Hesperidin Effects on Gut Microbiota and Gut-Associated Lymphoid Tissue in Healthy Rats

Abstract

Hesperidin, found in citrus fruits, has shown a wide range of biological properties. Nonetheless, a more in-depth investigation is required on the effects on the immune system, and in particular, on the gut-associated lymphoid tissue, together with its relationship with the gut microbiota. Therefore, we aimed to establish the influence of oral hesperidin administration on the intestinal lymphoid tissue and on the gut microbiota composition in healthy animals. Lewis rats were orally administrated 100 or 200 mg/kg hesperidin three times per week for four weeks. Microbiota composition and IgA-coated bacteria were determined in caecal content. Mesenteric lymph node lymphocyte (MLNL) composition and functionality were assessed. IgA, cytokines, and gene expression in the small intestine were quantified. Hesperidin administration resulted in a higher number of bacteria and IgA-coated bacteria, with changes in microbiota composition such as higher Lactobacillus proportion. Hesperidin was also able to increase the small intestine IgA content. These changes in the small intestine were accompanied by a decrease in interferon-γ and monocyte chemotactic protein-1 concentration. In addition, hesperidin increased the relative proportion of TCRαβ+ lymphocytes in MLNL. These results show the immunomodulatory actions of hesperidin on the gut-associated lymphoid tissue and reinforce its role as a prebiotic.

Protective Effect of Hesperidin on the Oxidative Stress Induced by an Exhausting Exercise in Intensively Trained Rats

“…This effect was more evident in the first four weeks and even hesperidin-supplemented animals achieved the maximum performance one week later, which was higher than that in non-supplemented animals. The amount of hesperidin used was based on previous studies [37,38] evidencing its immunomodulatory effects. This amount in rats could be transformed to a human dosage by taking into account the body surface area [44]; accordingly, 200 mg/rat kg would be equal to 32.43 mg/human kg, and given that 1 L of orange juice provides about 600 mg hesperidin [45], the hesperidin amount per week would be supplied by a total of 13 L of orange juice per week.…”

“…The flavanone was administered by oral gavage three times per week at a dose of 200 mg/kg of rat BW. This dosage was chosen following a previous study demonstrating its beneficial effects on the immune system [37,38].…”

“…Hesperidin and its aglycone form, hesperetin, are a type of polyphenols found mainly in citrus fruits [33]. Besides having an antioxidant ability [34], they also exert beneficial biological activities in obesity [35], cancer [36] and in systemic and intestinal immunity [37,38]. The antioxidant activity of hesperidin has been observed in a rat model of pleurisy by reducing liver ROS production and increasing both catalase and SOD liver activities [39].…”

“…Hesperidin also protects against oxidative damage induced by exercise through a decrease in lipid peroxidation in swimmer rats [41]. However, although in previous studies hesperidin has shown its effects in the immune system [37,38], there are no studies focused on the oxidative status in lymphoid tissues under intensive exercise-induced oxidative stress. For this reason, the aim of the present study is to assess the impact of hesperidin supplementation on the oxidant and antioxidant status of lymphoid tissues in rats after an intensive training program and after an additional exhaustion test.…”

Metabolomics and 16S rRNA Gene Sequencing Analyses of Changes in the Intestinal Flora and Biomarkers Induced by Gastrodia-Uncaria Treatment in a Rat Model of Chronic Migraine

“…Recently, several studies have indicated that DNA sequence variants affect the risk of migraine subtypes (Sutherland et al, 2019;van den et al, 2019;Grieco et al, 2018), and 16S rRNA gene sequencing and metabolomics have been used as effective tools for studying disease and drug treatment mechanisms (Estruel-Amades et al, 2019). 16S rRNA gene sequencing studies can accurately identify the structure and metabolic functions of the gut microbe.…”