Holothurian Wall Hydrolysate Ameliorates Cyclophosphamide-Induced Immunocompromised Mice via Regulating Immune Response and Improving Gut Microbiota

Abstract

Some biologically active compounds isolated from sea cucumbers stimulate the body’s immune response by activating immune cells. Immune function is closely related to the integrity intestinal barrier and balanced gut microbiota. However, it is unknown whether the daily administration of holothurian wall hydrolysate (HWH) ameliorated intestinal dysbiosis and barrier injury induced by immunodeficiency. This study aimed to investigate the immunomodulatory effect and the underlying mechanism of HWH in cyclophosphamide (CTX)-induced immunocompromised mice. BALB/c mice received CTX (80 mg/kg, intraperitoneally) once a day for 3 days to induce immunodeficiency, and then they received the oral administration of HWH (80 or 240 mg/kg) or levamisole hydrochloride (LH, 40 mg/kg, positive control), respectively, once a day for 7 days. We utilized 16S rRNA sequencing for microbial composition alterations, histopathological analysis for splenic and colonic morphology, Western blotting for expressions of tight junction proteins (TJs), and quantitative real-time (qRT)-PCR for measurements of pro-inflammatory cytokines. HWH attenuated the immune organ damage induced by CTX, increased the secretions of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, and promoted the recovery of goblet cells and the production of TJs (claudin-1, occludin, and ZO-1) in the colon of the immunocompromised mice. Moreover, HWH promoted the growth of beneficial microorganisms such as Lactobacillus, Lachnospiraceae, Christensenellaceae, and Bifidobacterium, while it suppressed the populations of Ruminococcus, Staphylococcus, and Streptococcus. These results demonstrate that HWH elicits intestinal mucosal immunity, repairs the damage to intestinal mucosal integrity, and normalizes the imbalanced intestinal microbial profiles in immunocompromised mice. It may be helpful to identify the biological activities of HWH to support its potential use in new prebiotics, immunomodulatory agents, and medical additives for intestinal repair.

Effect of bovine colostrum liposomes on the bioavailability of immunoglobulin G and their immunoregulatory function in immunosuppressed BALB/c mice

“…29–31 As important immune organs, the spleen and thymus play crucial roles in regulating immune function. Consistent with the investigations of other researchers, 32–34 our current research indicated that CTX could decrease the body weight, spleen weight, and thymus weight in BALB/c mice, which indicated that CTX could cause damage to the immune system in the mice; however, the supplementation of BC encapsulated by liposomes improved these adverse alterations and exhibited a better effect than BC alone (Fig. 3 and 4).…”

“…39 Detrimental environments can cause the oxidation and inflammation of the intestine, and numerous studies have indicated that CTX can induce a shortening and shedding of the intestinal villus, ultimately leading to damage of the intestinal mucosal layer. 32,33,40 Our current research suggested that CTX triggered damage to the jejunum structure, as manifested by the disappearance of muscle layers and exposure of the lamina propria structure; however, supplementation with BCL restored the structures of the jejunal epithelial cells (Fig. 6).…”