Profiling of faecal water and urine metabolites among Papua New Guinea highlanders believed to be adapted to low protein intake

Introduction: Adequate amount of proteins from foods are normally needed to maintain muscle mass of the human body. Although protein intakes of Papua New Guinea (PNG) highlanders are less than biologically adequate, protein deficiency related disorders have rarely been reported. It has been postulated that gut microbiota play a role in such low-protein-adaptation. Objective: To explore underlying biological mechanisms of low-protein adaptation among PNG highlanders by investigating metabolomic profiles of faecal water and urine. Methods: We performed metabolome analysis using faecal water extracted from faecal samples of PNG highlanders, PNG non-highlanders and Japanese subjects. We paid special attention to amino acids and other metabolites produced by gut microbiota, as well as to metabolites involved in nitrogen recycling in the human gut. Results: Our results indicated that amino acid levels were higher in faecal water from PNG highlanders than PNG non-highlanders, but amino acid levels did not differ between PNG highlanders and Japanese subjects. Among PNG highlander samples, amino acid levels tended to be higher in those who consumed less protein. Conclusion: We speculated that a greater proportion of urea was excreted to the intestine among the PNG highlanders than other groups, and that the urea was used for nitrogen salvage. Intestinal bacteria are essential for producing ammonia from urea and also for producing amino acids from ammonia, which is a key process in low-protein adaptation. Profiling the gut microbiota of PNG highlanders is an important avenue for further research into the mechanisms of low-protein adaptation.