Bifidobacterium adolescentis IM38 ameliorates high-fat diet-induced colitis in mice by inhibiting NF-κB activation and lipopolysaccharide production by gut microbiota.

Gut microbiota play essential roles in the regulation of human metabolism via symbiotic interactions with the host. Prolonged consumption of high-fat diet (HFD) elevates the Firmicutes to Bacteroidetes ratio and lipopolysaccharide (LPS) production by gut microbiota, thereby increasing the probability of developing metabolic and immune disorders such as obesity and colitis. The use of probiotics with anti-inflammatory properties has been suggested to counteract this effect. Here, we tested whether Bifidobacterium adolescentis IM38, which inhibited nuclear factor-kappa B (NF-κB) activation in Caco-2 cells and peritoneal macrophages and inhibited Escherichia coli LPS production, exerted an anticolitic effect in mice with HFD-induced obesity. Oral administration of IM38 (2×109CFU/mouse per day) for 6 weeks in mice with HFD-induced obesity inhibited whole-body and epididymal fat weight gain. IM38 also increased HFD-suppressed expression of interleukin (IL)-10 and tight junction proteins but significantly downregulated HFD-induced NF-κB activation and tumor necrosis factor expression in the colon. IM38 inhibited differentiation into helper T17 cells and reduced IL-17 levels in the colon of mice with HFD-induced obesity but increased HFD-suppressed differentiation into regulatory T cells and IL-10 levels. Furthermore, treatment with IM38 lowered the HFD-induced LPS levels in blood and colonic fluid, as well as the Proteobacteria to Bacteroidetes ratio in gut microbiota. Therefore, we suggest that IM38 can inhibit HFD-induced LPS production in gut microbiota through the regulation of Proteobacteria to Bacteroidetes ratio and NF-κB activation in the colon, which ultimately attenuates colitis. Thus, IM38 may be a suitable ingredient of functional foods designed for treating or preventing colitis.

Lim SM ，Kim DH 《-》

Lactobacillus sakei OK67 ameliorates high-fat diet-induced blood glucose intolerance and obesity in mice by inhibiting gut microbiota lipopolysaccharide production and inducing colon tight junction protein expression.

A high-fat diet (HFD) induces obesity and the associated increases in blood glucose and inflammation through changes in gut microbiota, endotoxemia, and increased gut permeability. To counteract this, researchers have suggested that the use of probiotics that suppress production of proinflammatory lipopolysaccharide (LPS). Here, we tested whether Lactobacillus sakei OK67, which inhibits gut microbiota LPS production selected from among the lactic acid bacteria isolated from kimchi, exerted antihypoglycemic or anti-inflammatory effects in HFD-fed mice. Mice were randomly divided into 2 groups and fed an HFD or a low-fat diet for 4 weeks. These groups were further subdivided; 1 subgroup was treated with L sakei OK67 and fed the experimental diet for 4.5 weeks, whereas the other subgroup was fed the experimental diet alone. L sakei OK67 treatment lowered HFD-elevated LPS levels in blood and colonic fluid and significantly decreased HFD-elevated fasting blood glucose levels and the area under the curve in an oral glucose tolerance test. L sakei OK67 treatment inhibited HFD-induced body and epididymal fat weight gains, suppressed HFD-induced tumor necrosis factor-α and interleukin-1β expression and nuclear factor-κB activation in the colon, and significantly increased HFD-suppressed interleukin-10 and tight junction protein expression in the colon. Oral administration of L sakei OK67 significantly downregulated HFD-induced expression of peroxisome proliferator-activated receptor γ, fatty acid synthase, and tumor necrosis factor-α in adipose tissue. In addition, L sakei OK67 treatment strongly inhibited nuclear factor-κB activation in LPS-stimulated peritoneal macrophages. We report that L sakei OK67 ameliorates HFD-induced hyperglycemia and obesity by reducing inflammation and increasing the expression of colon tight junction proteins in mice.

