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Background The emergence of antimicrobial resistance has necessitated the development of effective alternatives to antibiotics for livestock and poultry production. This study investigated a possible synergy between butyrate and forskolin (a natural labdane diterpene) in enhancing innate host defense, barrier function, disease resistance, growth performance, and meat quality of broilers. Methods The expressions of representative genes involved in host defense ( AvBD9  and  AvBD10 ), barrier function ( MUC2 ,  CLDN1 , and  TJP1 ), and inflammation ( IL-1β ) were measured in chicken HD11 macrophages in response to butyrate and forskolin in the presence or absence of bacterial lipopolysaccharides (LPS). Intestinal lesions and the  Clostridium perfringens  titers were also assessed in  C. perfringens- challenged chickens fed butyrate and forskolin-containing  Coleus forskohlii  (CF) extract individually or in combination. Furthermore, growth performance and carcass characteristics were evaluated in broilers supplemented with butyrate and the CF extract for 42 d. Results Butyrate and forskolin synergistically induced the expressions of  AvBD9 ,  AvBD10 , and  MUC2  in chicken HD11 cells ( P  &lt; 0.05) and the synergy was maintained in the presence of LPS. Butyrate and forskolin also suppressed LPS-induced  IL-1β  gene expression in HD11 cells in a synergistic manner ( P  &lt; 0.05). The two compounds significantly reduced the intestinal lesions of  C. perfringens- challenged chickens when combined ( P  &lt; 0.05), but not individually. Furthermore, butyrate in combination with forskolin-containing CF extract had no influence on weight gain, but significantly reduced feed intake ( P  &lt; 0.05) with a strong tendency to improve feed efficiency ( P  = 0.07) in a 42-d feeding trial. Desirably, the butyrate/forskolin combination significantly decreased abdominal fat deposition ( P  = 0.01) with no impact on the carcass yield, breast meat color, drip loss, or pH of d-42 broilers. Conclusions Butyrate and forskolin has potential to be developed as novel antibiotic alternatives to improve disease resistance, feed efficiency, and carcass composition of broilers.

Butyrate in combination with forskolin alleviates necrotic enteritis, increases feed efficiency, and improves carcass composition of broilers