Dietary ellagic acid supplementation attenuates intestinal damage and oxidative stress by regulating gut microbiota in weanling piglets.

Intestinal oxidative stress triggers gut microbiota dysbiosis, which is involved in the etiology of post-weaning diarrhea and enteric infections. Ellagic acid (EA) can potentially serve as an antioxidant supplement to facilitate weaning transition by improving intestinal oxidative stress and gut microbiota dysbiosis. Therefore, we aimed to investigate the effects of dietary EA supplementation on the attenuation of intestinal damage, oxidative stress, and dysbiosis of gut microbiota in weanling piglets. A total of 126 piglets were randomly assigned into 3 groups and treated with a basal diet and 2 mL saline orally (Ctrl group), or the basal diet supplemented with 0.1% EA and 2 mL saline orally (EA group), or the basal diet and 2 mL fecal microbiota suspension from the EA group orally (FEA group), respectively, for 14 d. Compared with the Ctrl group, EA group improved growth performance by increasing average daily feed intake and average daily weight gain (P < 0.05) and decreasing fecal scores (P < 0.05). EA group also alleviated intestinal damage by increasing the tight junction protein occludin (P < 0.05), villus height, and villus height-to-crypt depth ratio (P < 0.05), while decreasing intestinal epithelial apoptosis (P < 0.05). Additionally, EA group enhanced the jejunum antioxidant capacity by increasing the total antioxidant capacity (P < 0.01), catalase (P < 0.05), and glutathione/oxidized glutathione (P < 0.05), but decreased the oxidative metabolite malondialdehyde (P < 0.05) compared to the Ctrl group. Compared with the Ctrl group, EA and FEA groups increased alpha diversity (P < 0.05), enriched beneficial bacteria (Ruminococcaceae and Clostridium ramosum), and increased metabolites short-chain fatty acids (P < 0.05). Correspondingly, FEA group gained effects comparable to those of EA group on growth performance, intestinal damage, and intestinal antioxidant capacity. In addition, the relative abundance of bacteria shifted in EA and FEA groups was significantly related to the examined indices (P < 0.05). Overall, dietary EA supplementation could improve growth performance and attenuate intestinal damage and oxidative stress by regulating the gut microbiota in weanling piglets.

Berberine Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis and Inhibits the Secretion of Gut Lysozyme via Promoting Autophagy.

Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease, the occurrence of which has been increasing worldwide. Research in recent years has found that the level of lysozyme in the feces and blood of UC patients is abnormally elevated, and the bacterial product after the action of lysozyme can be used as an agonist to recognize different cell pattern receptors, thus regulating the process of intestinal inflammation. Berberine (BBR), as a clinical anti-diarrhea and anti-inflammatory drug, has been used in China for hundreds of years. In this study, results showed that BBR can significantly inhibit the expression and secretion of lysozyme in mice. Therefore, we try to investigate the mechanism behind it and elucidate the new anti-inflammatory mechanism of BBR. In vitro, lipopolysaccharide (LPS) was used to establish an inflammatory cell model, and transcriptomic was used to analyze the differentially expressed genes (DEGs) between the LPS group and the LPS + BBR treatment group. In vivo, dextran sulfate sodium salt (DSS) was used to establish a UC mice model, and histologic section and immunofluorescence trails were used to estimate the effect of BBR on UC mice and the expression of lysozyme in Paneth cells. Research results showed that BBR can inhibit the expression and secretion of lysozyme by promoting autophagy via the AMPK/MTOR/ULK1 pathway, and BBR promotes the maturation and expression of lysosomes. Accordingly, we conclude that inhibiting the expression and secretion of intestinal lysozyme is a new anti-inflammatory mechanism of BBR.

LncRNA SNHG16 promotes colorectal cancer cell proliferation, migration, and epithelial-mesenchymal transition through miR-124-3p/MCP-1.

Colorectal cancer (CRC) has been the third leading cause of cancer-associated deaths. LncRNA SNHG16 is reported to be involved in metastasis of CRC cells. However, the mechanism by which SNHG16 regulates CRC progression is poorly understood. The proliferation of CRC cells was examined by MTT. Wound healing and transwell assay were used to measure migration and invasion ability. RT-qPCR and western blot were used to examine gene expression. Immunofluorescence was conducted to evaluate the EMT of CRC cells. Luciferase reporter assay were used to confirm direct interaction between miR-124-3p and SNHG16 or MCP-1. The interaction between miR-124-3p and SNHG16 was detected by RIP and RNA pull down assay. H&E staining was used to test the histomorphological changes of hepatic metastatic nodules. Finally, xenograft tumor experiment was utilized to determine tumor growth in vivo. SNHG16 and miR-124-3p were dysregulated in human colorectal tumors or cells. Knockdown of SNHG16 led to attenuate cell proliferation, migration, invasion, and EMT of CRC cells. And xenograft tumor experiment showed that SNHG16 might influence tumor growth. In contrast, miR-124-3p exerted the antitumor effects. Knockdown of miR-124-3p can reverse the effect of sh-SNHG16 on CRC cells. miR-124-3p could directly bind to SNHG16 or MCP-1. More importantly, MCP-1 acts as a critical effector mediating the role of SNHG16/ miR-124-3p in CRC cells. In summary, our data suggest that SNHG16 plays a contributory role in proliferation, migration, and EMT of CRC cells via miR-124-3p/MCP-1 axis, which offers a rationale for targeting SNHG16 and developing therapeutic drugs to treat CRC.