RESUMO
The increased global prevalence of chronic respiratory diseases in recent years has caused a substantial public health burden. Lactiplantibacillus plantarum KC3 and Leonurus japonicus Houtt. (LJH) extracts can alleviate respiratory symptoms and improve lung function in vitro and in vivo. However, the clinical efficacy and safety profile of this combination in patients with respiratory diseases remain unclear. Therefore, this multicenter, randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy and safety of L. plantarum KC3 and LJH extracts in adults with respiratory discomfort. This mixture was termed 'CKDB-315'. Participants, randomly assigned to the CKDB-315 or placebo groups, were treated for 12 weeks. Assessments included the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). The CKDB-315 group showed considerably improved SGRQ and CAT scores compared with the placebo group. Secondary outcomes, including dyspnea, pulmonary function, total antioxidant status, and inflammatory cytokine levels, were consistent with the primary outcomes. Exploratory analyses of the gut microbiota and short-chain fatty acid contents revealed the potential mechanisms underlying the effects of CKDB-315. Finally, safety analysis indicated that CKDB-315 was well tolerated and caused few adverse events. Our findings indicate that CKDB-315 is a promising therapeutic option for respiratory discomfort in adults.
Assuntos
Leonurus , Extratos Vegetais , Probióticos , Humanos , Método Duplo-Cego , Masculino , Feminino , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Pessoa de Meia-Idade , Leonurus/química , Probióticos/administração & dosagem , Lactobacillus plantarum , Idoso , Resultado do Tratamento , Microbioma Gastrointestinal/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/microbiologia , AdultoRESUMO
Air pollutants, such as particulate matter (PM) and diesel exhaust particles (DEP), are associated with respiratory diseases. Therefore, preventive and therapeutic strategies against PM-and DEP (PM10D)-induced respiratory diseases are needed. Herein, we evaluate the protective effects of a mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt (LJH) extract against airway inflammation associated with exposure to PM10D. To determine the anti-inflammatory effects of the LJH extract, reactive oxygen species (ROS) production and the expression of inflammatory pathways were determined in PM10-induced MH-S cells. For the respiratory protective effects, BALB/c mice were exposed to PM10D via intranasal injection, and a mixture of L. plantarum KC3 and LJH extract was administered orally for 12 days. LJH extract inhibited ROS production and the phosphorylation of downstream factors of NF-κB in PM10-stimulated MH-S cells. The mixture of L. plantarum KC3 and LJH repressed the infiltration of neutrophils, reduced the immune cells number, and suppressed the proinflammatory mediators and cyclooxygenase (COX)-2 expressions in PM10D-induced airway inflammation with reduced phosphorylation of downstream factors of NF-κB. In addition, these effects were not observed in an alveolar macrophage depleted PM10D-induced mouse model using clodronate liposomes. The extract mixture also regulated gut microbiota in feces and upregulated the mRNA expression of Foxp3, transforming growth factor (TGF)-ß1, and interleukin (IL)-10 in the colon. The L. plantarum KC3 and LJH extract mixture may inhibit alveolar macrophage- and neutrophil-mediated inflammatory responses and regulate gut microbiota and immune response in PM10D-induced airway inflammation, suggesting it is a potential remedy to prevent and cure airway inflammation and respiratory disorders.
Assuntos
Leonurus , Doenças Respiratórias , Camundongos , Animais , Leonurus/metabolismo , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Emissões de Veículos , Material Particulado , InflamaçãoRESUMO
Probiotics have been shown to possess anti-inflammatory effects in the gut by directly reducing the production of pro-inflammatory cytokines and by secreting anti-inflammatory molecules. However, their systemic anti-inflammatory effects have not been thoroughly investigated. In this study, we aimed to develop probiotics that have efficacy in both intestinal and lung inflammation. Lactobacillus plantarum KC3 (KC3), which was isolated from kimchi, was selected as a pre-candidate based on its inhibitory effects on the production of pro-inflammatory cytokines in vitro. To further validate the effectiveness of KC3, we used ear edema, DSS-induced colitis, and ambient particulate-matter-induced lung inflammation models. First, KC3 exhibited direct anti-inflammatory effects on intestinal cells with the inhibition of IL-1ß and TNF-α production. Additionally, KC3 treatment alleviated ear edema and DSS-induced colic inflammation, improving colon length and increasing the number of regulatory T cells. Beyond its local intestinal anti-inflammatory activity, KC3 inhibited pro-inflammatory cytokines in the bronchoalveolar fluid and prevented neutrophil infiltration in the lungs. These results suggest that KC3 could be a potential functional ingredient with respiratory protective effects against air-pollutant-derived inflammation, as well as for the treatment of local gut disorders.
RESUMO
Probiotics modulate the gut microbiota, which in turn regulate immune responses to maintain balanced immune homeostasis in the host. However, it is unclear how probiotic bacteria regulate immune responses. In this study we investigated the immunomodulatory effects of heat-killed probiotics, including Lactiplantibacillus plantarum KC3 (LP3), Lactiplantibacillus plantarum CKDB008 (LP8), and Limosilactobacillus fermentum SRK414 (LF4), via phagocytosis, nitric oxide (NO), and pro-inflammatory cytokine production in macrophages. We thus found that heat-killed LP8 could promote the clearance of foreign pathogens by enhancing the phagocytosis of macrophages. Treatment with heat-killed LP8 induced the production of NO and pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1ß. In addition, heat-killed LP8 suppressed the production of NO and cytokines in LPS-induced RAW264.7 cells, suggesting that heat-killed LP8 exerts immunomodulatory effects depending on the host condition. In sum, these results indicate that heat-killed LP8 possesses the potential for immune modulation while providing a molecular basis for the development of functional probiotics prepared from inactivated bacterial cells.
Assuntos
Temperatura Alta , Probióticos , Animais , Citocinas , Macrófagos , Camundongos , Óxido Nítrico , Probióticos/farmacologia , Células RAW 264.7RESUMO
The safety of the probiotic strain Q180, which exerts postprandial lipid-lowering effects, was bioinformatically and phenotypically evaluated. The genome of strain Q180 was completely sequenced, and single circular chromosome of 3,197,263 bp without any plasmid was generated. Phylogenetic and related analyses using16S rRNA gene and whole-genome sequences revealed that strain Q180 is a member of Lactiplantibacillus (Lp., formerly Lactobacillus) plantarum. Antimicrobial resistance (AMR) genes were bioinformatically analyzed using all Lp. plantarum genomes available in GenBank, which showed that AMR genes are present differently depending on Lp. plantarum strains. Bioinformatic analysis demonstrated that some mobile genetic elements such as prophages and insertion sequences were identified in the genome of strain Q180, but because they did not contain harmful genes such as AMR genes and virulence factor (VF)- and toxin-related genes, it was suggested that there is no transferability of harmful genes. The minimum inhibition concentrations of seven tested antibiotics suggested by the European Food Safety Authority guidelines were slightly lower than or equal to the microbiological cut-off values for Lp. plantarum. Strain Q180 did not show hemolytic and gelatinase activities and biogenic amine-producing ability. Taken together, this study demonstrated the safety of strain Q180 in terms of absence of AMR genes and VF- and toxin-related genes as a probiotic strain.