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.
To explore underlying biological mechanisms of low-protein adaptation among PNG highlanders by investigating metabolomic profiles of faecal water and urine.
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.
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.
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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Bergen, W. G., Wu, G. (2009). Intestinal nitrogen recycling and utilization in health and disease. Journal of Nutrition, 139(5), 821–825.
Bistrian, B. R. (1990). Recent advances in parenteral and enteral nutrition: A personal perspective. The Journal of Parenteral and Enteral Nutrition, 14(4), 329–334.
Bourke, R. M. (1985). Sweet potato (Ipomoea batatas) production and research in Papua New Guinea. Papua New Guinea Journal of Agriculture, Forestry and Fisheries, 33(3–4), 89–108.
Date, C., Baba, M., Kajiwara, N. M., Minamide, T., Fujita, Y., Ichikawa, M., Miyatani, S., Hayashi, M., Tanaka, H., Heywood, P., Alpers, M., & Koishi, H. (1988). Nutritional status of some Papua New Guinea highlanders as assessed by physical measurements and blood analysis. Ecology of Food and Nutrition, 20, 185–196.
De Angelis, M., Montemurno, E., Piccolo, M., Vannini, L., Lauriero, G., Maranzano, V., Gozzi, G., Serrazanetti, D., Dalfino, G., Gobbetti, M., Gesualdo, L. (2014). Microbiota and metabolome associated with immunoglobulin A nephropathy (IgAN). PLoS ONE, 9(6), e99006.
Debnam ES, Grimble GK. (2001) Methods for assessing intestinal absorptive function in relation to enteral nutrition. Current Opinion in Clinical Nutrition & Metabolic Care, 4(5):355–367.
Di Cagno, R., De Angelis, M., De Pasquale, I., Ndagijimana, M., Vernocchi, P., Ricciuti, P., Gagliardi, F., Laghi, L., Crecchio, C., Guerzoni, M. E., Gobbetti, M., Francavilla, R (2011). Duodenal and faecal microbiota of celiac children: Molecular, phenotype and metabolome characterization. BMC Microbiology, 11, 219.
Eben, H., Clements, F. W. (1947). Report of the New Guinea Nutrition Survey Expedition.
Ferro-Luzzi, A., Norgan, N. G., & Durnin, J. V. (1975). Food intake, its relationship to body weight and age, and its apparent nutritional adequacy in New Guinean children. The American Journal of Clinical Nutrition, 28(12), 1443–1453.
Greenhill, A. R., Tsuji, H., Ogata, K., Natsuhara, K., Morita, A., Soli, K., Larkins, J. A., Tadokoro, K., Odani, S., Baba, J., Naito, Y., Tomitsuka, E., Nomoto, K., Siba, P. M., Horwood, P. F., Umezaki, M. (2015). Characterization of the Gut Microbiota of Papua New Guineans Using Reverse Transcription Quantitative PCR. PLoS ONE, 10(2), e0117427.
Hipsley, E. H., & Clements, F. W. (1950). Reports of the New Guinea nutrition expedition 1947. Canberra: Department of External Territories.
Itoh, S., Sugawa-Katayama, Y., Koishi, H., & Izumi, S. (1982). Serum concentration of protein, triglyceride, β-lipoproteins and cholesterol in Papua New Guinean highlanders. The Journal of Nutritional Science and Vitaminology, 28, 411–417.
Jansson, J., Willing, B., Lucio, M., Fekete, A., Dicksved, J., Halfvarson, J., Tysk, C., & Schmitt-Kopplin, P. (2009). Metabolomics reveals metabolic biomarkers of Crohn’s disease. PLoS ONE, 4(7), e6386.
Kajiwara, N. M., Okuda, T., Miyatani, S., Date, C., Minamide, T., Fujita, Y., Ichikawa, M., Baba, M., Heywood, P., & Koishi, H. (1984). Nutritional status of Papua New Guinea highlanders: Seasonal comparison of festival and non-festival times. Journal of Food and Nutrition Research, 41, 55–61.
