Infant age inversely correlates with gut carriage of resistance genes, reflecting modifications in microbial carbohydrate metabolism during early life
Xinming Xu,
Qingying Feng,
Tao Zhang,
Yunlong Gao,
Qu Cheng,
Wanqiu Zhang,
Qinglong Wu,
Ke Xu,
Yucan Li,
Nhu Nguyen,
Diana H. Taft,
David A. Mills,
Danielle G. Lemay,
Weiyun Zhu,
Shengyong Mao,
Anyun Zhang,
Kelin Xu,
Jinxin Liu
Affiliations
Xinming Xu
Laboratory of Gastrointestinal Microbiology, College of Animal Science & Technology Nanjing Agricultural University Nanjing China
Qingying Feng
Laboratory of Gastrointestinal Microbiology, College of Animal Science & Technology Nanjing Agricultural University Nanjing China
Tao Zhang
Laboratory of Gastrointestinal Microbiology, College of Animal Science & Technology Nanjing Agricultural University Nanjing China
Yunlong Gao
Laboratory of Gastrointestinal Microbiology, College of Animal Science & Technology Nanjing Agricultural University Nanjing China
Qu Cheng
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Wanqiu Zhang
Laboratory of Gastrointestinal Microbiology, College of Animal Science & Technology Nanjing Agricultural University Nanjing China
Qinglong Wu
Department of Pathology and Immunology Baylor College of Medicine Houston Texas USA
Ke Xu
Department of Statistics University of Chicago Chicago Illinois
Yucan Li
State Key Laboratory of Genetic Engineering, Human Phenome Institute Fudan University Shanghai China
Nhu Nguyen
Department of Food Science and Technology University of California, Davis Davis California USA
Diana H. Taft
Department of Food Science and Technology University of California, Davis Davis California USA
David A. Mills
Department of Food Science and Technology University of California, Davis Davis California USA
Danielle G. Lemay
USDA ARS Western Human Nutrition Research Center Davis California USA
Weiyun Zhu
Laboratory of Gastrointestinal Microbiology, College of Animal Science & Technology Nanjing Agricultural University Nanjing China
Shengyong Mao
Laboratory of Gastrointestinal Microbiology, College of Animal Science & Technology Nanjing Agricultural University Nanjing China
Anyun Zhang
Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education, College of Life Sciences Sichuan University Chengdu China
Kelin Xu
Department of Biostatistics, Key Laboratory of Public Health Safety, NHC Key Laboratory of Health Technology Assessment, School of Public Health Fudan University Shanghai China
Jinxin Liu
Laboratory of Gastrointestinal Microbiology, College of Animal Science & Technology Nanjing Agricultural University Nanjing China
Abstract The infant gut microbiome is increasingly recognized as a reservoir of antibiotic resistance genes, yet the assembly of gut resistome in infants and its influencing factors remain largely unknown. We characterized resistome in 4132 metagenomes from 963 infants in six countries and 4285 resistance genes were observed. The inherent resistome pattern of healthy infants (N = 272) could be distinguished by two stages: a multicompound resistance phase (Months 0–7) and a tetracycline‐mupirocin‐β‐lactam‐dominant phase (Months 8–14). Microbial taxonomy explained 40.7% of the gut resistome of healthy infants, with Escherichia (25.5%) harboring the most resistance genes. In a further analysis with all available infants (N = 963), we found age was the strongest influencer on the resistome and was negatively correlated with the overall resistance during the first 3 years (p < 0.001). Using a random‐forest approach, a set of 34 resistance genes could be used to predict age (R2 = 68.0%). Leveraging microbial host inference analyses, we inferred the age‐dependent assembly of infant resistome was a result of shifts in the gut microbiome, primarily driven by changes in taxa that disproportionately harbor resistance genes across taxa (e.g., Escherichia coli more frequently harbored resistance genes than other taxa). We performed metagenomic functional profiling and metagenomic assembled genome analyses whose results indicate that the development of gut resistome was driven by changes in microbial carbohydrate metabolism, with an increasing need for carbohydrate‐active enzymes from Bacteroidota and a decreasing need for Pseudomonadota during infancy. Importantly, we observed increased acquired resistance genes over time, which was related to increased horizontal gene transfer in the developing infant gut microbiome. In summary, infant age was negatively correlated with antimicrobial resistance gene levels, reflecting a composition shift in the gut microbiome, likely driven by the changing need for microbial carbohydrate metabolism during early life.
