High-fat diet (HFD) consumption leads to metabolic disorders, gastrointestinal dysfunction and intestinal dysbiosis. Antibiotics also disrupt the composition of intestinal microbiota. The aim of the present study was to investigate the impact of a short-term feeding with HFD on oxidative status, enteric microbiota, intestinal motility and the effects of antibiotics and/or melatonin treatments on diet-induced hepato-intestinal dysfunction and inflammation. Male Sprague–Dawley rats were pair-fed with either standard chow or HFD (45 % fat) and were given tap water or melatonin (4 mg/kg per d) or melatonin plus antibiotics (ABX; neomycin, ampicillin, metronidazole; each 1 g/l) in drinking water for 2 weeks. On the 14th day, colonic motility was measured and the next day intestinal transit was assessed using charcoal propagation. Trunk blood, liver and intestine samples were removed for biochemical and histopathological evaluations, and faeces were collected for microbiota analysis. A 2-week HFD feeding increased blood glucose level and perirenal fat weight, induced low-level hepatic and intestinal inflammation, delayed intestinal transit, led to deterioration of epithelial tight junctions and overgrowth of colonic bacteria. Melatonin intake in HFD-fed rats reduced ileal inflammation, colonic motility and perirenal fat accumulation. ABX abolished increases in fat accumulation and blood glucose, reduced ileal oxidative damage, suppressed HFD-induced overgrowth in colonic bacteria, and reversed HFD-induced delay in intestinal transit; however, hepatic neutrophil accumulation, hepatic injury and dysfunction were further enhanced. In conclusion, the results demonstrate that even a short-term HFD ingestion results in hepato-intestinal inflammatory state and alterations in bacterial populations, which may be worsened with antibiotic intake, but alleviated by melatonin.

The objective of this study was to determine the protective effect of glutamate (Glu) in Cu-induced oxidative injury in fish intestine in vivo and enterocytes in vitro. The results indicated that exposure to 6 mg/l Cu for 72 h induced the production of reactive oxygen species, thereby increasing protein oxidation and lipid peroxidation in enterocytes of grass carp in vitro. Cells exposed to Cu alone resulted in a significant increase in lactate dehydrogenase release, which is accompanied by depletions of antioxidants, including total superoxide dismutase (T-SOD), glutathione S-transferase (GST), glutathione reductase (GR), anti-superoxide anion (ASA), anti-hydroxy radical (AHR) activities and GSH content. Pre-treatment with Glu remarkably prevented the toxic effects of Cu on the T-SOD, GST, GR, AHR, and ASA activities and GSH content in enterocytes. However, Cu induced an adaptive increase in the activities of catalase and glutathione peroxidase (GPx). Glu supplementation further increased GPx activity in enterocytes. Interestingly, the experiment in vivo showed that Glu pre-supplementation significantly elevated SOD, GPx, GST, GR, ASA and AHR activities, as well as GSH content. Further results showed that pre-treatment with Glu could alleviate Cu-induced oxidative injury by elevating antioxidant enzyme activities through regulating the expression of NF-E2-related nuclear factor 2 (Nrf2) mRNA. Together, these results indicated that Glu could attenuate Cu-induced cellular oxidative damage in fish intestine, likely mediated through Nrf2 signalling pathways regulating mRNA expressions of antioxidant enzyme genes and synthesis of GSH.