Long-term consequences of reduced availability and compensatory supplementation of sialylated HMOs on cognitive capabilities
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 i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1091890/full |
| _version_ | 1811175375421571072 |
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| author | Edoardo Pisa Alice Traversa Viviana Caputo Angela Maria Ottomana Angela Maria Ottomana Jonas Hauser Simone Macrì |
| author_facet | Edoardo Pisa Alice Traversa Viviana Caputo Angela Maria Ottomana Angela Maria Ottomana Jonas Hauser Simone Macrì |
| author_sort | Edoardo Pisa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T19:36:09Z |
| format | Article |
| id | doaj.art-fec6e64ae8124d5d9aa779d0c3a35efc |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-10T19:36:09Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-fec6e64ae8124d5d9aa779d0c3a35efc2023-01-30T07:22:21ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-01-011710.3389/fncel.2023.10918901091890Long-term consequences of reduced availability and compensatory supplementation of sialylated HMOs on cognitive capabilitiesEdoardo Pisa0Alice Traversa1Viviana Caputo2Angela Maria Ottomana3Angela Maria Ottomana4Jonas Hauser5Simone Macrì6Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Rome, ItalyLaboratory of Clinical Genomics, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Casa Sollievo della Sofferenza, San Giovanni Rotondo, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Rome, ItalyCentre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Rome, ItalyDepartment of Medicine and Surgery, University of Parma, Parma, ItalyBrain Health, Nestlé Institute of Health Sciences, Nestlé Research, Société des Produits Nestlé Société Anonyme, Lausanne, SwitzerlandCentre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Rome, ItalyBreast 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.https://www.frontiersin.org/articles/10.3389/fncel.2023.1091890/fullbreast milk bioactive componentsexecutive functionsmemorysialic acidsialyllactosebreastfeeding |
| spellingShingle | Edoardo Pisa Alice Traversa Viviana Caputo Angela Maria Ottomana Angela Maria Ottomana Jonas Hauser Simone Macrì Long-term consequences of reduced availability and compensatory supplementation of sialylated HMOs on cognitive capabilities Frontiers in Cellular Neuroscience breast milk bioactive components executive functions memory sialic acid sialyllactose breastfeeding |
| title | Long-term consequences of reduced availability and compensatory supplementation of sialylated HMOs on cognitive capabilities |
| title_full | Long-term consequences of reduced availability and compensatory supplementation of sialylated HMOs on cognitive capabilities |
| title_fullStr | Long-term consequences of reduced availability and compensatory supplementation of sialylated HMOs on cognitive capabilities |
| title_full_unstemmed | Long-term consequences of reduced availability and compensatory supplementation of sialylated HMOs on cognitive capabilities |
| title_short | Long-term consequences of reduced availability and compensatory supplementation of sialylated HMOs on cognitive capabilities |
| title_sort | long term consequences of reduced availability and compensatory supplementation of sialylated hmos on cognitive capabilities |
| topic | breast milk bioactive components executive functions memory sialic acid sialyllactose breastfeeding |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1091890/full |
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