Bacterial peptidoglycan acts as a digestive signal mediating host adaptation to diverse food resources in C. elegans.

Food availability and usage is a major adaptive force for the successful survival of animals in nature, yet little is known about the specific signals that activate the host digestive system to allow for the consumption of varied foods. Here, by using a food digestion system in C. elegans, we discover that bacterial peptidoglycan (PGN) is a unique food signal that activates animals to digest inedible food. We identified that a glycosylated protein, Bacterial Colonization Factor-1 (BCF-1), in the gut interacts with bacterial PGN, leading to the inhibition of the mitochondrial unfolded protein response (UPRmt) by regulating the release of Neuropeptide-Like Protein (NLP-3). Interestingly, activating UPRmt was found to hinder food digestion, which depends on the innate immune p38 MAPK/PMK-1 pathway. Conversely, inhibiting PMK-1 was able to alleviate digestion defects in bcf-1 mutants. Furthermore, we demonstrate that animals with digestion defects experience reduced natural adaptation capabilities. This study reveals that PGN-BCF-1 interaction acts as "good-food signal" to promote food digestion and animal growth, which facilitates adaptation of the host animals by increasing ability to consume a wide range of foods in their natural environment.

N-glycosylated intestinal protein BCF-1 shapes microbial colonization by binding bacteria via its fimbrial protein.

Microbial colonization plays an instrumental role in the health of the host. However, the host factors that facilitate the establishment of the microbial colonization remain unclear. Here, we establish a screening method to identify host factors regulating E. coli colonization in C. elegans. We find that a BCF-1 possessing N-glycosylation promotes E. coli colonization by directly binding to E. coli via its fimbrial protein, YdeR. BCF-1 is activated by the bacteria and interacts with an oligosaccharyl transferase, OSTB-1, which is critical for regulating E. coli colonization. We also show that the N-glycosylation of BCF-1 is critical for E. coli colonization. In addition, we find that the microbiota composition is shaped by BCF-1. In summary, this study shows a "scaffold model" for bacterial colonization between a host glycoprotein and E. coli, and it also introduces a powerful research approach to identify individual host factors involved in modulating bacterial colonization.

Gut commensal E. coli outer membrane proteins activate the host food digestive system through neural-immune communication.

The gastrointestinal tract facilitates food digestion, with the gut microbiota playing pivotal roles in nutrient breakdown and absorption. However, the microbial molecules and downstream signaling pathways that activate food digestion remain unexplored. Here, by establishing a food digestion system in C. elegans, we discover that food breakdown is regulated by the interaction between bacterial outer membrane proteins (OMPs) and a neural-immune pathway. E. coli OmpF/A activate digestion by increasing the neuropeptide NLP-12 that acts on the receptor CCKR. NLP-12 is homologous to mammalian cholecystokinin, known to stimulate dopamine, and we found that loss of dopamine receptors or addition of a dopamine antagonist inhibited OMP-mediated digestion. Dopamine and NLP-12-CKR-1 converge to inhibit PMK-1/p38 innate immune signaling. Moreover, directly inhibiting PMK-1/p38 boosts food digestion. This study uncovers a role of bacterial OMPs in regulating animal nutrient uptake and supports a key role for innate immunity in digestion.