Mechanisms of Microbial Hydrogen Disposal in the Human Colon and Implications for Health and Disease

Abstract

In the human gastrointestinal tract, dietary components, including fiber, that reach the colon are fermented principally to short-chain fatty acids, hydrogen, and carbon dioxide. Microbial disposal of the hydrogen generated during anaerobic fermentation in the human colon is critical to optimal functioning of this ecosystem. However, our understanding of microbial hydrogenotrophy is fragmented and, at least as it occurs in the colon, is mostly theoretical in nature. Thorough investigation and integration of knowledge on the diversity of hydrogenotrophic microbes, their metabolic variation and activities as a functional group, as well as the nature of their interactions with fermentative bacteria, are necessary to understand hydrogen metabolism in the human colon. Here, we review the limited data available on the three major groups of H(2)-consuming microorganisms found in the human colon [methanogens, sulfate-reducing bacteria (SRB), and acetogens] as well as evidence that end products of their metabolism have an important impact on colonic health.

H2metabolism is widespread and diverse among human colonic microbes

“…It indicates that the predominant mechanism of H 2 evolution in this ecosystem is through fermentative processes mediated by Bacteroidetes and Clostridial members of the Firmicutes. Of the major pathways of hydrogenogenesis, 4,19 ferredoxin-coupled H 2 fermentation appears to the predominant; [FeFe]- -hydrogenases that mediate ferredoxin-dependent H 2 evolution. NADPH-or formate-dependent H 2 evolution appears to be quantitatively less important.…”

“…It is probable that the best-characterized pathways of colonic H 2 reoxidation, namely methanogenesis, sulfate-reduction, and potentially acetogenesis, 4,12,14,39 serve as only fractional sinks in the colonic H 2 budget. These processes have a major influence on the chemical composition of the human colon and its flatus, 4,12 enhance the diversity of gut microbiota, 3 and, particularly in the case of sulfate-reducers, have been extensively linked to human health and disease.…”

“…Our findings that over 70% of sequenced human colonic microorganisms harbor hydrogenases indicates H 2 cycling may be a far more important process in human health and disease than previously recognized. 4,5 Finally, there is also need for biochemical and physiological studies to resolve the physiological roles of the unexplored Group A2, B, and C [FeFe]-hydrogenases, as well as the wider roles of H 2 cycling in Bacteroidetes. A deeper understanding of phylogeny as it pertains to function is necessary to fully understand the relationship among hydrogenogenic and hydrogenotrophic microbes in the human colon.…”

“…One especially abundant metabolite in the gastrointestinal tract is molecular hydrogen (H 2 ), a diffusible gas produced and consumed by resident anaerobic microorganisms. 4 The dynamics of hydrogen cycling are thought to be central to colonic metabolic homeostasis and shaping of the microbial community. As we have recently reviewed, [4][5][6] there is growing evidence that colonic H 2 metabolism in turn influences inflammatory bowel disease, colorectal cancer, gastrointestinal infections, obesity and associated metabolic disorders.…”

“…12,16,17 We have hypothesized that this is due to the large spatial and temporal variations in the chemical composition of the human colon, which would enable the formation of specific microhabitats dominated by different types of hydrogenotrophs. 4 Interspecies hydrogen transfer has been proposed to occur in the hydrogen-rich human colon, though microenvironmental niches in this mucosal ecosystem have not been studied and both the cellular and genetic bases for H 2 cycling are underexplored. 11,18 To gain a better understanding of H 2 metabolism in the colon, we identified the classes of hydrogenases in genomic and metagenomic databases.…”