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Anoxic Conditions Promote Species-Specific Mutualism between Gut Microbes In Silico
Open accessAbstract
The human gut is inhabited by thousands of microbial species, most of which are still uncharacterized. Gut microbes have adapted to each other's presence as well as to the host and engage in complex cross feeding. Constraint-based modeling has been successfully applied to predicting microbe-microbe interactions, such as commensalism, mutualism, and competition. Here, we apply a constraint-based approach to model pairwise interactions between 11 representative gut microbes. Microbe-microbe interactions were computationally modeled in conjunction with human small intestinal enterocytes, and the microbe pairs were subjected to three diets with various levels of carbohydrate, fat, and protein in normoxic or anoxic environments. Each microbe engaged in species-specific commensal, parasitic, mutualistic, or competitive interactions. For instance, Streptococcus thermophilus efficiently outcompeted microbes with which it was paired, in agreement with the domination of streptococci in the small intestinal microbiota. Under anoxic conditions, the probiotic organism Lactobacillus plantarum displayed mutualistic behavior toward six other species, which, surprisingly, were almost entirely abolished under normoxic conditions. This finding suggests that the anoxic conditions in the large intestine drive mutualistic cross feeding, leading to the evolvement of an ecosystem more complex than that of the small intestinal microbiota. Moreover, we predict that the presence of the small intestinal enterocyte induces competition over host-derived nutrients. The presented framework can readily be expanded to a larger gut microbial community. This modeling approach will be of great value for subsequent studies aiming to predict conditions favoring desirable microbes or suppressing pathogens.
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“In polymicrobial environments, Lactobacilli engage in advantageous, mutualistic interactions with other bacteria to survive under hypoxia and alter NO generation[217,413]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [413]
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Cites
Dermyshi, E., Wang, Y., Yan, C., Hong, W., Qiu, G., Gong, X., & Zhang, T. (2017) · Neonatology · doi:10.1159/000454668 · Cited by 24,586
A human gut microbial gene catalogue established by metagenomic sequencing
MetaHIT Consortium, Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., et al. (2010) · Nature · doi:10.1038/nature08821 · Cited by 11,624
Diversity of the Human Intestinal Microbial Flora
Eckburg, P. B., Bik, E. M., Bernstein, C. N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S. R., Nelson, K. E., & Relman, D. A. (2005) · Science · doi:10.1126/science.1110591 · Cited by 7,913
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
What is flux balance analysis?
Orth, J. D., Thiele, I., & Palsson, B. Ø. (2010) · Nature Biotechnology · doi:10.1038/nbt.1614 · Cited by 3,903
Self-citationQuantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0
Schellenberger, J., Que, R., Fleming, R. M. T., Thiele, I., Orth, J. D., Feist, A. M., Zielinski, D. C., Bordbar, A., Lewis, N. E., Rahmanian, S., et al. (2011) · Nature Protocols · doi:10.1038/nprot.2011.308 · Cited by 1,835
Self-citationH OW H OST -M ICROBIAL I NTERACTIONS S HAPE THE N UTRIENT E NVIRONMENT OF THE M AMMALIAN I NTESTINE
Hooper, L. V., Midtvedt, T., & Gordon, J. I. (2002) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.22.011602.092259 · Cited by 1,623
The influence of diet on the gut microbiota
Scott, K. P., Gratz, S. W., Sheridan, P. O., Flint, H. J., & Duncan, S. H. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2012.10.020 · Cited by 1,052
Bacteria, Colonic Fermentation, and Gastrointestinal Health
Macfarlane, G. T., & Macfarlane, S. (2012) · Journal of AOAC INTERNATIONAL · doi:10.5740/jaoacint.sge_macfarlane · Cited by 970
