Synbiotics Combined with Glutamine Stimulate Brain Development and the Immune System in Preterm Pigs
Preterm infants are born with an immature gut, brain, and immune system, predisposing them to short- and long-term complications. We hypothesized that a milk diet supplemented with pre- and probiotics (i.e. synbiotics) and glutamine would improve gut, brain, and immune maturation in preterm neonates...
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| Veröffentlicht in: | The Journal of nutrition 2019-01, Vol.149 (1), p.36-45 |
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| creator | Andersen, Anders D Nguyen, Duc Ninh Langhorn, Louise Renes, Ingrefid B van Elburg, Ruurd M Hartog, Anita Tims, Sebastian van de Looij, Yohan Sangild, Per T Thymann, Thomas |
| description | Preterm infants are born with an immature gut, brain, and immune system, predisposing them to short- and long-term complications.
We hypothesized that a milk diet supplemented with pre- and probiotics (i.e. synbiotics) and glutamine would improve gut, brain, and immune maturation in preterm neonates, using preterm pigs as a model.
Preterm pigs (Landrace x Yorkshire x Duroc, n = 40, delivered by c-section at 90% of gestation) were reared individually until day 23 after birth under highly standardized conditions. Piglets in the intervention group (PPG, n = 20) were fed increasing volumes of bovine milk supplemented with prebiotics (short-chain galacto- and long chain fructo-oligosaccharefides 9:1, 4–12 g/L), probiotics (Bifidobacterium breve M16-V, 3 × 109 CFU/d) and l-glutamine [0.15–0.30 g/(kg · d)], and compared with pigs fed bovine milk with added placebo compounds as control (CON, n = 20). Clinical, gastrointestinal, immunological, cognitive, and neurological endpoints were measured.
The PPG pigs showed more diarrhea but weight gain, body composition, and gut parameters were similar between the groups. Cognitive performance, assessed in a T-maze, was significantly higher in PPG pigs (P |
| doi_str_mv | 10.1093/jn/nxy243 |
| format | Article |
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We hypothesized that a milk diet supplemented with pre- and probiotics (i.e. synbiotics) and glutamine would improve gut, brain, and immune maturation in preterm neonates, using preterm pigs as a model.
Preterm pigs (Landrace x Yorkshire x Duroc, n = 40, delivered by c-section at 90% of gestation) were reared individually until day 23 after birth under highly standardized conditions. Piglets in the intervention group (PPG, n = 20) were fed increasing volumes of bovine milk supplemented with prebiotics (short-chain galacto- and long chain fructo-oligosaccharefides 9:1, 4–12 g/L), probiotics (Bifidobacterium breve M16-V, 3 × 109 CFU/d) and l-glutamine [0.15–0.30 g/(kg · d)], and compared with pigs fed bovine milk with added placebo compounds as control (CON, n = 20). Clinical, gastrointestinal, immunological, cognitive, and neurological endpoints were measured.
The PPG pigs showed more diarrhea but weight gain, body composition, and gut parameters were similar between the groups. Cognitive performance, assessed in a T-maze, was significantly higher in PPG pigs (P < 0.01), whereas motor function and exploratory interest were similar between the groups. Using ex vivo diffusion imaging, the orientation dispersion index in brain cortical gray matter was 50% higher (P = 0.04), and fractional anisotropy value was 7% lower (P = 0.05) in PPG pigs compared with CON pigs, consistent with increased dendritic branching in PPG. In associative fibers, radial diffusivity was lower and fractional anisotropy was higher in PPG pigs compared with CON pigs (all P < 0.05), while measures in the internal capsule showed a tendency towards reduced radial diffusivity and mean diffusivity (both P = 0.09). On day 23 pigs in the PPG group showed higher blood leukocyte numbers (+43%), neutrophil counts (+100%), and phagocytic rates (+24%), relative to CON, all P < 0.05.
