Exposure to 3′Sialyllactose-Poor Milk during Lactation Impairs Cognitive Capabilities in Adulthood

Pisa, Edoardo; Martire, Alberto; Chiodi, Valentina; Traversa, Alice; Caputo, Viviana; Hauser, Jonas; Macrı̀, Simone

doi:10.3390/nu13124191

Cited by 22 publications

(34 citation statements)

References 61 publications

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“…Our data show that WT mice reared with a reduction of 3 SL and an absence of 6 SL exhibited, in adulthood, reduced spatial, working and recognition memory compared to WT mice receiving normal milk. These findings confirm our previous studies evaluating the effect of the lack of 6 SL and reduction of 3 SL alone on memory capabilities (Hauser et al, 2021;Pisa et al, 2021). Furthermore, this result is also in agreement with other studies that reported beneficial effects of dietary supplementation of sialic acid in piglets (Wang et al, 2007) and sialylated oligosaccharides in preterm pigs (Obelitz-Ryom et al, 2019) and mice (Tarr et al, 2015).…”

Section: Selective Deprivation Of 3 Sl and 6 Sl Impaired Memory And A...supporting

confidence: 93%

“…Adult WT and heterozygous (HZ) B6.129-St6gal1 tm2Jxm /J and HZ B6.129-St3gal4 tm1.1Jxm /J were purchased from a commercial breeder (the Jackson Laboratory, Bar Harbor, ME, USA). Then, homozygous knock-out (KO-ST3) B6.129-St3gal4 tm1.1Jxm / tm1.1Jxm and homozygous knock-out (KO-ST6) B6.129-St6gal1 tm2Jxm / tm2Jxm were derived from heterozygous St3gal4 B6.129-St3gal4 tm1.1Jxm /J 10.3389/fncel.2023.1091890 and St6gal1 B6.129-St6gal1 tm2Jxm /J mice [as described in Pisa et al (2021) and Hauser et al (2021), respectively]. Mice were housed in same-sex groups of 2-3 animals, in type-1 polycarbonate cages (33.0 × 13.0 × 14.0 cm) equipped with sawdust bedding, an enrichment bag (Mucedola, Settimo Milanese, Italy), metal top and ad libitum water and food pellets (Mucedola, Settimo Milanese, Italy).…”

Section: Animals and Rearing Conditionsmentioning

confidence: 99%

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Long-term consequences of reduced availability and compensatory supplementation of sialylated HMOs on cognitive capabilities

Pisa

Traversa

Caputo

et al. 2023

Front. Cell. Neurosci.

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Breast milk (BM) is the optimal source of nutrition for mammals’ early life. It exerts multiple benefits, including the development of cognitive capabilities and protection against several diseases like obesity and infection of the respiratory tract. However, which components of BM are involved in individual development has remained elusive. Sialylated human milk oligosaccharides (HMOs) may constitute a valid candidate, whereby they represent the principal source of sialic acid and act as building blocks for brain development. We hypothesize that the reduced availability of two HMOs, sialyl(alpha2,6)lactose (6′SL) and sialyl(alpha2,3)lactose (3′SL), may impair attention, cognitive flexibility, and memory in a preclinical model and that the exogenous supplementation of these compounds may contrast the observed deficits. We evaluated cognitive capabilities in a preclinical model exposed to maternal milk containing reduced concentrations of 6′SL and 3′SL during lactation. To modulate their concentrations, we utilized a preclinical model characterized by the absence of genes that synthesize 3′SL and 6′SL (B6.129-St3gal4tm1.1Jxm and St6gal1tm2Jxm, double genetic deletion), producing milk lacking 3′SL and 6′SL. Then, to ensure exposure to 3′SL–6′SL-poor milk in early life, we adopted a cross-fostering protocol. The outcomes assessed in adulthood were different types of memory, attention and information processing, some of which are part of executive functions. Then, in the second study, we evaluated the long-term compensatory potential of the exogenous oral supplementation of 3′SL and 6′SL during lactation. In the first study, exposure to HMO-poor milk resulted in reduced memory and attention. Specifically, it resulted in impaired working memory in the T-maze test, in reduced spatial memory in the Barnes maze, and in impaired attentional capabilities in the Attentional set-shifting task. In the second part of the study, we did not observe any difference between experimental groups. We hypothesize that the experimental procedures utilized for the exogenous supplementation may have impacted our ability to observe the cognitive read-out in vivo. This study suggests that early life dietary sialylated HMOs play a crucial role in the development of cognitive functions. Future studies are needed to clarify if an exogenous supplementation of these oligosaccharides may compensate for these affected phenotypes.

