Effects of Fucoidan Isolated From Laminaria japonica on Immune Response and Gut Microbiota in Cyclophosphamide-Treated Mice

We are continually exposed to organisms that are inhaled, swallowed, or inhabit our skin and mucous membranes. Whether these organisms penetrate and cause disease is a result of both the pathogenicity of the organism (the virulence factors at its disposal) and the integrity of host defence mechanisms. The immune system is an interactive network of lymphoid organs, cells, humoral factors, and cytokines. The essential function of the immune system in host defence is best illustrated when it goes wrong; underactivity resulting in the severe infections and tumours of immunodeficiency, overactivity in allergic and autoimmune disease. In this review we have covered the normal function of the immune system in recognising, repelling, and eradicating pathogens and other foreign molecules.

Cyclophosphamide is an alkylating agent belonging to the group of oxazaphosporines. As cyclophosphamide is in clinical use for more than 40 years, there is a lot of experience using this drug for the treatment of cancer and as an immunosuppressive agent for the treatment of autoimmune and immune-mediated diseases. Besides antimitotic and antireplicative effects, cyclophosphamide has immunosuppressive as well as immunomodulatory properties. Cyclophosphamide shows selectivity for T cells and is therefore now frequently used in tumour vaccination protocols and to control post-transplant allo-reactivity in haplo-identical unmanipulated bone marrow after transplantation. The schedule of administration is of special importance for the immunological effect: while cyclophosphamide can be used in high-dose therapy for the complete eradication of haematopoietic cells, lower doses of cyclophosphamide are relatively selective for T cells. Of special interest is the fact that a single administration of low-dose cyclophosphamide is able to selectively suppress regulatory T cells (Tregs). This effect can be used to counteract immunosuppression in cancer. However, cyclophosphamide can also increase the number of myeloid-derived suppressor cells. Combination of cyclophosphamide with other immunomodulatory agents could be a promising approach to treat different forms of advanced cancer.

The impact of the gut microbiota on immune homeostasis within the gut and, importantly, also at systemic sites has gained tremendous research interest over the last few years. The intestinal microbiota is an integral component of a fascinating ecosystem that interacts with and benefits its host on several complex levels to achieve a mutualistic relationship. Host-microbial homeostasis involves appropriate immune regulation within the gut mucosa to maintain a healthy gut while preventing uncontrolled immune responses against the beneficial commensal microbiota potentially leading to chronic inflammatory bowel diseases (IBD). Furthermore, recent studies suggest that the microbiota composition might impact on the susceptibility to immune-mediated disorders such as autoimmunity and allergy. Understanding how the microbiota modulates susceptibility to these diseases is an important step toward better prevention or treatment options for such diseases.