Mechanisms of Prevotella copri Induced Intestinal Damage in Piglets and Modulation by Protocatechuic Acid

Gut microbiota has been reported to play an important role in weaned piglets. Our previous study demonstrated a notable enrichment of intestinal Prevotella in weaned piglets experiencing diarrhea, although the mechanisms are not clear. In this study, we elucidated the mechanism of Prevotella copri (P. copri) in causing diarrhea, and the protective effect by protocatechuic acid (PCA). A total of 108 healthy Duroc × Landrace × Yorkshire weaned piglets, aged 21 d, were randomly assigned into 3 groups, with 6 replicates and 6 piglets per replicate. The piglets were fed a basal diet, a basal diet containing 1.0 × 108 CFU/kg P. copri or 1.0 × 108 CFU/kg P. copri + 400 mg/kg PCA for 28 d. Results showed that P. copri decreased the final body weight and average daily gain (ADG), while increased the feed-to-gain ratio (F/G) , with increased serum levels of interleukin (IL) -2 and IL-8 in piglets (P &lt; 0.05), and reduced the expression of intestinal tight junction protein (P &lt; 0.05). In vitro experiments indicated that argininosuccinic acid, indole-3-aldehyde, and N-acetylpurine are the primary virulence factors of P. copri in inducing inflammation. PCA suppressed inflammatory cytokines both in vivo and in vitro (P &lt; 0.05), and enhanced the expression of tight junction proteins in piglets (P &lt; 0.05). In conclusion, P. copri can reduce the growth performance of weaned piglets by inducing intestinal inflammation, while argininosuccinic acid, indole-3-aldehyde, and N-acetylpurine are the primary virulence factors, and PCA has shown a protective effect.已有研究表明，肠道菌群（gut microbiota）对断奶仔猪发挥着关键调控作用。本团队前期研究发现，腹泻断奶仔猪的肠道普雷沃氏菌属（Prevotella）丰度显著升高，但其具体作用机制尚未阐明。本研究旨在阐明普通普雷沃氏菌（Prevotella copri，简称P. copri）诱发仔猪腹泻的作用机制，以及原儿茶酸（protocatechuic acid，PCA）的保护效果。 本试验共选取108头21日龄健康杜洛克×长白×约克夏断奶仔猪，随机分为3组，每组设6个重复，每个重复6头仔猪。试验期28天，各组仔猪分别饲喂基础日粮、基础日粮添加1.0×10^8 菌落形成单位（colony-forming unit，CFU）/kg P. copri，以及基础日粮添加1.0×10^8 CFU/kg P. copri与400 mg/kg PCA。 结果显示，P. copri可显著降低仔猪的终末体重与平均日增重（average daily gain，ADG），升高料重比（feed-to-gain ratio，F/G；P<0.05）；同时升高仔猪血清白细胞介素（interleukin，IL）-2与IL-8水平，并下调肠道紧密连接蛋白（tight junction protein）的表达（P<0.05）。体外试验表明，精氨琥珀酸、吲哚-3-甲醛与N-乙酰嘌呤是P. copri诱发炎症的主要毒力因子。PCA可在体内（in vivo）与体外（in vitro）抑制炎症因子的产生（P<0.05），并上调仔猪肠道紧密连接蛋白的表达（P<0.05）。 综上，P. copri可通过诱发肠道炎症降低断奶仔猪的生长性能，其主要毒力因子为精氨琥珀酸、吲哚-3-甲醛与N-乙酰嘌呤；而PCA对断奶仔猪具有明确的保护作用。