Fecal menaquinone profiles of overweight adults are associated with gut microbiota composition during a gut microbiota–targeted dietary intervention
Open accessAbstract
Background Emerging evidence supports novel roles for vitamin K in cardiometabolic health, some of which may be unique to the bacterially synthesized vitamin K forms known as menaquinones. However, factors influencing menaquinone biosynthesis by the gut microbiota and associations with cardiometabolic health have not been examined.Objective The objective of this study was to identify associations between fecal menaquinone profiles, gut microbiota composition, and biomarkers of cardiometabolic health.Design The menaquinone profile and gut microbiota structure were periodically measured in fecal samples collected from 77 overweight Chinese adults who consumed a prescribed diet previously shown to alter gut microbiota composition and to improve cardiometabolic biomarkers.Results Covariance among menaquinones within individual fecal samples partitioned individuals into 2 distinct groups, herein introduced as menaquinotypes of the human gut. Menaquinotypes were characterized by differences in menaquinone (MK) 5 and MK9-MK13 and differences in the relative abundance of several operational taxonomic units (OTUs) delineated at the species level, predominantly within the genera Prevotella spp. and Bacteroides spp. Fecal MK4, MK6, and MK8 decreased during the intervention (P < 0.05); and longitudinal changes in the relative abundance of >100 OTUs were associated with altered fecal content of ≥1 individual menaquinone. The strongest and most consistent relations were between Prevotella spp. and MK5 and MK11-MK13, between Bacteroides spp. and MK9 and MK10, and between Escherichia/Shigella spp. and MK8. Neither individual menaquinones nor menaquinotypes were longitudinally associated with markers of glycemia, insulin resistance, or inflammation.Conclusions These findings suggest that variability in fecal menaquinone content is predominantly determined by relatively few genera within the gut microbiota and that diet-mediated alterations in gut microbiota composition may provide a feasible approach for altering gut menaquinone content. This trial was registered at the Chinese Clinical Trials Registry as ChiCTR-TRC-09000353.
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Fecal menaquinone levels have been correlated with the abundance of Prevotella and Bacteroides species and are susceptible to microbiome-targeted diets.
“Fecal menaquinone levels have been correlated with the abundance of Prevotella and Bacteroides species and are susceptible to microbiome-targeted diets32, suggesting that menaquinol could represent an early marker of nonresponse that is amenable to dietary intervention.”
From Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma (2024) · cites this paper as [32]
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Cites
Naive Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial Taxonomy
Wang, Q., Garrity, G. M., Tiedje, J. M., & Cole, J. R. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.00062-07 · Cited by 19,770 · see citing works
Metagenomic biomarker discovery and explanation
Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W. S., & Huttenhower, C. (2011) · Genome Biology · doi:10.1186/gb-2011-12-6-r60 · Cited by 16,192 · see citing works
Structure, function and diversity of the healthy human microbiome
The Human Microbiome Project Consortium (2012) · Nature · doi:10.1038/nature11234 · Cited by 11,726 · see citing works
Enterotypes of the human gut microbiome
MetaHIT Consortium (additional members), Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D. R., Fernandes, G. R., Tap, J., Bruls, T., et al. (2011) · Nature · doi:10.1038/nature09944 · Cited by 7,548 · see citing works
