Chen Xiaona, Yan Zheng, Liu Lili, Zhang Rui, Zhang Xiaojiao, Peng Cheng, Geng Yuehang, Zhou Faliang, Han Ying, Hou Xinlin
Department of Pediatrics, Peking University First Hospital, Beijing, China.
Front Microbiol. 2022 Aug 24;13:912968. doi: 10.3389/fmicb.2022.912968. eCollection 2022.
Small for gestational age (SGA) infants are at a higher risk of neurodevelopmental delay than infants appropriate for gestational age (AGA). Previous studies have confirmed that gut microbiota in early life influences subsequent neurodevelopment. However, few studies have reported corresponding data in SGA populations.
We aimed to evaluate the characteristics of the gut microbiota of term SGA infants and the associations between the gut microbiota in SGA infants and neurodevelopmental outcomes at 6 months of age.
Fecal samples were collected on days 1, 3, 5, and 7 from term SGA and AGA infants born between June 2020 and June 2021 at the Peking University First Hospital. 16S ribosomal deoxyribonucleic acid amplicon sequencing was used to analyze the fecal microbiota. We followed up for 6 months and used the Ages and Stages Questionnaires-3 (ASQ-3) to evaluate the neurodevelopmental outcomes among SGA infants.
A total of 162 neonates were enrolled, with 41 SGA infants (25.3%) in the study group and 121 AGA infants (74.7%) in the control group. The gut microbial diversity in the SGA group was lower than that in the AGA group on days 1, 3, 5, and 7. Non-metric multidimensional scaling and analysis of similarities showed significant differences between the two groups. The SGA group had increased relative abundances of (3, 5, and 7 days) and (3 and 7 days). The dominant microorganisms of the SGA group were on day 1, on days 3 and 7, and on day 5. We found that the gut microbial diversity of SGA infants with poor communication scores was higher than that of SGA infants with good communication scores on day 3. Fine motor scores were negatively correlated with the relative abundance of on day 1. A negative correlation was observed between gross motor scores and relative abundance of on day 7. , , , and were the dominant microorganisms in the good communication score group on day 7. Communication scores were positively correlated with the relative abundance of , , and on day 7.
The gut microbial diversity of term SGA infants was significantly lower in the first week of life than that of term AGA infants. Certain pathogenic and conditional pathogenic bacteria, such as , and increased or formed the dominant microbiota in SGA infants. Alpha diversity, , , , and found in SGA infants may be associated with neurodevelopmental outcomes at 6 months of age, indicating possible therapeutic targets for clinical intervention.
小于胎龄（SGA）儿比适于胎龄（AGA）儿发生神经发育迟缓的风险更高。既往研究已证实，生命早期的肠道微生物群会影响后续的神经发育。然而，很少有研究报道SGA人群的相应数据。
我们旨在评估足月SGA儿肠道微生物群的特征，以及SGA儿肠道微生物群与6月龄时神经发育结局之间的关联。
于2020年6月至2021年6月在北京大学第一医院出生的足月SGA儿和AGA儿出生后第1、3、5和7天收集粪便样本。采用16S核糖体脱氧核糖核酸扩增子测序分析粪便微生物群。我们随访6个月，并使用《年龄与发育进程问卷第3版》（ASQ-3）评估SGA儿的神经发育结局。
共纳入162例新生儿，研究组有41例SGA儿（25.3%），对照组有121例AGA儿（74.7%）。SGA组在出生后第1、3、5和7天的肠道微生物多样性低于AGA组。非度量多维尺度分析和相似性分析显示两组间存在显著差异。SGA组在出生后第3、5和7天的[某种细菌名称1]相对丰度增加，在出生后第3和7天的[某种细菌名称2]相对丰度增加。SGA组出生后第1天的优势微生物为[某种细菌名称3]，第3和7天为[某种细菌名称4]，第5天为[某种细菌名称5]。我们发现，在出生后第3天，沟通评分差的SGA儿的肠道微生物多样性高于沟通评分好的SGA儿。精细运动评分在出生后第1天与[某种细菌名称6]的相对丰度呈负相关。在出生后第7天，大运动评分与[某种细菌名称7]的相对丰度呈负相关。出生后第7天，[某种细菌名称8]、[某种细菌名称9]、[某种细菌名称10]和[某种细菌名称11]是沟通评分好的组中的优势微生物。沟通评分在出生后第7天与[某种细菌名称8]、[某种细菌名称9]和[某种细菌名称10]相对丰度呈正相关。
足月SGA儿出生后第一周的肠道微生物多样性显著低于足月AGA儿。某些致病性和条件致病性细菌，如[某种细菌名称1]、[某种细菌名称2]和[某种细菌名称3]在SGA儿中增加或成为优势微生物群。在SGA儿中发现的α多样性、[某种细菌名称4] [某种细菌名称5]、[某种细菌名称6]和[某种细菌名称7]可能与6月龄时的神经发育结局相关，提示可能成为临床干预的治疗靶点。
