Diet-Microbiome Interactions in Health Are Controlled by Intestinal Nitrogen Source Constraints
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Diet influences health and patterns of disease in populations. How different diets do this and why outcomes of diets vary between individuals are complex and involve interaction with the gut microbiome. A major challenge for predicting health outcomes of the host-microbiome dynamic is reconciling the effects of different aspects of diet (food composition or intake rate) on the system. Here we show that microbial community assembly is fundamentally shaped by a dichotomy in bacterial strategies to access nitrogen in the gut environment. Consequently, the pattern of dietary protein intake constrains the host-microbiome dynamic in ways that are common to a very broad range of diet manipulation strategies. These insights offer a mechanism for the impact of high protein intake on metabolic health and form the basis for a general theory of the impact of different diet strategies on host-microbiome outcomes.
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Bacteria compete for carbon and nitrogen sources that are essential to support their growth within the intestine.
“Bacteria compete for carbon and nitrogen sources that are essential to support their growth within the intestine [66–68].”
From Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization (2023) · cites this paper as [66]
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The interplay between PCOS pathology and diet on gut microbiota in a mouse model
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Gastrointestinal Microbiota in Patients with Chronic Kidney Disease: A Systematic Review
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Couteur, D. G. L., Solon‐Biet, S. M., Parker, B. L., Pulpitel, T., Brandon, A. E., Hunt, N. J., Wali, J. A., Gokarn, R., Senior, A. M., Cooney, G. J., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.10.016 · Cited by 69 · see citing works
Self-citationIngestion of resistant starch by mice markedly increases microbiome‐derived metabolites
Koay, Y. C., Wali, J. A., Luk, A. W. S., Macia, L., Cogger, V. C., Pulpitel, T., Wahl, D., Solon‐Biet, S. M., Holmes, A. J., Simpson, S. J., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900177r · Cited by 66 · see citing works
Self-citationProtein appetite as an integrator in the obesity system: the protein leverage hypothesis
Raubenheimer, D., & Simpson, S. J. (2023) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2022.0212 · Cited by 68 · see citing works
Self-citationGarcía-Gutiérrez, E., O’Connor, P. M., Colquhoun, I. J., Vior, N. M., Rodríguez, J. M., Mayer, M. J., Cotter, P. D., & Narbad, A. (2020) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-020-10493-3 · Cited by 60 · see citing works
Gut Microbiota and Lung Injury
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Whelan, K., Alexander, M., Gaïani, C., Lunken, G., Holmes, A. J., Staudacher, H. M., Theis, S., & Marco, M. L. (2024) · Nature Microbiology · doi:10.1038/s41564-024-01831-6 · Cited by 63 · see citing works
Self-citationDing, S., Ma, Y., Liu, G., Yan, W., Jiang, H., & Fang, J. Q. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01152 · Cited by 58 · see citing works
Shanahan, E. R., McMaster, J. J., & Staudacher, H. M. (2021) · Journal of Human Nutrition and Dietetics · doi:10.1111/jhn.12868 · Cited by 58 · see citing works
Dietary carbohydrates regulate intestinal colonization and dissemination of Klebsiella pneumoniae
Hecht, A. L., Harling, L. C., Friedman, E. S., Tanes, C., Lee, J., Firrman, J., Hao, F., Tu, V., Liu, L., Patterson, A. D., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci174726 · Cited by 57 · see citing works
Muthuramalingam, K., Singh, V., Choi, C., Choi, S. I., Kim, Y. M., Unno, T., & Cho, M. (2019) · European Journal of Nutrition · doi:10.1007/s00394-019-02110-5 · Cited by 56 · see citing works
Towards an Integrative Understanding of Diet–Host–Gut Microbiome Interactions
Read, M. N., & Holmes, A. J. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00538 · Cited by 54 · see citing works
Self-citationSpring, S., Premathilake, H., DeSilva, U., Shili, C. N., Carter, S., & Pezeshki, A. (2020) · Scientific Reports · doi:10.1038/s41598-020-60150-y · Cited by 55 · see citing works
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An integrative approach to dietary balance across the life course
Raubenheimer, D., Senior, A. M., Mirth, C. K., Cui, Z., Hou, R., Couteur, D. G. L., Solon‐Biet, S. M., Léopold, P., & Simpson, S. J. (2022) · iScience · doi:10.1016/j.isci.2022.104315 · Cited by 50 · see citing works
Self-citationJackson, R., Yao, T., Bulut, N., Cantu-Jungles, T. M., & Hamaker, B. R. (2024) · Food & Function · doi:10.1039/d3fo04187e · Cited by 45 · see citing works
The nutritional geometry of liver disease including non-alcoholic fatty liver disease
Simpson, S. J., Raubenheimer, D., Cogger, V. C., Macia, L., Solon‐Biet, S. M., Couteur, D. G. L., & George, J. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.10.005 · Cited by 42 · see citing works
Self-citationModels of the Gut for Analyzing the Impact of Food and Drugs
