دورية أكاديمية
Human milk oligosaccharides reduce necrotizing enterocolitis-induced neuroinflammation and cognitive impairment in mice.
العنوان: | Human milk oligosaccharides reduce necrotizing enterocolitis-induced neuroinflammation and cognitive impairment in mice. |
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المؤلفون: | Sodhi CP; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Ahmad R; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Fulton WB; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Lopez CM; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Eke BO; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Scheese D; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Duess JW; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Steinway SN; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Raouf Z; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Moore H; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Tsuboi K; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Sampah ME; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Jang HS; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Buck RH; Nutrition Division, Abbott, Columbus, Ohio, United States., Hill DR; Nutrition Division, Abbott, Columbus, Ohio, United States., Niemiro GM; Nutrition Division, Abbott, Columbus, Ohio, United States., Prindle T Jr; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Wang S; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Wang M; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Jia H; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Catazaro J; Department of Chemistry, Johns Hopkins University, Baltimore, Maryland, United States., Lu P; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Hackam DJ; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States. |
المصدر: | American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2023 Jul 01; Vol. 325 (1), pp. G23-G41. Date of Electronic Publication: 2023 Apr 25. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901227 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1547 (Electronic) Linking ISSN: 01931857 NLM ISO Abbreviation: Am J Physiol Gastrointest Liver Physiol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Bethesda, MD : American Physiological Society |
مواضيع طبية MeSH: | Enterocolitis, Necrotizing*/etiology , Cognitive Dysfunction*/prevention & control , Cognitive Dysfunction*/complications , Brain Injuries*/complications , Brain Injuries*/metabolism, Humans ; Infant, Newborn ; Infant ; Female ; Animals ; Mice ; Milk, Human/metabolism ; Brain-Derived Neurotrophic Factor ; Neuroinflammatory Diseases ; Oligosaccharides/pharmacology ; Oligosaccharides/therapeutic use ; Oligosaccharides/analysis |
مستخلص: | Necrotizing enterocolitis (NEC) is the leading cause of morbidity and mortality in premature infants. One of the most devastating complications of NEC is the development of NEC-induced brain injury, which manifests as impaired cognition that persists beyond infancy and which represents a proinflammatory activation of the gut-brain axis. Given that oral administration of the human milk oligosaccharides (HMOs) 2'-fucosyllactose (2'-FL) and 6'-sialyslactose (6'-SL) significantly reduced intestinal inflammation in mice, we hypothesized that oral administration of these HMOs would reduce NEC-induced brain injury and sought to determine the mechanisms involved. We now show that the administration of either 2'-FL or 6'-SL significantly attenuated NEC-induced brain injury, reversed myelin loss in the corpus callosum and midbrain of newborn mice, and prevented the impaired cognition observed in mice with NEC-induced brain injury. In seeking to define the mechanisms involved, 2'-FL or 6'-SL administration resulted in a restoration of the blood-brain barrier in newborn mice and also had a direct anti-inflammatory effect on the brain as revealed through the study of brain organoids. Metabolites of 2'-FL were detected in the infant mouse brain by nuclear magnetic resonance (NMR), whereas intact 2'-FL was not. Strikingly, the beneficial effects of 2'-FL or 6'-SL against NEC-induced brain injury required the release of the neurotrophic factor brain-derived neurotrophic factor (BDNF), as mice lacking BDNF were not protected by these HMOs from the development of NEC-induced brain injury. Taken in aggregate, these findings reveal that the HMOs 2'-FL and 6'-SL interrupt the gut-brain inflammatory axis and reduce the risk of NEC-induced brain injury. NEW & NOTEWORTHY This study reveals that the administration of human milk oligosaccharides, which are present in human breast milk, can interfere with the proinflammatory gut-brain axis and prevent neuroinflammation in the setting of necrotizing enterocolitis, a major intestinal disorder seen in premature infants. |
