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Objective: To determine the impact of supplemental bovine lactoferrin on the gut microbiome and metabolome of preterm infants.Design: Cohort study nested within a randomised controlled trial (RCT). Infants across different trial arms were matched on several clinical variables. Bacteria and metabolite compositions of longitudinal stool and urine samples were analysed to investigate the impact of lactoferrin supplementation.Setting: Thirteen UK hospitals participating in a RCT of lactoferrin.Patients: 479 infants born <32 weeks' gestation between June 2016 and September 2017.Results: 10 990 stool and 22 341 urine samples were collected. Analyses of gut microbiome (1304 stools, 201 infants), metabolites (171 stools, 83 infants; 225 urines, 90 infants) and volatile organic compounds (314 stools, 117 infants) were performed. Gut microbiome Shannon diversity at 34 weeks corrected age was not significantly different between infants in the lactoferrin (mean=1.24) or placebo (mean=1.06) groups (p=0.11). Lactoferrin receipt explained less than 1% variance in microbiome compositions between groups. Metabolomic analysis identified six discriminative features between trial groups. Hospital site (16%) and postnatal age (6%) explained the greatest variation in microbiome composition.Conclusions: This multiomic study identified minimal impacts of lactoferrin but much larger impacts of hospital site and postnatal age. This may be due to the specific lactoferrin product used, but more likely supports the findings of the RCT in which this study was nested, which showed no impact of lactoferrin on reducing rates of sepsis. Multisite mechanistic studies nested within RCTs are feasible and help inform trial interpretation and future trial design. [ABSTRACT FROM AUTHOR]

Bovine lactoferrin (bLF), a naturally occurring glycoprotein found in milk, has bioactive characteristics against many microbes, viruses, and other pathogens. Bovine lactoferrin strongly inhibits SARS-CoV-2 infection in vitro through direct entry inhibition and immunomodulatory mechanisms. This study reports on the anti-SARS-CoV-2 efficacy of commercially available bLF and common dairy ingredients in the human lung cell line H1437 using a custom high-content imaging and analysis pipeline. We also show for the first time that bLF has potent efficacy across different viral strains including the South African B.1.351, UK B.1.1.7, Brazilian P.1, and Indian Delta variants. Interestingly, we show that bLF is most potent against the B.1.1.7 variant [half-maximal inhibitory concentration (IC 50) = 3.7 µg/mL], suggesting that this strain relies on entry mechanisms that are strongly inhibited by bLF. We also show that one of the major proteolysis products of bLF, lactoferricin B 17–41, has a modest anti-SARS-CoV-2 activity that could add to the clinical significance of this protein for SARS-CoV-2 treatment as lactoferricin is released by pepsin during digestion. Finally, we show that custom chewable lactoferrin tablets formulated in dextrose or sorbitol have equivalent potency to unformulated samples and provide an option for future human clinical trials. Lactoferrin's broad inhibition of SARS-CoV-2 variants in conjunction with the low cost and ease of production make this an exciting clinical candidate for treatment or prevention of SARS-CoV-2 in the future. [ABSTRACT FROM AUTHOR]

Results from previous studies have suggested that supplemental bovine lactoferrin (BLF) given to preterm infants (<32 weeks gestation) reduces late-onset sepsis (LOS) and necrotising enterocolitis (NEC). The Enteral Lactoferrin in Neonates (ELFIN) study, performed in the UK, aimed to further address this issue with a well powered double-blind placebo controlled trial of >2200 preterm infants. The results from ELFIN did not demonstrate a reduction in LOS or NEC, or several other clinically important measures. Of the 1093 infants, 316 (29%) in the intervention group developed late-onset sepsis versus 334 (31%) of 1089 in the control group, with an adjusted risk ratio of 0.95 (95% CI = 0.86–1.04; p = 0.233). Reasons for the differences in ELFIN trial results and other studies may include population differences, the routine use of antifungal prophylaxis in the UK, timing of administration of the lactoferrin in relation to disease onset, or specific properties of the lactoferrin used in the different trials. The UK National Institutes for Health Research funded "Mechanisms Affecting the Guts of Preterm Infants in Enteral feeding trials" (MAGPIE) study is further exploring the use of lactoferrin, and the results should be available soon. [ABSTRACT FROM AUTHOR]

