Integrated multiomics analysis reveals the effect of glucose selenol improves rat immunity

Selenium (Se), a well-known micronutrient, plays a critical role in biological function of plants and animals. Se possesses functions such as antioxidant, anti-inflammatory, and immune maintenance [[1], [2], [3]]. Its deficiency might render negative impacts on human health, potentially leading to diseases such as Keshan disease and Kashin-Beck disease [1,4]. There is a low Se zone in China (Se content ≤0.125 mg/kg), extending from northeastern to southwest China [5]. Residents in this region need additional Se supplements, and Se-enriched food supplements are considered a key source of Se supplementation [6]. In the process of digesting orally ingested Se, it is first absorbed by the small intestine and subsequently transported to the liver, where it is primarily metabolized into selenocysteine and subsequently synthesized into selenoproteins [7]. The absorption and conversion efficiency of Se compounds can vary depending on their chemical structures, with conversion efficiency influencing on both the detoxification and antioxidant properties of Se. In light of this, modifications to Se have been explored, resulting in the development of various organic selenides such as selenocystine [8], selenomethionine [9] and selenized glucose [10,11], in addition to the traditional inorganic Se salts such as sodium nitrite. Multiple experiments have shown that organic Se exhibits greater bioavailability and conversion rates in comparison to inorganic Se [12,13,2].

Omic approaches have become a valuable method for in-depth investigation of dietary Se responses, contributing greatly to a deeper and more comprehensive understanding of the metabolism of this element and its biological roles, includes its impact on gut microbiome composition and metabolites profiles [14,15]. For instance, [16] combined metabolomics, metallomics, and amplicon sequencing to demonstrated the effect of Se on brain metabolome through specific selenoproteins gene expression and gut microbiota. Using transcriptomics, Dioithona rigida was employed as a copepod model to study nanoselenium for the first time [17,18] comprehensively detailed omics studies on Se and selenoproteins, with a focus on neuropsychiatric disorders and brain pathophysiology.

The spleen is a multifaceted lymphoid organ and a key hematopoietic center, serving as the site for B cell maturation and T cell activation, and playing a vital role in both innate and acquired immunity [19]. Composed of red pulp and white pulp, the spleen is responsible for clearing pathogens, cell debris, and aged red blood cells from the blood in the former, while being filled with lymphocytes in the latter. Within the spleen, B cells recognize specific antigens, subsequently differentiating into plasma cells which then produce specific immunoglobulins, such as IgM, IgG, IgA, IgE, and IgD. These immunoglobulins circulate through the bloodstream to various parts of the body, thereby providing defense against pathogenic invasion. An increasing body of evidence supports the benefit of Se on splenic immunity [20]. Additionally, research on the effect of Se deficiency on the spleen is common in mammals and poultry [21] have shown that Se deficiency can lead to spleen damage in pigs by reducing selenoprotein expression, causing oxidative stress, triggering inflammation, and activating cell apoptosis. Similarly, [22] found that Se deficiency has been found to alter cytokine levels, affect selenoprotein synthesis, increase oxidative stress, and ultimately impair the immune function of laying hens. Supplementation with organic yeast-derived Se provides immune protection in broiler chickens [23].

Glucose selenol (SeGlu), also known as selenized glucose, has been reported to enhance male sperm vitality [24], and to have protective effects on cadmium-induced testicular toxicity and liver toxicity [25,26]. Furthermore, [27] confirmed that SeGlu can regulate tryptophan metabolism by modulating the gut microbiome. From a safety perspective, SeGlu does not damage various indicators in rats, but there is a lack of research on the impact on individual organs. To our knowledge, the effects of SeGlu supplementation on the body's immune capacity, such as the expression of cytokines and immunoglobulins, have not been assessed. To bridge this gap, we utilized rats as model organisms, designed comparative experiments on certain serum cytokines and immunoglobulins in rats under different Se levels in drinking water, and identified the key regulatory genes and shared metabolites of SeGlu through splenic transcriptomics and metabolomics. Our study provides new insights into evaluating the immunostimulatory effects of SeGlu, contributing to the advancement of human health and the global livestock industry. This research also lays a theoretical foundation for the development and promotion of Se-rich products.

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