极早产儿肠道菌群分布对纠正年龄2周岁时神经心理发育影响探讨

doi:10.20274/j.cnki.issn.1674-3865.2026.03.014

Abstract

Abstract:

Objective To investigate the influence of gut microbiota composition on neuropsychological development of very preterm infants(gestational age 28–32?? weeks) at a corrected age of 2 years. Methods Totally 31 very preterm infants were chosen, who were admitted for various reasons to NICU of Affiliated Sanming First Hospital of Fujian Medical University from Jan. 1, 2023 to Dec. 31, 2023. Based on the scores of developmental quotient assessment, they were divided into two groups: 20 in the normal neurodevelopment group and 11 in the delayed neurodevelopment group. At the corrected age of 2 years, neuropsychological development was assessed using the Intelligent Child Development Examination System(developmental scale for children aged 0-6 years). A developmental quotient(DQ) score of ≥85 was considered normal, while a score below 85 in one or more domains indicated developmental delay. The structure and diversity of the infant gut microbiota were analyzed using 16S rRNA sequencing, and the relationship between early-life gut microbiota and neuropsychological development scores was analyzed. Results The relative abundance of Actinobacteria within 24 hours after birth was higher in the normal neurodevelopment group than in the delayed group(P<0.001), while the abundance of Bacteroidetes was lower(P<0.001). No significant difference in alpha diversity was observed between the two groups(P>0.05). Spearman's correlation analysis revealed a positive correlation between the relative abundance of Bifidobacterium in the intestines within the first 24 hours after birth and scores in fine motor and language development domains at the corrected age of 2 years. In contrast, the relative abundance of Staphylococcus was negatively correlated with scores in fine motor and social behavior development domains. Conclusion Early-life gut microbiota composition differs in very preterm infants, and the difference is associated with their neurodevelopmental levels.

Key words: Very preterm infant, Gut microbiota, Age, Neuropsychological, Development

CLC Number:

R748

Juan LIN, Wei CHEN, Wanrong CHEN, Wei LIN, Enhuan WEI. Impact of gut microbiota composition on neuropsychological development of very preterm infants at corrected age of 2 years[J]. Chinese Pediatrics of Integrated Traditional and Western Medicine, 2026, 18(3): 265-271.

