*Article* **Establishment of a Newborn Lamb Gut-Loop Model to Evaluate New Methods of Enteric Disease Control and Reduce Experimental Animal Use**

**Ambre Baillou 1,2,†, Nathalie Kasal-Hoc 3,†, Céline Barc <sup>3</sup> , Juliette Cognié 4 , Anne Pinard <sup>3</sup> , Jérémy Pezant <sup>3</sup> , Julie Schulthess <sup>2</sup> , Pauline Peltier-Pain <sup>2</sup> , Sonia Lacroix-Lamandé 1,\* ,‡ and Fabrice Laurent 1,\* ,‡**


**Abstract:** Enteric infectious diseases are not all well controlled, which leads to animal suffering and sometimes death in the most severe cases, in addition to economic losses for farmers. Typical symptoms of enteric infections include watery diarrhea, stomach cramps or pain, dehydration, nausea, vomiting, fever and weight loss. Evaluation of new control methods against enteric infections requires the use of many animals. We aimed to develop a new method for an initial in vivo screen of promising compounds against neonatal diseases such as cryptosporidiosis while limiting experimental animal use. We therefore adapted an in vivo method of multiple consecutive but independent intestinal loops to newborn lambs delivered by cesarean section, in which endotoxin responsiveness is retained. This new method allowed for the screening of natural yeast fractions for their ability to stimulate immune responses and to limit early *Cryptosporidium parvum* development. This model may also be used to investigate host–pathogen interactions and immune responses in a neonatal controlled environment.

**Keywords:** newborn lamb; multiple intestinal loop model; 3R; *Cryptosporidium parvum*; yeast cell wall fractions
