Animals living in high latitude areas have to encounter low temperature environment and the threat of cold stress. Studies showed that cold stress significantly affects the physiological state of animals in cold areas [13]. Acute cold exposure and long-term cold feeding have negative effects on the growth performance, muscle performance and meat quality of livestock, and even lead to normal liver function and damage, reducing the relative weight of immune organs ([30,40]). Moreover, severe cold stress can cause pathological changes in the brain, cardiovascular diseases, and reproductive system diseases [31].

The intestinal tract is the largest digestive and absorption organ in the mammal body, and the important immune organ to resist the invasion of pathogenic microorganisms [44]. As the largest contact area between the internal environment and the external environment of organism, the intestine is the major target organ which has more susceptible to damage from cold stress due to its’ unique anatomical characteristics of mucosal blood vessels [50]. Studies have shown that cold stress negatively affects the intestinal health. Cold stress significantly reduced the height of jejunal villi, with thinning, swelling, and breakage of the villi, as well as decreased the expression of duodenal mucosal occluding genes, thereby disrupting the mechanical barrier of the intestine [22,48]. It has been shown that the antioxidant capacity of the small intestine of mice in the cold stress group was reduced [21]. It was shown that cold stress induced the raise of TLR4 and MYD88 proteins, the activation of the NF-κB signaling pathway as well as an increase in the concentration of TNF-α and IL-6, which may negatively affect immune function of mouse gut [6]. The cold stress also can cause changes in the quantity and species of gut microorganisms, which leads to impairments of the intestinal bio-barrier function [34]. To prevent the body damage of animals caused by cold stress, it is not only improving the ambient temperature in which animals are located, but also using effective nutritional regulation means, such as dietary additive that mitigates the effects of cold stress on the intestinal immune barrier and intestinal flora.

Rutin is one of the common flavonoids with a wide range of sources, such as mulberry leaves, small thistle, and other fruits and vegetables. It was resulted that rutin had superior phytochemical therapeutic potential which have many bioactivities such as antioxidant, anti-inflammatory, anti-apoptotic, cell-protective and digestive system protective effects [14]. Rutin inhibited functional and inflammatory changes, histopathological and morphological changes, and oxidative damage in intestinal mucositis induced by 5-fluorouracil [11]. Chen et al. [7] found that rutin can improve intestinal digestive enzyme activity and thus enhance intestinal digestive ability. However, the effect of rutin on the intestinal barrier function injury induced by cold stress has not been reported. The objective of this study was to investigate the mitigating effect of dietary rutin on the intestinal inflammatory response, tight junction proteins and impairment of intestinal microflora in cold-stressed mice