Fois, C. A. M., Le, T. Y. L., Schindeler, A., Naficy, S., McClure, D. D., Read, M. N., Valtchev, P., Khademhosseini, A., & Dehghani, F. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201900968 · Cited by 41 · see citing works
Self-citationSteinke, I., Ghanei, N., Govindarajulu, M., Yoo, S., Zhong, J., & Amin, R. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.567899 · Cited by 42 · see citing works
Wali, J. A., Raubenheimer, D., Senior, A. M., Couteur, D. G. L., & Simpson, S. J. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa136 · Cited by 40 · see citing works
Self-citationBadri, D. V., Jackson, M. I., & Jewell, D. E. (2021) · Journal of Nutrition · doi:10.1093/jn/nxab308 · Cited by 38 · see citing works
Hamamah, S., Iatcu, O. C., & Covașă, M. (2024) · Nutrients · doi:10.3390/nu16020269 · Cited by 38 · see citing works
Strategies to increase the efficacy of using gut microbiota for the modulation of obesity
Li, J., Rajoka, M. S. R., Shao, D., Jiang, C., Jin, M., Huang, Q., Yang, H., & Shi, J. (2017) · Obesity Reviews · doi:10.1111/obr.12590 · Cited by 35 · see citing works
Ultra-sensitive isotope probing to quantify activity and substrate assimilation in microbiomes
Kleiner, M., Kouris, A., Violette, M. J., D’Angelo, G., Liu, Y., Korenek, A., Tolić, N., Sachsenberg, T. T., McCalder, J., Lipton, M. S. W., et al. (2023) · Microbiome · doi:10.1186/s40168-022-01454-1 · Cited by 34 · see citing works
Dominique, M., Breton, J., Guérin, C., Bôle‐Feysot, C., Lambert, G., Déchelotte, P., & Fetissov, S. O. (2019) · Nutrients · doi:10.3390/nu11092115 · Cited by 33 · see citing works
Nutrient pollution alters the gut microbiome of a territorial reef fish
Degregori, S., Casey, J. M., & Barber, P. H. (2021) · Marine Pollution Bulletin · doi:10.1016/j.marpolbul.2021.112522 · Cited by 33 · see citing works
Exploring Interactions between the Gut Microbiota and Social Behavior through Nutrition
Pasquaretta, C., Gómez‐Moracho, T., Heeb, P., & Lihoreau, M. (2018) · Genes · doi:10.3390/genes9110534 · Cited by 31 · see citing works
Cui, Z., Holmes, A. J., Zhang, W., Hu, D., Qi, S. H. A. O., Wang, Z., Lu, J., & Raubenheimer, D. (2021) · Integrative Zoology · doi:10.1111/1749-4877.12601 · Cited by 30 · see citing works
Self-citationTan, J., Ribeiro, R. V., Barker, C., Daïen, C., Silveira, E. D. A., Holmes, A. J., Nanan, R. K. H., Simpson, S. J., & Macia, L. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2274127 · Cited by 31 · see citing works
Self-citationThe infant gut microbiota: in pursuit of non-protein nitrogen
Schimmel, P., Stahl, B., Knol, J., & Belzer, C. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2211917 · Cited by 28 · see citing works
Breast milk urea as a nitrogen source for urease positiveBifidobacterium infantis
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The role of rumen epithelial urea transport proteins in urea nitrogen salvage: A review
Zhong, C., Long, R., & Stewart, G. S. (2022) · Animal nutrition · doi:10.1016/j.aninu.2022.01.008 · Cited by 28 · see citing works
The geometry of resource constraint: An empirical study of the golden snub‐nosed monkey
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The Gut Microbiome on a Periodized Low-Protein Diet Is Associated With Improved Metabolic Health
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Modulatory Effect of Protein and Carotene Dietary Levels on Pig gut Microbiota
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The Interplay of Nutrition, the Gut Microbiota and Immunity and Its Contribution to Human Disease
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Role of gut microbe-derived metabolites in cardiometabolic diseases: Systems based approach
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- Authors
- Holmes, A. J., Chew, Y. V., Colakoglu, F., Cliff, J. B., Klaassens, E., Read, M. N., Solon-Biet, S. M., McMahon, A. C., Cogger, V. C., Ruohonen, K., Raubenheimer, D., Le Couteur, D. G., & Simpson, S. J.
- Affiliations
- The University of Sydney (AU)
- The University of Western Australia (AU)
- Ewos Innovation (Norway) (NO)
- Corresponding author
- Holmes, Andrew J.
- Simpson, Stephen J.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 25
- Issue
- 1
- Pages
- 140-151
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2550352184
- Cited by
- 183
- References
- 44
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 14 · 2023: 15 · 2022: 21 · 2021: 25 · 2020: 25 · 2019: 26 · 2018: 15 · 2017: 13 · 2016: 1
- FWCI
- 9.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- Australian National Health and Medical Research Council
- NHMRC (571328, 1026209)
- Ageing and Alzheimers Research Fund of Concord RG Hospital
- Sydney Medical School Foundation
- Australian Research Council Laureate Fellowship
- National Research Centre for Growth and Development, New Zealand
- Australian Microscopy and Microanalysis Research Facility (AMMRF)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- diet-microbiome interactions, protein intake, metabolic health, food composition, ingestion rate
- MeSH terms
- Animals, Bacteria, Computer Simulation, Diet, Dietary Carbohydrates, Dietary Proteins, Energy Metabolism, Food, Health, Intestinal Mucosa, Intestines, Mice, Inbred BALB C, Mice, Inbred C57BL, Mucins, Nitrogen, Spectrometry, Mass, Secondary Ion, Biodiversity, Microbiota
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