Diroleuton

The impact of Human Milk (HM) bioactive compounds on infant health is crucial yet complex. Current research highlights their role in immune system development and disease prevention. This review aims to synthesize existing literature on the role of HM's bioactive compounds in the onset of diagnosed allergies, immunological diseases, and responses to infectious diseases by infants and children up to 18 years. The systematic review adhered to Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA). A comprehensive search strategy was employed across PubMed, Web of Science, SCOPUS, Scientific Electronic Library Online (SciELO), Cochrane Library, Latin American and Caribbean Health Sciences Literature (LILACS), and LIVIVO. Quality assessment utilized Joanna Briggs Institute checklists for various study designs. Protocol: CRD42023432030. The systematic review encompassed 34 studies, published from 1983 to 2024, representing a total of 9,298 mother–infant dyads. Included studies reported that allergic‐related conditions, particularly food allergy, sensitization, and atopic dermatitis, were inversely associated with HM linolenic and linoleic acid. In a meta‐analysis of three studies, infants with atopic dermatitis showed lower total omega‐3 levels (SMD = ‐0.46, 95% CI: ‐1.82 to ‐0.90, I 2 = 91%, p < 0.01), with reduced EPA and DGLA, suggesting, but not confirming, a potential protective role of omega‐3 and involvement of inflammatory pathways. Furthermore, results on infectious‐related conditions, primarily diarrhoea and Group B Streptococcus (GBS) infections, suggested inverse associations with 2'‐fucosyllactose (2´‐FL), lacto‐ N ‐difucohexaose I (LDFH‐I), and immunoglobulins (Anti‐GBS secretory immunoglobulin A (SIgA), anti‐lipopolysaccharide IgA (Anti‐LPS IgA), anti‐cholera toxin IgA, respectively). Results of studies on upper and lower respiratory tract infections, otitis media, and dental caries suggested inverse associations with galectins and galectin‐3, lacto‐ N ‐tetraose (LNT), 2´‐FL, and Haemophilus influenzae. Data suggest that HM bioactive compounds, such as polyunsaturated fatty acids (PUFAs), HMOs, and a number of specific immunoglobulin A (IgA) antibodies may influence allergic and infectious outcomes in infants. In pooled analyses of omega‐3 levels, HM fed to infants with atopic dermatitis showed reduced EPA and DGLA. However, these pooled estimates are severely limited by high statistical heterogeneity (I 2 = 91%) and should be interpreted as exploratory findings. Despite of the limited overall evidence due to heterogeneity, low replication, and methodological variability, this review offers a broad synthesis of current findings and highlights key knowledge gaps, providing a foundation for future research focused on elucidating the immunological roles of understudied components, such as antimicrobial peptides, through multi‐omics and longitudinal approaches.

The failed regimens for sepsis include but are not limited to steroids, antibiotic coverage for gram-negatives, and activated protein C. Reports of dramatic successes with vitamin C, its low cost and virtual absence of side effects in sepsis are encouraging despite some negative reports. I propose that this discrepancy in the results could be attributed to the altered status of essential fatty acid (EFA) metabolism in sepsis. Patients with sepsis have reduced plasma phospholipid concentrations of gamma-linolenic acid (GLA, 18:3 ω-6), dihomo-GLA (20:3 ω-6), arachidonic acid (AA, 20:4 ω-6), alpha-linolenic acid (ALA, 8:3 ω-3), and eicosapentaenoic acid (EPA, 20:5 ω-3) that are generated from dietary essential fatty acids {EFAs: cis-linoleic acid (LA) and α-linolenic acid (ALA)}. EFAs form the precursors to both pro-inflammatory and anti-inflammatory eicosanoids. Lipoxin A4 (LXA4), an anti-inflammatory eicosanoid derived from AA, enhances blood and peritoneal neutrophil phagocytic action, improves survival and promotes a more complete resolution of inflammation in sepsis. Prostaglandin E1 (PGE1), derived from DGLA, has actions like LXA4 and augments LXA4 generation. Vitamin C enhances the formation of PGE1 that may account for its beneficial action in sepsis and other conditions. EFAs metabolism is interfered with by corticosteroids and pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). EFAs need several co-factors including but not limited to vitamins B1, B6, and B12 for their optimum metabolism. Hence, it is proposed that co-administration of EFAs along with vitamins C, B1, B6, and B12 with or without corticosteroids may be of significant benefit in sepsis and septic shock.