Transplantation of fecal filtrate to neonatal pigs reduces post-weaning diarrhea, - a pilot study. AVANT farm FFT

Post-weaning diarrhea (PWD) remains a major source of mortality and morbidity in swine production. Transplantation of bacteria-free filtrate of feces (fecal filtrate transplant, FFT) has shown gut protective effects in neonatal pigs, and early postnatal establishment of the gut microbiome is suggested to determine later stability and robustness of the gut. We, therefore, hypothesized that early postnatal transplantation of bacteria-free feces would have a protective effect against PWD. Using fecal filtrates derived from healthy lactating sows, we compared oral administration of fecal filtrate transplantation (FFT, n=20) and saline (CON, n=18) in newborn piglets. We assessed growth, diarrhea prevalence, blood parameters, organ measurements, morphology, and gut brush border enzymes and analyzed luminal bacterial composition using 16S rRNA gene amplicon sequencing. The two groups showed similar average daily gain (ADG) during the suckling period, whereas in the post-weaning period, a negative ADG was observed in both groups. While diarrhea was largely absent in both groups before weaning, there was a lower diarrhea prevalence on days 27 (p=2.07*10-9), 28 (p=0.04), and 35 (p=0.04) in the FFT group relative to CON. At weaning on day 27, the FFT group had higher numbers of red blood cells, monocytes, and lymphocytes, while on day 35, i.e. one week after weaning, the two groups were similar regarding hematology. The biochemical profile was largely similar between FFT and CON on days 27 and 35, except for a higher level of alanine aminotransferase and a lower level of Mg in the FFT group. Likewise, organ weights relative to body weight were largely similar on day 35, albeit with a lower stomach weight and more colon content in FFT relative to CON. Gut mucosal percentage and mucosal enzyme activity were similar between the two groups on days 27 and 35. Gut bacterial composition was slightly different on day 35 but not on day 27. In conclusion, early postnatal administration of FFT, showed positive clinical effects in post-weaning pigs, albeit with subtle effects on the gut mucosa and microbiome. Prophylactic treatment with FFT may offer a means to reduce morbidity, yet larger studies are required to document effect size.

断奶后腹泻（Post-weaning diarrhea, PWD）仍是生猪养殖中死亡率与发病率的主要诱因。粪便无菌滤液移植（Fecal Filtrate Transplant, FFT）已被证实可对新生仔猪发挥肠道保护作用，而产后早期肠道微生物组的建立被认为决定了肠道后续的稳定性与健壮性。基于此，我们提出假设：产后早期实施粪便无菌滤液移植可对断奶后腹泻起到防护作用。本研究采用健康泌乳母猪来源的粪便滤液，在新生仔猪中开展对照实验，分别给予粪便无菌滤液移植灌服（FFT组，n=20）与生理盐水灌服（CON组，n=18）。我们评估了仔猪的生长性能、腹泻发生率、血液学指标、脏器测量数据、组织形态以及肠道刷状缘酶活性，并通过16S rRNA基因扩增子测序（16S rRNA gene amplicon sequencing）分析了肠腔细菌组成。哺乳期内两组仔猪的平均日增重（Average Daily Gain, ADG）无显著差异，但断奶后两组均出现了平均日增重为负的情况。断奶前两组仔猪几乎未出现腹泻症状；相较于对照组，FFT组在第27天（p=2.07×10^-9）、第28天（p=0.04）及第35天（p=0.04）的腹泻发生率更低。在第27天断奶时，FFT组仔猪的红细胞、单核细胞与淋巴细胞数量更高；而在断奶后一周的第35天，两组的血液学指标无显著差异。在第27天与第35天，两组的生化指标整体相似，仅FFT组的丙氨酸氨基转移酶水平更高，镁离子水平更低。第35天时，两组仔猪的脏器系数整体相近，仅FFT组的胃重量更低、结肠内容物更多。在第27天与第35天，两组的肠黏膜占比与黏膜酶活性均无显著差异。肠腔细菌组成在第35天时存在细微差异，但在第27天时无显著区别。综上，产后早期实施粪便无菌滤液移植灌服，可对断奶仔猪产生积极的临床防护效果，仅对肠黏膜与微生物组产生细微影响。采用FFT进行预防性治疗或可降低仔猪发病率，但仍需开展更大规模的研究以明确其效应量。