Abstract
Berberine (BBR), an isoquinoline alkaloid, is a major pharmacological component of the Chinese herb Coptis chinensis, which has been listed in the Chinese Fisheries Pharmacopeia as a common drug for the control of bacterial fish diseases. However, BBR is poorly absorbed into the systemic circulation but is significantly accumulated in the intestine. It is difficult to explain the mechanism of clinical effects of BBR based on systemic genes and pathways; it has been proved that the function of BBR in mammals is associated with the host metabolic phenotypes mediated by the structural modulation of gut microbiota. The mechanism of pharmacological effects of BBR in fish remains unclear. Here, we fed grass carp (Ctenopharyngodon idellus) a diet supplemented with BBR at a dose of 30 mg/Kg body weight daily and compared them with grass carp fed a regular fish feed diet. Biochemical analysis revealed that fish fed BBR had significantly reduced serum glucose, total cholesterol (TC), and triglyceride (TG) levels, and increased TC (p < 0.05) and TG (p < 0.01) levels in the liver. Deep amplicon sequencing of the V4 region of 16S rRNA genes of the gut microbiota revealed: (i) the composition of gut microbiota after BBR feeding was more diverse than that in the control group; (ii)before fish were fed BBR, the enriched operational taxonomic units (OTUs) mainly belonged to Firmicutes while most enriched OTUs came from Proteobacteria, Planctomycetes, Bacteroidetes, and Firmicutes during BBR feeding and after BBR feeding stopped; (iii) the ratio of Firmicutes to Bacteroidetes was significantly decreased in fish fed BBR. Spearman’s rank correlation showed that 32 berberine-OTUs were significantly negative correlated with glucose (p < 0.05). It indicates that BBR may affect the levels of serum glucose by the structural modulation of gut microbiota. Our results provide insight into the effect of BBR on fish metabolism and gut microbiomes, which would be beneficial for the fish welfare.
Highlights
The grass carp is a herbivorous freshwater fish and one of the most important economic farmed fish in China; it has been introduced into more than 100 countries (Wu et al, 2012; Hao et al, 2017)
The body weight and relative fatness were not significantly different between the BBR-fed and control group (Supplementary Figure S1), the levels of glucose and lipids in serum and liver were significantly affected by BBR in grass carp (Figure 1)
The levels of glucose, total cholesterol (TC), and TG in blood sera in the BBR-fed group were significantly (p < 0.05, p < 0.05 and P < 0.05, respectively) lower than those in the control group from days 3 to 9; these significant differences disappeared after day 14 when BBR-supplemented feeding stopped (Figures 1A–C)
Summary
The grass carp is a herbivorous freshwater fish and one of the most important economic farmed fish in China; it has been introduced into more than 100 countries (Wu et al, 2012; Hao et al, 2017). Fish do not utilize dietary carbohydrate effectively (Furuichi and Yone, 1980; Walton and Cowey, 1982; Shiau, 1997; Stone, 2003; Polakof et al, 2012) and most carnivorous fish exhibit. Grass carp can utilize dietary carbohydrate better than other carnivorous fish species (Stone, 2003), they utilize carbohydrates less efficiently than lipids (Gao et al, 2010). BBR show hypolipidemic (lipid-lowering) effects in the freshwater fish, blunt-snout bream (Megalobrama amblycephala) (Xu et al, 2017). The hypoglycemic (glucose-lowering) effects of BBR in fish have not been reported to date
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