The results showed that there was no significant increase in the incidence of reverse mutations or chromosomal aberrations following exposure to TWK10. Moreover, no significant changes were detected either in the number of reticulocytes or the incidence of micronuclei in ICR mice, and no subacute toxicity was recorded in SD rats at the oral TWK10 dosage of 2000 mg/kg body weight/day repeated for 28 days. Additionally, TWK10 exhibited no hemolytic activity and was susceptible to all the antibiotics tested, except kanamycin. However, no antimicrobial resistance genes, virulence factors, or genes involved in biogenic amine synthesis were found in the genome of TWK10. Our findings demonstrated that TWK10 has high potential of being safe for human consumption as a probiotic.

Lactobacillus plantarum TWK10 Attenuates Aging-Associated Muscle Weakness, Bone Loss, and Cognitive Impairment by Modulating the Gut Microbiome in Mice.

In humans, aging is characterized by the progressive decline in biological, physiological, and psychological functions, and is a major risk factor in the development of chronic diseases. Therefore, the development of strategies aimed at attenuating aging-related disorders and promoting healthy aging is critical. In a previous study, we have demonstrated that Lactobacillus plantarum TWK10 (TWK10), a probiotic strain isolated from Taiwanese pickled cabbage, improved muscle strength, exercise endurance, and overall body composition in healthy humans. In this study, the effect of TWK10 on the progression of age-related impairments was investigated in mice. We found that TWK10 not only enhanced muscle strength in young mice, but also prevented the aging-related loss of muscle strength in aged mice, which was accompanied by elevated muscle glycogen levels. Furthermore, TWK10 attenuated the aging-associated decline in learning and memory abilities, as well as bone mass. Further analyses of gut microbiota using next-generation sequencing (NGS) of the 16S rRNA gene showed that the pattern of gut microbial composition was clearly altered following 8 weeks of TWK10 administration. TWK10-treated mice also experienced an increase in short-chain fatty acid (SCFA)-producing bacteria and higher overall levels of gut SCFA. Furthermore, TWK10 administration to some extent reversed the aging-associated accumulation of pathogenic bacterial taxa. In conclusion, TWK10 could be viewed as a potential therapeutic agent that attenuates aging-related disorders and provides health benefits by modulating the imbalance of gut microbiota.

Lactobacillus plantarum TWK10 Improves Muscle Mass and Functional Performance in Frail Older Adults: A Randomized, Double-Blind Clinical Trial.

Sarcopenia is a condition in which there is a loss of muscle caused by aging and it is one of the most significant factors that affects physical fragility. In recent years, the role of the gut-muscle axis has garnered attention as, along with the gut microbiota, it potentially plays a significant role in muscle regeneration, in addition to nutritional supplements and exercise training. Past studies have found that supplementation with Lactobacillus plantarum TWK10 could effectively increase the muscle mass of animals or adult humans. Therefore, in this study, we investigated whether the supplementation of L. plantarum TWK10 produces increased muscle mass and improves the functional performance of elderly persons with mild fragility. A total of 68 elderly subjects were recruited, of which 13 subjects were excluded or withdrew from the study. We adopted a double-blind design, and the 55 subjects were randomly divided into three groups: the placebo group, the TWK10 low-dose group (2 × 1010 CFU/day) (TWK10-L), and the TWK10 high-dose group (6 × 1010 colony-forming unit (CFU)/day) (TWK10-H). For 18 weeks, all subjects were required to regularly take experimental samples, perform functional activity testing, and have their body composition analyzed before the study and every six weeks after the intervention. Finally, 17 subjects in the placebo group, 12 subjects in the TWK10-L group, and 13 subjects in the TWK10-H group finished the study. It was found that supplementation with TWK10 had a tendency to increase and improve muscle mass, left hand grip strength, lower limb muscle strength, and gait speed and balance after the sixth week, especially in the TWK10-H group, and, as the supplement time was longer up to the 18th week, it had an even greater effect (p < 0.05). In conclusion, consecutive supplementation of L. plantarum TWK10 for more than six weeks could effectively improve the muscle strength and endurance of the elderly, reducing sarcopenia and physical fragility. This trial was registered as NCT04893746.