Kim, S. W., Suda, W., Kim, S., Oshima, K., Fukuda, S., Ohno, H., Morita, H., & Hattori, M. (2013). Robustness of gut microbiota of healthy adults in response to probiotic intervention revealed by high-throughput pyrosequencing. DNA Research, 20(3), 241–253.
Klinder, A., Karlsson, P. C., Clune, Y., Hughes, R., Glei, M., Rafter, J. J., Rowland, I., Collins, J. K., & Pool-Zobel, B. L. (2007). Fecal water as a non-invasive biomarker in nutritional intervention: Comparison of preparation methods and refinement of different endpoints. Nutrition and Cancer, 57(2), 158–167.
Koishi, H. (1990). Nutritional adaptation of Papua New Guinea Highlanders. European Journal of Clinical Nutrition, 44(12), 851–911.
Luyken, R., Pikaar, N. A., & Luekenko, F. W. (1964). Nutrition studies in New Guinea. The American Journal of Clinical Nutrition, 14, 13–27.
Millward, D. J. (1979). Protein deficiency, starvation and protein metabolism. Proceedings of the Nutrition Society, 38(1), 77–88.
Ministry of Health, Labour and Welfare in Japan. (2015). Annual report of National Health and Nutrition Survey.
Mora, D., & Arioli, S. (2014). Microbial urease in health and disease. PLoS Pathogens, 10(12), e1004472.
Morita, A., Natsuhara, K., Tomitsuka, E., Odani, S., Baba, J., Tadokoro, K., Igai, K., Greenhill, A. R., Horwood, P. F., Soli, K. W., Phuanukoonnon, S., Siba, P. M., & Umezaki, M. (2015). Development, validation, and use of a semi-quantitative food frequency questionnaire for assessing protein intake in Papua New Guinean Highlanders. American Journal of Human Biology, 27(3), 349–357.
Naito, Y. I., Morita, A., Natsuhara, K., Tadokoro, K., Baba, J., Odani, S., Tomitsuka, E., Igai, K., Tsutaya, T., Yoneda, M., Greenhill, A. R., Horwood, P. F., Soli, K. W., Suparat, P., Siba, P. M., & Umezaki, M. (2015). Association of protein intakes and variation of diet-scalp hair nitrogen isotopic discrimination factor in Papua New Guinea Highlanders. American Journal of Physical Anthropology, 158(3), 359–370.
Nishijima, S., Suda, W., Oshima, K., Kim, S. W., Hirose, Y., Morita, H., & Hattori, M. (2016). The gut microbiome of healthy Japanese and its microbial and functional uniqueness. DNA Research, 23(2), 125–133.
Norgan, N. G., Ferroluz, A., & Durnin, J. V. G. (1974). Energy and nutrient intake and energy expenditure of 204 New Guineas adults. Philosophical transactions of the Royal Society of London B, Biological Science, 268(893), 309–348.
Okuda, T., Kajiwara, N., Date, C., Sugimoto, K., Rikimaru, T., Fujita, Y., & Koishi, H. (1981). Nutritional status of Papua New Guinea highlanders. Journal of Nutritional Science and Vitaminology, 27, 319–331.
Okuda, T., Yamaguchi, Y., Fujita, Y., Minamide, T., Kajiwara, N. M., Miyatani, S., Rikimaru, T., Oi, Y., Izuta, A., Nakano, Y., & Koishi, H. (1984). The change of the diet on Papua New Guinea highlanders. Annual report of science of living (vol. 32, pp. 39–50). Osaka: Osaka City University.
Oomen, H. A. (1961). The nutrition situation in western New Guinea. Tropical and Geographical Medicine, 3, 321–335.
Oomen, H. A. (1972). Distribution of nitrogen and composition of nitrogen compounds in food, urine and faeces in habitual consumers of sweet potato and taro. Nutrition and Metabolism, 14(2), 65–82.