Preterm pigs supplemented with Bifidobacterium breve, galacto- and fructo-oligosaccharefides, and l-glutamine showed enhanced neuronal and immunological development. The findings indicate the potential for targeted nutritional interventions after preterm birth, to support development of important systems such as immunity and brain.</description><identifier>ISSN: 0022-3166</identifier><identifier>EISSN: 1541-6100</identifier><identifier>DOI: 10.1093/jn/nxy243</identifier><identifier>PMID: 30608604</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Animals, Newborn ; Anisotropy ; Bifidobacterium breve ; Body composition ; Brain ; Brain - drug effects ; Brain - growth & development ; Chains ; cognition ; Cognitive ability ; Cortex ; Cow's milk ; Dendritic branching ; Diarrhea ; Diffusivity ; Digestive system ; Fatty Acids ; Fructooligosaccharides ; Gastrointestinal Microbiome ; Gastrointestinal tract ; Gestation ; Glutamine ; Glutamine - chemistry ; Glutamine - pharmacology ; Hogs ; Immune system ; Immunity ; Immunology ; Infants ; Leukocytes ; Milk ; MRI ; Neonates ; Neuroimaging ; oligosaccharefides ; Oligosaccharides ; Phagocytes ; Prebiotics ; Premature Birth ; Preterm birth ; Probiotics ; Substantia grisea ; Swine ; Swine - growth & development ; Synbiotics - administration & dosage ; Weight gain measurement</subject><ispartof>The Journal of nutrition, 2019-01, Vol.149 (1), p.36-45</ispartof><rights>2019 American Society for Nutrition.</rights><rights>2019 American Society for Nutrition. 2019</rights><rights>Copyright American Institute of Nutrition Jan 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-79343063e22e37ece0364895ec1e222fb3907eadefb98e1193a476321f8d3df53</citedby><cites>FETCH-LOGICAL-c421t-79343063e22e37ece0364895ec1e222fb3907eadefb98e1193a476321f8d3df53</cites><orcidid>0000-0001-7480-6064</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27906,27907</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30608604$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Andersen, Anders D</creatorcontrib><creatorcontrib>Nguyen, Duc Ninh</creatorcontrib><creatorcontrib>Langhorn, Louise</creatorcontrib><creatorcontrib>Renes, Ingrefid B</creatorcontrib><creatorcontrib>van Elburg, Ruurd M</creatorcontrib><creatorcontrib>Hartog, Anita</creatorcontrib><creatorcontrib>Tims, Sebastian</creatorcontrib><creatorcontrib>van de Looij, Yohan</creatorcontrib><creatorcontrib>Sangild, Per T</creatorcontrib><creatorcontrib>Thymann, Thomas</creatorcontrib><title>Synbiotics Combined with Glutamine Stimulate Brain Development and the Immune System in Preterm Pigs</title><title>The Journal of nutrition</title><addtitle>J Nutr</addtitle><description>Preterm infants are born with an immature gut, brain, and immune system, predisposing them to short- and long-term complications.
We hypothesized that a milk diet supplemented with pre- and probiotics (i.e. synbiotics) and glutamine would improve gut, brain, and immune maturation in preterm neonates, using preterm pigs as a model.
Preterm pigs (Landrace x Yorkshire x Duroc, n = 40, delivered by c-section at 90% of gestation) were reared individually until day 23 after birth under highly standardized conditions. Piglets in the intervention group (PPG, n = 20) were fed increasing volumes of bovine milk supplemented with prebiotics (short-chain galacto- and long chain fructo-oligosaccharefides 9:1, 4–12 g/L), probiotics (Bifidobacterium breve M16-V, 3 × 109 CFU/d) and l-glutamine [0.15–0.30 g/(kg · d)], and compared with pigs fed bovine milk with added placebo compounds as control (CON, n = 20). Clinical, gastrointestinal, immunological, cognitive, and neurological endpoints were measured.
The PPG pigs showed more diarrhea but weight gain, body composition, and gut parameters were similar between the groups. Cognitive performance, assessed in a T-maze, was significantly higher in PPG pigs (P < 0.01), whereas motor function and exploratory interest were similar between the groups. Using ex vivo diffusion imaging, the orientation dispersion index in brain cortical gray matter was 50% higher (P = 0.04), and fractional anisotropy value was 7% lower (P = 0.05) in PPG pigs compared with CON pigs, consistent with increased dendritic branching in PPG. In associative fibers, radial diffusivity was lower and fractional anisotropy was higher in PPG pigs compared with CON pigs (all P < 0.05), while measures in the internal capsule showed a tendency towards reduced radial diffusivity and mean diffusivity (both P = 0.09). On day 23 pigs in the PPG group showed higher blood leukocyte numbers (+43%), neutrophil counts (+100%), and phagocytic rates (+24%), relative to CON, all P < 0.05.
