4. Microbiota and immune functions

In the last years, many scientific studies demonstrated that the commensal is an important participant to the host metabolism, inflammatory process, and immune response.

Nowadays, gut microbiota is particularly the most studied, and it has been proven to be essential for the development of the intestinal immune system, protecting the host against pathogens and harmful inflammatory processes. Germ-free animals have smaller Peyer's patches, fewer immune cells and impaired immunoglobulin A (IgA) secretion, fewer intraepithelial lymphocytes, as well as compromised production of antimicrobial peptides [28–30].

Gut microbiota is involved in the immune responses and inflammatory processes both local and systemic. The link between inflammation and cancer is well known raising the questions about the potential interference of microbiota. This area of research is new, and astonishing recent results revealed that microbiota is a key player in the immunomodulatory mechanisms of cancer and impact of the therapeutic responsiveness [31–35].

The present knowledge sustains that the presence and the quality of gut microbiota may induce inflammation and promote cancer or may induce tumor-destructive immune responses and favor anticancer treatment. Most studies involved experimental animal model of transplantable tumors, and only few data are sustained by clinical evidence.

The inflammation induced by microbiota may contribute to cancer by stimulating the release of cytokines involved in the cell proliferation and apoptosis inhibition pathways.

In a study regarding a hepatocellular carcinoma mouse model, the intestinal microbiota was essential for the promotion and initiation of cancer by signaling pathways involving toll-like receptor 4 (TLR4), a surface immune cell receptor, which senses the microbial molecular patterns. The activation of this receptor induced an increased level of a hepatomitogen, which mediates the proliferative and antiapoptotic effects in tumors [36].

The beneficial immunomodulatory effect in cancer regression is supported by the use of some microbial in anticancer therapy. The intravesical bacillus Calmette-Guerin (BCG) therapy is one of the standard methods of management of intermediate- and high-risk non-muscle invasive bladder cancer. Also, intratumoral inoculation of heat-killed Propionibacterium acnes in subcutaneous melanoma promotes local and systemic Th1 and Tc1 responses associated with tumor regression.

More other evidences are presented and discussed by the scientific literature about the key role of microbiota and the possibility to modulate it. However, the specific mechanisms are far to be elucidated due to the complex composition and the multifactorial interaction between gene and environment.
