Multiomics analysis reveals the presence of a microbiome in the gut of fetal lambs
Authors: Qiyu Diao
Shiqing Wang
Yanliang Bi
Garret Suen
Dafu Shao
Shengli Li
Naifeng Zhang
Yan Tu
Fan Zhang
Journal: Gut (2021)
Discipline: CLINICAL MEDICINE
Keywords: intestinal microbiology.
Affiliations: Feed Research Institute, Chinese Academy of Agricultural Sciences, National Engineering Research Center of Biological Feed, Beijing, China., State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China., Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA., Agricultural Informaition Institute, Chinese Academy of Agricultural Sciences, Beijing, China., State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China., Feed Research Institute, Chinese Academy of Agricultural Sciences, National Engineering Research Center of Biological Feed, Beijing, China .

Abstract:  Objective: Microbial exposure is critical to neonatal and infant development, growth and immunity. However, whether a microbiome is present in the fetal gut prior to birth remains debated. In this study, lambs delivered by aseptic hysterectomy at full term were used as an animal model to investigate the presence of a microbiome in the prenatal gut using a multiomics approach. Design: Lambs were euthanised immediately after aseptic caesarean section and their cecal content and umbilical cord blood samples were aseptically acquired. Cecal content samples were assessed using metagenomic and metatranscriptomic sequencing to characterise any existing microbiome. Both sample types were analysed using metabolomics in order to detect microbial metabolites. Results: We detected a low-diversity and low-biomass microbiome in the prenatal fetal gut, which was mainly composed of bacteria belonging to the phyla Proteobacteria, Actinobacteria and Firmicutes. Escherichia coli was the most abundant species in the prenatal fetal gut. We also detected multiple microbial metabolites including short chain fatty acids, deoxynojirimycin, mitomycin and tobramycin, further indicating the presence of metabolically active microbiota. Additionally, bacteriophage phiX174 and Orf virus, as well as antibiotic resistance genes, were detected in the fetal gut, suggesting that bacteriophage, viruses and bacteria carrying antibiotic resistance genes can be transmitted from the mother to the fetus during the gestation period. Conclusions: This study provides strong evidence that the prenatal gut harbours a microbiome and that microbial colonisation of the fetal gut commences in utero. 

Retracted: No

PubPeer comments:
 Figure 3 in this paper appears to contain multiple identical or near-identical sections of 95%CI boundaries. (with thanks to Elisabeth Bik and others for assistance) ![file] , 
 #1 Thanks for professor John A Loadsmanu2019s careful reading our papers. We checked the original data of this paper and found that there was no problem with this paper. We have sent the original data to the editor. With thanks to Elisabeth Bik. , 
 Dear Dr. Tan, Although you concluded that there is no problem with the data, Dr. Loadsman and I disagree. Could you provide a bit more data than  there was no problem , please? In particular, how can different experiments yield identical or repetitive curves? Maybe you have a perfectly good biological explanation that Dr. Loadsman and I have not been able to come up with, but just saying  there was no problem is not good enough for a constructive scientific discussion. , 
 #3 Thanks for the patience and time paid on our paper. It is my pleasure to talk the scientific questions with prof. Elisabeth Bik. The results and conclusion of our research are negative, and there are little changes of regional cerebral oxygen saturation with two kinds of intervention. ![file] ![file] ![file] ![file] , 
 #4 1. Based on your figure caption of fig 3,  Data were collected every 2 s from induction until 50 min . Then the x-axis should go all the way to 3,000 seconds, rather than 1,500 s. Correct me if I misunderstood 2. Basically, you posted exactly the same 4 plots as used in your paper, which had been the focus of concern. Reposting the same figures offers little help. What I would suggest is for you to provide raw data to support the plots. ,