Lim SM ，Jeong JJ ，Woo KH ，Han MJ ，Kim DH ... -  《-》

β-Sitosterol attenuates high-fat diet-induced intestinal inflammation in mice by inhibiting the binding of lipopolysaccharide to toll-like receptor 4 in the NF-κB pathway.

β-Sitosterol, a common phytosterol, has been shown to exhibit anti-inflammatory effects. Here, we investigated the effect of β-sitosterol on high-fat diet (HFD) induced colitis in mice and on LPS-stimulated mouse intestinal macrophages. C57BL/6J mice were maintained on an LFD (10 kcal% fat), an HFD (60 kcal% fat), or an HFD with β-sitosterol (20 mg/kg) administration for 8 weeks. The increased levels of body weight and epididymal fat pad weight as well as the concentrations of circulating proinflammatory cytokines and LPS in HFD mice compared with LFD mice were decreased by oral administration of β-sitosterol. The HFD-induced colonic inflammation evidenced by the increased expression of proinflammatory cytokines and the activation of nuclear factor kappa B (NF-κB) in the colon was also inhibited by β-sitosterol. In LPS-stimulated intestinal macrophages, β-sitosterol inhibited the production of proinflammatory cytokines and inflammatory enzymes as well as NF-κB activation. In addition, β-sitosterol significantly prevented the binding of LPS to intestinal as well as peritoneal macrophages. Furthermore, β-sitosterol potently inhibited the interaction between LPS and toll-like receptor 4 in intestinal macrophages transfected with control siRNA or MyD88 siRNA. These findings indicate that β-sitosterol ameliorates HFD-induced colitis by inhibiting the binding of LPS to toll-like receptor 4 in the NF-κB pathway.

Kim KA ，Lee IA ，Gu W ，Hyam SR ，Kim DH ... -  《-》

Orally administrated Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent colitis by inhibiting the nuclear factor-kappa B signaling pathway via the regulation of lipopolysaccharide production by gut microbiota.

Jeong JJ ，Kim KA ，Jang SE ，Woo JY ，Han MJ ，Kim DH ... -  《PLoS One》

Lactobacillus plantarum LC27 and Bifidobacterium longum LC67 simultaneously alleviate high-fat diet-induced colitis, endotoxemia, liver steatosis, and obesity in mice.

Long-term feeding of a high-fat diet (HFD) induces endotoxemia and gastrointestinal inflammation by disturbing gut microbiota composition and membrane permeability, resulting in the acceleration of obesity. Some probiotics exhibit anti-inflammatory effects in vitro and in vivo. Therefore, we hypothesized that anti-inflammatory probiotics could lead to the simultaneous attenuation of endotoxemia, liver steatosis, obesity, and colitis in mice with HFD-induced obesity. Herein, we examined whether Lactobacillus plantarum LC27 and/or Bifidobacterium longum LC, which significantly suppressed NF-κB activation in lipopolysaccharide- or fecal lysate-stimulated Caco-2 cells, could simultaneously alleviate liver steatosis and colitis in mice with HFD-induced obesity. Oral administration of LC27, LC67, or their (3:1) mixture (LM) reduced HFD-induced aspartate transaminase, alanine transaminase, triglyceride, total cholesterol, and lipopolysaccharide levels in the blood and liver. Their treatments also suppressed HFD-induced NF-κB activation and increased AMP-activated protein kinase (AMPK) activation and claudin-1 and occludin expression in the liver and colon. Moreover, LC27, LC67, or LM treatment reduced HFD-induced Firmicutes and Proteobacteria populations in gut microbiota and fecal lipopolysaccharide production. The hypothesis was supported by the findings that anti-inflammatory LC27 and/or LC67 simultaneously alleviated liver steatosis, obesity, and colitis by regulating NF-κB and AMPK activation through the inhibition of gut microbiota lipopolysaccharide production.

In Kim H ，Kim JK ，Kim JY ，Jang SE ，Han MJ ，Kim DH ... -  《-》