Ingesting probiotic yogurt containing Lactiplantibacillus plantarum OLL2712 improves glycaemic control in adults with prediabetes in a randomized, double-blind, placebo-controlled trial.

AIM: The ingestion of Lactiplantibacillus plantarum OLL2712 (OLL2712) cells has been shown to improve glucose metabolism by suppressing chronic inflammation in murine models and clinical studies. This study aimed to clarify the effect of OLL2712 on glycaemic control in healthy adults with prediabetes. MATERIALS AND METHODS: The study was a randomized, double-blind, placebo-controlled, parallel-group design. Adult participants with prediabetes [n = 148, glycated haemoglobin (HbA1c) range: 5.6%-6.4%, age range: 20-64 years] were assigned randomly to placebo or OLL2712 groups (n = 74/group) and administered daily for 12 weeks either conventional yogurt or yogurt containing >5 × 109 heat-treated OLL2712 cells, respectively. In addition, the participants were followed for 8 weeks after the discontinuation of either yogurt. The primary outcome was the changes in HbA1c levels at weeks 12 and 16 by analysis of covariance. RESULTS: The levels of HbA1c and glycoalbumin decreased significantly in both groups at week 12 in comparison with those at week 0, but only in the OLL2712 group at week 16. HbA1c levels decreased significantly at weeks 12 and 16 in the OLL2712 group in comparison with the placebo group (p = .014 and p = .006, respectively). No significant inter- and intragroup differences in HbA1c levels were observed at week 20. CONCLUSIONS: The ingestion of OLL2712 prevents the deterioration of glycaemic control and maintains the HbA1c levels within the normal range in adults with prediabetes; yogurt probably exhibits similar effects, which may contribute to reducing the risk of developing type 2 diabetes.

Lactiplantibacillus plantarum OLL2712 Induces Autophagy via MYD88 and Strengthens Tight Junction Integrity to Promote the Barrier Function in Intestinal Epithelial Cells.

Autophagy is an important system conserved in eukaryotes that maintains homeostasis by degrading abnormal proteins. Autophagy incompetence in intestinal epithelial cells causes the abnormal function of intestinal stem cells and other cells and damages intestinal barrier function. The disruption of the intestinal barrier causes chronic inflammation throughout the body, followed by impaired glucose and lipid metabolism. Lactiplantibacillus plantarum OLL2712 (OLL2712) is a lactic acid bacterium that induces interleukin-10 production from immune cells, alleviates chronic inflammation, and improves glucose and lipid metabolism. In this study, we hypothesized that OLL2712 exerts anti-inflammatory effects by inducing autophagy and ameliorating intestinal barrier dysfunction, and we investigated its autophagy-inducing activities and functions. Caco-2 cells stimulated with OLL2712 for 24 h showed an increased number of autolysosomes per cell, compared with unstimulated cells. Therefore, the permeability of fluorescein isothiocyanate dextran 4000 (FD-4) was suppressed by inducing autophagy. In contrast, mucin secretion in HT-29-MTX-E12 cells was also increased by OLL2712 but not via autophagy induction. Finally, the signaling pathway involved in autophagy induction by OLL2712 was found to be mediated by myeloid differentiation factor 88 (MYD88). In conclusion, our findings suggest that OLL2712 induces autophagy in intestinal epithelial cells via MYD88, and that mucosal barrier function is strengthened by inducing autophagy.

Ingesting Yogurt Containing Lactobacillus plantarum OLL2712 Reduces Abdominal Fat Accumulation and Chronic Inflammation in Overweight Adults in a Randomized Placebo-Controlled Trial.

