Human milk oligosaccharide secretion dynamics during breastfeeding and its antimicrobial role: A systematic review

Table 6 Studies on human milk oligosaccharides levels, geographic variations, and antimicrobial activity

Ref.	Population/region	Key findings on HMO levels	Key antimicrobial activity	Geographic influence
Mao et al[144]	Urban Chinese mothers	High 2′-FL and sialylated HMOs (6′-SL) in early lactation; Gradual decline of 2′-FL and HMOs in mature milk	2′-FL inhibits Campylobacter jejuni and EPEC; 6′-SL protects against Rotavirus and Influenza	Secretor status influences early lactation HMO profile, optimizing pathogen defense in neonates
Liu et al[146]	Chinese mothers	3-FL increases significantly during later lactation; Sialylated HMOs decline after the first month	3-FL supports microbial diversity and inhibits Salmonella enterica and Pseudomonas aeruginosa	Extended breastfeeding in rural areas maintains high HMO levels, supporting long-term pathogen defense
Austin et al[129]	Chinese urban settings	Early high levels of fucosylated HMOs (2′-FL); Non-fucosylated LNT remains stable across lactation stages.	LNT neutralizes Vibrio cholera toxin; 2′-FL is critical for early pathogen defense	Urban mothers exhibit shorter lactation duration, potentially limiting long-term HMO-mediated benefits
Siziba et al[145]	German infants	High variability in HMO profiles across lactation; Secretor mothers show enriched 2′-FL levels	Sialylated HMOs reduce inflammatory responses and protect against respiratory pathogens (RSV, Influenza)	Differences in breastfeeding practices and complementary feeding influence microbiota outcomes
Derrien et al[65]	Rural Kenyan infants	High prevalence of 3-FL and LNT in late lactation; Enriched secretor group III (Se+, Le-)	3-FL supports Bifidobacterium infantis, lowering pH and reducing enteropathogen colonization; LNT neutralizes toxins	Rural diet and prolonged breastfeeding enhance microbiota dominated by B. infants
Kortesniemi et al[147]	Chinese mothers across lactation stages	Rapid decline in total HMOs from colostrum to mature milk; Sialylated HMOs persist in significant amounts	Sialylated HMOs prevent Helicobacter pylori adhesion and inhibit rotavirus infections	Secretor mothers exhibit early robust protection through 2′-FL, but benefits decline as lactation progresses
Asher et al[142]	Israeli mothers (Tel Aviv)	2′-FL dominant in secretors; LNT and 3-FL dominate in non-secretors; Seasonal and sex-dependent variations in HMO levels	2′-FL protects against infections via TLR4 inhibition; High DSLNT in non-secretors' colostrum protects against NEC	Urban breastfeeding with lower 2′-FL levels compared to global averages; shorter lactation may limit long-term benefits

The table summarizes findings from seven studies investigating human milk oligosaccharide (HMO) levels, geographic variations, and antimicrobial activity. Each study highlights the unique aspects of HMO concentrations across lactation stages, the role of specific HMOs in pathogen defense, and the influence of geographic and environmental factors. From this table, we found that across all regions, 2′-FL peaks in early lactation provide strong pathogen defense in neonates. 3-FL increases in later lactation, maintaining microbiota and pathogen defense during weaning. Rural settings like Kenya show sustained HMO levels due to prolonged breastfeeding, enriching microbiota that is beneficial for pathogen resistance. Urban populations like Israel and China experience sharper declines in HMOs due to shorter breastfeeding periods, potentially affecting long-term antimicrobial activity. Fucosylated HMOs (e.g., 2′-FL) are critical for early pathogen protection. Sialylated HMOs (e.g., 6′-SL) offer dual gastrointestinal and respiratory protection. Non-fucosylated HMOs (e.g., LNT and DSLNT) neutralize toxins and promote gut health throughout lactation. 2'-FL: 2'-Fucosyllactose; 3-FL: 3-Fucosyllactose; 6'-SL: 6'-Sialyllactose; DSLNT: Disialyllacto-N-tetraose; EPEC: Enteropathogenic E. coli; HMOs: Human milk oligosaccharides; LNT: Lacto-N-tetraose; NEC: Necrotizing enterocolitis; RSV: Respiratory syncytial virus; TLR4: Toll-like receptor 4.