Identification of a Lactobacillus plantarum strain that ameliorates chronic inflammation and metabolic disorders in obese and type 2 diabetic mice

Abstract

In this study, we identified a strain of lactic acid bacteria (LAB) that induces high levels of IL-10 production by immune cells, and evaluated the ability of the strain to suppress chronic inflammation and ameliorate metabolic disorders in in vitro and in vivo models. Among a collection of LAB strains, Lactobacillus plantarum strain OLL2712 (OLL2712) induced the highest levels of IL-10 production in mouse-derived dendritic cells and peritoneal macrophages. The anti-inflammatory effects of this strain were evaluated using a co-culture system comprising RAW 264.7 and 3T3-L1 cells. We also administered heat-killed OLL2712 to obese and type 2 diabetic KKAy mice for 3 wk to evaluate the in vivo effects of the strain. The OLL2712 significantly decreased the production of proinflammatory cytokines in vitro. Likewise, the administration of OLL2712 significantly suppressed proinflammatory cytokine levels in both the visceral adipose tissue and the serum of KKAy mice, and reduced serum triglyceride concentrations. The strain also alleviated oxidative stress and adrenaline levels in the serum of KKAy mice. On the other hand, Lactobacillus gasseri strain MEP222804 (a moderate IL-10 inducer) did not ameliorate the systemic inflammation and hyperlipidemia in KKAy mice. Our results suggest that treatment with strong IL-10-inducing LAB has the potential to ameliorate metabolic disorders by suppressing chronic inflammation in the host animal.

Effects of Lactobacillus plantarum Strain OLL2712 Culture Conditions on the Anti-inflammatory Activities for Murine Immune Cells and Obese and Type 2 Diabetic Mice

“…These results suggest that OLL2712 stimulation of immune cell IL-10 production depends on MyD88 and TLR2. In addition, we confirmed that OLL2712 cells cultured statically for 18 h in de Man, Rogosa, and Sharpe (MRS) broth, which we had used in a previous study (15), exhibited higher levels of IL-10 and IL-12 production than 8-h (ϩ) cells.…”

“…Here, the bacterial cells cultured for 8 h, 14 h, and 16 h with Q-17S are described as 8-h (ϩ), 14-h (ϩ), and 16-h (ϩ) cells. We examined the effect of culture phases and adding Q-17S on the immunomodulatory properties of MEP222801, an L. plantarum strain with high IL-10-inducing activity second to OLL2712 in our LAB library (15), and obtained almost the same result as OLL2712 (Fig. 2).…”

“…Out of many strains in our LAB library, we had previously selected the optimal OLL2712 strain, which has high IL-10-inducing activity (15). On the other hand, the health-promoting properties of LAB may change in response to their culture conditions, even when the strain remains the same (7)(8)(9)(10)(11).…”

“…OLL2712 and Lactobacillus plantarum MEP222801 were isolated from the feces from a young Japanese woman volunteer and identified as previously described (15). The preculture of OLL2712 or MEP222801 was grown in de Man, Rogosa, and Sharpe (MRS) broth (Becton Dickinson, Cockeysville, MD) at 37°C under an anaerobic atmosphere for 18 h. In a pH-controlled culture for industrial production, the medium was prepared as follows.…”

“…Administration of heat-killed OLL2712 cells for 3 weeks alleviated chronic inflammation and improved hyperlipidemia in KKAy mice, an obesity and diabetes model (15). IL-10 is an anti-inflammatory cytokine secreted by immune cells in intestinal and adipose tissues (16,17).…”