Butyrate, forskolin, and lactose synergistically enhance disease resistance of chickens by inducing host defense peptide and barrier function gene expression

Authors: YANG, QING - Oklahoma State University; WHITMORE, MELANIE - Oklahoma State University; Robinson, Kelsy; LYU, WENTAO - Oklahoma State University; ZHANG, GUOLONG - Oklahoma State University

Submitted to: Antibiotics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/20/2021
Publication Date: 9/27/2021
Citation: Yang, Q., Whitmore, M.A., Robinson, K., Lyu, W., Zhang, G. 2021. Butyrate, forskolin, and lactose synergistically enhance disease resistance of chickens by inducing host defense peptide and barrier function gene expression. Antibiotics. 10(10). Article 1175. https://doi.org/10.3390/antibiotics10101175.
DOI: https://doi.org/10.3390/antibiotics10101175

Interpretive Summary: Routine use of in-feed antibiotics in livestock production has been linked to the development of antibiotic-resistant bacteria. This has led to the removal of antibiotics from livestock feed and created an urgent need for antibiotic alternatives capable of maintaining health and production efficiency of livestock animals. Increasing animal innate immunity through stimulation of endogenous host defense peptide (HDP) synthesis has emerged as one novel approach. This study investigated the ability of three natural compounds (butyrate, forskolin, and lactose) to enhance immunity and production of broiler chickens in a synergistic manner to protect against necrotic enteritis. Results revealed a strong synergy among the three compounds in inducing expression of HDP and barrier function genes in chicken cells. Furthermore, dietary supplementation with all three compounds dramatically reduced mortality, weight loss, intestinal lesions, and pathogen colonization during necrotic enteritis infection. These results indicate that the combination of butyrate, forskolin, and lactose may be further explored as a promising alternative to antibiotics for disease control and prevention in livestock animals.

Technical 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), 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 from 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.