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[1]	Zhang ZY, Xiao WX, Ma LY, et al. Physical growth and neurodevelopment of preterm infants at the corrected age of 18-24 months[J]. Zhongguo Dang Dai Er Ke Za Zhi， 2023,25(1):25-30.
[2]	魏恩焕, 陈玮, 陈婉蓉,等.早产儿促甲状腺素轻度增高与体格及神经心理发育关联性探讨[J].中国中西医结合儿科学,2025,17(4):320-323.
[3]	Longo S, Rizza S, Federici M. Microbiota-gut-brain axis: relationships among the vagus nerve, gut microbiota, obesity, and diabetes[J]. Acta Diabetol，2023,60(8):1007-1017.
[4]	Palepu MSK, Dandekar MP. Remodeling of microbiota gut-brain axis using psychobiotics in depression[J]. Eur J Pharmacol, 2022,931:175171.
[5]	Enayati A, Soghi A, Butler AE, et al. The Effect of curcumin on the gut-brain axis: therapeutic implications[J]. J Neurogastroen⁃terol Motil, 2023,29(4):409-418.
[6]	Mohiuddin M, Asghar T, Hameed H,et al. The psychobiotic revolution: comprehending the optimistic role of gut microbiota on gut-brain axis during neurological and Gastrointestinal(GI) disorders[J]. World J Microbiol Biotechnol, 2025,41(10):401.
[7]	杨玉凤.儿童发育行为心理评定量表[M].2版.北京:人民卫生出版社, 2023：58-67.
[8]	Lau C, Stewart SL, Saklofske DH, et al. Development and psychometric validation of the interRAI ChYMH externalizing subscale[J]. Clin Child Psychol Psychiatry， 2021，26(1):295-305.
[9]	Laister D, Stammler M, Vivanti G, et al. Social-communicative gestures at baseline predict verbal and nonverbal gains for children with autism receiving the Early Start Denver Model[J]. Autism， 2021，25(6):1640-1652.
[10]	Michaelis IA, Krägeloh-Mann I, Mazinu M, et al. Growth of a cohort of very low birth weight and preterm infants born at a single tertiary health care center in South Africa[J]. Front Pediatr, 2023, 10:1075645.
[11]	Brinkis R, Albertsson-Wikland K, Tamelienė R, et al. Nutrient intake with early progressive enteral feeding and growth of very low-birth-weight newborns[J]. Nutrients, 2022,14(6):1181.
[12]	Frerichs NM, de Meij TGJ, Niemarkt HJ. Microbiome and its impact on fetal and neonatal brain development: current opinion in pediatrics[J]. Curr Opin Clin Nutr Metab Care， 2024，27(3):297-303.
[13]	Doroszkiewicz J, Groblewska M, Mroczko B. The role of gut microbiota and gut-brain interplay in selected diseases of the central nervous system[J]. Int J Mol Sci, 2021,22(18):10028.
[14]	Rautava S. Feeding the preterm infant gut microbiota[J]. Cell Host Microbe， 2022,30(9):1199-1200.
[15]	Klymiuk I, Singer G, Castellani C, et al. Characterization of the luminal and mucosa-associated microbiome along the gastrointestinal tract: results from surgically treated preterm infants and a murine model[J]. Nutrients， 2021，13(3):1030.
[16]	Buffet-Bataillon S, Bellanger A, Boudry G, et al. New insights into microbiota modulation-based nutritional interventions for neurodevelopmental outcomes in preterm infants[J]. Front Microbiol， 2021，12:676622.
[17]	贾雯，刘美汛，周志谟，等.生命早期肠道菌群与婴儿神经发育的关系初探[J].卫生研究，2024，53(2):250-256.
[18]	Park JC, Im SH. The gut-immune-brain axis in neurodevelop⁃ment and neurological disorders[J]. Microbiome Res Rep， 2022，1(4):23.
[19]	Guo L, Wang R, Han L, et al. Multi-omics integration identifies key biomarkers in retinopathy of prematurity through 16S rRNA sequencing and metabolomics[J]. Front Microbiol， 2025，16:1601292.
[20]	Zhang D, Lan Y, Zhang J, et al. Effects of early-life gut microbiota on the neurodevelopmental outcomes of preterm infants: a multi-center, longitudinal observational study in China[J]. Eur J Pediatr， 2024，183(4):1733-1740.
[21]	Ma J, Song XQ. Correlation between cognitive impairment and metabolic imbalance of gut microbiota in patients with schizophrenia[J]. World J Psychiatry， 2023，13(10):724-731.
[22]	Dong Y, Qi Y, Chen J, et al. Neuroprotective Effects of Bifidobacterium animalis subsp. lactis NJ241 in a Mouse Model of Parkinson's Disease: Implications for Gut Microbiota and PGC-1α[J]. Mol Neurobiol， 2024，61(10):7534-7548.
[23]	Narrowe AB, Lemons JMS, Mahalak KK, et al. Targeted remodeling of the human gut microbiome using Juemingzi (Senna seed extracts)[J]. Front Cell Infect Microbiol， 2024，14:1296619.
[24]	Hortensius LM, van den Hooven EH, Dudink J, et al. NutriBrain: protocol for a randomised, double-blind, controlled trial to evaluate the effects of a nutritional product on brain integrity in preterm infants[J]. BMC Pediatr， 2021，21(1):132.
[25]	Sun J, Li H, Jin Y, et al. Probiotic Clostridium butyricum ameliorated motor deficits in a mouse model of Parkinson's disease via gut microbiota-GLP-1 pathway[J]. Brain Behav Immun, 2021,91:703-715.
[26]	Baucells BJ, Sebastiani G, Herrero-Aizpurua L, et al. Effectiveness of a probiotic combination on the neurodevelop⁃ment of the very premature infant[J]. Sci Rep，2023,13(1):10344.
[27]	Abdullahi AM, Zhao S, Xu Y. Efficacy of probiotic supplementa⁃tion in preventing necrotizing enterocolitis in preterm infants: a systematic review and meta-analysis[J]. J Matern Fetal Neonatal Med， 2025，38(1):2485215.
[28]	Zhang L, Mei Q, Wang L, et al. Yak DEFB124 alleviates intestinal injury caused by Staphylococcus aureus infection[J]. Int Immunopharmacol， 2023，114:109531.
[29]	Gravina G, Ardalan M, Chumak T, et al. Transcriptome network analysis links perinatal Staphylococcus epidermidis infection to microglia reprogramming in the immature hippocampus[J]. Glia， 2023，71(9):2234-2249.
[30]	Wang Y, Zhu J, Zou N, et al. Pathogenesis from the microbial-gut-brain axis in white matter injury in preterm infants: A review[J]. Front Integr Neurosci， 2023，17:1051689.
[31]	Liu L, Xiang M, Cai X, et al. Multi-omics analyses of gut microbiota via 16S rRNA gene sequencing, LC-MS/MS and diffusion tension imaging reveal aberrant microbiota-gut-brain axis in very low or extremely low birth weight infants with white matter injury[J]. BMC Microbiol， 2023，23(1):387.
[32]	Jafari-Nakhjavanlou A, Irajian P, Zahedi Bialvaei A. Potential mechanisms linking bacterial factors to the development and progression of multiple sclerosis[J]. Infect Med (Beijing)， 2025，4(4):100219.