ARB: a software environment for sequence data
Ludwig, W. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh293 · Cited by 6,649 · see citing works
Linking long-term dietary patterns with gut microbial enterotypes
Wu, G. D., Chen, J., Hoffmann, C., Bittinger, K., Chen, Y.-Y., Keilbaugh, S. A., Bewtra, M., Knights, D., Walters, W. A., Knight, R., et al. (2011) · Science · doi:10.1126/science.1208344 · Cited by 6,513 · see citing works
TM4: a free, open-source system for microarray data management and analysis
Saeed, A. I., Sharov, V., White, J., Li, J., Liang, W., Bhagabati, N., Braisted, J., Klapa, M., Currier, T., Thiagarajan, M., et al. (2003) · BioTechniques · doi:10.2144/03342mt01 · Cited by 4,837 · see citing works
Host-gut microbiota metabolic interactions
Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., & Pettersson, S. (2012) · Science · doi:10.1126/science.1223813 · Cited by 4,760 · see citing works
Frank, D. N., St. Amand, A. L., Feldman, R. A., Boedeker, E. C., Harpaz, N., & Pace, N. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706625104 · Cited by 4,611 · see citing works
Caspi, R., Billington, R., Ferrer, L., Foerster, H., Fulcher, C. A., Keseler, I. M., Kothari, A., Krummenacker, M., Latendresse, M., Mueller, L. A., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1164 · Cited by 3,395 · see citing works
Schloss, P. D., & Handelsman, J. (2005) · Applied and Environmental Microbiology · doi:10.1128/aem.71.3.1501-1506.2005 · Cited by 2,503 · see citing works
Distribution of isoprenoid quinone structural types in bacteria and their taxonomic implication
Collins, M. D., & Jones, D. A. (1981) · Microbiological Reviews · doi:10.1128/mr.45.2.316-354.1981 · Cited by 1,457 · see citing works
Caspi, R., Altman, T., Billington, R., Dreher, K., Foerster, H., Fulcher, C. A., Holland, T. A., Keseler, I. M., Kothari, A., Kubo, A., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1103 · Cited by 1,204 · see citing works
Intestinal permeability: an overview
Bjarnason, I., Macpherson, A., & Hollander, D. (1995) · Gastroenterology · doi:10.1016/0016-5085(95)90708-4 · Cited by 927 · see citing works
Goodman, A. L., Kallstrom, G., Faith, J. J., Reyes, A., Moore, A. M., Dantas, G. A., & Gordon, J. I. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102938108 · Cited by 779 · see citing works
An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice
Fei, N., & Zhao, L.-P. (2012) · The ISME Journal · doi:10.1038/ismej.2012.153 · Cited by 713 · see citing works
Self-citationGeleijnse, J. M., Vermeer, C., Grobbee, D. E., Schurgers, L. J., Knapen, M. H. J., van der Meer, I. M., Albert Hofman, D., & Witteman, J. C. M. (2004) · Journal of Nutrition · doi:10.1093/jn/134.11.3100 · Cited by 563 · see citing works
Koren, O., Knights, D., Gonzalez, A., Waldron, L., Segata, N., Knight, R., Huttenhower, C., & Ley, R. E. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002863 · Cited by 508 · see citing works
Biosynthesis of vitamin K (menaquinone) in bacteria
Bentley, R., & Meganathan, R. (1982) · Microbiological Reviews · doi:10.1128/mr.46.3.241-280.1982 · Cited by 500 · see citing works
Metabolism and cell biology of vitamin K
Newman, P., & Shearer, M. J. (2008) · Thrombosis and Haemostasis · doi:10.1160/th08-03-0147 · Cited by 465 · see citing works
Schurgers, L. J., Teunissen, K. J. F., Hamulyák, K., Knapen, M. H. J., Vik, H., & Vermeer, C. (2006) · Blood · doi:10.1182/blood-2006-08-040709 · Cited by 424 · see citing works
Determination of Phylloquinone and Menaquinones in Food
Schurgers, L. J., & Vermeer, C. (2000) · Pathophysiology of Haemostasis and Thrombosis · doi:10.1159/000054147 · Cited by 397 · see citing works
Xiao, S., Fei, N., Pang, X., Shen, J., Wang, L., Zhang, B., Zhang, M. H., Zhang, X., Zhang, C., Li, M., et al. (2013) · FEMS Microbiology Ecology · doi:10.1111/1574-6941.12228 · Cited by 376 · see citing works
