Prebiotic treatment reduced preneoplastic lesions through the downregulation of toll like receptor 4 in a chemo-induced carcinogenic model

Germinated barley foodstuff contains prebiotics which are reported to have anti-cancerous effects in colorectal cancer model, but the detailed mechanism remains unclear. Recent studies revealed that the role of microbiota was strongly related to the regulation of incidence and progression of colorectal cancer. The aim of this study was to examine the anti-neoplastic mechanism by prebiotics. Azoxymethane treated F344 rats were used as the sporadic cancerous model. After azoxymethane injection, either a control or germinated barley foodstuff diet was administered to the rats for another 5 weeks, and the number of abberant crypt foci, toll like receptor 4, Kirsten rat sarcoma viral oncogene homolog, adenomatous polyposis coli tumor suppressor gene and cyclooxygenase 2 mRNA expression of colonic mucosa and cecal short chain fatty acids were examined. The germinated barley food stuff significantly attenuated the number of abberant crypt focis and the expression of toll like receptor 4 and cyclooxygenase 2 mRNA, compared to the control group. In addition, the cecal butyrate production in the germinated barley foodstuff group was significantly higher than that in the control. In conclusion, this prebiotic treatment for colorectal cancer may be useful without causing the adverse effects seen in either anti-cancer drugs or anti-inflammatory drugs

発芽大麦食品素材の消化管内環境および便通改善材としての研究

京都大学0048新制・論文博士博士(農学)乙第10049号論農博第2219号新制||農||775(附属図書館)学位論文||H11||N3235(農学部図書室)UT51-99-D253(主査)教授 伏木 亨, 教授 佐々木 隆造, 教授 熊谷 英彦学位規則第4条第2項該当Doctor of Agricultural ScienceKyoto UniversityDA

Effect of Heat-Killed Lactobacillus paracasei KW3110 Ingestion on Ocular Disorders Caused by Visual Display Terminal (VDT) Loads: A Randomized, Double-Blind, Placebo-Controlled Parallel-Group Study

Background: Visual display terminals (VDTs) emitting blue light can cause ocular disorders including eye fatigue. Some dietary constituents have been reported to be effective in improving ocular disorders while few clinical studies have been performed. We evaluated the effects of heat-killed Lactobacillus paracasei KW 3110 on improving ocular disorders and symptoms of eye fatigue among healthy human subjects with VDT loads. Methods: In vitro, the effect of L. paracasei KW3110 on blue light-induced human retinal pigment epithelial (ARPE-19) cell damage. For clinical studies, 62 healthy Japanese volunteers of 35 to 45 years of age who had experienced eye fatigue were randomized into two groups and given a placebo or L. paracasei KW3110-containing supplements for eight weeks. The primary endpoint was changes in VDT load-induced eye fatigue as determined by critical flicker frequency four and eight weeks after the start of supplementation. Results: In vitro, blue light-induced human retinal cell death was suppressed with the culture supernatants of cells treated with L. paracasei KW3110. In clinical study, the VDT load-induced reduction of critical flicker frequency tended to be milder in the L. paracasei KW3110 group when compared with the placebo group during the fourth week. Subgroup analysis classified by the degree of eye fatigue showed that the VDT load-induced reduction of critical flicker frequency was significantly better in the high-level eye fatigue subjects from the L. paracasei KW3110 group when compared with the placebo group during the fourth week (p = 0.020). Conclusions: L. paracasei KW3110 suppressed blue light-induced retinal pigment epithelial cell death. In the clinical study, ingestion of L. paracasei KW3110 had a potential to improve eye fatigue induced by VDT loads especially high levels of eye fatigue. However, further studies should be required to show more dependable clinical efficacy of L. paracasei KW3110

Stress-induced visceral analgesia assessed non-invasively in rats is enhanced by prebiotic diet

AIM: To investigate the influence of repeated water avoidance stress (rWAS) on the visceromotor response (VMR) to colorectal distension (CRD) and the modulation of the response by a prebiotic diet in rats using a novel surgery-free method of solid-state manometry

<i>Lactobacillus paracasei</i> KW3110 Prevents Blue Light-Induced Inflammation and Degeneration in the Retina