项目	神经心理发育正常组（n=20）	神经心理发育迟缓组（n=11)	χ²或t值	P值
产妇年龄（岁）	31.50±3.13	32.10±3.75	-0.48	0.64
产妇体质量指数(kg/m²)	22.51±3.18	22.92±2.76	-0.36	0.72
胎龄（周）	30.12±1.18	29.73±1.25	0.86	0.40
胎膜早破[n(%)]	12(60.00)	7(63.63)	-	0.98
顺产[n(%)]	17（85.00）	8（72.72）	-	0.63
1 min Apgar评分（分）	8.20±0.21	8.30±0.51	-0.77	0.45
5 min Apgar评分（分）	8.50±0.33	8.70±0.72	-1.07	0.30
出生体质量（g）	1 037.30±132.12	1 012.32±225.71	0.39	0.70
出生身长（cm）	41.23±2.75	40.55±5.32	0.47	0.64
男婴[n(%)]	11（55.00）	6（54.54）	-	0.97
出生胎粪排出时间(h)	10.72±2.27	11.23±1.19	-0.69	0.49

项目	神经心理发育正常组（n=20）	神经心理发育迟缓组（n=11)	P值
生后6个月内喂养方式			0.92
母乳喂养	4	3
人工喂养	6	3
混合喂养	10	5
纠正年龄2周岁内采取回应式科学教育人数	5	4	0.70
参加早期干预的人数	5	6	0.12

体格发育指标	纠正月龄	神经心理发育正常组（n=20）	神经心理发育迟缓组（n=11)	t值	P值
年龄别体质量	3	0.39±0.78	0.36±0.69	0.11	0.91
	6	0.35±0.63	0.15±0.54	0.93	0.36
	12	0.04±1.01	0.08±1.06	-0.10	0.91
	18	-0.16±1.01	0.73±0.92	-2.49	0.02
	24	-0.15±1.15	-0.13±1.02	-0.05	0.95
年龄别身高	3	-0.87±1.13	-0.09±1.20	-1.77	0.09
	6	-0.02±1.01	-0.45±1.13	1.05	0.30
	12	0.26±1.21	0.17±1.24	-0.20	0.84
	18	0.23±1.08	0.41±1.26	-0.40	0.69
	24	0.10±1.25	0.22±1.16	-0.27	0.79
年龄别头围	3	0.02±1.12	0.35±0.72	-1.06	0.32
	6	0.01±1.14	0.36±0.89	-0.95	0.35
	12	0.28±1.03	0.15±0.98	0.35	0.73
	18	-0.63±1.21	0.31±0.96	-2.37	0.02
	24	-0.31±1.21	-0.43±1.14	0.27	0.76