Self-citationShea, M. K., Booth, S. L., Massaro, J. M., Jacques, P. F., D'Agostino, R. B., Dawson-Hughes, B., Ordovas, J. M., O'Donnell, C. J., Kathiresan, S., Keaney, J. F., et al. (2007) · American Journal of Epidemiology · doi:10.1093/aje/kwm306 · Cited by 316 · see citing works
Self-citationA high menaquinone intake reduces the incidence of coronary heart disease
Herber-Gast, G.-C. M., de Roos, N. M., Sluijs, I., Bots, M. L., Beulens, J. W. J., Geleijnse, J. M., Witteman, J. C. M., Grobbee, D. E., Peeters, P. H. M., & van der Schouw, Y. T. (2009) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2008.10.004 · Cited by 279 · see citing works
Walther, B., Karl, J. P., Booth, S. L., & Boyaval, P. (2013) · Advances in Nutrition · doi:10.3945/an.113.003855 · Cited by 271 · see citing works
Self-citationConversion of Phylloquinone (Vitamin K1) into Menaquinone-4 (Vitamin K2) in Mice
Okano, T., Shimomura, Y., Yamane, M., Suhara, Y., Kamao, M., Sugiura, M., & Nakagawa, K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702971200 · Cited by 263 · see citing works
Roles for Vitamin K Beyond Coagulation
Booth, S. L. (2009) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-080508-141217 · Cited by 259 · see citing works
Self-citationHigh dietary menaquinone intake is associated with reduced coronary calcification
Beulens, J. W. J., Bots, M. L., Atsma, F., Bartelink, M.-L. E. L., Prokop, M., Geleijnse, J. M., Witteman, J. C. M., Grobbee, D. E., & van der Schouw, Y. T. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.07.010 · Cited by 258 · see citing works
The Importance of Menaquinones in Human Nutrition
Suttie, J. W. (1995) · Annual Review of Nutrition · doi:10.1146/annurev.nu.15.070195.002151 · Cited by 231 · see citing works
Mucosa-Associated Bacterial Diversity in Relation to Human Terminal Ileum and Colonic Biopsy Samples
Ahmed, S., Macfarlane, G. T., Fite, A., McBain, A. J., Gilbert, P., & Macfarlane, S. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.01143-07 · Cited by 227 · see citing works
Shearer, M. J., & Newman, P. (2014) · Journal of Lipid Research · doi:10.1194/jlr.r045559 · Cited by 220 · see citing works
Vitamin K: food composition and dietary intakes
Booth, S. L. (2012) · Food & Nutrition Research · doi:10.3402/fnr.v56i0.5505 · Cited by 211 · see citing works
Self-citationPrevotella copri sp. nov. and Prevotella stercorea sp. nov., isolated from human faeces
Hayashi, H., Shibata, K., Sakamoto, M., Tomita, S., & Benno, Y. (2007) · INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY · doi:10.1099/ijs.0.64778-0 · Cited by 183 · see citing works
Dietary Phylloquinone and Menaquinones Intakes and Risk of Type 2 Diabetes
Beulens, J. W. J., van der A, D. L., Grobbee, D. E., Sluijs, I., Spijkerman, A. M. W., & van der Schouw, Y. T. (2010) · Diabetes Care · doi:10.2337/dc09-2302 · Cited by 177 · see citing works
Production of Menaquinones by Intestinal Anaerobes
Ramotar, K., Conly, J. M., Chubb, H., & Louie, T. (1984) · The Journal of Infectious Diseases · doi:10.1093/infdis/150.2.213 · Cited by 164 · see citing works
Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women
Sato, T., Schurgers, L. J., & Uenishi, K. (2012) · Nutrition Journal · doi:10.1186/1475-2891-11-93 · Cited by 161 · see citing works
Vitamin K concentrations in the plasma and liver of surgical patients
Usui, Y., Tanimura, H., Nishimura, N., et al. (1990) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/51.5.846 · Cited by 150 · see citing works
Schurgers, L. J., Shearer, M. J., Hamulyák, K., Stöcklin, E., & Vermeer, C. (2004) · Blood · doi:10.1182/blood-2004-04-1525 · Cited by 149 · see citing works
Conly, J. M., & Stein, K. (1993) · PubMed · Cited by 141 · see citing works
Vitamin K, an emerging nutrient in brain function
