Recombinant human lactoferrin enhances the efficacy of triple therapy in mice infected with Helicobacter pylori

Abstract

Helicobacter pylori (H. pylori) is a life-threatening pathogen which causes chronic gastritis, gastric ulcers and even stomach cancer. Treatment normally involves bacterial eradication; however, this type of treatment only has a rate of effectiveness of <80%. Thus, it is a matter of some urgency to develop new therapeutic strategies. Lactoferrin, a member of the transferrin family of iron-binding proteins, has been proven to be effective in removing a vast range of pathogens, including H. pylori. In the present study, we examined the effectiveness of recombinant human lactoferrin (rhLf) isolated from transgenic goats as a treatment for H. pylori in vitro and in vivo. For the in vivo experiments, BALB/c mice received an intragastric administration of 0.1 ml of a suspension of H. pylori. The mice were then divided into 4 groups: group A, treated with saline; group B, treated with 1.5 g of rhLF; group C, treated with the standard triple therapy regimen; and group D, treated with the standard triple therapy regimen plus.5 g of rhLF. Following sacrifice, the stomach tissues of the mice were histologically examined for the presence of bacteria. For the in vitro experiments, the bacteria were cultured in BHI broth and RT-qPCR and western blot analysis were carried out to determine the mRNA and protein levels of virulence factors (CagA and VacA) in the cultures. Our results revealed that rhLf not only inhibited the growth of H. pylori, but also suppressed the expression of two major virulence factors. Moreover, rhLf markedly increased bacterial eradication and effectively reduced the inflammatory response when combined with the standard triple therapy regimen. These results provide evidence supporting the use of rhLF as an adjuvant to traditional therapeutic strategies in the treatment of H. pylori.

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

“…In particular, after the pioneering study by Miehlke and colleagues [ 289 ], who demonstrated the in vitro bactericidal activity of rhLf against 13 clinical isolates of H. pylori , both bLf and rhLf were shown to promote bacterial growth and gastric inflammation in mice [ 290 ]. In the same field, inconclusive results have been obtained so far in humans, with two open randomized trials showing the efficacy [ 291 , 292 ] and one the inefficacy [ 293 ] of bLf in improving eradication rates of H. pylori when applied in combination therapies. Moreover, despite the abovementioned studies proving the efficacy of Lf on animal models of colitis, the failure of bLf in decreasing risk of sepsis and necrotizing enterocolitis (NEC) in preterm infants was recently reported [ 294 ].…”

Bovine lactoferrin enhances the efficacy of levofloxacin-based triple therapy as first-line treatment ofHelicobacter pyloriinfection: anin vitroandin vivostudy

“… 48 It has also been shown that recombinant human lactoferrin can bind and disrupt some bacterial cell membranes, 49 , 50 and when it is co-administered with amoxicillin against Gram-negative bacteria it increases its efficacy, as found in animal models. Furthermore, in a recent study Yuan et al 51 examined the effectiveness of recombinant human lactoferrin isolated from transgenic goats as a treatment for H. pylori in vitro and in vivo . For the in vitro experiments, the results revealed that recombinant human lactoferrin not only inhibited the growth of H. pylori , but also suppressed the expression of two major virulence factors, cagA and vacA .…”

Lactoferrin: Balancing Ups and Downs of Inflammation Due to Microbial Infections

“…Interestingly, Lf as a single component failed to eradicate the H. pylori infection but in combination with triple esomeprazole, clarithromycin and amoxicillin therapy and with probiotics, favored the resolution of infection and ameliorated the inflammatory response more effectively than in combination with two-antibiotic treatment, as described in experimental mice treated with r-hLf from transgenic goats, and also in trails of patients treated with native bLf. Interestingly, r-hLf not only inhibited the growth of H. pylori , but also suppressed the expression of two of its major virulence factors [133,134]. …”