5-Fluorouracil (5-FU) is a common anti-tumor drug, but there is no effective treatment for its side effect, intestinal mucositis. The inflammatory reaction of macrophages in intestinal mucosa induced by 5-FU is an important cause of intestinal mucositis. In this study, we investigated the anti-inflammatory effects of the three important short-chain fatty acids (SCFAs), including sodium acetate (NaAc), sodium propionate (NaPc), and sodium butyrate (NaB), on human mononuclear macrophage-derived THP-1 cells induced by 5-FU. The expressions of intracellular ROS, pro-inflammatory/anti-inflammatory cytokines, as well as the nuclear factor-κB/NLR family and pyrin domain-containing protein 3 (NF-κB/NLRP3) signaling pathway proteins were determined. Furthermore, the cell metabolites were analyzed by untargeted metabolomics techniques. Our results revealed that the three SCFAs inhibited pro-inflammatory factor expressions, including IL-1β and IL-6, when treated with 5-FU (p < 0.05). The ROS expression and NF-κB activity of 5-FU-treated THP-1 cells were inhibited by the three SCFAs pre-incubated (p < 0.05). Moreover, NLRP3 knockdown abolished 5-FU-induced IL-1β expression (p < 0.05). Further experiments showed that the three SCFAs affected 20 kinds of metabolites that belong to amino acid and phosphatidylcholine metabolism in THP-1 cells. These significantly altered metabolites were involved in amino acid metabolism and glycerolphospholipid and sphingolipid metabolism. It is the first time that three important SCFAs (NaAc, NaPc, and NaB) were identified as inhibiting 5-FU-induced macrophage inflammation through inhibiting ROS/NF-κB/NLRP3 signaling pathways and regulating glycerolphospholipid and sphingolipid metabolism.
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic disease in modern society. It is characterized by an accumulation of lipids in the liver and an excessive inflammatory response. Clinical trials have provided evidence that probiotics may prevent the onset and relapse of NAFLD. The aim of this study was to explore the effect of Lactiplantibacillus plantarum NKK20 strain (NKK20) on high-fat-diet-induced NAFLD in an ICR murine model and propose the underlying mechanism whereby NKK20 protects against NAFLD. The results showed that the administration of NKK20 ameliorated hepatocyte fatty degeneration, reduced total cholesterol and triglyceride concentrations, and alleviated inflammatory reactions in NAFLD mice. In addition, the 16S rRNA sequencing results indicated that NKK20 could decrease the abundance of Pseudomonas and Turicibacter and increase the abundance of Akkermansia in NAFLD mice. LC-MS/MS analysis showed that NKK20 could significantly increase the concentration of short-chain fatty acids (SCFAs) in the colon contents of mice. The obtained non-targeted metabolomics results revealed a significant difference between the metabolites in the colon contents of the NKK20 administration group and those in the high-fat diet group, in which a total of 11 different metabolites that were significantly affected by NKK20 were observed, and these metabolites were mainly involved in bile acid anabolism. UPLC-MS technical analysis revealed that NKK20 could change the concentrations of six conjugated and free bile acids in mouse liver. After being treated with NKK20, the concentrations of cholic acid, glycinocholic acid, and glycinodeoxycholic acid in livers of the NAFLD mice were significantly decreased, while the concentration of aminodeoxycholic acid was significantly increased. Thus, our findings indicate that NKK20 can regulate bile acid anabolism and promote the production of SCFA, which can inhibit inflammation and liver damage and thus prevent the development of NAFLD.
Obesity is a common global problem. There are many fat-reducing herbal prescriptions in traditional Chinese medicine that have been proven to be safe and functional during long-term application. Microbial fermentation can improve the efficacy of herbal medicine and improve the unsavory flavor. In this study, Shenheling extract (SHLE) composed of six medicine food homology materials was used as the research object. The purpose of this study was to evaluate the effects of Lactobacillusfermentum grx08 fermentation on the antiobesity efficacy and flavor of SHLE. We found that L. fermentum grx08 grew well in SHLE. After 72 h of fermentation, the total polysaccharides, total flavonoids, total polyphenols and total saponins of SHLE decreased, but the lipase inhibitory activity and total antioxidant capacity (FRAP) were significantly increased (p < 0.01). There were no significant differences in the α-glucosidase inhibition rate and DPPH· clearance rate before or after fermentation (p > 0.05). In addition, the fermentation reduces the unpleasant flavors of SHLE such as bitterness and grassy and cassia flavors. This study demonstrates that SHLE fermented by L. fermentum grx08 improved some anti-obesity functions and improved the unpleasant flavor.
In this study, high-throughput sequencing technology was used to analyze the bacterial diversity of sauerkraut produced at home and in factories in Chaozhou. The differences in bacterial community structure among different sauerkraut samples were studied by diversity analysis and heat map analysis, and the dominant bacterial genera were analyzed. The results showed that 54 phyla and 622 genera were identified from 10 Chaozhou sauerkraut samples. The bacterial community structures of Chaozhou sauerkraut produced by five factories were similar, and the dominant bacterial genera were the same, which were Lactobacillus, Pediococcus and Weissella. The dominant genus in the sauerkraut samples produced by three families was similar to that in samples produced by the factories. However, the samples from two other families were quite different, and there may be environmental pollution. The samples may also contain possible pathogenic microorganisms such as Pseudomonas and Vibrio. Overall, there were still some differences in the bacterial community structure of Chaozhou sauerkraut factory-produced and household-handmade samples. To the best of our knowledge, this paper is the first to compare the bacterial diversity of homemade and factory-produced Chaozhou sauerkraut, laying the foundation for further research on Chaozhou sauerkraut.