组别	n	大运动	精细动作	适应能力	语言发育	社交行为
神经心理发育正常组	20	89.12±12.25	87.58±15.38	86.79±18.43	88.42±15.76	85.19±16.35
神经心理发育迟缓组	11	79.12±15.17	60.78±12.62	77.69±19.73	49.32±16.46	58.36±12.52
t值		1.87	5.22	1.25	6.42	5.10
P值		0.07	<0.001	0.22	<0.001	<0.001

组别	n	ACE指数	Chao1指数	Shannon指数	Simpson指数
神经心理发育正常组	20	289.14±115.02	278.13±132.26	1.86±0.52	0.71±0.17
神经心理发育迟缓组	11	261.75±108.19	213.52±112.24	1.91±0.67	0.85±0.20
t值		1.04	1.63	-0.23	-1.92
P值		0.31	0.11	0.82	0.06

Impact of gut microbiota composition on neuropsychological development of very preterm infants at corrected age of 2 years

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组别	n	放线菌门	拟杆菌门	厚壁菌门	变形杆菌门
神经心理发育正常组	20	62.57(35.60，95.50)	7.95(1.19，13.96)	6.72(2.68，10.74)	2.84(1.15，4.53)
神经心理发育迟缓组	11	29.58（17.39，40.70）	37.86(11.46，52.39)	8.78(3.13，14.13)	1.32(0.61，2.03)
u值		202	27	107	112
P值		<0.001	<0.001	0.930	0.900

组别	n	肠球菌	链球菌	拉尔斯特菌	不动杆菌
神经心理发育正常组	20	1.82（0.62，22.51）	1.76（0.52，11.45）	1.52（0.45，10.21）	1.42（0.42，9.13）
神经心理发育迟缓组	11	1.51（0.51，20.16）	1.62（0.43，9.25)	1.57(0.37，9.14)	1.36(0.37，9.02)
u值		141	97	111	88
P值		0.200	0.600	0.980	0.370
组别	n	埃希菌	双歧杆菌	葡萄球菌	芽生单胞菌
神经心理发育正常组	20	1.12（0.38，8.94）	1.01（0.29，11.28）	0.81（0.25，6.12）	0.52（0.19，4.21）
神经心理发育迟缓组	11	1.21(0.33，8.71)	0.42(0.21，6.18)	2.12(1.24，10.14)	0.92(0.17，3.86)
u值		97	180	39	95
P值		0.600	0.040	0.003	0.550

优势菌属	大动作		精细动作		适应能力		语言发育		社交行为
优势菌属	rs值	P值	rs值	P值	rs值	P值	rs值	P值	rs值	P值
肠球菌	0.13	0.55	0.03	0.93	0.15	0.51	-0.29	0.07	-0.26	0.18
链球菌	-0.20	0.30	-0.27	0.06	-0.25	0.07	0.08	0.69	-0.16	0.45
拉尔斯特菌	-0.25	0.07	0.19	0.37	-0.28	0.09	-0.25	0.10	-0.07	0.75
不动杆菌	0.08	0.74	0.06	0.81	0.13	0.57	0.27	0.10	0.25	0.19
埃希菌	-0.09	0.71	-0.16	0.47	-0.13	0.56	-0.10	0.69	-0.13	0.51
双歧杆菌	0.18	0.25	0.38	0.04	0.10	0.64	0.42	0.02	0.07	0.76
葡萄球菌	-0.21	0.28	-0.36	0.03	0.22	0.27	0.11	0.65	-0.48	0.02
芽生单胞菌	0.08	0.74	0.05	0.85	0.25	0.07	0.08	0.74	0.10	0.69

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