`LeakyCow` – Heat stress-induced local and systemic immune responses in dairy cows with leaky gut syndrome

Contact: Dr. rer. nat. Franziska Koch

Duration: 2020-2023

Funding: Deutsche Forschungsgemeinschaft, DFG KO 5972/2-1 / AOBJ: 666828

The frequency of extreme weather phenomena and heat weaves are predicted to increase over the next decades. Dairy cows may not acclimate to high ambient temperatures due to their enormous metabolic heat production and reduced capacity to lose heat through panting and sweating. During high ambient temperatures, dairy cows show reduced feed intake, milk yield, and reproductive performance as well as a compromised welfare, cumulating in a condition known as heat stress. In order to increase heat loss through body surface area, blood flow is directed from the viscera towards the periphery. The decrease in local blood flow leads to a reduced supply of oxygen that causes local hypoxia in the intestinal mucosa modulating gut barrier function. Heat stress seems to directly alter tight junction proteins and affect gut integrity of cows. Penetrating pathogens and bacteria may initiate the individual immune response. Furthermore, high ambient temperatures might affect the intestinal microbiota composition towards a higher abundance of pathogenic bacteria enhancing immune response intensity. The aim of this DFG proposal is to investigate the long- and short-term effect of high ambient temperatures on the humoral immune response, gut permeability and its interaction with the intestinal gut microbiota in mid-lactation, primiparous Holstein cows. Dairy cows will be allocated into either a control (C; 15°C, temperature-humidity-index (THI) 60, ad libitum), heat-stress (HS; 28°C, THI 76, ad libitum) or pair-feeding (PF; 15°C, THI 60, restrictive feeding) group for seven days of treatment. The PF-group is needed to maintain isoenergetic conditions between the HS- and PF-groups. Heat stress effects on the gut integrity and the humoral immunity will be characterized by the systemic and local inflammation activated by circulating endotoxin and Heat shock protein 70 via the Toll-like receptor 2/4 signaling pathway in peripheral leucocytes, peripheral blood mononuclear cells and mesenteric lymph nodes, thereby releasing pro-inflammatory cytokines to maintain homeostasis. Furthermore, the characterization of the intestinal microbiota is required to confer heat-induced microbial dysbiosis in the jejunum that could be linked to endotoxemia, `leaky gut` and individual immune response intensity. New insights into the activation and modulation of the local and systemic immunity and alteration of the gut microbiota will improve our understanding of the underlying molecular immune response observed in the `leaky gut syndrome` model; thereby eliciting new feeding and treatment strategies to maintain animal health and reduce economical loss.