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Section: Selective Deprivation Of 3 Sl and 6 Sl Impaired Memory And A...supporting

confidence: 93%

Section: Animals and Rearing Conditionsmentioning

confidence: 99%

Long-term consequences of reduced availability and compensatory supplementation of sialylated HMOs on cognitive capabilities

Pisa

Traversa

Caputo

et al. 2023

Front. Cell. Neurosci.

Self Cite

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“…In both term and preterm infants, human milk feeding is associated with improved neurodevelopmental outcomes [ 157 , 158 ]. This has been partially attributed to hMOS, including 2’FL, 3’-sialyllactose (3’SL) and 6’-sialyllactose (6’SL), for their contribution to synaptic formation, neuro-transmission, and memory improvement [ 159 , 160 , 161 , 162 , 163 , 164 , 165 ]. HMEV-derived miR-148a-3p may work in concert with hMOS and other human milk components on brain development during infancy.…”

Section: Biology Of Hmevsmentioning

confidence: 99%

Human Milk Extracellular Vesicles: A Biological System with Clinical Implications

Chutipongtanate

Morrow

Newburg

2022

Cells

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The consumption of human milk by a breastfeeding infant is associated with positive health outcomes, including lower risk of diarrheal disease, respiratory disease, otitis media, and in later life, less risk of chronic disease. These benefits may be mediated by antibodies, glycoproteins, glycolipids, oligosaccharides, and leukocytes. More recently, human milk extracellular vesicles (hMEVs) have been identified. HMEVs contain functional cargos, i.e., miRNAs and proteins, that may transmit information from the mother to promote infant growth and development. Maternal health conditions can influence hMEV composition. This review summarizes hMEV biogenesis and functional contents, reviews the functional evidence of hMEVs in the maternal–infant health relationship, and discusses challenges and opportunities in hMEV research.

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“…On the other hand, 3-fucosyllactose, lacto-N-neotetraose and lactodifucotetraose reduce inflammation by blocking the activation of TNF-α [ 28 ]. Sialyated HMOs have been described to increase host susceptibility to colitis [ 50 ] and improve cognitive function in vivo [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Variations in the Composition of Human Milk Oligosaccharides Correlates with Effects on Both the Intestinal Epithelial Barrier and Host Inflammation: A Pilot Study

Botts

Johnson‐Henry

et al. 2022

Nutrients

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Background: Human milk oligosaccharides are complex, non-digestible carbohydrates that directly interact with intestinal epithelial cells to alter barrier function and host inflammation. Oligosaccharide composition varies widely between individual mothers, but it is unclear if this inter-individual variation has any impact on intestinal epithelial barrier function and gut inflammation. Methods: Human milk oligosaccharides were extracted from the mature human milk of four individual donors. Using an in vitro model of intestinal injury, the effects of the oligosaccharides on the intestinal epithelial barrier and select innate and adaptive immune functions were assessed. Results: Individual oligosaccharide compositions shared comparable effects on increasing transepithelial electrical resistance and reducing the macromolecular permeability of polarized (Caco-2Bbe1) monolayers but exerted distinct effects on the localization of the intercellular tight junction protein zona occludins-1 in response to injury induced by a human enteric bacterial pathogen Escherichia coli, serotype O157:H7. Immunoblots showed the differential effects of oligosaccharide compositions in reducing host chemokine interleukin 8 expression and inhibiting of p38 MAP kinase activation. Conclusions: These results provide evidence of both shared and distinct effects on the host intestinal epithelial function that are attributable to inter-individual differences in the composition of human milk oligosaccharides.

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Exposure to 3′Sialyllactose-Poor Milk during Lactation Impairs Cognitive Capabilities in Adulthood

Cited by 22 publications

References 61 publications

Long-term consequences of reduced availability and compensatory supplementation of sialylated HMOs on cognitive capabilities

Long-term consequences of reduced availability and compensatory supplementation of sialylated HMOs on cognitive capabilities

Human Milk Extracellular Vesicles: A Biological System with Clinical Implications

Variations in the Composition of Human Milk Oligosaccharides Correlates with Effects on Both the Intestinal Epithelial Barrier and Host Inflammation: A Pilot Study

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