Belenguer, A., Duncan, S. H., Calder, A. G., Holtrop, G., Louis, P., Lobley, G. E., & Flint, H. J. (2006) · Applied and Environmental Microbiology · doi:10.1128/aem.72.5.3593-3599.2006 · Cited by 856
Recognition and Degradation of Plant Cell Wall Polysaccharides by Two Human Gut Symbionts
Martens, E. C., Lowe, E. C., Chiang, H. C., Pudlo, N. A., Wu, M., McNulty, N. P., Abbott, D. W., Henrissat, B., Gilbert, H. J., Bolam, D. N., et al. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001221 · Cited by 847
Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla
Mahowald, M. A., Rey, F. E., Seedorf, H., Turnbaugh, P. J., Fulton, R. S., Wollam, A., Shah, N., Wang, C., Magrini, V. J., Wilson, R. K., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901529106 · Cited by 752
Duncan, S. H., Barcenilla, A., Stewart, C. S., Pryde, S. E., & Flint, H. J. (2002) · Applied and Environmental Microbiology · doi:10.1128/aem.68.10.5186-5190.2002 · Cited by 743
Zoetendal, E. G., Raes, J., van den Bogert, B., Arumugam, M., Booijink, C. C. G. M., Troost, F. J., Bork, P., Wels, M., de Vos, W. M., & Kleerebezem, M. (2012) · The ISME Journal · doi:10.1038/ismej.2011.212 · Cited by 722
A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism
Samuel, B. S., & Gordon, J. I. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602187103 · Cited by 674
Flint, H. J., Duncan, S. H., Scott, K. P., & Louis, P. (2007) · Environmental Microbiology · doi:10.1111/j.1462-2920.2007.01281.x · Cited by 632
Monostrain, multistrain and multispecies probiotics—A comparison of functionality and efficacy
Timmerman, H. M., Koning, C. J. M., Mulder, L., Rombouts, F. M., & Beynen, A. C. (2004) · International Journal of Food Microbiology · doi:10.1016/j.ijfoodmicro.2004.05.012 · Cited by 631
Synthetic microbial communities
Großkopf, T., & Soyer, O. S. (2014) · Current Opinion in Microbiology · doi:10.1016/j.mib.2014.02.002 · Cited by 585
Competitive and cooperative metabolic interactions in bacterial communities
Freilich, S., Zarecki, R., Eilam, O., Segal, E. S., Henry, C. S., Kupiec, M., Gophna, U., Sharan, R., & Ruppin, E. (2011) · Nature Communications · doi:10.1038/ncomms1597 · Cited by 557
Dysbiosis in inflammatory bowel diseases: the oxygen hypothesis
Rigottier‐Gois, L. (2013) · The ISME Journal · doi:10.1038/ismej.2013.80 · Cited by 451
Multidimensional Optimality of Microbial Metabolism
Schuetz, R., Zamboni, N., Zampieri, M., Heinemann, M., & Sauer, U. (2012) · Science · doi:10.1126/science.1216882 · Cited by 420 · cited 1×
“Although the presented framework currently limits Pareto optimality analysis to two biomass functions, it is possible to compute the trade-offs for three or more competing objectives using constraint-based methods (48), which may lead to novel insights into multispecies interactions.”
BackgroundDissecting the in Vivo Metabolic Potential of Two Human Gut Acetogens
Rey, F. E., Faith, J. J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Newgard, C. B., & Gordon, J. I. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.117713 · Cited by 417
Levy, R., & Borenstein, E. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300926110 · Cited by 413
Zomorrodi, A. R., & Maranas, C. D. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002363 · Cited by 408
Espey, M. G. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.10.554 · Cited by 396
He, G., Shankar, R. A., Chzhan, M., Samouilov, A., Kuppusamy, P., & Zweier, J. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.8.4586 · Cited by 383
Faith, J. J., Ahern, P. P., Ridaura, V. K., Cheng, J., & Gordon, J. I. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008051 · Cited by 373
Computationally efficient flux variability analysis
Guðmundsson, S., & Thiele, I. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-489 · Cited by 360
Emergent cooperation in microbial metabolism
Wintermute, E. H., & Silver, P. A. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.66 · Cited by 347
Environments that Induce Synthetic Microbial Ecosystems
