Lysozyme improves gut performance and protects against enterotoxigenic Escherichia coli infection in neonatal piglets

Guangping Huang,Qiuyan Li,Dan Lu,Xiangqing Li,Shen Liu,Xun Suo,Ning Li

doi:10.1186/s13567-018-0511-4

Guangping Huang, Qiuyan Li + Show 5 more

Open Access

https://doi.org/10.1186/s13567-018-0511-4

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Abstract

Diarrhea remains one of the leading causes of morbidity and mortality globally, with enterotoxigenic Escherichia coli (ETEC) constituting a major causative pathogen. The development of alternative treatments for diarrhea that do not involve chemotherapeutic drugs or result in antibiotic resistance is critical. Considering that lysozyme is a naturally occurring antimicrobial peptide, in a previous study we developed a transgenic pig line that expresses recombinant human lysozyme (hLZ) in its milk. In the present study, we examined the protective effects of the consumption of this milk against ETEC infection in neonatal piglets. We found that consuming hLZ milk facilitated faster recovery from infection and decreased mortality and morbidity following an ETEC oral inoculation or infection acquired by contact-exposure. The protective effect of hLZ was associated with the enrichment of intestinal bacteria that improve gut health, such as Lactobacillus, and the enhancement of the mucosal IgA response to the ETEC-induced diarrhea. Our study revealed potential protective mechanisms underlying the antimicrobial activity of human lysozyme, validating the use of lysozyme as an effective preventive measure for diarrhea.

Highlights

Enterotoxigenic Escherichia coli (ETEC) is one of the most devastating pathogens associated with diarrhea in animals and humans, annually accounting for 157 000 deaths among children [1]
We examined the ability of lysozyme, a natural antimicrobial protein, to protect neonatal piglets against ETEC K88 infection
We found that the consumption of human lysozyme (hLZ) milk helped ETEC-challenged piglets to recover from infection faster with lower mortality, and helped cohabitated piglets to decrease the morbidity with less intestinal damage, and enhanced IgA production and Lactobacillus enrichment

Summary

Introduction

Enterotoxigenic Escherichia coli (ETEC) is one of the most devastating pathogens associated with diarrhea in animals and humans, annually accounting for 157 000 deaths among children [1]. ETEC pathogenicity is dependent on colonizing factors ( known as adhesins) and enterotoxins [2]. ETEC that is associated with diarrhea in neonatal pigs expresses one or more fimbrial adhesins, including F4 (K88), F5 (K99), F6 (987P), F7 (F41) and F18, while ETEC in older pigs most commonly produces F4 (K88) or F18 fimbriae. Fimbrial adhesins bind to glycoprotein receptors on the enterocyte brush border, enabling E. coli colonization in the small intestine. The bacteria secrete heat-labile enterotoxins and/or heat-stable enterotoxins that alter tight junction integrity and disrupt the paracellular passages of ions, solutes and water, leading to diarrhea [3, 4].

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