Lactoferrin in the Prevention and Treatment of Intestinal Inflammatory Pathologies Associated with Colorectal Cancer Development

Simple Summary Colorectal cancer is the third most deadly and fourth most commonly diagnosed cancer in the world. Beside incorrect lifestyles, such as smoking or excessive consumption of red meat and alcohol, inflammatory bowel diseases are considered driving factors for colorectal cancer onset and development. It is known that chronic inflammatory processes can lead to both intestinal barrier disruption and perturbation of microbial flora, thus increasing cancer risk. To date, no treatment against these inflammatory pathologies has proved efficient and resolutive. The glycoprotein lactoferrin, a safe supplement for infant and adult foods, is involved in immune defense and endowed with a number of properties, including anti-microbial, anti-inflammatory and anti-cancer activities. This review outlines the most recent studies on lactoferrin as a potential candidate in the prevention and treatment of intestinal inflammatory pathologies that are associated with increased risk of colorectal cancer. The connection between inflammation and cancer is well-established and supported by genetic, pharmacological and epidemiological data. The inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, have been described as important promoters for colorectal cancer development. Risk factors include environmental and food-borne mutagens, dysbalance of intestinal microbiome composition and chronic intestinal inflammation, with loss of intestinal epithelial barrier and enhanced cell proliferation rate. Therapies aimed at shutting down mucosal inflammatory response represent the foundation for IBDs treatment. However, when applied for long periods, they can alter the immune system and promote microbiome dysbiosis and carcinogenesis. Therefore, it is imperative to find new safe substances acting as both potent anti-inflammatory and anti-pathogen agents. Lactoferrin (Lf), an iron-binding glycoprotein essential in innate immunity, is generally recognized as safe and used as food supplement due to its multifunctionality. Lf possesses a wide range of immunomodulatory and anti-inflammatory properties against different aseptic and septic inflammatory pathologies, including IBDs. Moreover, Lf exerts anti-adhesive, anti-invasive and anti-survival activities against several microbial pathogens that colonize intestinal mucosa of IBDs patients. This review focuses on those activities of Lf potentially useful for the prevention/treatment of intestinal inflammatory pathologies associated with colorectal cancer development.