Modulation of Pro-inflammatory and Anti-inflammatory Cytokines in the Fat by an Aloe Gel-based Formula, QDMC, Is Correlated with Altered Gut Microbiota

Abnormal inflammatory responses are closely associated with intestinal microbial dysbiosis. Oral administration of Qmatrix-diabetes-mellitus complex (QDMC), an Aloe gel-based formula, has been reported to improve inflammation in type 2 diabetic mice; however, the role of the gut microbiota in ameliorating efficacy of QDMC remains unclear. We investigated the effect of QDMC on the gut microbiota in a type 2 diabetic aged mouse model that was administered a high-fat diet. Proinflammatory (TNF-α and IL-6) and anti-inflammatory (IL-4 and IL-10) cytokine levels in the fat were normalized via oral administration of QDMC, and relative abundances of Bacteroides, Butyricimonas, Ruminococcus, and Mucispirillum were simultaneously significantly increased. The abundance of these bacteria was correlated to the expression levels of cytokines. Our findings suggest that the immunomodulatory activity of QDMC is partly mediated by the altered gut microbiota composition.

Downregulation of IL-18 Expression in the Gut by Metformin-induced Gut Microbiota Modulation

IL-18 is a crucial pro-inflammatory cytokine that mediates chronic intestinal inflammation. Metformin, an anti-diabetic drug, was reported to have ameliorative effects on inflammatory bowel disease. Recently, the mechanism of action of metformin was explained as a modulation of gut microbiota. In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet. Further, FMT downregulated the expression of the inflammatory cytokine IL-18. Within the genera Akkermansia, Bacteroides, and Butyricimonas, which were promoted by metformin therapy, Butyricimonas was found to be consistently abundant following FMT. Our findings suggest that modulation of gut microbiota is a key factor for the anti-inflammatory effects of metformin which is used for the treatment of hyperglycemia.

Restoration of Declined Immune Responses and Hyperlipidemia by Rubus occidenalis in Diet-Induced Obese Mice

Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor (TNF)-α level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.