Gut microbial features can predict host phenotype response to protein deficiency

Malnutrition remains a major health problem in low‐ and middle‐income countries. During low protein intake, <0.67 g/kg/day, there is a loss of nitrogen (N 2 ) balance, due to the unavailability of amino acid for metabolism and unbalanced protein catabolism results. However, there are individuals, who consume the same low protein intake, and preserve N 2 balance for unknown reasons. A novel factor, the gut microbiota, may account for these N 2 balance differences. To investigate this, we correlated gut microbial profiles with the growth of four murine strains (C57Bl6/J, CD ‐1, FVB , and NIH ‐Swiss) on protein deficient ( PD ) diet. Results show that a PD diet exerts a strain‐dependent impact on growth and N 2 balance as determined through analysis of urinary urea, ammonia and creatinine excretion. Bacterial alpha diversity was significantly ( P  < 0.05, FDR ) lower across all strains on a PD diet compared to normal chow ( NC ). Multi‐group analyses of the composition of microbiomes ( ANCOM ) revealed significantly differential microbial signatures between the four strains independent of diet. However, mice on a PD diet demonstrated differential enrichment of bacterial genera including, Allobaculum (C57Bl6/J), Parabacteroides ( CD ‐1), Turicibacter ( FVB ), and Mucispirillum ( NIH ‐Swiss) relative to NC . For instance, selective comparison of the CD ‐1 (gained weight) and C57Bl6/J (did not gain weight) strains on PD diet also demonstrated significant pathway enrichment of dihydroorodate dehydrogenase, rRNA methyltransferases, and RNA splicing ligase in the CD ‐1 strains compared to C57Bl6/J strains; which might account in their ability to retain growth despite a protein deficient diet. Taken together, these results suggest a potential relationship between the specific gut microbiota, N 2 balance and animal response to malnutrition.