Klitgord, N., & Segrè, D. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1001002 · Cited by 337
Zhuang, K. H., Izallalen, M., Mouser, P., Richter, H., Risso, C., Mahadevan, R., & Lovley, D. R. (2010) · The ISME Journal · doi:10.1038/ismej.2010.117 · Cited by 328
Teusink, B., Wiersma, A., Molenaar, D., Francke, C., de Vos, W. M., Siezen, R. J., & Smid, E. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606263200 · Cited by 284
Monk, J. M., Charusanti, P., Aziz, R. K., Lerman, J. A., Premyodhin, N., Orth, J. D., Feist, A. M., & Palsson, B. Ø. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307797110 · Cited by 284
Newell, P. D., & Douglas, A. E. (2013) · Applied and Environmental Microbiology · doi:10.1128/aem.02742-13 · Cited by 278
Large-scale reconstruction and phylogenetic analysis of metabolic environments
Borenstein, E., Kupiec, M., Feldman, M. W., & Ruppin, E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806162105 · Cited by 246
Functional Metabolic Map of Faecalibacterium prausnitzii, a Beneficial Human Gut Microbe
Heinken, A., Khan, M. T., Paglia, G., Rodionov, D. A., Harmsen, H. J. M., & Thiele, I. (2014) · Journal of Bacteriology · doi:10.1128/jb.01780-14 · Cited by 244
Thiele, I., Vo, T. D., Price, N. D., & Palsson, B. Ø. (2005) · Journal of Bacteriology · doi:10.1128/jb.187.16.5818-5830.2005 · Cited by 229
Systems-level characterization of a host-microbe metabolic symbiosis in the mammalian gut
Heinken, A., Sahoo, S., Fleming, R. M. T., & Thiele, I. (2013) · Gut Microbes · doi:10.4161/gmic.22370 · Cited by 225
Marzorati, M., Vanhoecke, B. W. A., Ryck, T. D., Sadabad, M. S., Pinheiro, I., Possemiers, S., den Abbeele, P. V., Derycke, L., Bracke, M., Pieters, J., et al. (2014) · BMC Microbiology · doi:10.1186/1471-2180-14-133 · Cited by 208
A road map for the development of community systems (CoSy) biology
Zengler, K., & Palsson, B. Ø. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2763 · Cited by 189
Ethanol metabolism and its effects on the intestinal epithelial barrier
Elamin, E. E., Masclee, A., Dekker, J. P., & Jonkers, D. M. A. E. (2013) · Nutrition Reviews · doi:10.1111/nure.12027 · Cited by 188
From meta-omics to causality: experimental models for human microbiome research
Fritz, J. V., Desai, M. S., Shah, P., Schneider, J. G., & Wilmes, P. (2013) · Microbiome · doi:10.1186/2049-2618-1-14 · Cited by 181
The gut microbiota and the metabolic health of the host
Joyce, S. A., & Gahan, C. G. M. (2014) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000039 · Cited by 147
Thiele, I., Hyduke, D. R., Steeb, B., Fankam, G., Allen, D. K., Bazzani, S., Charusanti, P., Chen, F., Fleming, R. M. T., Hsiung, C. A., et al. (2011) · BMC Systems Biology · doi:10.1186/1752-0509-5-8 · Cited by 141
Chassard, C., & Bernalier‐Donadille, A. (2005) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2005.00016.x · Cited by 131
Flahaut, N. A. L., Wiersma, A., van de Bunt, B., Martens, D. E., Schaap, P. J., Sijtsma, L., dos Santos, V. A. P. M., & de Vos, W. M. (2013) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-013-5140-2 · Cited by 131
Pastink, M. I., Teusink, B., Pascal Hols, A., Visser, S., de Vos, W. M., & Hugenholtz, J. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.00138-09 · Cited by 129
Liao, Y.-C., Huang, T., Chen, F.-C., Charusanti, P., Hong, J. S.-J., Chang, H., Tsai, S., Palsson, B. Ø., & Hsiung, C. A. (2011) · Journal of Bacteriology · doi:10.1128/jb.01218-10 · Cited by 121
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Thiele, I., Heinken, A., & Fleming, R. M. (2013) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2012.10.001 · Cited by 114
Heinken, A., & Thiele, I. (2015) · Gut Microbes · doi:10.1080/19490976.2015.1023494 · Cited by 107
Marteyn, B., Scorza, F. B., Sansonetti, P. J., & Tang, C. (2011) · Cellular Microbiology · doi:10.1111/j.1462-5822.2010.01549.x · Cited by 102
Manor, O., Levy, R., & Borenstein, E. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.07.021 · Cited by 84
Colonization Resistance: Battle of the Bugs or Ménage à Trois with the Host?