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Lactoferrin is a critical glycoprotein that accounts for the major component in tear protein composition. Tear lactoferrin has been indicated as a potential biomarker in ocular health screening, such as dry eye disease diagnosis. Fluorescent biosensors are a desirable alternative to current diagnostic methods, due to their high selectivity and sensitivity, and rapid and cost-effective detection technologies at point-of-care (POC) platforms. Herein, fluorescent lactoferrin sensing is examined and applied on nitrocellulose membrane, capillary tube, and contact lens platforms in cooperation with a developed smartphone software for data collection and analysis. Fluorescent sensors based on trivalent terbium (TbCl 3) are integrated into different platforms, including nitrocellulose membranes, capillary tubes, and contact lenses, and tested in artificial tear fluid. A bespoke 3D printed readout device integrated with a smartphone camera was employed for image acquisition and readout. The detection range of the lactoferrin sensors could be varied from 0 to 5 mg mL−1 with a strong linear relation and yielded a limit of detection (LOD) of 0.57 mg mL−1 for lateral flow sensing, 0.12 mg mL−1 for capillary tube sensing, and 0.44 mg mL−1 for contact lens sensing. The contact lens sensor obtained the highest linear regression, while the capillary tube sensor achieved a lowest LOD. This work could pave the way towards accessible lactoferrin monitoring at POC and could induce hospitalization at the UK national health service (NHS) for future clinical trials and examinations. • Fluorescent multi-sensing platforms for tear lactoferrin detection at point of care. • Lactoferrin variation for ocular physiological monitoring. • Smartphone readout device for tear lactoferrin quantification and analysis. • Portable black box for data collection from different sensing platforms. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics of Great Britain which include the clinical trials on inflammatory bowel disease, efficacy of the faecal lactoferrin on the inflammatory bowel disease and the results of cytomegalovirus colitis on patients.

Summary: The maintenance and multiplication of Mycobacteria tuberculosis (TB) and many other species of parasitic pathogen are dependent to varying, largely unidentified degrees upon a source of free iron within the host tissues. To combat these infections, the mammalian biosystem expresses an iron binding exocrine protein, lactoferrin, which scavenges and competes for free iron, thereby starving the parasite of its vital iron supply. TB mycobacteria are naturally endemic in the external environment, and once a latent, low level TB infection is established within the host tissues, a full blown proliferation of the mycobacteria population can be activated as soon as the levels of free iron are elevated within the host tissues. The increase in iron can be induced by several environmental and/or eco-genetic prerequisites that operate either singly or in a synergistic combination; factors such as iron rich water/foods, increased iron uptake/retention in the host tissues or an environmental/genetic induced reduction in the turn over of iron binding lactoferrin mediated immune defence against TB. Susceptibility to the full blown proliferation of TB pathogenesis is markedly increased as a result. This paper proposes that the recent dramatic increase in the incidence of bovine/badger TB across the UK can be correlated to the overall increase in acidification of the agricultural ecosystem, which, in turn, has induced a substantial elevation of soluble iron within the farm foodchain, thereby exacerbating susceptibility to TB infection within any mammalian species that is dependent upon these high iron ecosystems. The problem is further compounded by the routine use of ‘anti-lactoferrin’ levamisole based cattle wormers, which ‘sensitise’ the levamisole’s target receptors, thereby down regulating the secretion of the iron binding lactoferrin molecule, which causes a reduction in the host’s main line of defence against TB infection. [Copyright &y& Elsevier]

Results from previous studies have suggested that supplemental bovine lactoferrin (BLF) given to preterm infants (<32 weeks gestation) reduces late-onset sepsis (LOS) and necrotising enterocolitis (NEC). The Enteral Lactoferrin in Neonates (ELFIN) study, performed in the UK, aimed to further address this issue with a well powered double-blind placebo controlled trial of >2200 preterm infants. The results from ELFIN did not demonstrate a reduction in LOS or NEC, or several other clinically important measures. Of the 1093 infants, 316 (29%) in the intervention group developed late-onset sepsis versus 334 (31%) of 1089 in the control group, with an adjusted risk ratio of 0.95 (95% CI = 0.86-1.04; p  = 0.233). Reasons for the differences in ELFIN trial results and other studies may include population differences, the routine use of antifungal prophylaxis in the UK, timing of administration of the lactoferrin in relation to disease onset, or specific properties of the lactoferrin used in the different trials. The UK National Institutes for Health Research funded "Mechanisms Affecting the Guts of Preterm Infants in Enteral feeding trials" (MAGPIE) study is further exploring the use of lactoferrin, and the results should be available soon.