生命早期肠道菌群特征与婴幼儿神经发育相关性的研究进展

Advances in the correlation between early-life gut microbiota characteristics and neurodevelopment in infants and young children

摘要

生命早期肠道菌群是调控婴幼儿神经发育的关键生物组成部分,其影响始于生命初期并持续终生。了解肠道微生物组如何通过关键菌群影响婴幼儿神经认知行为以及大脑结构、功能,是当前肠-脑轴研究领域的核心前沿与挑战。本文总结了儿童肠道菌群特征与神经发育的关系,旨在挖掘潜在的临床生物标志物,为婴幼儿神经发育障碍的预测及治疗提供新的思路和方向。

Abstract

The early-life gut microbiota is a crucial biological determinant of neurodevelopment in infants and young children, exerting effects that initiate in early life and persist throughout the lifespan.Understanding how the gut microbiota influences neurocognitive behavior and brain structure/function via key microbial communities represents a major frontier and challenge in gut-brain axis research.This review summarizes the relationship between infant gut microbiota characteristics and neurodevelopment, with the aim of identifying potential clinical biomarkers and providing new insights and directions for predicting and treating neurodevelopmental disorders.

关键词

生命早期微生物组 / 肠-脑轴 / 神经发育 / 拟杆菌

Key words

early life microbiome / gut-brain axis / neurodevelopment / bacteroides

[1] Wernroth ML, Peura S, Hedman AM, et al.Development of gut microbiota during the first 2 years of life[J].Sci Rep, 2022, 12: 9080.
[2] Stewart CJ, Ajami NJ, O′Brien JL, et al.Temporal development of the gut microbiome in early childhood from the TEDDY study[J].Nature, 2018, 562(7728): 583-588.
[3] 汪姝敏, 翟齐啸.婴幼儿肠道菌群的发育、成熟及影响因素研究进展[J].乳业科学与技术, 2022, 45(1): 38-47.
Wang SM, Zhai QX.Development and maturation of the intestinal flora during infancy and early childhood and influencing factors[J].Journal of Dairy Science and Technology, 2022, 45(1): 38-47.(in Chinese)
[4] Cowan CSM, Dinan TG, Cryan JF.Annual research review: Critical windows - the microbiota-gut-brain axis in neurocognitive development[J].J Child Psychol Psychiatry, 2020, 61(3): 353-371.
[5] Aatsinki AK, Lahti L, Uusitupa HM, et al.Gut microbiota composition is associated with temperament traits in infants[J].Brain Behav Immun, 2019, 80: 849-858.
[6] Carlson AL, Xia K, Azcarate-Peril MA, et al.Infant gut microbiome associated with cognitive development[J].Biol Psychiatry, 2018, 83(2): 148-159.
[7] Laue HE, Karagas MR, Coker MO, et al.Sex-specific relationships of the infant microbiome and early-childhood behavioral outcomes[J].Pediatr Res, 2022, 92(2): 580-591.
[8] Kelsey CM, Prescott S, McCulloch JA, et al.Gut microbiota composition is associated with newborn functional brain connectivity and behavioral temperament[J].Brain Behav Immun, 2021, 91: 472-486.
[9] Gao W, Salzwedel AP, Carlson AL, et al.Gut microbiome and brain functional connectivity in infants - A preliminary study focusing on the amygdala[J].Psychopharmacology, 2019, 236(5): 1641-1651.
[10] Fox M, Lee SM, Wiley KS, et al.Development of the infant gut microbiome predicts temperament across the first year of life[J].Dev Psychopathol, 2022, 34(5): 1914-1925.
[11] Carlson AL, Xia K, Azcarate-Peril MA, et al.Infant gut microbiome composition is associated with non-social fear behavior in a pilot study[J].Nat Commun, 2021, 12: 3294.
[12] Acuña I, Cerdó T, Ruiz A, et al.Infant gut microbiota associated with fine motor skills[J].Nutrients, 2021, 13(5): 1673.
[13] Oliphant K, Ali M, D′Souza M, et al.Bacteroidota and Lachnospiraceae integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment[J].Gut Microbes, 2021, 13(1): 1997560.
[14] Beghetti I, Barone M, Turroni S, et al.Early-life gut microbiota and neurodevelopment in preterm infants: Any role for Bifidobacterium?[J].Eur J Pediatr, 2022, 181(4): 1773-1777.
[15] Barone M, Ramayo-Caldas Y, Estellé J, et al.Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery[J].Microbiome, 2023, 11(1): 140.
[16] Erny D, Hrabě de Angelis AL, Jaitin D, et al.Host microbiota constantly control maturation and function of microglia in the CNS[J].Nat Neurosci, 2015, 18(7): 965-977.
[17] Arentsen T, Khalid R, Qian Y, et al.Sex-dependent alterations in motor and anxiety-like behavior of aged bacterial peptidoglycan sensing molecule 2 knockout mice[J].Brain Behav Immun, 2018, 67: 345-354.
[18] Lu J, Lu L, Yu Y, et al.Effects of intestinal microbiota on brain development in humanized gnotobiotic mice[J].Sci Rep, 2018, 8: 5443.
[19] Marcobal A, Barboza M, Sonnenburg ED, et al.Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways[J].Cell Host Microbe, 2011, 10(5): 507-514.
