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

Sheila Estruel-Amades,Mariona Camps-Bossacoma,Francisco Pérez-Cano,Àngels Franch,Margarida Castell,Malén Massot-Cladera

doi:10.3390/nu11020324

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.

Highlights

Polyphenols, extensively found in plants as a product of their secondary metabolism [1] can be classified into different groups regarding their chemical structure: Phenolic acids, flavonoids, anthocyanidins, stilbenes, and lignans [2]
In the small intestine this flavanone is poorly absorbed via the paracellular pathway and it is highly dependent on the conversion to hesperetin [5,11]
The administration of 100 mg/kg or 200 mg/kg of hesperidin three times per week for four weeks did not modify the body weight compared to the REF group (Table 2)

Summary

Introduction

Polyphenols, extensively found in plants as a product of their secondary metabolism [1] can be classified into different groups regarding their chemical structure: Phenolic acids, flavonoids, anthocyanidins, stilbenes, and lignans [2]. The most distinguished subgroups are flavonols (e.g., quercetin, kaempferol, and myricetin), flavanones (e.g., eriodictyol, hesperetin, and naringenin), isoflavones (e.g., daidzein, genistein, and glycetein), flavones (e.g., apigenin, and luteolin), flavan-3-ols (e.g., catechin), and anthocyanins (e.g., cyanidin, delphinidin, and malvidin) [3]. Hesperidin is the major flavanone present in citrus fruits, such as orange [9,10]. It is composed by hesperetin being conjugated to rutinose. In the small intestine this flavanone is poorly absorbed via the paracellular pathway and it is highly dependent on the conversion to hesperetin [5,11]. Hesperidin reaches the large intestine where gut microbiota cleaves the attached rutinose moiety, forming hesperetin for further colonic absorption [12].

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