References: | Pediatrics. 2015 Jun;135(6):e1530-4. (PMID: 25963006) J Neuroinflammation. 2018 Jun 7;15(1):175. (PMID: 29880000) J Immunol. 2006 Sep 1;177(5):3273-82. (PMID: 16920968) Sci Transl Med. 2021 Sep 22;13(612):eabg3459. (PMID: 34550727) Shock. 2017 Jan;47(1):22-32. (PMID: 27488085) J Clin Invest. 2016 Feb;126(2):495-508. (PMID: 26690704) BMC Microbiol. 2015 Aug 25;15:172. (PMID: 26303932) Am J Physiol Gastrointest Liver Physiol. 2014 Jun 1;306(11):G917-28. (PMID: 24763555) J Neurosci Res. 2023 Jan;101(1):3-19. (PMID: 36200530) Semin Perinatol. 2017 Feb;41(1):36-40. (PMID: 27836421) Dev Neurosci. 2022;44(4-5):295-308. (PMID: 35697005) Nutrients. 2019 Jun 14;11(6):. (PMID: 31207876) PLoS One. 2013 Jun 12;8(6):e65779. (PMID: 23776545) J Neurotrauma. 2004 Oct;21(10):1457-67. (PMID: 15672635) Nutrients. 2018 Oct 20;10(10):. (PMID: 30347801) Mol Nutr Food Res. 2022 Feb;66(4):e2100893. (PMID: 34921749) Mol Nutr Food Res. 2019 Jul;63(13):e1900035. (PMID: 31125176) J Biol Chem. 2014 Apr 4;289(14):9584-99. (PMID: 24519940) Nat Commun. 2021 Feb 15;12(1):1042. (PMID: 33589625) Pediatr Res. 2022 Apr;91(5):1182-1195. (PMID: 34103675) Proc Natl Acad Sci U S A. 2021 Jun 22;118(25):. (PMID: 34161279) Gastroenterology. 2006 May;130(6):1776-92. (PMID: 16697741) Nat Protoc. 2006;1(2):848-58. (PMID: 17406317) Microvasc Res. 2023 Jul;148:104517. (PMID: 36894025) Tetrahedron Lett. 2015 Jun 3;56(23):3097-3100. (PMID: 26236050) Nutr Neurosci. 2021 Nov;24(11):885-895. (PMID: 31746283) Gastroenterology. 2012 Sep;143(3):708-718.e5. (PMID: 22796522) Pediatr Res. 2021 Jan;89(1):91-101. (PMID: 32221473) J Nutr Biochem. 2017 Feb;40:141-154. (PMID: 27889684) Br J Nutr. 2022 Sep 28;128(6):1050-1063. (PMID: 34632971) Pediatr Res. 2017 Apr;81(4):582-588. (PMID: 27893720) J Neuroinflammation. 2019 May 10;16(1):97. (PMID: 31077225) J Pediatr Surg. 2019 Mar;54(3):398-404. (PMID: 29980346) Neurol Res Int. 2012;2012:561494. (PMID: 22530124) Mol Nutr Food Res. 2021 Aug;65(16):e2100045. (PMID: 34139057) Br J Nutr. 2016 Sep;116(5):834-41. (PMID: 27452119) Brain Res Brain Res Rev. 2001 Aug;36(1):60-90. (PMID: 11516773) J Neurotrauma. 2011 Sep;28(9):1813-25. (PMID: 21635175) Br J Nutr. 2016 Jul;116(2):294-9. (PMID: 27212112) Mol Nutr Food Res. 2019 Feb;63(3):e1800658. (PMID: 30407734) Semin Perinatol. 2017 Feb;41(1):61-69. (PMID: 27836427) Nature. 2020 Jul;583(7816):441-446. (PMID: 32641826) J Thromb Thrombolysis. 2016 Jul;42(1):46-55. (PMID: 26743063) J Neurosci. 2003 Apr 15;23(8):3308-15. (PMID: 12716938) Pediatr Res. 2020 Jul;88(1):66-76. (PMID: 31242501) Br J Nutr. 2016 Oct;116(7):1175-1187. (PMID: 27609061) Front Pediatr. 2018 Jul 02;6:190. (PMID: 30013961) Mucosal Immunol. 2015 Sep;8(5):1166-79. (PMID: 25899687) Brain Behav Immun. 2022 Jun 1;104:122-136. (PMID: 35661680) J Trauma. 2007 Aug;63(2):439-42. (PMID: 17693848) Mol Nutr Food Res. 2020 Mar;64(5):e1900976. (PMID: 31800974) J Immunol. 2006 Mar 1;176(5):3070-9. (PMID: 16493066) Lancet. 2016 May 7;387(10031):1928-36. (PMID: 26969089) J Biol Chem. 2012 Oct 26;287(44):37296-308. (PMID: 22955282) Nutrients. 2022 Jun 19;14(12):. (PMID: 35745275) J Immunol. 2013 Apr 1;190(7):3541-51. (PMID: 23455503) Mol Neurobiol. 2019 May;56(5):3295-3312. (PMID: 30117106) Nat Rev Gastroenterol Hepatol. 2022 Jul;19(7):468-479. (PMID: 35347256) Sci Transl Med. 2018 Dec 12;10(471):. (PMID: 30541786) Sci Transl Med. 2021 Jan 6;13(575):. (PMID: 33408187) Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9451-6. (PMID: 23650378) Annu Rev Neurosci. 2001;24:677-736. (PMID: 11520916) Semin Pediatr Surg. 2018 Feb;27(1):11-18. (PMID: 29275810) J Am Coll Surg. 2014 Jun;218(6):1148-55. (PMID: 24468227) Front Pediatr. 2018 Dec 04;6:385. (PMID: 30564564) J Neuroinflammation. 2022 May 23;19(1):114. (PMID: 35606817) Gut. 2018 Jun;67(6):1064-1070. (PMID: 28381523) J Pediatr Surg. 2017 Oct 12;:. (PMID: 29079317) Gut. 2021 Dec;70(12):2273-2282. (PMID: 33328245) Front Pediatr. 2021 Oct 12;9:713344. (PMID: 34712628) Dis Model Mech. 2020 Jun 24;13(6):. (PMID: 32764156) |
معلومات مُعتمدة: | R35 GM141956 United States GM NIGMS NIH HHS; T32 DK007713 United States DK NIDDK NIH HHS |
فهرسة مساهمة: | Keywords: gut-brain axis; human milk oligosaccharides; necrotizing enterocolitis; neonate; neuroinflammation |
سلسلة جزيئية: | figshare 10.6084/m9.figshare.22277875 |
المشرفين على المادة: | 0 (Brain-Derived Neurotrophic Factor) 0 (Oligosaccharides) |
تواريخ الأحداث: | Date Created: 20230430 Date Completed: 20230608 Latest Revision: 20240702 |
رمز التحديث: | 20240702 |
مُعرف محوري في PubMed: | PMC10259852 |
DOI: | 10.1152/ajpgi.00233.2022 |
PMID: | 37120853 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1522-1547 |
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DOI: | 10.1152/ajpgi.00233.2022 |