Ecological and evolutionary implications of the sharing of metabolites between different microbes in the gut microbiome

By Dr. Priyom Bose, Ph.D.Reviewed by Benedette Cuffari, M.Sc.Apr 18 2023

Cross-feeding involves the exchange of nutrients and energy between different strains or species of microorganisms. In a recent Cell Host & Microbe review, scientists discuss the evolutionary and ecological implications of cross-feeding across trophic levels and their health outcomes.

Study: Cross-feeding in the gut microbiome: Ecology and mechanisms. Image Credit: Fedorov Oleksiy / Shutterstock.com

Microbial activity in the gut

The human body hosts about 100 trillion microbial symbionts, with the most abundant microbial communities found within the gastrointestinal tract. These include bacteria, fungi, viruses, and other microbes. In the context of these microbes, cross-feeding or metabolite sharing can occur between the host and microbe, in addition to sharing between microbes themselves.

Understanding cross-feeding is instrumental for determining the impact of the microbiome on host health. Cross-feeding shapes the composition of the microorganism community, its integrated metabolome, and its response to perturbation.

The current review elucidates the ecological forces and consequences of cross-feeding interactions. Herein, the researchers also provide important insights into the various cross-feeding mechanisms of nutrients in the gut microbiome and their subsequent impacts on host health.

Ecology of cross-feeding in the gut microbiome

Cross-feeding in the gut microbiome can be mutualistic, exploitative, or commensalistic. Interactions are mutualistic when species feed on metabolites produced by each other or

when a microbe feeds on metabolites from other species and modifies the environment for the producer. Cooperative interactions are known as syntrophy, which includes obligately mutualistic metabolism.

During exploitative interactions, the consumer organism only benefits from the substrate produced by other organisms; however, the producer is harmed by the synthesis of toxic waste products. Comparatively commensalistic cross-feeding occurs when one microbe benefits from the product of another microbe without causing any harm to the producing organism.

Based on ecological theory, positive syntrophic interactions may lead to an unstable and low-diversity microorganism community, which is a characteristic of dysbiosis. Competitive interactions stabilize microbial communities because they control mutualism and inhibit the proliferation of a single species out-competing others. 

It is important to understand how microbial communities remain stable amidst cross-feeding interactions in the gut. This could be due to the ecological forces in the gut that cannot be assessed through experiments or computational models. Multiple hypotheses have been formulated to explain how cooperation stably exists in the gut microbiome. 

Underlying mechanisms

Metabolites linked with cross-feeding in the gut microbiome are categorized as either those associated with central metabolism, such as electron donors/acceptors and sugars, or those that are essential nutrients required for biosynthesis such as cofactors, amino acids, and vitamins.  

In the context of central metabolism, cross-feeding establishes four different trophic levels. The first trophic level, which consists of organisms otherwise known as primary degraders, is equipped with specialized machinery that can hydrolyze complex polysaccharides and release oligo- and monosaccharides accessible to other species. 

Bacteroidales organisms present in the human gut have been identified as primary degraders and are essential players in the carbon food web. The three dominant genera of the first trophic level include Parabacteroides, Bacteroides, and Prevotella.

These gut bacteria can degrade plant polysaccharides that escape digestion in the small intestine by human enzymes. Cross-feeding at this level depends on glycan and the interacting microbes.

The second trophic level comprises primary fermenters that generate these sugars by themselves or obtain them from other microbes. Subsequently, these sugars undergo glycolysis and generate phosphoenolpyruvate (PEP), which is used for substrate-level phosphorylation that releases organic acids, such as acetate, succinate, and formate, or alcohols like 1,2-propanediol.

For primary fermenters, amino acids act as an energy source by participating in central metabolism, wherein they provide nitrogen for transamination reactions and are essential nutrients for auxotrophs. In contrast to the carbon food web, the nitrogen web is driven by diverse microbial species, such as Fusobacterium, Clostridium, Actinomyces, Propionibacterium, and Peptostreptococci.

The third trophic level constitutes secondary fermenters, which utilize the byproducts of second trophic level organisms in various respiratory or fermentative pathways. As a result, these organisms generate short-chain fatty acids (SCFA) such as acetate, butyrate, and propionate.

The molecular hydrogen produced by primary/secondary fermenters acts as an electron donor for sulfate-reducing bacteria (SRB), acetogens, and methanogens.

Besides cross-feeding from carbon and nitrogen sources, vitamins and cofactors are also cross-fed in the gut microbiome. Vitamins are essential for enzymatic functions and are suitable for inter-microbial cross-feeding in the distal gut. The association between vitamin B12 and corrinoids is related to vitamin cross-feeding in microbial communities.