Untangling human milk oligosaccharides and infant gut microbiome

Masi, A; Stewart, Christopher J.

doi:10.1016/j.isci.2021.103542

Cited by 61 publications

(45 citation statements)

References 101 publications

(248 reference statements)

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“…HMOs are known to support the development and maintenance of a healthy microbiota and immune system, two systems that mature in tandem in early life. HMOs steer microbiome development by influencing its composition via , e.g., bifidogenic ( 3 – 5 ) and anti-pathogenic effects ( 6 ), and may also directly interact with the gut epithelium, modulating physical microbe–host interactions ( 7 ). Age-appropriate development and maturation of the microbiome have been shown to be crucial for lifelong health through the modulation of immune competence ( 8 – 11 ).…”

Section: Introductionmentioning

confidence: 99%

Host–microbial co-metabolites modulated by human milk oligosaccharides relate to reduced risk of respiratory tract infections

et al. 2022

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Human milk oligosaccharides (HMOs) are structurally diverse oligosaccharides present in breast milk, supporting the development of the gut microbiota and immune system. Previously, 2-HMO (2'fucosyllactose, lacto-N-neotetraose) compared to control formula feeding was associated with reduced risk of lower respiratory tract infections (LRTIs), in part linked to lower acetate and higher bifidobacteria proportions. Here, our objective was to gain further insight into additional molecular pathways linking the 2-HMO formula feeding and LRTI mitigation. From the same trial, we measured the microbiota composition and 743 known biochemical species in infant stool at 3 months of age using shotgun metagenomic sequencing and untargeted mass spectrometry metabolomics. We used multivariate analysis to identify biochemicals associated to 2-HMO formula feeding and LRTI and integrated those findings with the microbiota compositional data. Three molecular pathways stood out: increased gamma-glutamylation and N-acetylation of amino acids and decreased inflammatory signaling lipids. Integration of stool metagenomic data revealed some Bifidobacterium and Bacteroides species to be implicated. These findings deepen our understanding of the infant gut/microbiome co-metabolism in early life and provide evidence for how such metabolic changes may influence immune competence at distant mucosal sites such as the airways.

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Section: Introductionmentioning

confidence: 99%

Host–microbial co-metabolites modulated by human milk oligosaccharides relate to reduced risk of respiratory tract infections

et al. 2022

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“…Human milk oligosaccharides (HMOs) are specific breast milk components with multiple beneficial properties for infant health and are believed to participate in the favorable microbiota modulation by human milk. To date, there are more than 200 different HMOs described, highlighting their rich structural diversity, yet 20-25 account for >95% of total HMOs [8]. In human milk, HMOs are present in significant levels, with the highest amount described in human colostrum (up to 25 g/L) [9] and lower (but variable) levels in mature human milk, which depend on multiple factors such as maternal genetics, lactation period, and premature delivery [10].…”

Section: Introductionmentioning

confidence: 99%

Human Milk Oligosaccharides and Lactose Differentially Affect Infant Gut Microbiota and Intestinal Barrier In Vitro

et al. 2022

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Background: The infant gut microbiota establishes during a critical window of opportunity when metabolic and immune functions are highly susceptible to environmental changes, such as diet. Human milk oligosaccharides (HMOs) for instance are suggested to be beneficial for infant health and gut microbiota. Infant formulas supplemented with the HMOs 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT) reduce infant morbidity and medication use and promote beneficial bacteria in the infant gut ecosystem. To further improve infant formula and achieve closer proximity to human milk composition, more complex HMO mixtures could be added. However, we currently lack knowledge about their effects on infants’ gut ecosystems. Method: We assessed the effect of lactose, 2′-FL, 2′-FL + LNnT, and a mixture of six HMOs (HMO6: consisting of 2′-FL, LNnT, difucosyllactose, lacto-N-tetraose, 3′- and 6′-sialyllactose) on infant gut microbiota and intestinal barrier integrity using a combination of in vitro models to mimic the microbial ecosystem (baby M-SHIME®) and the intestinal epithelium (Caco-2/HT29-MTX co-culture). Results: All the tested products had bifidogenic potential and increased SCFA levels; however, only the HMOs’ fermented media protected against inflammatory intestinal barrier disruption. 2′-FL/LNnT and HMO6 promoted the highest diversification of OTUs within the Bifidobactericeae family, whereas beneficial butyrate-producers were specifically enriched by HMO6. Conclusion: These results suggest that increased complexity in HMO mixture composition may benefit the infant gut ecosystem, promoting different bifidobacterial communities and protecting the gut barrier against pro-inflammatory imbalances.

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“…Maternal obesity further appears to impact breastmilk human milk oligosaccharide (HMO) composition. 20,21 As there are well-established connections between HMOs and the developing gut microbiome in infants, 22 infant microbial changes related to maternal obesity may be in part secondary to differences in HMO composition.…”

Section: Introductionmentioning

confidence: 99%

Associations between maternal obesity and offspring gut microbiome in the first year of life

et al. 2022

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Background: Maternal obesity is an important determinant of offspring obesity risk, which may be mediated via changes in the infant microbiome.Objectives: We examined infant faecal microbiome, short-chain fatty acids (SCFA), and maternal human milk oligosaccharides (HMO) in mothers with overweight/obese body mass index (BMI) (OW) compared with normal weight (NW) (Clinicaltrials.gov NCT01131117).Methods: Infant stool samples at 1, 6, and 12 months were analysed by 16S rRNA sequencing. Maternal (BODPOD) and infant (quantitative nuclear magnetic resonance [QMR]) adiposity were measured. HMOs at 2 months postpartum and faecal SCFAs at 1 month were also assessed. Statistical analyses included multivariable and mixed linear models for assessment of microbiome diversity, composition, and associations of taxonomic abundance with metabolic and anthropometric variables.

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Untangling human milk oligosaccharides and infant gut microbiome

Cited by 61 publications

References 101 publications

Host–microbial co-metabolites modulated by human milk oligosaccharides relate to reduced risk of respiratory tract infections

Host–microbial co-metabolites modulated by human milk oligosaccharides relate to reduced risk of respiratory tract infections

Human Milk Oligosaccharides and Lactose Differentially Affect Infant Gut Microbiota and Intestinal Barrier In Vitro

Associations between maternal obesity and offspring gut microbiome in the first year of life

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