Butyrate, Forskolin, and Lactose Synergistically Enhance Disease Resistance by Inducing the Expression of the Genes Involved in Innate Host Defense and Barrier Function.

Qing Yang,Wentao Lyu,Kelsy Robinson,Melanie A Whitmore,Guolong Zhang

doi:10.3390/antibiotics10101175

Abstract

The rising concern of antimicrobial resistance highlights a need for effective alternatives to antibiotics for livestock production. Butyrate, forskolin, and lactose are three natural products known to induce the synthesis of host defense peptides (HDP), which are a critical component of innate immunity. In this study, the synergy among butyrate, forskolin, and lactose in enhancing innate host defense, barrier function, and resistance to necrotic enteritis and coccidiosis was investigated. Our results indicated that the three compounds synergistically augmented the expressions of multiple HDP and barrier function genes in chicken HD11 macrophages. The compounds also showed an obvious synergy in promoting HDP gene expressions in chicken jejunal explants. Dietary supplementation of a combination of 1 g/kg sodium butyrate, 10 mg/kg forskolin-containing plant extract, and 10 g/kg lactose dramatically improved the survival of chickens from 39% to 94% (p < 0.001) in a co-infection model of necrotic enteritis. Furthermore, the three compounds largely reversed growth suppression, significantly alleviated intestinal lesions, and reduced colonization of Clostridium perfringens or Eimeria maxima in chickens with necrotic enteritis and coccidiosis (p < 0.01). Collectively, dietary supplementation of butyrate, forskolin, and lactose is a promising antibiotic alternative approach to disease control and prevention for poultry and possibly other livestock species.

Highlights

Necrotic enteritis (NE) is caused by the Gram-positive bacterium Clostridium perfringens [1], while the etiological agents of coccidiosis are Eimeria, a genus of apicomplexan parasites [2]
Butyrate in combination with forskolin or lactose induced a higher level of AvBD3 expression relative to butyrate alone, while the forskolin/lactose combination had no effect on AvBD3 gene expression
It is noted that different host defense peptides (HDP) genes were apparently regulated at different magnitudes

Summary

Introduction

Necrotic enteritis (NE) is caused by the Gram-positive bacterium Clostridium perfringens [1], while the etiological agents of coccidiosis are Eimeria, a genus of apicomplexan parasites [2]. Both NE and coccidiosis are among the most economically significant infectious diseases facing the poultry industry causing growth retardation, morbidity, and even mortality [1,2]. Enhancing the production of endogenous host defense peptides (HDPs) is being actively explored as a promising antibiotic-free strategy for disease control and prevention [7,8,9,10]. A variety of small-molecule compounds such as fatty acids, phytochemicals, and vitamin D3 have been shown to induce HDP expression and are being developed for antimicrobial therapies [7,8,9,10,16]

Objectives

Methods

Results

Conclusion