Picou, D., & Phillips, M. (1972). Urea metabolism in malnourished and recovered children receiving a high or low protein diet. American Journal of Clinical Nutrition, 25(11), 1261–1266.
Richards, P., Metcalfe-Gibson, A., Ward, E. E., Wrong, O., & Houghton, B. J. (1967). Utilisation of ammonia nitrogen for protein synthesis in man, and the effect of protein restriction and uraemia. Lancet, 2(7521), 845–849.
Soga, T., & Heiger, D. N. (2000). Amino acid analysis by capillary electrophoresis electrospray ionization mass spectrometry. Analytical Chemistry, 72(6), 1236–1241.
Soga, T., Ohashi, Y., Ueno, Y., Naraoka, H., Tomita, M., & Nishioka, T. (2003). Quantitative metabolome analysis using capillary electrophoresis mass spectrometry. Journal of Proteome Research, 2(5), 488–494.
Soga, T., Ueno, Y., Naraoka, H., Ohashi, Y., Tomita, M., & Nishioka, T. (2002). Simultaneous determination of anionic intermediates for Bacillus subtilis metabolic pathways by capillary electrophoresis electrospray ionization mass spectrometry. Analytical Chemistry, 74(10), 2233–2239.
Stewart, G. S., & Smith, C. P. (2005). Urea nitrogen salvage mechanisms and their relevance to ruminants, non-ruminants and man. Nutrition Research Reviews, 18(1), 49–62.
Takahashi, M., Benno, Y., & Mitsuoka, T. (1980). Utilization of ammonia nitrogen by intestinal bacteria isolated from pigs. Applied and Environmental Microbiology, 39(1), 30–35.
Tomé D, Bos C. (2000) Dietary protein and nitrogen utilization. Journal of Nutrition, 130(7):1868S–1873S.
Walser, M., & Bodenlos, L. J. (1959). Urea metabolism in man. The Journal of Clinical Investigation, 38, 1617–1626.
Wapnir, R. A., Hawkins, R. L., & Lifshitz, F. (1972). Hyperaminoacidemia effects on intestinal transport of related amino acids. American Journal of Physiology, 223(4), 788–793.
WHO/FAO/UNU. (2007). Protein and amino acid requirements in human nutrition. World Health Organization Technical Report Series, 935, 1–265.
Wolpert, E., Phillips, S. F., & Summerskill, W. H. (1971). Transport of urea and ammonia production in the human colon. Lancet, 2(7739), 1387–1390.
Younes, H., Alphonse, J. C., Behr, S. R., Demigné, C., & Rémésy, C. (1999). Role of fermentable carbohydrate supplements with a low-protein diet in the course of chronic renal failure: Experimental bases. American Journal of Kidney Diseases, 33(4), 633–646.
This work was supported by the Funding Program for Next Generation World-Leading Researchers (LS024), Grants-in-Aid for Scientific Research (15H04430), Takeda Science Foundation, and the TANITA Healthy Weight Community Trust.
Conflict of interest
The authors state no conflict of interest.
This study was approved by the Research Ethics Committee of the Graduate School of Medicine, University of Tokyo (10188), the Institutional review Board of the Papua New Guinea Institute of Medical Research (1025), and the Medical Research Advisory Board of Papua New Guinea (07.18, 11.16).
Informed consent was obtained from all participants included in the study.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Scatter plot between the first and the second principal components obtained from principle component analysis for 228 metabolites identified in urinary samples. Closed circles indicate PNG highlanders samples (n=6), open circles indicate PNG non-highlanders samples (n=4). Percentages of variation explained by the first component and the second component are shown. Supplementary Material 1 (PPTX 58 KB)
About this article
Cite this article
Tomitsuka, E., Igai, K., Tadokoro, K. et al. Profiling of faecal water and urine metabolites among Papua New Guinea highlanders believed to be adapted to low protein intake. Metabolomics 13, 105 (2017). https://doi.org/10.1007/s11306-017-1243-6
- Gut microbiota