Lactoferrin is an iron-binding glycoprotein found in the milk of most mammals for which various biological functions have been reported, such as antimicrobial activity and bifidogenic activity. In this study, we compared the bifidogenic activity of bovine lactoferrin (bLF) and pepsin hydrolysate of bLF (bLFH), isolated bifidogenic peptide from bLFH, and investigated the bifidogenic spectra of bLF, bLFH, and its active peptide against 42 bifidobacterial strains comprising nine species. Against Bifidobacterium breve ATCC 15700 ^T , minimal effective concentrations of bLF and bLFH were 300 and 10 μg/ml. Against Bifidobacterium longum subsp. infantis ATCC 15697 ^T , the minimal effective concentration of bLFH was 30 μg/ml, and bLF did not show bifidogenic activity within 300 μg/ml. As an active peptide, a heterodimer of A ¹ -W ¹⁶ and L ⁴³ -A ⁴⁸ linked by a disulfide bond was isolated. Previously, this peptide was identified as having antibacterial activity. An amino acid mixture with the same composition as this peptide showed no bifidogenic activity. The strains of each species whose growth was highly promoted (>150%) by this peptide at 3.75 μM were as follows: B. breve (7 out of 7 strains [7/7]), B. longum subsp. infantis (5/5), Bifidobacterium bifidum (2/5), B. longum subsp. longum (1/3), Bifidobacterium adolescentis (3/6), Bifidobacterium catenulatum (1/4), Bifidobacterium pseudocatenulatum (0/4), Bifidobacterium dentium (0/5), and Bifidobacterium angulatum (0/3). Growth of none of the strains was highly promoted by bLF at 3.75 μM. We demonstrated that bLFH showed stronger bifidogenic activity than natural bLF, especially against infant-representative species, B. breve and B. longum subsp. infantis ; furthermore, we isolated its active peptide. This is the first report about a bifidogenic peptide derived from bLF.

In this study, we examined the protective effect of lactoferrin against DNA damage induced by various hydroxyl radical generation systems. Lactoferrin (LF) was examined with regard to its potential role as a scavenger against radical oxygen species using bovine milk LF. Native LF, iron-saturated LF (holo-LF), and apolactoferrin (apo-LF) effectively suppressed strand breaks in plasmid DNA due to hydroxyl radicals produced by the Fenton reaction. In addition, both native LF and holo-LF clearly protected calf thymus DNA from fragmentation due to ultraviolet irradiation in the presence of H₂O₂. We also demonstrated a protective effect of all three LF molecules against 8-hydroxydeoxyguanosine (8-OHdG) formation in calf thymus DNA following ultraviolet (UV) irradiation with H₂O₂. Our results clearly indicate that native LF has reactive oxygen species-scavenging ability, independent of its nature as a masking component for transient metals. We also demonstrated that the protective effect of LF against oxidative DNA damage is due to degradation of LF itself, which is more susceptible to degradation than other bovine milk proteins.

Human noroviruses cause significant morbidity and mortality worldwide, but lack approved antivirals or vaccines to treat or prevent infections. The recent development of two cell culture systems in human transformed B cells (BJABs) and non-transformed human intestinal enteroid cultures overcomes a main limitation in identifying molecules with anti-norovirus activities. Lactoferrin is an iron-binding glycoprotein found in the milk of most mammals, with broad spectrum antimicrobial activities, including against the related murine norovirus in cell culture. In a Japanese clinical trial, ingestion of lactoferrin reduced the incidence of infectious gastroenteritis in the participants. Because human noroviruses were the most common cause of gastroenteritis in Japan during the clinical trial period, we sought to determine whether lactoferrin could inhibit infection with human norovirus. Our study, using a B cell culture model, demonstrates that lactoferrin reduces human norovirus infection. The mechanism of antiviral action is likely indirect and may involve the induction of innate interferon responses. Therefore, future studies are warranted to test the antiviral efficacy of lactoferrin against human norovirus infection in patients.

To investigate the effects of lactoferrin (LF) on infectious diseases in Japanese summer. An intake of placebo, 200 mg, or 600 mg of LF were administered to healthy adults in Kyushu University of Health and Welfare for 12 weeks in a randomized, double-blinded, placebo-controlled parallel-group comparative trial. The primary endpoints were the prevalence and duration of infectious diseases and changes in immune parameters. Three hundred and ten subjects were randomized (placebo, n = 104; 200 mg, n = 103; 600 mg, n = 103). Twenty subjects were lost to the follow-up, leaving 290 for a full analysis set (n = 99; n = 95; n = 96). The duration (day) of total infectious diseases was shorter in the 200 mg group (2.0, p = 0.045) and 600 mg group (2.0, p = 0.010) than in the placebo group (3.0). The duration of summer colds was shorter in the 600 mg group (2.0, p = 0.036) than in the placebo group (3.0). No significant differences were observed in the prevalence of infectious diseases or changes in immune parameters. In exploratory investigations, changes in the neutrophil phagocytic capacity, cortisol concentrations, and T score of "Vigor/Activity" in the Profile of Mood States 2 were greater in the 600 mg group than in the placebo group, when analysis was done on the lower half groups at the baseline. Adverse events were similar in each group and none had a causal relationship with the intake of the test foods. In summer, the intake of LF attenuates infectious diseases, including summer colds.

To evaluate the effects of bovine lactoferrin (LF)-containing yogurt on gastroenteritis in nursery school children during the winter season, we conducted a randomized prospective study. A total of 1296 children were randomized into a group in which LF was provided in yogurt (LF group, n = 661) and a non-LF consumption group (control group, n = 635). The LF group was given LF-containing yogurt (100 mg/day) on all 5 weekdays for approximately 15 weeks, and the control group consumed fruit jelly instead of the yogurt. The final totals of 578 children as the LF group and 584 as the control group were analyzed. The total number of children who were absent from school due to vomiting was significantly lower in the LF group compared to the control, accounting for ≥3 days in any week: 10/234 (4.3%) vs. 49/584 (8.4%), respectively; p = 0.04. Regarding the relationship between absences due to vomiting and the consumption of the LF-containing yogurt, the adjusted odds ratio for absence due to vomiting was 2.48 (95% CI: 1.19–5.14) in the LF children who consumed LF-containing yogurt ≤2 days/week compared to the LF children who consumed the yogurt ≥ 3 days/week. The consumption of LF-containing yogurt (100 mg/day) for ≥3 days/week might help alleviate the symptom of vomiting in nursery school children during the winter.