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. Additionally, statistical model fitting revealed that the relative abundance of genera such as Bifidobacterium, Ruminococcus, and Lactobacillus were significantly positively correlated with body weight, while Anaerofustis, Roseburia , and Bilophila were significantly positively correlated with ammonia excretion. Taken together, these results suggest a potential relationship between the specific gut microbiota, N 2 balance and animal response to malnutrition.