Microbial Respiration and Formate Oxidation as Metabolic Signatures of Inflammation-Associated Dysbiosis.
Intestinal inflammation is frequently associated with an alteration of the gut microbiota, termed dysbiosis, which is characterized by a reduced abundance of obligate anaerobic bacteria and an expansion of facultative Proteobacteria such as commensal E. coli. The mechanisms enabling the outgrowth of Proteobacteria during inflammation are incompletely understood. Metagenomic sequencing revealed bacterial formate oxidation and aerobic respiration to be overrepresented metabolic pathways in a chemically induced murine model of colitis. Dysbiosis was accompanied by increased formate levels in the gut lumen. Formate was of microbial origin since no formate was detected in germ-free mice. Complementary studies using commensal E. coli strains as model organisms indicated that formate dehydrogenase and terminal oxidase genes provided a fitness advantage in murine models of colitis. In vivo, formate served as electron donor in conjunction with oxygen as the terminal electron acceptor. This work identifies bacterial formate oxidation and oxygen respiration as metabolic signatures for inflammation-associated dysbiosis.
Department of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Elizabeth R
ER
Hughes
Department of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Maria G
MG
Winter
Department of Immunology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Breck A
BA
Duerkop
Department of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Luisella
L
Spiga
Departamento de Clínica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, 31270 Brazil.
Tatiane
T
Furtado de Carvalho
Department of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Wenhan
W
Zhu
Department of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Caroline C
CC
Gillis
Department of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Lisa
L
Büttner
Department of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Madeline P
MP
Smoot
Department of Immunology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Cassie L
CL
Behrendt
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Sara
S
Cherry
Departamento de Clínica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, 31270 Brazil.
Renato L
RL
Santos
Department of Immunology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Lora V
LV
Hooper
Department of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: sebastian.winter@utsouthwestern.edu.
Sebastian E
SE
Winter
D000818:Animals; D003092:Colitis / Q000382:microbiology; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000382:microbiology*; D004926:Escherichia coli / Q000378:metabolism*; D005260:Female; D005561:Formates / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome; D007249:Inflammation / Q000382:microbiology*; D007422:Intestines / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020560:Proteobacteria / Q000378:metabolism
D005561:Formates
bacterial respiration; dysbiosis; formate metabolism; gut microbiota; intestinal inflammation; metagenomics