Lactobacillus sakei Alleviates High-Fat-Diet-Induced Obesity and Anxiety in Mice by Inducing AMPK Activation and SIRT1 Expression and Inhibiting Gut Microbiota-Mediated NF-κB Activation.

Long-term feeding of a high-fat diet (HFD) causes gastrointestinal inflammation and gut microbiota disturbance, leading to the increased occurrence of obesity and anxiety. In the present study, the effects of heat-labile Lactobacillus sakei OK67, tyndallized OK67 (tOK67), and heat-stable Lactobacillus sakei PK16 on HFD-induced obesity and anxiety in mice are examined. Obesity is induced in mice by feeding with HFD. Oral administration of live OK67, tOK67, or PK16 reduces HFD-induced body and liver weights and blood triglyceride, total cholesterol, corticosterone, and lipopolysaccharide levels. These treatments also suppress HFD-induced NF-κB activation and increased HFD-suppressed AMP-activated protein kinase (AMPK) activation and SIRT-1 expression in the liver. OK67 or PK16 treatment alleviates HFD-induced anxiety-like behaviors and increases BDNF expression and NF-κB activation in the hippocampus. Moreover, OK67 or PK16 treatment suppresses HFD-induced colitis and suppresses the Proteobacteria population and fecal lipopolysaccharide levels in mice. OK67 or PK16 treatment inhibits NF-κB activation and induced AMPK activation and SIRT-1 expression in lipopolysaccharide-stimulated Caco-2 cells. Overall, the antiobesity and anxiolytic effects of live OK67 are more potent than those of tOK67. Lactobacillus sakei can alleviate HFD-induced obesity, colitis, and anxiety by regulating gut microbiota-mediated AMPK and NF-κB activation and SIRT-1 expression.

Jang HM ，Han SK ，Kim JK ，Oh SJ ，Jang HB ，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 ... -  《-》

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 ... -  《-》

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 《-》

High-fat diet causes psychiatric disorders in mice by increasing Proteobacteria population.

The excessive intake of a high-fat diet (HFD) leads to obesity, including metabolic syndromes, disturbs gut microbiota composition, causes colitis, and increases the plasma concentration of lipopolysaccharide (LPS). In the present study, we examined the role of gut microbiota in the occurrence of HFD-induced psychiatric disorders in mice. C57BL/6 J male mice fed a HFD for 9 weeks were led to obesity; their memory impairment was assessed by the Y-maze and novel object recognition test, and anxiety-like behaviors by the elevated plus maze. The intake of a HFD suppressed brain-derived neurotrophic factor (BDNF) expression in the hippocampus and increased blood TNF-α and LPS levels. HFD treatment more potently increased NF-κB activation and Iba1+ (microglial) cell populations in the hippocampus. Furthermore, HFD feeding increased TNF-α expression, myeloperoxidase activity, and CD11b+/CD11c+ cell (macrophages and dendritic cells) populations in the colon and altered gut microbiota composition including increases in the Proteobacteria population, and increases in fecal LPS levels. The stool lysates of HFD-treated mice suppressed BDNF expression and CREB phosphorylation in SH-SY5Y cells and increased NF-κB activation in BV-2 microglial cells compared to those of low-fat diet-treated mice while these effects were attenuated by treatment with anti-LPS antibody. These findings suggest that excessive intake of HFD can simultaneously cause obesity and psychiatric disorders by suppressing hippocampal BDNF expression with the disturbance of gut microbiota composition, particularly the increase in Proteobacteria population and LPS production.

Jeong MY ，Jang HM ，Kim DH 《-》