[20] Naspolini NF, Schüroff PA, Figueiredo MJ, et al.The gut microbiome in the first one thousand days of neurodevelopment: A systematic review from the microbiome perspective[J].Microorganisms,2024, 12(3): 424.
[21] Zhang W, Sun Z, Zhang Q, et al.Preliminary evidence for an influence of exposure to polycyclic aromatic hydrocarbons on the composition of the gut microbiota and neurodevelopment in three-year-old healthy children[J].BMC Pediatri, 2021, 21(1): 86.
[22] Sakamoto M, Ohkuma M.Bacteroides sartorii is an earlier heterotypic synonym of Bacteroides chinchillae and has priority[J].Int J Syst Evol Microbiol, 2012, 62(Pt 6): 1241-1244.
[23] Tamana SK, Tun HM, Konya T, et al.Bacteroides-dominant gut microbiome of late infancy is associated with enhanced neurodevelopment[J].Gut Microbes, 2021, 13(1): 1930875.
[24] Hsiao EY, McBride SW, Hsien S, et al.Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders[J].Cell, 2013, 155(7): 1451-1463.
[25] Aatsinki AK, Kataja EL, Munukka E, et al.Infant fecal microbiota composition and attention to emotional faces[J].Emotion, 2022, 22(6): 1159-1170.
[26] Guzzardi MA, Ederveen THA, Rizzo F, et al.Maternal pre-pregnancy overweight and neonatal gut bacterial colonization are associated with cognitive development and gut microbiota composition in pre-school-age offspring[J].Brain Behav Immun, 2022, 100: 311-320.
[27] Wu W, Zhao A, Liu B, et al.Neurodevelopmental outcomes and gut bifidobacteria in term infants fed an infant formula containing high sn-2 palmitate: A cluster randomized clinical trial[J].Nutrients, 2021, 13(2): 693.
[28] Seki D, Mayer M, Hausmann B, et al.Aberrant gut-microbiota-immune-brain axis development in premature neonates with brain damage[J].Cell Host Microbe, 2021, 29(10): 1558-1572.e6.
[29] Engevik MA, Luck B, Visuthranukul C, et al.Human-derived Bifidobacterium dentium modulates the mammalian serotonergic system and gut-brain axis[J].Cell Mol Gastroenterol HepatoL, 2021, 11(1): 221-248.
[30] Yano JM, Yu K, Donaldson GP, et al.Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis[J].Cell, 2015, 161(2): 264-276.
[31] Cohen Kadosh K, Basso M, Knytl P, et al.Psychobiotic interventions for anxiety in young people: A systematic review and meta-analysis, with youth consultation[J].Transl Psychiatry, 2021, 11: 352.
[32] Warner BB.The contribution of the gut microbiome to neurodevelopment and neuropsychiatric disorders[J].Pediatr Res, 2019, 85(2): 216-224.
[33] Rothenberg SE, Chen Q, Shen J, et al.Neurodevelopment correlates with gut microbiota in a cross-sectional analysis of children at 3 years of age in rural China[J].Sci Rep, 2021, 11: 7384.
[34] Loughman A, Ponsonby AL, O′Hely M, et al.Gut microbiota composition during infancy and subsequent behavioural outcomes[J].EBioMedicine, 2020, 52: 102640.
[35] Zhang X, Liu L, Bai W, et al.Evolution of intestinal microbiota of asphyxiated neonates within 1 week and its relationship with neural development at 6 months[J].Front Pediatr, 2021, 9: 690339.
[36] Hoyles L, Snelling T, Umlai UK, et al.Microbiome-host systems interactions: Protective effects of propionate upon the blood-brain barrier[J].Microbiome, 2018, 6(1): 55.
[37] Richard ML, Liguori G, Lamas B, et al.Mucosa-associated microbiota dysbiosis in colitis associated cancer[J].Gut Microbes, 2018, 9(2): 131-142.
[38] Umesaki Y, Setoyama H, Matsumoto S, et al.Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system[J].Infect Immun, 1999, 67(7): 3504-3511.
[39] Weston B, Fogal B, Cook D, et al.An agent-based modeling framework for evaluating hypotheses on risks for developing autism: Effects of the gut microbial environment[J].Med Hypotheses, 2015, 84(4): 395-401.
[40] Sordillo JE, Korrick S, Laranjo N, et al.Association of the infant gut microbiome with early childhood neurodevelopmental outcomes: An ancillary study to the VDAART randomized clinical trial[J].JAMA Netw Open, 2019, 2(3): e190905.
[41] 梁胜男, 柯楚新, 黄鹤, 等.肠道内产丁酸细菌及其产物丁酸生理功能的研究进展[J].微生物学通报, 2021, 48(3): 948-959.
Liang SN,Ke CX,Huang H, et al.Butyrate-producing bacteria in the intestinal tract and the physiological function of their metabolite butyrate: A review[J].Microbiol China, 2021, 48(3): 948-959.(in Chinese)
[42] Vinithakumari AA, Padhi P, Hernandez B, et al.Clostridioides difficile infection dysregulates brain dopamine metabolism[J].Microbiol Spectr, 2022, 10(2): e0007322.
[43] Manion J, Musser MA, Kuziel GA, et al.C.difficile intoxicates neurons and pericytes to drive neurogenic inflammation[J].Nature, 2023, 622(7983): 611-618.

基金资助

上海申康医院发展中心促进市级医院临床技能与临床创新能力三年行动计划项目(SHDC2020CR1030B)