HMOs Exert Marked Bifidogenic Effects on Children’s Gut Microbiota Ex Vivo, Due to Age-Related Bifidobacterium Species Composition

Abstract

Prebiotics are substrates that are selectively utilized by host microorganisms, thus conferring a health benefit. There is a growing awareness that interpersonal and age-dependent differences in gut microbiota composition impact prebiotic effects. Due to the interest in using human milk oligosaccharides (HMOs) beyond infancy, this study evaluated how HMOs [2’Fucosyllactose (2’FL), Lacto-N-neotetraose (LNnT), 3’Sialyllactose (3’SL), 6’Sialyllactose (6’SL)] and blends thereof affect the microbiota of 6-year-old children (n = 6) and adults (n = 6), compared to prebiotics inulin (IN) and fructooligosaccharides (FOS). The ex vivo SIFR® technology was used, given its demonstrated predictivity in clinical findings. First, HMOs and HMO blends seemed to maintain a higher α-diversity compared to FOS/IN. Further, while 2′FL/LNnT were bifidogenic for both age groups, 3′SL/6′SL and FOS/IN were exclusively bifidogenic for children and adults, respectively. This originated from age-related differences in microbiota composition because while 3′SL/6′SL stimulated B. pseudocatenulatum (abundant in children), FOS/IN enhanced B. adolescentis (abundant in adults). Moreover, all treatments significantly increased acetate, propionate and butyrate (only in adults) with product- and age-dependent differences. Among the HMOs, 6′SL specifically stimulated propionate (linked to Bacteroides fragilis in children and Phocaeicola massiliensis in adults), while LNnT stimulated butyrate (linked to Anaerobutyricum hallii in adults). Indole-3-lactic acid and 3-phenyllactic acid (linked to immune health) and gamma-aminobutyric acid (linked to gut-brain axis) were most profoundly stimulated by 2′FL and HMO blends in both children and adults, correlating with specific Bifidobacteriaceae. Finally, 2′FL/LNnT increased melatonin in children, while 3′SL remarkably increased folic acid in adults. Overall, age-dependent differences in microbiota composition greatly impacted prebiotic outcomes, advocating for the development of age-specific nutritional supplements. HMOs were shown to be promising modulators in the adult, and particularly the children’s microbiota. The observed HMO-specific effects, likely originating from their structural heterogeneity, suggest that blends of different HMOs could maximize treatment effects.

Impacts of combining Limosilactobacillus reuteri KUB‐AC5 and Limosilactobacillus fermentum KUB‐D18 on overweight gut microbiota using a simulated human colon model

“…Supplementation of probiotics also resulted in the induction of beneficial metabolites, including L‐(−)‐3‐phenyllactic acid and trans‐cinnamic acid. These metabolites created an acidic environment, which serves as a favourable condition for beneficial microbes, especially Bifidobacteriaceae (Álvarez et al ., 2022; Bajic et al ., 2023). Moreover, both metabolites were found to be linked with a decrease in the possibility of accumulating fat.…”

The effect of non-genetic determinants of human milk oligosaccharide profiles in milk of Ugandan mothers

“…In prior literature, 2’FL has been implicated in multiple functions including protection against infections, reduction of morbidity and use of antipyretics and antibiotics (26, 27); stimulation of brain development (28, 29); weight gain (19); and improvement of cognitive functions (30). 2’FL also promotes the selective growth of bifidobacteria and therefore probably influences the composition of gut microbiota (31) and microbiota-induced immune functions (32) in breastfeeding infants. 2’FL and 3’FL, which also increased during lactation in Ugandan mothers, have been implicated in the prevention of mortality in uninfected Zambian infants born to HIV-positive mothers (33).…”

“…2’FL and 3’FL, which also increased during lactation in Ugandan mothers, have been implicated in the prevention of mortality in uninfected Zambian infants born to HIV-positive mothers (33). The exact mechanisms by which HMOs reduce morbidity, prevent mortality and promote growth and development are unknown but could be associated with their reported anti-infective activities and effects on immunity (31,32, 34). The mechanisms underlying differences in HMO profiles during lactation remain speculative (10).…”

“…The exact mechanisms by which HMOs reduce morbidity, prevent mortality and promote growth and development are unknown but could be associated with their reported anti-infective activities and effects on immunity (31,32,34). The mechanisms underlying differences in HMO profiles during lactation remain speculative (10).…”

Treatment of preterm brain injury via gut‐microbiota–metabolite–brain axis

“…Another pig study showed that gut microbes could leverage metabolites produced by HMOs to induce structural changes in the brain and enhance cognitive function 120 . Additionally, human studies have demonstrated multiple roles for HMOs as modulators of the GM in children, influencers of colonization of Bifidobacteria in the infant gut, and facilitators of neonatal neurological development 121,122 …”