Effects of vaginal microbiota transfer on the neurodevelopment and microbiome of cesarean-born infants: A blinded randomized controlled trial

Lepeng Zhou; Wen Qiu; Jie Wang; Aihua Zhao; Chuhui Zhou; Tao Sun; Ziyu Xiong; Peihua Cao; Wei Shen; Jingfen Chen; Xiaolu Lai; Liu-Hong Zhao; Yue Wu; Meng Li; Feng Qiu; Yanhong Yu; Zhenjiang Zech Xu; Hongwei Zhou; Wei Jia; Yan Liao; Ravi Retnakaran; Daniel Krewski; Shi Wu Wen; Jose C Clemente; Tianlu Chen; Ri-Hua Xie; Yan He

doi:10.1016/j.chom.2023.05.022

Effects of vaginal microbiota transfer on the neurodevelopment and microbiome of cesarean-born infants: A blinded randomized controlled trial

Cell Host Microbe. 2023 Jul 12;31(7):1232-1247.e5. doi: 10.1016/j.chom.2023.05.022. Epub 2023 Jun 15.

Authors

Lepeng Zhou¹, Wen Qiu², Jie Wang³, Aihua Zhao⁴, Chuhui Zhou³, Tao Sun⁴, Ziyu Xiong⁵, Peihua Cao⁶, Wei Shen⁷, Jingfen Chen³, Xiaolu Lai³, Liu-Hong Zhao³, Yue Wu⁸, Meng Li⁹, Feng Qiu¹⁰, Yanhong Yu¹¹, Zhenjiang Zech Xu¹², Hongwei Zhou¹³, Wei Jia⁴, Yan Liao¹⁴, Ravi Retnakaran¹⁵, Daniel Krewski¹⁶, Shi Wu Wen¹⁷, Jose C Clemente¹⁸, Tianlu Chen¹⁹, Ri-Hua Xie²⁰, Yan He²¹

Affiliations

¹ School of Nursing, Affiliated Foshan Maternity & Child Healthcare Hospital, Department of Laboratory Medicine in Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; School of Nursing; Department of Nursing, Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, Guangdong 528100, China; Department of Nursing, The Seventh Affiliated Hospital, Southern Medical University, Foshan, Guangdong 528244, China.
² Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
³ School of Nursing; Department of Nursing, Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, Guangdong 528100, China.
⁴ Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai 200233, China.
⁵ Department of Nursing, The Seventh Affiliated Hospital, Southern Medical University, Foshan, Guangdong 528244, China.
⁶ Clinical Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China; Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China.
⁷ Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China; Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
⁸ Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
⁹ Department of Obstetrics, The Seventh Affiliated Hospital, Southern Medical University, Foshan, Guangdong 528244, China.
¹⁰ Department of Laboratory Medicine, The Seventh Affiliated Hospital, Southern Medical University, Foshan, Guangdong 528244, China.
¹¹ Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
¹² Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China; State Key Laboratory of Food Science and Technology, Institute of Nutrition and College of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China.
¹³ Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, Guangdong 510515, China.
¹⁴ Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada.
¹⁵ Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; Division of Endocrinology, University of Toronto, Toronto, ON M5S 2E8, Canada.
¹⁶ McLaughlin Centre for Population Health Risk Assessment, Faculty of Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada; Risk Science International, Ottawa, ON K1P 5J6, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
¹⁷ Ottawa Hospital Research Institute, Ottawa, ON K1H8L6, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1N 6N5, Canada; Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
¹⁸ Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: jose.clemente@mssm.edu.
¹⁹ Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: chentianlu@sjtu.edu.cn.
²⁰ School of Nursing; Department of Nursing, Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, Guangdong 528100, China. Electronic address: xierihua928@hotmail.com.
²¹ Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Provincial Clinical Research Center for Laboratory Medicine, Guangzhou, Guangdong 510033, China. Electronic address: yanhe@i.smu.edu.cn.

PMID: 37327780
DOI: 10.1016/j.chom.2023.05.022

Abstract

The microbiomes of cesarean-born infants differ from vaginally delivered infants and are associated with increased disease risks. Vaginal microbiota transfer (VMT) to newborns may reverse C-section-related microbiome disturbances. Here, we evaluated the effect of VMT by exposing newborns to maternal vaginal fluids and assessing neurodevelopment, as well as the fecal microbiota and metabolome. Sixty-eight cesarean-delivered infants were randomly assigned a VMT or saline gauze intervention immediately after delivery in a triple-blind manner (ChiCTR2000031326). Adverse events were not significantly different between the two groups. Infant neurodevelopment, as measured by the Ages and Stages Questionnaire (ASQ-3) score at 6 months, was significantly higher with VMT than saline. VMT significantly accelerated gut microbiota maturation and regulated levels of certain fecal metabolites and metabolic functions, including carbohydrate, energy, and amino acid metabolisms, within 42 days after birth. Overall, VMT is likely safe and may partially normalize neurodevelopment and the fecal microbiome in cesarean-delivered infants.

Keywords: cesarean section; gut metabolome; gut microbiome; infants; neurodevelopment; randomized controlled trial; vaginal microbiota transfer.

Publication types

Randomized Controlled Trial

MeSH terms

Cesarean Section / adverse effects
Delivery, Obstetric
Feces
Female
Gastrointestinal Microbiome*
Humans
Infant
Infant, Newborn
Microbiota*
Pregnancy