Assessing the viability of transplanted gut microbiota by sequential tagging with D-amino acid-based metabolic probes

Wei Wang; Liyuan Lin; Yahui Du; Yanling Song; Xiaoman Peng; Xing Chen; Chaoyong James Yang

doi:10.1038/s41467-019-09267-x

Assessing the viability of transplanted gut microbiota by sequential tagging with D-amino acid-based metabolic probes

Nat Commun. 2019 Mar 21;10(1):1317. doi: 10.1038/s41467-019-09267-x.

Authors

Wei Wang^{1

2}, Liyuan Lin^{1

3}, Yahui Du³, Yanling Song¹, Xiaoman Peng¹, Xing Chen⁴, Chaoyong James Yang^{5

6}

Affiliations

¹ Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
² College of Chemistry and Molecular Engineering, Peking-Tsinghua Center for Life Sciences, Synthetic and Functional Biomolecules Center, and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing, 100871, China.
³ Collaborative Innovation Center of Chemistry for Energy Materials, The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
⁴ College of Chemistry and Molecular Engineering, Peking-Tsinghua Center for Life Sciences, Synthetic and Functional Biomolecules Center, and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing, 100871, China. xingchen@pku.edu.cn.
⁵ Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China. cyyang@xmu.edu.cn.
⁶ Collaborative Innovation Center of Chemistry for Energy Materials, The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China. cyyang@xmu.edu.cn.

Abstract

Currently, there are more than 200 fecal microbiota transplantation (FMT) clinical trials worldwide. However, our knowledge of this microbial therapy is still limited. Here we develop a strategy using sequential tagging with D-amino acid-based metabolic probes (STAMP) for assessing the viabilities of transplanted microbiotas. A fluorescent D-amino acid (FDAA) is first administered to donor mice to metabolically label the gut microbiotas in vivo. The labeled microbiotas are transplanted to recipient mice, which receive a second FDAA with a different color. The surviving transplants should incorporate both FDAAs and can be readily distinguished by presenting two colors simultaneously. Isolation of surviving bacteria and 16S rDNA sequencing identify several enriched genera, suggesting the importance of specific bacteria in FMT. In addition, using STAMP, we evaluate the effects on transplant survival of pre-treating recipients using different antibiotics. We propose STAMP as a versatile tool for deciphering the complex biology of FMT, and potentially improving its treatment efficacy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / administration & dosage*
Amino Acids / chemistry
Animals
Anti-Bacterial Agents / pharmacology
Fecal Microbiota Transplantation / methods*
Feces / microbiology
Fluorescent Dyes / chemistry
Gastrointestinal Microbiome / drug effects*
Gastrointestinal Microbiome / genetics
Gastrointestinal Tract / microbiology*
Male
Mice
Mice, Inbred C57BL
Microbial Viability / drug effects
RNA, Ribosomal, 16S / genetics*
Staining and Labeling / methods*
Stereoisomerism

Substances

Amino Acids
Anti-Bacterial Agents
Fluorescent Dyes
RNA, Ribosomal, 16S