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Review
. 2023 Apr 12;31(4):485-499.
doi: 10.1016/j.chom.2023.03.016.

Cross-feeding in the gut microbiome: Ecology and mechanisms

Elizabeth J Culp  1 , Andrew L Goodman  2
Affiliations
Review

Cross-feeding in the gut microbiome: Ecology and mechanisms

Elizabeth J Culp et al. Cell Host Microbe. .

Abstract

Microbial communities are shaped by positive and negative interactions ranging from competition to mutualism. In the context of the mammalian gut and its microbial inhabitants, the integrated output of the community has important impacts on host health. Cross-feeding, the sharing of metabolites between different microbes, has emergent roles in establishing communities of gut commensals that are stable, resistant to invasion, and resilient to external perturbation. In this review, we first explore the ecological and evolutionary implications of cross-feeding as a cooperative interaction. We then survey mechanisms of cross-feeding across trophic levels, from primary fermenters to H2 consumers that scavenge the final metabolic outputs of the trophic network. We extend this analysis to also include amino acid, vitamin, and cofactor cross-feeding. Throughout, we highlight evidence for the impact of these interactions on each species' fitness as well as host health. Understanding cross-feeding illuminates an important aspect of microbe-microbe and host-microbe interactions that establishes and shapes our gut communities.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

Figure 1.
Figure 1.. Landscape of microbe-microbe interactions
Microbe-microbe interactions can result in positive (+) or negative (−) impacts on fitness of participating species. These interactions are often mediated by diffusible metabolites, shown here as stars. Cross-feeding can result in mutualism (a-b), commensalism (c) or exploitation (d). These interactions are often through the production of a metabolite by one species that benefits or harms another species (a, c, d, e, f, g), but can also occur when a harmful metabolite to one species is consumed by and benefits another species (b). Amensalism (e) and competition (f-g) can also occur through metabolite exchange, but do not represent cross-feeding interactions.
Figure 2.
Figure 2.. Central metabolism pathways involved in cross-feeding
An overview of central metabolism pathways involved in cross-feeding interactions. (a) Flags along the left show how the pathways in (b) roughly divide into four trophic levels through cross-feeding. Key cross-fed intermediates released by primary degraders/fermenters, highlighted in blue, can be released and utilized by secondary fermenters ultimately for the production of SCFA, highlighted in green. Throughout, H2 is produced in one of two ways: first, the Pyruvate-Formate Lyase (PFL) pathway that splits formate into H2 and CO2, and second through the oxidation of NADH. (c) NADH oxidation can be coupled to ferredoxin reduction and reoxidation by ferredoxin (Fd)-dependent hydrogenase (Fd-[FeFe]), directly by an NADH-dependent hydrogenase (NADH-[FeFe]), or directly by a bifurcating NADH-Fdred-dependent hydrogenase (NADH-Fdred-[FeFe]). (d) H2 is consumed by various types of metabolism, indicated in red. Pathway stoichiometry is not represented in this figure.
Figure 3.
Figure 3.. Nitrogen metabolism in the gut
(a) Stickland metabolism couples reduction of one amino acid (left) with oxidation of a second amino acid (right) via electron carriers indicated by [H]. Deamination of the amino acids results in production of carboxylic acid intermediates and ammonium. Stoichiometric equivalents are indicated by n. (b) Deamination of urea by ureases also produces ammonia. (c) Nitrogen and fiber metabolism vary along the length of the colon. Whereas ample dietary fiber in the proximal colon leads to high concentrations of SCFA, amino acid fermentation is more common in the distal colon. Ammonium and SCFA concentrations shown are estimated from human samples.
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