Symbiotic gut microbes modulate human metabolic phenotypes.
Humans have evolved intimate symbiotic relationships with a consortium of gut microbes (microbiome) and individual variations in the microbiome influence host health, may be implicated in disease etiology, and affect drug metabolism, toxicity, and efficacy. However, the molecular basis of these microbe-host interactions and the roles of individual bacterial species are obscure. We now demonstrate a"transgenomic" approach to link gut microbiome and metabolic phenotype (metabotype) variation. We have used a combination of spectroscopic, microbiomic, and multivariate statistical tools to analyze fecal and urinary samples from seven Chinese individuals (sampled twice) and to model the microbial-host metabolic connectivities. At the species level, we found structural differences in the Chinese family gut microbiomes and those reported for American volunteers, which is consistent with population microbial cometabolic differences reported in epidemiological studies. We also introduce the concept of functional metagenomics, defined as "the characterization of key functional members of the microbiome that most influence host metabolism and hence health." For example, Faecalibacterium prausnitzii population variation is associated with modulation of eight urinary metabolites of diverse structure, indicating that this species is a highly functionally active member of the microbiome, influencing numerous host pathways. Other species were identified showing different and varied metabolic interactions. Our approach for understanding the dynamic basis of host-microbiome symbiosis provides a foundation for the development of functional metagenomics as a probe of systemic effects of drugs and diet that are of relevance to personal and public health care solutions.
Li
Min
M
Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine at Shanghai Jiao Tong University, Shanghai 200240, China.
Wang
Baohong
B
Zhang
Menghui
M
Rantalainen
Mattias
M
Wang
Shengyue
S
Zhou
Haokui
H
Zhang
Yan
Y
Shen
Jian
J
Pang
Xiaoyan
X
Zhang
Meiling
M
Wei
Hua
H
Chen
Yu
Y
Lu
Haifeng
H
Zuo
Jian
J
Su
Mingming
M
Qiu
Yunping
Y
Jia
Wei
W
Xiao
Chaoni
C
Smith
Leon M
LM
Yang
Shengli
S
Holmes
Elaine
E
Tang
Huiru
H
Zhao
Guoping
G
Nicholson
Jeremy K
JK
Li
Lanjuan
L
Zhao
Liping
L
D001419:Bacteria / Q000145:classification / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D009682:Magnetic Resonance Spectroscopy; D008660:Metabolism; D008969:Molecular Sequence Data; D010641:Phenotype; D010802:Phylogeny; D013559:Symbiosis