Deciphering fitness trade-offs in metabolite exchange at the origin of a bacterial cross-feeding community

Obligate cross-feeding is a common type of interaction among microbial communities, yet gaps persist in understanding its maintenance and limit practical applications. In particular, little is known about how contextualised metabolite exchange intensities affect community fitness, despite their influential role in shaping interdependencies1, diversities 2, and lifespan 3 of cross-feeding community members. Here I computationally test how amino acids isoleucine (ile) and lysine (lys) exchange intensities affect individual and community fitness of a two-strain auxotroph cross-feeding community. I innovatively integrated metabolite exchange intensities and multi-strain growth using Flux Balance Analysis (FBA) and evolutionary game theory, and showed that crossfeeding communities have the highest fitness when the metabolite exchange intensity is slightly above individual amino acid uptake demands, stimulated by cheaters presence. Using FBA with different metabolite uptake / secretion combinations, I discovered the individual amino acid demands are linearly correlated with sole carbon source (glucose) availability. Additionally, as cheating mutants emerge, costly exchange intensities can be better sustained when accumulated shared metabolites are accessible. This is the first study linking metabolite exchange intensities and cross-feeding community fitness considering all known metabolic reactions of a bacterial strain. The fittest metabolite exchange range and its relationships with glucose and shared metabolite availability shed lights on resilient microbial community engineering as well as metabolite exchange parameter constraints for multi-species population / metabolism models 4-6.