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

Abstract

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.

The Prospect of Lactoferrin Use as Adjunctive Agent in Management of SARS-CoV-2 Patients: A Randomized Pilot Study

“…Accordingly, as expected, treatment of study participants with twice daily doses of Lf (200 mg orally twice daily) revealed increases in serum hemoglobin level, lymphocyte count and in platelet count between control and treatment groups through treatment days. This expected laboratory indices finding is similar to prior studies [ 37 , 38 ]. The plausible explanation for this observation can be attributed to broad spectrum anti-inflammatory and anti-infective properties of Lf.…”

A Review on Lactoferrin and Central Nervous System Diseases

“…Lf is a multifunctional protein. In addition to its well-known function of regulating iron homeostasis [ 14 ], Lf also exerts multiple important biological effects, such as anti-inflammatory, antibacterial, reactive oxygen species (ROS) modulator, antiviral, and antitumor immunity effects [ 1 , 2 , 4 , 5 , 12 , 15 , 16 ]. These activities are largely mediated by the capacity of Lf to bind iron [ 7 , 17 , 18 , 19 ] and the binding constant [ 20 , 21 , 22 ].…”

The Functional Role of Lactoferrin in Intestine Mucosal Immune System and Inflammatory Bowel Disease

“…or Bifidobacterium sp ., which is generally considered as a beneficial effect ( 18 , 19 ). In addition to its antibacterial properties, LF also has both epithelial barrier protection and immunomodulatory properties, which play key roles in the intestine mucosal immune system ( 20 – 22 ). The studies cited above indicate that the physiological functions of LF not only depend on the iron-binding capacity but also on the interaction with molecular and cellular components of both the host and pathogens ( 23 ).…”

“…Inflammatory bowel disease (IBD), mainly divided into ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory and relapsing disorder of the gastrointestinal tract, in which the interactions among mucosal immune, barrier function, nutrition, and commensal enteric flora are involved ( 24 – 28 ). Accumulating studies report that LF can be considered as a potent anti-inflammatory and immunomodulatory substrate for the prevention and treatment of IBD through regulating intestine mucosal immune response ( 9 , 22 , 29 , 30 ). Breakdown of intestinal barrier underpins IBD and other diseases ( 31 ).…”

“…Accumulating evidence indicate that LF has been reported to enhance intestinal epithelial cell proliferation, cytokines production, and immune cell functions in counteracting inflammatory processes and maintaining immune homeostasis ( 9 , 22 , 29 , 30 ). This review aims to outline the intestine mucosal immune system and the functional role of LF (bovine LF, bLF; human LF, hLF; porcine LF, pLF; LF enzymatic hydrolysate; LF peptide-derivatives) on the intestine mucosal immune system and IBD.…”