Dissecting the in vivo metabolic potential of two human gut acetogens.
Fermenting microbial communities generate hydrogen; its removal through the production of acetate, methane, or hydrogen sulfide modulates the efficiency of energy extraction from available nutrients in many ecosystems. We noted that pathway components for acetogenesis are more abundantly and consistently represented in the gut microbiomes of monozygotic twins and their mothers than components for methanogenesis or sulfate reduction and subsequently analyzed the metabolic potential of two sequenced human gut acetogens, Blautia hydrogenotrophica and Marvinbryantia formatexigens in vitro and in the intestines of gnotobiotic mice harboring a prominent saccharolytic bacterium. To do so, we developed a generally applicable method for multiplex sequencing of expressed microbial mRNAs (microbial RNA-Seq) and, together with mass spectrometry of metabolites, showed that these organisms have distinct patterns of substrate utilization. B. hydrogenotrophica targets aliphatic and aromatic amino acids. It increases the efficiency of fermentation by consuming reducing equivalents, thereby maintaining a high NAD(+)/NADH ratio and boosting acetate production. In contrast, M. formatexigens consumes oligosaccharides, does not impact the redox state of the gut, and boosts the yield of succinate. These findings have strategic implications for those who wish to manipulate the hydrogen economy of gut microbial communities in ways that modulate energy harvest.
Rey
Federico E
FE
Center for Genome Sciences, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Faith
Jeremiah J
JJ
Bain
James
J
Muehlbauer
Michael J
MJ
Stevens
Robert D
RD
Newgard
Christopher B
CB
Gordon
Jeffrey I
JI
D000085:Acetates / Q000378:metabolism*; D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D002432:Cecum / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000382:microbiology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005856:Germ-Free Life; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D054892:Metagenome / Q000235:genetics; D051379:Mice; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA
D000085:Acetates
Lett Appl Microbiol. 2006 Jul;43(1):58-63
16834722
Gut. 1992 Sep;33(9):1234-8
1427377
Appl Environ Microbiol. 2003 Oct;69(10):6321-6
14532100
Appl Environ Microbiol. 2004 Mar;70(3):1307-14
15006747
Appl Environ Microbiol. 1983 May;45(5):1602-13
16346296
J Bacteriol. 1999 Mar;181(5):1489-95
10049380
Br J Nutr. 1965;19(4):511-22
5852118
Sci Total Environ. 2008 Jun 25;396(2-3):121-31
18394682
Nature. 2009 Jan 22;457(7228):480-4
19043404
Environ Microbiol. 2008 Oct;10(10):2550-73
18631365
Cell Host Microbe. 2008 Nov 13;4(5):447-57
18996345
J Appl Bacteriol. 1988 Sep;65(3):241-7
2852666
Science. 2005 Jun 10;308(5728):1635-8
15831718
Fed Proc. 1983 Jan;42(1):109-13
6848372
J Appl Bacteriol. 1988 Aug;65(2):103-11
3204069
Cell Host Microbe. 2009 Sep 17;6(3):279-89
19748469
J Biol Chem. 1994 Jun 17;269(24):16726-32
8206994
Nat Rev Microbiol. 2008 Oct;6(10):776-88
18794915
Annu Rev Food Sci Technol. 2010;1:363-95
22129341
Am J Clin Nutr. 1984 Feb;39(2):338-42
6320630
Nucleic Acids Res. 2009 Jan;37(Database issue):D233-8
18838391
Appl Environ Microbiol. 1996 May;62(5):1589-92
8633856
Proc Nutr Soc. 2003 Feb;62(1):67-72
12740060
Science. 2005 Mar 25;307(5717):1955-9
15790854
J Bacteriol. 1996 Aug;178(15):4597-603
8755890
Appl Environ Microbiol. 2007 Oct;73(20):6391-403
17675444
Anaerobe. 1997 Oct;3(5):307-15
16887606
Proc Natl Acad Sci U S A. 1981 Jan;78(1):464-8
6787588
Appl Environ Microbiol. 1989 Jul;55(7):1735-41
16347966
Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3976-81
19234113
Appl Environ Microbiol. 1986 Oct;52(4):623-30
16347157
J Bacteriol. 2009 May;191(10):3203-11
19304856
Mol Cancer Res. 2006 Jan;4(1):9-14
16446402
Am J Physiol Endocrinol Metab. 2005 Oct;289(4):E716-20
16150956
Appl Environ Microbiol. 2009 Apr;75(7):1860-6
19201957
FEMS Microbiol Lett. 1995 Jul 15;130(1):7-12
7557299
J Biol Chem. 2009 Sep 11;284(37):24673-7
19553672
Nat Rev Microbiol. 2008 Feb;6(2):121-31
18180751
Appl Environ Microbiol. 1993 Nov;59(11):3551-6
8285662
Bacteriol Rev. 1977 Mar;41(1):100-80
860983
Arch Microbiol. 1996 Sep;166(3):176-83
8703194