Haematococcus pluvialis peptides restore cyclophosphamide-induced immunodeficiency in mice by enhancing gut barrier and microbiota.

Immunodeficiency, characterized by impaired immune system integrity, contributes to various diseases. Current treatments often have side effects or limited efficacy, prompting interest in natural bioactive compounds. This study explores Haematococcus pluvialis peptides (HPP) as a promising option to improve immune function, specifically addressing the gut-immune axis, which is crucial for maintaining host defense and often compromised in immunodeficient states. The focus is on how HPP might restore intestinal barrier function and modulate gut microbiota to alleviate immune suppression.

Researchers investigated the therapeutic effects of Haematococcus pluvialis peptides (HPP) on cyclophosphamide (CTX)-induced immunodeficiency in mice. The study assessed various physiological and immunological parameters, including bodyweight, immune organ indices, and blood cell counts. Serum cytokine levels (IFN-γ, IL-2, IgA) were measured, alongside intestinal morphology and antioxidant enzyme activities (SOD, GSH-PX). Tight junction protein expression (ZO-1, occludin) in the colon was analyzed. Fecal microbiota composition was profiled, and metabolites were analyzed. Finally, fecal microbiota transplantation (FMT) experiments were conducted to confirm the role of gut microbiota.

HPP treatment significantly increased bodyweight, immune organ indices, and blood cell counts, including white blood cells, red blood cells, platelets, hemoglobin, lymphocytes, and granulocytes, in immunodeficient mice. Serum levels of IFN-γ, IL-2, and IgA were also elevated. Intestinal morphology improved, with increased villus length and crypt depth, alongside enhanced intestinal antioxidant capacity (increased SOD and GSH-PX) and local immunity (increased SIgA). > Colonic expression of tight junction proteins, ZO-1 and occludin, was notably up-regulated. Fecal microbiota analysis revealed HPP promoted beneficial genera like Ligilactobacillus, norank_f_Muribaculaceae, and Alistipes, while suppressing pathogenic Escherichia-Shigella and Klebsiella. Furthermore, HPP altered various fecal metabolites linked to lipids, organoheterocyclic compounds, phenylpropanoids, polyketides, and organic acids. FMT experiments conclusively demonstrated the critical role of gut microbiota in HPP's immunomodulatory effects.