BACKGROUND: Chronic inflammation and insulin resistance are factors that are related to obesity. We have suggested that the administration of heat-treated Lactobacillus plantarum OLL2712 (OLL2712) cells can improve glucose and lipid metabolism by suppressing chronic inflammation in mouse models and a preliminary clinical study. OBJECTIVE: The aim of this study was to investigate whether ingesting OLL2712 cells can reduce body fat accumulation and improve metabolic risk factors, in overweight, healthy adults. METHODS: This study was a randomized, double-blind, placebo-controlled, parallel-group trial conducted at a single center in Japan. The study participants included 100 overweight (BMI range, ≥25 to <30 kg/m2) adults aged 20-64 y. They were randomly assigned to either the placebo or OLL2712 group (n = 50 each) and were administered conventional yogurt or yogurt containing >5 × 109 heat-treated OLL2712 cells, respectively, daily for 12 wk. The primary outcome was the 12-wk change in the abdominal fat area, as assessed by computed tomography, and the secondary outcomes were glucose and lipid metabolism-related parameters and chronic inflammation markers, which were analyzed using a linear mixed model. RESULTS: The 12-wk change of abdominal fat area (difference: 8.5 cm2; 95% CI: 0.3, 16.6 cm2; P = 0.040) and fasting plasma glucose (difference: 3.2 mg/dL; 95% CI: 0.8, 5.6 mg/dL; P = 0.021) were significantly less in the OLL2712 group than the placebo group. The overall trend of serum IL-6 was significantly decreased in the OLL2712 group compared with baseline and the placebo group. CONCLUSIONS: The ingestion of heat-treated OLL2712 cells reduces body fat accumulation and the deterioration of glycemic control and chronic inflammation, in overweight, healthy adults. We hypothesize that OLL2712 cells may prevent obesity by regulating chronic inflammation. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000027709.

Effects of 12-Week Ingestion of Yogurt Containing Lactobacillus plantarum OLL2712 on Glucose Metabolism and Chronic Inflammation in Prediabetic Adults: A Randomized Placebo-Controlled Trial.

The ingestion of Lactobacillus plantarum OLL2712 (OLL2712) cells improved glucose metabolism by suppressing chronic inflammation in mouse models and in a preliminary clinical study. We aimed to clarify the effect of OLL2712 on glucose metabolism and chronic inflammation for healthy adults. Prediabetic adults (n = 130, age range: 20-64 years) were randomly assigned to either the placebo or OLL2712 groups (n = 65 each) and were administered conventional yogurt or yogurt containing more than 5 × 109 heat-treated OLL2712 cells, respectively, daily for 12 weeks. Reduced HbA1c levels after 12 weeks of treatment were observed in both groups compared to those at baseline; however, the 12-week reduction of HbA1c levels was significantly greater in the OLL2712 group than in the placebo group. Increased chronic inflammation marker levels and insulin-resistant index (HOMA-IR) occurred in the placebo group but not in the OLL2712 group. Fasting blood glucose (FBG) levels did not change significantly in both groups; however, in subgroup analyses including participants with higher FBG levels, FBG levels were significantly reduced only in the OLL2712 group compared to baseline. These results suggest that OLL2712 cell ingestion can reduce HbA1c levels and can prevent the aggravation of chronic inflammation and insulin resistance.

Effects of 12-wk Lactobacillus plantarum OLL2712 treatment on glucose metabolism and chronic inflammation in prediabetic individuals: A single-arm pilot study.

OBJECTIVE: Previously, we demonstrated that the administration of heat-killed OLL2712 cells suppressed chronic inflammation and improved hyperglycemia in a mouse model of obesity and diabetes. The aim of this study was to preliminarily examine the effect of OLL2712 supplementation on glucose metabolism and chronic inflammation in prediabetic subjects. METHODS: This study was a prospective, 12-wk, single-arm, open trial, followed by a 4-wk posttreatment period. Inclusion criteria were fasting plasma glucose levels of 105 to 130 mg/dL in an age range of 35 to 65 y. Thirty individuals consumed a dairy beverage containing ∼1 × 1010 heat-killed OLL2712 cells for 12 wk. RESULTS: The ingestion of the OLL2712 beverage significantly improved fasting plasma glucose levels, serum glycoalbumin levels, and insulin resistance indexes compared with baseline levels. The intervention also suppressed serum monocyte chemotactic protein-1 and interleukin-6 levels, which are proinflammatory cytokines involved in the development of insulin resistance and hyperglycemia. Furthermore, stratified analysis by these proinflammatory cytokine levels revealed that the beneficial effects of OLL2712 beverage were observed particularly in individuals with chronic inflammation at baseline. CONCLUSION: The results of this study suggested that heat-killed OLL2712 cells have the potential to improve insulin resistance and glucose metabolism by suppressing chronic inflammation.