Spees, A. M., Lopez, C. A., Kingsbury, D. D., Winter, S., & Bäumler, A. J. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003730 · Cited by 78
The evolution of metabolic networks of E. coli
Baumler, D. J., Peplinski, R. G., Reed, J. L., Glasner, J. D., & Perna, N. T. (2011) · BMC Systems Biology · doi:10.1186/1752-0509-5-182 · Cited by 73
Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells
Sahoo, S., & Thiele, I. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt119 · Cited by 70
The design of long‐term effective uranium bioremediation strategy using a community metabolic model
Zhuang, K. H., Ma, E., Lovley, D. R., & Mahadevan, R. (2012) · Biotechnology and Bioengineering · doi:10.1002/bit.24528 · Cited by 62
Thiele, I., Fleming, R. M. T., Bordbar, A., Schellenberger, J., & Palsson, B. Ø. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.01.060 · Cited by 60
Diet alters probiotic L actobacillus persistence and function in the intestine
Tachon, S., Lee, B., & Marco, M. L. (2013) · Environmental Microbiology · doi:10.1111/1462-2920.12297 · Cited by 59
Thomas, M., Wrzosek, L., Ben-Yahia, L., Noordine, M.-L., Gitton, C., Chevret, D., Langella, P., Mayeur, C., Cherbuy, C., & Rul, F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028789 · Cited by 48
Metabolic Proximity in the Order of Colonization of a Microbial Community
Mazumdar, V., Amar, S., & Segrè, D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077617 · Cited by 35
Proteomic investigation of the adaptation of Lactococcus lactis to the mouse digestive tract
Roy, K., Meyrand, M., Corthier, G., Monnet, V., & Mistou, M. (2008) · PROTEOMICS · doi:10.1002/pmic.200700698 · Cited by 32
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“The model predicted that the need to regenerate reducing equivalents enforced mutualism in certain pairs under anoxic conditions [153].”
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“…Salazar nuriasg@ipla.csic.es Specialty section: This article was submitted to Microbial Physiology and Metabolism, a section of the journal Frontiers in Microbiology Received: 04 December 2015 Accepted: 02 February 2016 Published: 17 February 2016 Citation: Ríos-Covián D, Ruas-Madiedo P,”
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“1), which is promoted by anoxic conditions in the colon 188 .”
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“This type of de- pendency is also seen in many other bacterial groups (Heinken & Thiele, 2015; Rowland et al., 2018).”
Background
Metadata
- Authors
- Heinken, A., & Thiele, I.
- Affiliations
- University of Luxembourg (LU)
- Venue
- Applied and Environmental Microbiology
- Publisher
- American Society for Microbiology
- Published
- 2015-06-15
- Volume
- 81
- Issue
- 12
- Pages
- 4049-4061
- ISSN
- 0099-2240 (ISSN-L)
- 1098-5336
- PMC
- PMC4524141
- OpenAlex
- W1976253726
- Cited by
- 123
- References
- 61
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 14 · 2023: 8 · 2022: 18 · 2021: 12 · 2020: 10 · 2019: 18 · 2018: 6 · 2017: 12 · 2016: 12 · 2015: 3
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Applied and Environmental Microbiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Keywords
- gut microbiota, microbial mutualism, anoxia, cross-feeding, constraint-based modeling, Lactobacillus plantarum, Streptococcus thermophilus, enterocytes, diet composition, small intestinal microbiota, large intestine, commensalism, competition (biology), probiotics
- MeSH terms
- Anaerobiosis, Computer Simulation, Diet, Humans, Oxygen, Species Specificity, Symbiosis, Enterocytes, Gastrointestinal Tract, Streptococcus thermophilus, Microbial Interactions, Microbiota
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