5. Microbiota and chemotherapy

inhibitors. Studies performed in gnotobiotic or in antibiotic-treated mice revealed the implica-

In the last years, many scientific studies demonstrated that the commensal is an important

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 lympho-

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

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 trans-

The inflammation induced by microbiota may contribute to cancer by stimulating the release

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

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

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

participant to the host metabolism, inflammatory process, and immune response.

cytes, as well as compromised production of antimicrobial peptides [28–30].

of cancer and impact of the therapeutic responsiveness [31–35].

plantable tumors, and only few data are sustained by clinical evidence.

mediates the proliferative and antiapoptotic effects in tumors [36].

regression.

and environment.

of cytokines involved in the cell proliferation and apoptosis inhibition pathways.

tion of microbes in tumorigenesis driven or not by inflammation.

4. Microbiota and immune functions

126 Anti-cancer Drugs - Nature, Synthesis and Cell

The intestinal epithelium is a single-cell layer, which functions as the largest barrier of the human body. It is characterized by a selective permeability for the nutrients, electrolytes, and water and has an effective role in defense against toxins and enteric microbiota. Intestinal epithelial cells maintain the local environmental balance by facilitating the interaction between commensal and the host immune cells [37].

In order to obtain the best anticancer drug bioavailability, the formulation must consider besides the physicochemical properties or drug adjuvants, the permeability of the intestinal barrier.

Mucositis (mucosal barrier injury) is a major oncological problem caused by chemotherapeutic agents. Intestinal mucositis translates into a broad spectra of clinical symptoms (diarrhea, vomiting) and can be worsened by neutropenia and antibiotics. Since IECs do not regulate intestinal homeostasis by themselves, but require symbiotic coordination with commensal bacteria and local gut leukocytic cells, the role of intestinal microbiota in the development and severity of mucositis induced by chemotherapeutic products became an issue [38].
