Abstract
Hepcidin, one kind of antimicrobial peptides, is one of the promising alternatives to antibiotics with broad spectrum of antimicrobial activity. Hepcidins cloned from different kinds of fishes have been produced using exogenous expression systems, and their in vitro antimicrobial effects have been verified. However their in vivo effects on gut microbiota and gut health of hosts remain unclear. Here we performed a safety study of hepcidin so that it can be used to reduce microbial contaminations in the food and feed. In this study, Pichia pastoris-expressed Pseudosciaena crocea hepcidin (PC-hepc) was first assessed by simulated digestion tests and then administered to male and female Sprague-Dawley (SD) rats in different concentrations. Subchronic toxicity testing, high throughput 16S rRNA sequencing of gut microbiota, and examinations on gut metabolism and permeability were conducted. The results showed PC-hepc could be digested in simulated intestinal fluid but not in simulated gastric fluid. PC-hepc had no adverse effects on general health, except causing increase of blood glucose (still in the normal value range of this index) in all trial groups of female rats and intestinal inflammation in HD group of female rats. Community composition of gut microbiota of female MD and HD groups shifted compared with control group, of which the decrease of genus Akkermansia might be related to the increase of blood glucose and intestinal inflammation. Significant increase of fecal nitroreductase activity was also observed in female MD and HD groups. Our results suggest the uses of exogenous PC-hepc in normal dosage are safe, however excess dosage of it may cause intestinal disorder of animals.
Highlights
Bacterial disease outbreaks are great threats to human health and agricultural industries
Pseudosciaena crocea hepcidin (PC-hepc) could be digested in simulated intestinal fluid but not in simulated gastric fluid
A previous study showed that Pichia pastoris-expressed PC-hepc has a wide spectrum of in vitro antimicrobial activity, including Micrococcus luteus, Corynebacterium glutamicum, Pseudomonas fluorescens, and Pseudomonas stutzeri [14], indicating its promising application as antimicrobial agent, and indicating the probability that PC-hepc could affect the bacteria in gut microbiota
Summary
Bacterial disease outbreaks are great threats to human health and agricultural industries. Several mechanisms have made bacterial pathogens either to be intrinsically resistant or to acquire resistance to certain antibiotics [1], which results in the emergence of multidrug-resistant strains among major Gram-positive and Gram-negative species [2], causing huge economic losses and public health crisis. Another concern regarding the use of antibiotics is their effects on the gut microbiota of animals. The challenges of antibiotics to the gut microbiota include alteration in bacterial membership [3] and reduction of the immune responses in peripheral organs [4]. There is an urgent need for the development and validation of alternatives to antibiotics
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