Bovine Colostrum Exerts Immunomodulatory and Intestinal Microbiota-Modifying Activity in Calves and Protects FMT Mice from Salmonella Infection

Abstract

Background: Zoonotic enteric pathogens (ZEP) are responsible for high morbidity and mortality worldwide. Calves are common reservoir resulting in the horizontal transmission of ZEP to human food chain and environment. Rising antimicrobial resistance of ZEP reduces the decolonization approaches, therefore novel host and microbiota-directed strategies are critically needed to overcome this problem. Bovine colostrum (BC) is the first milk produced by mammary glands postpartum and it is known to contain numerous bioactive molecules. Despite that, the ability to use BC as a host-directed antimicrobial remains poorly understood. Methods: The effects of BC on the adhesion of E. coli O157 to the Caco2 intestinal cells was evaluated using cell culture infection models. The BC effects on the intestinal microbiota in neonatal calves was determined by fecal 16S rRNA sequencing. The novel fecal microbiota transplantation (FMT) model in mice was developed to analyze the immunomodulatory activity of BC. Salmonella typhimurium (S. typhimurium) challenge studies in FMT mice were used to study the BC protective role during the intestinal infections. Results: The BC was able to significantly reduce the E. coli O157 adhesion to the Caco2 cells in comparison to untreated control (UC) of autologous milk control (AM) (p<0.05). The BC activity on STEC adhesion was significantly diminished by heat inactivation. Early administration of BC in neonatal calves resulted in the significant changes of intestinal microbiota in comparison to replacer control (RC). BC administration resulted in higher abundance of Clostridium IV, Anaerostipes, and Bifidobacterium. Interestingly Kandleria was only found in animals treated with BC. The novel murine FMT model revealed that BC can modulate lymphoid cell populations in comparison to UC. The feeding with BC significantly increased CD44high CD8+ T cells and GITR+ CD4+ cell populations in draining lymph nodes and decreased NK populations in Peyer’s patches, in comparison to UC (p<0.05). Moreover, BC increased the percentage of CD5+ B cells and plasma cells among FMT animals in comparison to UC (p<0.05). BC supplementation significantly prolonged FMT mice survival in S. typhimurium infection model (p<0.05). Conclusions: BC demonstrated strong immunomodulatory, microbiota modifying and anti-virulence activity both in cattle’s as well as FMT mice. BC can be further explored as host-directed antimicrobial. Further studies are needed to better understand the BC mechanism of action on the host, microbiota, and pathogens.