Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant’s optimal growth and development. The growing infant’s immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant’s innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk’s effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant’s intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs) have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant’s gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system and the developing infant.

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Three viruses (CMV, HIV, and HTLV-I) frequently cause infection or disease as a result of breast-milk transmission. Reasonable guidelines have been pro-posed for when and how to avoid breast milk in the case of maternal infection. For other viruses, prophylactic immune therapy to protect the infant against all modes of transmission are indicated (VZV, varicella-zoster immunoglobulin, HAV and immunoglobulin, HBV, and HBIg + HBV vaccine). In most maternal viral infections, breast milk is not an important mode of transmission, and continuation of breastfeeding is in the best interest of the infant and mother (see Tables 2 and 3). Maternal bacterial infections rarely are complicated by transmission of infection to their infants through breast milk. In a few situations, temporary cessation of breastfeeding or the avoidance of breast milk is appropriate for a limited time (24 hours for N gonorrheae, H infiuenzae, Group B streptococci, and staphylococci and longer for others including B burgdorferi, T pallidum, and M tuberculosis). In certain situations, prophylactic or empiric therapy may be advised for the infant (eg, T pallidum, M tuberculosis, H influenzae) (see Table 1). Antimicrobial use by the mother should not be a reason not to breastfeed. Alternative regimens that are compatible with breastfeeding can be chosen to treat the mother effectively. In most cases of suspected infection in the breastfeeding mother, the delay in seeking medical care and making the diagnosis means the infant has been ex-posed already. Stopping breastfeeding at this time only deprives the infant of the nutritional and potential immunologic benefits. Breastfeeding or the use of expressed breast milk, even if temporarily suspended, should be encouraged and supported. Decisions about breast milk and infection should balance the potential risk compared with the innumerable benefits of breast milk.

Background Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved for type 2 diabetes and obesity. Preclinical evidence in transgenic models of Alzheimer’s disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. The primary objective of the study is to evaluate the change in cerebral glucose metabolic rate after 12 months of treatment with liraglutide in participants with Alzheimer’s disease compared to those who are receiving placebo. Methods/design ELAD is a 12-month, multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild Alzheimer’s dementia. A total of 206 participants will be randomised to receive either liraglutide or placebo as a daily injection for a year. The primary outcome will be the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to follow-up in the treatment group compared with the placebo group. The key secondary outcomes are the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer’s Disease Assessment Scale—Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer’s Disease Cooperative Study—Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes are 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, reduction in microglial activation in a subgroup of participants, reduction in tau formation and change in amyloid levels in a subgroup of participants measured by tau and amyloid imaging, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group. Discussion Alzheimer’s disease is a leading cause of morbidity worldwide. As available treatments are only symptomatic, the search for disease-modifying therapies is a priority. If the ELAD trial is successful, liraglutide and GLP-1 analogues will represent an important class of compounds to be further evaluated in clinical trials for Alzheimer’s treatment. Trial registration ClinicalTrials.gov, NCT01843075 . Registration 30 April 2013. Electronic supplementary material The online version of this article (10.1186/s13063-019-3259-x) contains supplementary material, which is available to authorized users.