Ferland, G. (2012) · BioFactors · doi:10.1002/biof.1004 · Cited by 124 · see citing works
Phylloquinone intake, insulin sensitivity, and glycemic status in men and women
Yoshida, M., Booth, S. L., Meigs, J. B., Saltzman, E. J., & Jacques, P. F. (2008) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/88.1.210 · Cited by 110 · see citing works
Self-citationVitamin K, circulating cytokines, and bone mineral density in older men and women
Shea, M. K., Dallal, G. E., Dawson-Hughes, B. F., Ordovás, J. M., O’Donnell, C. J., Gundberg, C. M., Peterson, J. W., & Booth, S. L. (2008) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/88.2.356 · Cited by 103 · see citing works
Self-citationKarl, J. P., Fu, X., Dolnikowski, G. G., Saltzman, E. J., & Booth, S. L. (2014) · Journal of Chromatography B · doi:10.1016/j.jchromb.2014.05.056 · Cited by 86 · see citing works
Self-citationQuantitative and qualitative measurements of K vitamins in human intestinal contents.
Conly, J. M., & Stein, K. (1992) · PubMed · Cited by 74 · see citing works
An Overview of Clustering Applied to Molecular Biology
Nugent, R., & Meilă, M. (2009) · Methods in molecular biology · doi:10.1007/978-1-60761-580-4_12 · Cited by 69 · see citing works
VITAMIN K in Health and Disease
Suttie, J. W. (2009) · CRC Press eBooks · doi:10.1201/9781420005110 · Cited by 59 · see citing works
Shea, M. K., Booth, S. L., Miller, M. E., et al. (2013) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.056101 · Cited by 58 · see citing works
Self-citationSAKANO, T., Nagaoka, T., Morimoto, A., et al. (1986) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.34.4322 · Cited by 55 · see citing works
Vitamin K composition of anaerobic gut bacteria
Fernandez, F., & Collins, M. D. (1987) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1987.tb02191.x · Cited by 54 · see citing works
Akiyama, Y., Hara, K., Matsumoto, A., et al. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(94)00531-p · Cited by 36 · see citing works
Vitamin K in Health and Disease
Suttie, J. W. (2009) · CRC Press eBooks · doi:10.1201/9780849333927 · Cited by 13 · see citing works
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- Authors
- Karl, J. P., Fu, X., Wang, X., Zhao, Y., Shen, J., Zhang, C., Wolfe, B. E., Saltzman, E., Zhao, L., & Booth, S. L.
- Affiliations
- Tufts University (US)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Zhao, Liping
- Booth, Sarah L
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 102
- Issue
- 1
- Pages
- 84-93
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W1946608667
- Cited by
- 53
- References
- 52
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 7 · 2023: 9 · 2022: 7 · 2021: 2 · 2020: 6 · 2019: 6 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 1
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Nature Science Foundation of China (2008AA02Z315, 2009AA02Z310)
- International Cooperation Program (2007DFC30450, 075407001)
- National Science, and Technology Pillar Program (2006BAI11B08)
- USDA (58-1950-7-707)
- Dr. James Sadowski Memorial Internship
- Science, Mathematics, and Research Transformation Defense Education Program
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin K Research Studies
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- vitamin K2, vitamin K, gut microbiota, overweight adults, Prevotella, Bacteroides, Escherichia-Shigella, cardiometabolic health, insulin resistance, inflammation, glycemia, menaquinone biosynthesis
- MeSH terms
- Adult, Bacteroides, Cross-Sectional Studies, Diet, Feces, Female, Humans, Longitudinal Studies, Male, Middle Aged, Body Mass Index, Prevotella, Vitamin K 2, Gastrointestinal Tract, Asian People, Overweight, Waist Circumference, Young Adult, Microbiota
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