Therapeutic Effects of Gleditsia sinensis Thorn Extract Fermented by Lactobacillus casei 3260 in a Type II Collagen-Induced Rheumatoid Arthritis Mouse Model.

This study aimed to assess the anti-inflammatory effect of Lactobacillus casei 3260 (LC) alone and LC-fermented Gleditsia sinensis thorn (GST) extract in mouse model of type II collagen induced rheumatoid arthritis (RA). In our previous work, we confirmed the anti-inflammatory effects of LC and GST against LPS-induced inflammation in vitro. In this study, LC and GST were fermented and their effects were assessed in an animal model of RA. Both LC and fermented GST (fGST) treatment reduced mice serum nitrite and total cholesterol and triggered myeloperoxidase (MPO) activity. In addition, both LC and fGST reduced inflammation-related serum biomarkers such as tumor necrosis factor-α, interleukin (IL)-6, IL-17, and IL-1ß. As per the morphological analysis, both LC and fGST protected hind paw joints against RA, and its related mRNA markers improved. Finally, arthritis scores were measured as an indicator of RA of the whole experimental period; the scores suggested that both LC and fGST protect against collagen-induced RA-related inflammation in a mouse model.

Neuroprotective effect of both synbiotics and ketogenic diet in a pentylenetetrazol-induced acute seizure murine model.

OBJECTIVE: We aimed to maximize the efficacy of both ketogenic diet (KD) and other treatments to protect brain from acute seizure. METHODS: L. fermentum MSK 408 strain, galactooligosaccharide (GOS), and L. fermentum MSK 408 with GOS were administered with two different diets for 8 weeks. To reveal the relationships among gut microbiota, fecal short-chain fatty acids (SCFAs) and brain related action against pentylenetetrazole (PTZ)-induced kindling, qPCR, NGS, and GC-MS analyses were used. RESULTS: KD administration significantly reduced PTZ-induced seizure through reducing cell damage in the specific part of the brain; this effect was not interrupted by co-administration of synbiotics. Additionally, the synbiotic-treated normal diet (ND) group showed reduced seizure-related scores. SCFA concentrations of both KDs and ND with synbiotics (NDS) were dramatically reduced compared to those with NDs. Interestingly, NDS group showed independently different SCFAs ratios compared to both ND and KD group, possibly related to a reduction in seizure symptoms compared with that by KD groups. The gut microbiota modulation by KD suggested that the gut microbiota aids the host in generating energy, thus increase the usage of SCFAs such as butyrate and acetate. SIGNIFICANCE: The results suggest that KD could reduce PTZ-induced seizures through modulating various factors such as the neuroendocrine system, brain protection, gut microbiota, fecal SCFAs, and gene expression in the gut and brain. Additionally, synbiotic treatment with KD could be a better method to reduce the side effects of KD without interrupting its anti-seizure effect. However, ND with synbiotics seizure reducing effect requires further analysis.

Gut microbiota modulation by both Lactobacillus fermentum MSK 408 and ketogenic diet in a murine model of pentylenetetrazole-induced acute seizure.

PURPOSE: Seizures are a threat to the host brain and body and can even cause death in epileptic children. Ketogenic diet (KD) is suggested for children suffering from epileptic seizures and has been investigated for its anti-seizure effect. However, the relationships between KD and gut microbiota (GM) is not yet been deeply understood. Herein, we investigated the anti-seizure effect by administering KD and a lactic acid bacteria (LAB) in murine model of chemically induced seizures. We hypothesized that a single Lactobacillus fermentum MSK 408 (MSK 408) strain with or without KD may exert a neuroprotection by modulating host gut microbiota. METHOD: We performed animal study using pentylenetetrazole (PTZ) to induce seizure. Thirty 3-week-old male Institute of Cancer research (ICR) mice were divided in six groups, Normal diet (ND), ND + PTZ, ND + PTZ + LAB, KD, KD + PTZ, and KD + PTZ. Based on our previous study, 4:1 KD and selected MSK 408 strain was orally gavaged (4 × 109 CFU/mL) with both diets for 4 weeks. PTZ (40 mg/kg) was injected intraperitoneally 30 min before euthanization. RESULTS: Compared to ND, KD significantly reduced the seizure frequency. Administration of MSK 408 with both ND and KD for 4 weeks restored serum lipid profile and tight junction protein mRNA expression of the gut and brain. Additionally, PCoA revealed that MSK 408 independently affected fecal short chain fatty acid (SCFA) content via gut microbiota (GM) modulation. PICRUSt suggested that the modulation of microbiota by KD and MSK 408 led to increased GABA (gamma-aminobutyric acid) metabolism. SIGNIFICANCE: Our findings suggest that MSK 408 strain can be consumed with KD as supplement without interfering the anti-seizure action of KD, and may improve the serum lipid profile, and brain barrier function via gut microbiota and SCFA modulation.