Macronutrient metabolism by the human gut microbiome: major fermentation by-products and their impact on host health

Abstract

The human gut microbiome is a critical component of digestion, breaking down complex carbohydrates, proteins, and to a lesser extent fats that reach the lower gastrointestinal tract. This process results in a multitude of microbial metabolites that can act both locally and systemically (after being absorbed into the bloodstream). The impact of these biochemicals on human health is complex, as both potentially beneficial and potentially toxic metabolites can be yielded from such microbial pathways, and in some cases, these effects are dependent upon the metabolite concentration or organ locality. The aim of this review is to summarize our current knowledge of how macronutrient metabolism by the gut microbiome influences human health. Metabolites to be discussed include short-chain fatty acids and alcohols (mainly yielded from monosaccharides); ammonia, branched-chain fatty acids, amines, sulfur compounds, phenols, and indoles (derived from amino acids); glycerol and choline derivatives (obtained from the breakdown of lipids); and tertiary cycling of carbon dioxide and hydrogen. Key microbial taxa and related disease states will be referred to in each case, and knowledge gaps that could contribute to our understanding of overall human wellness will be identified.

Keywords: Human gut microbiome; Human health; Macronutrients; Microbial metabolism.

Fig. 1

Strategies of pyruvate catabolism by the human gut microbiome. Carbohydrates are first degraded to pyruvate. Pyruvate may then be converted to succinate, lactate, acetyl CoA + formate/carbon dioxide + hydrogen, ethanol, or 2,3-butanediol. Succinate may, however, also be a direct product of carbohydrate fermentation. Succinate and lactate do not typically reach high concentrations in fecal samples, as they can be further catabolized to produce energy, but certain species do secrete them as their final fermentation end-product, which enables cross-feeding. Acetate is produced by two pathways; (1) through direct conversion of acetyl CoA for the generation of energy (brown) or (2) acetogenesis (red). Formate/carbon dioxide + hydrogen can also be substrates for methanogenesis. Propionate is produced by three pathways; (1) the succinate pathway (orange), (2) the acrylate pathway (green), or (3) the 1,2-propanediol pathway (blue). 1,2-Propanediol is synthesized from lactaldehyde or dihydroxyacetone phosphate, which both are products of deoxy sugar fermentation (e.g., fucose, rhamnose). Alternatively, lactaldehyde can be produced from lactate, or 1,2-propanediol can be fermented to propanol. Propionate can be coupled with ethanol for fermentation to valerate (gray). The precursor for butyrate, butyryl CoA, is generated from either acetyl CoA or succinate. Butyrate is then produced by two pathways; (1) the butyrate kinase pathway (pink) or (2) the butyryl CoA:acetyl CoA transferase pathway (purple). Butyrate-producing bacteria may also cross-feed on lactate, converting it back to pyruvate. Lactate may also be catabolized as part of sulfate reduction