Stress-induced cross-feeding of internal metabolites provides a dynamic mechanism of microbial cooperation

Despite the ubiquity of microbial diversity observed across environments, mechanisms of cooperativity that enable species coexistence beyond the classical limit of one-species-per-niche have been elusive. Here we report the observation of a transient but substantial cross-feeding of internal metabolites between two marine bacterial species under acid stress, and further establish through quantitative physiological characterization of the individual strains that this cross-feeding is central to the survival and coexistence of these species in growth-dilution cycles. The coculture self-organizes into a limit cycle in which acid-stressed producers excrete various internal metabolites upon entering growth arrest, enabling the cross-feeders to grow, restore medium pH, and protect the producers from death. These results establish a rare, mechanistic example of inter-species cooperation under stress, as anticipated long ago by the stress gradient hypothesis. As the accumulation of acetate and other fermentation products occurs ubiquitously in habitats ranging from the gut to wastewater, and the excretion of internal metabolites is an obligatory physiological response by bacteria under weak acid stress, stress-induced cross-feeding provides a general physiological basis for the extensive sharing of metabolic resources to promote the coexistence of diverse species in microbial communities.