Profiling of faecal water and urine metabolites among Papua New Guinea highlanders believed to be adapted to low protein intake
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.
KeywordsGut microbiota Metabolomics CE-TOFMS
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.
Compliance with ethical standards
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.
- 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.Google Scholar
- 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.CrossRefGoogle Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- Eben, H., Clements, F. W. (1947). Report of the New Guinea Nutrition Survey Expedition.Google Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- Hipsley, E. H., & Clements, F. W. (1950). Reports of the New Guinea nutrition expedition 1947. Canberra: Department of External Territories.Google Scholar
- 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.Google Scholar
- 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.CrossRefPubMedGoogle Scholar
- Ministry of Health, Labour and Welfare in Japan. (2015). Annual report of National Health and Nutrition Survey.Google Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.Google Scholar
- Oomen, H. A. (1961). The nutrition situation in western New Guinea. Tropical and Geographical Medicine, 3, 321–335.Google Scholar
- 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.CrossRefPubMedGoogle Scholar
- WHO/FAO/UNU. (2007). Protein and amino acid requirements in human nutrition. World Health Organization Technical Report Series, 935, 1–265.Google Scholar