Cross-feeding between intestinal pathobionts promotes their overgrowth during undernutrition

Child undernutrition is a global health issue associated with a high burden of infectious disease. Undernourished children display an overabundance of intestinal pathogens and pathobionts, and these bacteria induce enteric dysfunction in undernourished mice; however, the cause of their overgrowth remains poorly defined. Here, we show that disease-inducing human isolates of Enterobacteriaceae and Bacteroidales spp. are capable of multi-species symbiotic cross-feeding, resulting in synergistic growth of a mixed community in vitro. Growth synergy occurs uniquely under malnourished conditions limited in protein and iron: in this context, Bacteroidales spp. liberate diet- and mucin-derived sugars and Enterobacteriaceae spp. enhance the bioavailability of iron. Analysis of human microbiota datasets reveals that Bacteroidaceae and Enterobacteriaceae are strongly correlated in undernourished children, but not in adequately nourished children, consistent with a diet-dependent growth synergy in the human gut. Together these data suggest that dietary cross-feeding fuels the overgrowth of pathobionts in undernutrition. Malnourished children experience a high burden of intestinal pathogens that exacerbate growth stunting, and preventing this pathogen overgrowth has proved challenging. Here the authors show that diet-specific bacterial crossfeeding contributes to the overgrowth of intestinal pathogens during child malnutrition.

Automated summary

Child undernutrition is a global health issue that is associated with an overabundance of intestinal pathogens. This study shows that disease-inducing human isolates of Enterobacteriaceae and Bacteroidales are capable of multi-species symbiotic cross-feeding, leading to synergistic growth of a mixed community. This diet-specific bacterial crossfeeding contributes to the overgrowth of intestinal pathogens during child malnutrition, exacerbating growth stunting.