Age-related macular degeneration and retinitis pigmentosa are leading causes of blindness and share a pathological feature, which is photoreceptor degeneration. To date, the lack of a potential treatment to prevent such diseases has raised great concern. Photoreceptor degeneration can be accelerated by excessive light exposure via an inflammatory response; therefore, anti-inflammatory agents would be candidates to prevent the progress of photoreceptor degeneration. We previously reported that a lactic acid bacterium, Lactobacillus paracasei KW3110 (L. paracasei KW3110), activated macrophages suppressing inflammation in mice and humans. Recently, we also showed that intake of L. paracasei KW3110 could mitigate visual display terminal (VDT) load-induced ocular disorders in humans. However, the biological mechanism of L. paracasei KW3110 to retain visual function remains unclear. In this study, we found that L. paracasei KW3110 activated M2 macrophages inducing anti-inflammatory cytokine interleukin-10 (IL-10) production in vitro using bone marrow-derived M2 macrophages. We also show that IL-10 gene expression was significantly increased in the intestinal immune tissues 6 h after oral administration of L. paracasei KW3110 in vivo. Furthermore, we demonstrated that intake of L. paracasei KW3110 suppressed inflammation and photoreceptor degeneration in a murine model of light-induced retinopathy. These results suggest that L. paracasei KW3110 may have a preventive effect against degrative retinal diseases

Lactococcus lactis Strain Plasma Intake Suppresses the Incidence of Dengue Fever-like Symptoms in Healthy Malaysians: A Randomized, Double-Blind, Placebo-Controlled Trial

Dengue fever (DF) is a mosquito-borne disease still with no effective treatment or vaccine available. A randomized, placebo-controlled, double-blinded, parallel-group trial was undertaken to evaluate the efficacy of oral intake of Lactococcus lactis strain plasma (LC-Plasma) on the presentation and severity of DF-like symptoms among healthy volunteers. Study participants (320) were assigned into two groups, and consumed either placebo or LC-Plasma tablets (approximately 100 billion cells/day) for 8 weeks. The clinical symptoms of DF were self-recorded through questionnaires, and exposure to DENV was determined by serum antibody and/or DENV antigen tests. No significant differences between groups were observed for exposure to DENV, or the symptomatic ratio. Results obtained showed that participants from the LC-Plasma group reported a significant reduction in the cumulative incidence days of DF-like symptoms, which include fever (p &lt; 0.001), muscle pain (p &lt; 0.005), joint pain (p &lt; 0.001), and pain behind the eyes (p &lt; 0.001), compared to that of the placebo group. Subgroup analysis revealed a significantly (p &lt; 0.05) reduced severity score in the LC-Plasma group when study sites were separately analyzed. Overall, our findings suggest that LC-Plasma supplementation reduces the cumulative days with DF-like symptoms, and the severity of the symptoms. Daily oral intake of LC-Plasma, hence, is shown to mitigate the DF-like symptoms

Impact of Infectious Disease after <i>Lactococcus lactis</i> Strain Plasma Intake in Vietnamese Schoolchildren: A Randomized, Placebo-Controlled, Double-Blind Study

Lactococcus lactis strain Plasma (LC-Plasma) is reported to have anti-viral effects via direct activation of plasmacytoid dendritic cells, which upregulate the production of type I and III interferons. A randomized, placebo-controlled, double-blind, parallel group study was designed for elementary schoolchildren, grades 1 to 3, in Vietnam. LC-Plasma or a control were administered to schoolchildren as a beverage (1.0 × 1011 count LC-Plasma/day/person). The primary endpoint was to determine the efficacy of LC-Plasma in reducing the cumulative days absent from school due to upper respiratory disease (URID) and gastrointestinal disease (GID), and the secondary endpoint was to evaluate the potency of LC-Plasma on URID/GID symptoms and general well-being scores. LC-Plasma intake significantly reduced the cumulative days absent from school due to URID/GID (Odds ratio (OR) = 0.57, p = 0.004) and URID alone (OR = 0.56, p = 0.005); LC-Plasma also significantly reduced the number of cumulative fever positive days during the first 4 weeks of intervention (OR = 0.58, p = 0.001) and cumulative days with diarrhea during the last 4 weeks of the intervention period (OR = 0.78, p = 0.01). The number of positive general wellbeing days was significantly improved in the LC-Plasma group compared with the control throughout the intervention period (OR = 0.93, 0.93, p = 0.03, 0.04 in the first and last 4 weeks of the intervention, respectively). These data suggest that LC-Plasma seems to improve the health condition of elementary schoolchildren and reduces school absenteeism due to infectious disease, especially URID