Preterm pigs supplemented with Bifidobacterium breve, galacto- and fructo-oligosaccharefides, and l-glutamine showed enhanced neuronal and immunological development. The findings indicate the potential for targeted nutritional interventions after preterm birth, to support development of important systems such as immunity and brain.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Anisotropy</subject><subject>Bifidobacterium breve</subject><subject>Body composition</subject><subject>Brain</subject><subject>Brain - drug effects</subject><subject>Brain - growth & development</subject><subject>Chains</subject><subject>cognition</subject><subject>Cognitive ability</subject><subject>Cortex</subject><subject>Cow's milk</subject><subject>Dendritic branching</subject><subject>Diarrhea</subject><subject>Diffusivity</subject><subject>Digestive system</subject><subject>Fatty Acids</subject><subject>Fructooligosaccharides</subject><subject>Gastrointestinal Microbiome</subject><subject>Gastrointestinal tract</subject><subject>Gestation</subject><subject>Glutamine</subject><subject>Glutamine - chemistry</subject><subject>Glutamine - pharmacology</subject><subject>Hogs</subject><subject>Immune system</subject><subject>Immunity</subject><subject>Immunology</subject><subject>Infants</subject><subject>Leukocytes</subject><subject>Milk</subject><subject>MRI</subject><subject>Neonates</subject><subject>Neuroimaging</subject><subject>oligosaccharefides</subject><subject>Oligosaccharides</subject><subject>Phagocytes</subject><subject>Prebiotics</subject><subject>Premature Birth</subject><subject>Preterm birth</subject><subject>Probiotics</subject><subject>Substantia grisea</subject><subject>Swine</subject><subject>Swine - growth & development</subject><subject>Synbiotics - administration & dosage</subject><subject>Weight gain measurement</subject><issn>0022-3166</issn><issn>1541-6100</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90E1rFTEUBuAgir2tLvwDEtBFXYzN12RmlvWqtVCwUF2HTHLG5jJJrkmmev-9KVNdiLg65PDk5fAi9IKSt5QM_GwXzsLPAxP8EdrQVtBGUkIeow0hjDWcSnmEjnPeEUKoGPqn6IgTSXpJxAbZm0MYXSzOZLyNfnQBLP7hyi2-mJeifX3jm-L8MusC-F3SLuD3cAdz3HsIBetgcbkFfOn9ck8PuYDHFV0nKJA8vnbf8jP0ZNJzhucP8wR9_fjhy_ZTc_X54nJ7ftUYwWhpuoGLehkHxoB3YIBwKfqhBUPrik0jH0gH2sI0Dj1QOnAtOskZnXrL7dTyE3S65u5T_L5ALsq7bGCedYC4ZMWoFJRw0faVvvqL7uKSQr2uqk6yVvYtqerNqkyKOSeY1D45r9NBUaLuq1e7oNbqq335kLiMHuwf-bvrCl6vIC77_-bwlUFt6s5BUtk4CAasS2CKstH949cvITedVg</recordid><startdate>201901</startdate><enddate>201901</enddate><creator>Andersen, Anders D</creator><creator>Nguyen, Duc Ninh</creator><creator>Langhorn, Louise</creator><creator>Renes, Ingrefid B</creator><creator>van Elburg, Ruurd M</creator><creator>Hartog, Anita</creator><creator>Tims, Sebastian</creator><creator>van de Looij, Yohan</creator><creator>Sangild, Per T</creator><creator>Thymann, Thomas</creator><general>Elsevier Inc</general><general>Oxford University Press</general><general>American Institute of Nutrition</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7480-6064</orcidid></search><sort><creationdate>201901</creationdate><title>Synbiotics Combined with Glutamine Stimulate Brain Development and the Immune System in Preterm Pigs</title><author>Andersen, Anders D ; Nguyen, Duc Ninh ; Langhorn, Louise ; Renes, Ingrefid B ; van Elburg, Ruurd M ; Hartog, Anita ; Tims, Sebastian ; van de Looij, Yohan ; Sangild, Per T ; Thymann, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-79343063e22e37ece0364895ec1e222fb3907eadefb98e1193a476321f8d3df53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Anisotropy</topic><topic>Bifidobacterium breve</topic><topic>Body composition</topic><topic>Brain</topic><topic>Brain - drug effects</topic><topic>Brain - growth & development</topic><topic>Chains</topic><topic>cognition</topic><topic>Cognitive ability</topic><topic>Cortex</topic><topic>Cow's milk</topic><topic>Dendritic branching</topic><topic>Diarrhea</topic><topic>Diffusivity</topic><topic>Digestive system</topic><topic>Fatty Acids</topic><topic>Fructooligosaccharides</topic><topic>Gastrointestinal Microbiome</topic><topic>Gastrointestinal tract</topic><topic>Gestation</topic><topic>Glutamine</topic><topic>Glutamine - chemistry</topic><topic>Glutamine - pharmacology</topic><topic>Hogs</topic><topic>Immune system</topic><topic>Immunity</topic><topic>Immunology</topic><topic>Infants</topic><topic>Leukocytes</topic><topic>Milk</topic><topic>MRI</topic><topic>Neonates</topic><topic>Neuroimaging</topic><topic>oligosaccharefides</topic><topic>Oligosaccharides</topic><topic>Phagocytes</topic><topic>Prebiotics</topic><topic>Premature Birth</topic><topic>Preterm birth</topic><topic>Probiotics</topic><topic>Substantia grisea</topic><topic>Swine</topic><topic>Swine - growth & development</topic><topic>Synbiotics - administration & dosage</topic><topic>Weight gain measurement</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Andersen, Anders D</creatorcontrib><creatorcontrib>Nguyen, Duc Ninh</creatorcontrib><creatorcontrib>Langhorn, Louise</creatorcontrib><creatorcontrib>Renes, Ingrefid B</creatorcontrib><creatorcontrib>van Elburg, Ruurd M</creatorcontrib><creatorcontrib>Hartog, Anita</creatorcontrib><creatorcontrib>Tims, Sebastian</creatorcontrib><creatorcontrib>van de Looij, Yohan</creatorcontrib><creatorcontrib>Sangild, Per T</creatorcontrib><creatorcontrib>Thymann, Thomas</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Andersen, Anders D</au><au>Nguyen, Duc Ninh</au><au>Langhorn, Louise</au><au>Renes, Ingrefid B</au><au>van Elburg, Ruurd M</au><au>Hartog, Anita</au><au>Tims, Sebastian</au><au>van de Looij, Yohan</au><au>Sangild, Per T</au><au>Thymann, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synbiotics Combined with Glutamine Stimulate Brain Development and the Immune System in Preterm Pigs</atitle><jtitle>The Journal of nutrition</jtitle><addtitle>J Nutr</addtitle><date>2019-01</date><risdate>2019</risdate><volume>149</volume><issue>1</issue><spage>36</spage><epage>45</epage><pages>36-45</pages><issn>0022-3166</issn><eissn>1541-6100</eissn><abstract>Preterm infants are born with an immature gut, brain, and immune system, predisposing them to short- and long-term complications.
We hypothesized that a milk diet supplemented with pre- and probiotics (i.e. synbiotics) and glutamine would improve gut, brain, and immune maturation in preterm neonates, using preterm pigs as a model.
Preterm pigs (Landrace x Yorkshire x Duroc, n = 40, delivered by c-section at 90% of gestation) were reared individually until day 23 after birth under highly standardized conditions. Piglets in the intervention group (PPG, n = 20) were fed increasing volumes of bovine milk supplemented with prebiotics (short-chain galacto- and long chain fructo-oligosaccharefides 9:1, 4–12 g/L), probiotics (Bifidobacterium breve M16-V, 3 × 109 CFU/d) and l-glutamine [0.15–0.30 g/(kg · d)], and compared with pigs fed bovine milk with added placebo compounds as control (CON, n = 20). Clinical, gastrointestinal, immunological, cognitive, and neurological endpoints were measured.
The PPG pigs showed more diarrhea but weight gain, body composition, and gut parameters were similar between the groups. Cognitive performance, assessed in a T-maze, was significantly higher in PPG pigs (P < 0.01), whereas motor function and exploratory interest were similar between the groups. Using ex vivo diffusion imaging, the orientation dispersion index in brain cortical gray matter was 50% higher (P = 0.04), and fractional anisotropy value was 7% lower (P = 0.05) in PPG pigs compared with CON pigs, consistent with increased dendritic branching in PPG. In associative fibers, radial diffusivity was lower and fractional anisotropy was higher in PPG pigs compared with CON pigs (all P < 0.05), while measures in the internal capsule showed a tendency towards reduced radial diffusivity and mean diffusivity (both P = 0.09). On day 23 pigs in the PPG group showed higher blood leukocyte numbers (+43%), neutrophil counts (+100%), and phagocytic rates (+24%), relative to CON, all P < 0.05.
Preterm pigs supplemented with Bifidobacterium breve, galacto- and fructo-oligosaccharefides, and l-glutamine showed enhanced neuronal and immunological development. The findings indicate the potential for targeted nutritional interventions after preterm birth, to support development of important systems such as immunity and brain.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30608604</pmid><doi>10.1093/jn/nxy243</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-7480-6064</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Animals, Newborn Anisotropy Bifidobacterium breve Body composition Brain Brain - drug effects Brain - growth & development Chains cognition Cognitive ability Cortex Cow's milk Dendritic branching Diarrhea Diffusivity Digestive system Fatty Acids Fructooligosaccharides Gastrointestinal Microbiome Gastrointestinal tract Gestation Glutamine Glutamine - chemistry Glutamine - pharmacology Hogs Immune system Immunity Immunology Infants Leukocytes Milk MRI Neonates Neuroimaging oligosaccharefides Oligosaccharides Phagocytes Prebiotics Premature Birth Preterm birth Probiotics Substantia grisea Swine Swine - growth & development Synbiotics - administration & dosage Weight gain measurement |
| title | Synbiotics Combined with Glutamine Stimulate Brain Development and the Immune System in Preterm Pigs |
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