Abstract: In the poultry industry, there is an urgent need to evaluate and introduce natural, effective,
and safe alternatives for synthetic antibiotics, which have been banned in most countries. The present
study aimed to investigate the effects of dietary supplementation with Piper sarmentosum extract (PSE)
on the growth performance, intestinal barrier function, and metabolism of growing chickens. A total
of 400 seven-day-old female chicks were randomly assigned to four dietary treatments, each of which
consisted of five replicates and twenty birds each. The four experimental treatments were fed a basal
diet containing 0, 100, 200, and 300 mg PSE/kg (BC, PSE1, PSE2, and PSE3 groups), respectively.
The experiment lasted for 28 days. The results showed that dietary supplementation with PSE had
no significant effects on the final body weight, average daily gain (ADG), average daily feed intake
(ADFI), and the ratio of ADFI to ADG (F/G) (p > 0.05). Compared with the BC group, dietary
supplementation with 200–300 mg/kg PSE increased the villus height in the jejunum and ileum of
chickens (p < 0.05). The PSE-treated groups significantly increased the mRNA expression of Occludin,
ZO-1, and Claudin-1 in the ileal mucosa of chickens (p < 0.05). In addition, a significant decrease in
ileal TNF- and IL-8 mRNA expression (p < 0.05) and a significant increase in IL-22 (p < 0.05) were
observed in the PSE2 treatment compared to the BC group. Additionally, three gut metabolites (i.e.,
citrate, isocitrate, and spermine) showed significant differences among treatments (p < 0.05) and
were involved in the tricarboxylic acid (TCA) cycle, the transfer of acetyl groups into mitochondria,
and spermidine and spermine biosynthesis, respectively. In conclusion, the findings obtained here
indicate that supplemental PSE can enhance the anti-inflammatory capacity and intestinal mucosal
barrier function of chickens.