CoChat
Sign Up
PreprintCited by 12Evolution and Genetic DynamicsBacterial Genetics and BiotechnologyGut microbiota and health

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Gut mélange à trois: fluctuating selection modulated by microbiota, host immune system, and antibiotics

Open access
Barreto, Hugo C., Abreu, Beatriz, Gordo, Isabel·2021·Current Biology
DOI 10.1101/2021.12.30.474527

Preprint — published as 10.1016/j.cub.2022.06.017 · Paper page

Open this paper in CoChat — free account

Abstract

SUMMARY: Iron is critical in host-microbe interactions, and its availability is tightly regulated in the mammalian gut. Antibiotics and inflammation can perturb iron availability in the gut, which could alter host-microbe interactions. Here, we show that an adaptive allele of iscR , a major regulator of iron homeostasis of Escherichia coli , is under fluctuating selection in the mouse gut. In vivo competitions in immune-competent, immune-compromised, and germ-free mice reveal that the selective pressure on an iscR mutant E. coli is modulated by the presence of antibiotics, the microbiota, and the immune system. In vitro assays show that iron availability is an important mediator of the iscR allele fitness benefits or costs. We identify Lipocalin-2, a host’s immune protein that prevents bacterial iron acquisition, as a major host mechanism underlying fluctuating selection of iscR . Our results provide a remarkable example of strong fluctuating selection acting on bacterial iron regulation in the mammalian gut.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2021.12.30.474527

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 1 references

Research works printed but not linked: 78

  1. 10.3389/fpsyg.2017.00456 · DOI
  2. 10.1017/S0007114510001637 · DOI
  3. 10.1016/j.cub.2020.01.037 · DOI
  4. 2020, Mutation accumulation and horizontal gene transfer in Escherichia coli colonizing the gut of old mice, Commun Integr Biol, 13, 89, 10.1080/19420889.2020.1783059 · DOI
  5. 10.1038/ncomms9945 · DOI
  6. 10.1038/nature08504 · DOI
  7. 2021, The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock, Cell, 184, 4154, 10.1016/j.cell.2021.07.001 · DOI
  8. 10.1007/s10534-012-9555-5 · DOI · Paper page
  9. 10.1016/j.cell.2018.02.005 · DOI
  10. 10.1371/journal.pone.0044328 · DOI
  11. 10.1093/bioinformatics/bty560 · DOI · Paper page
  12. 10.1128/microbe.10.324.1 · DOI
  13. 2017, Iron Supplements Modulate Colon Microbiota Composition and Potentiate the Protective Effects of Probiotics in Dextran Sodium Sulfate-induced Colitis, Inflamm Bowel Dis, 23, 753, 10.1097/MIB.0000000000001089 · DOI
  14. 10.1016/j.cmet.2019.10.005 · DOI · Paper page
  15. 10.1007/978-1-4939-0554-6_12 · DOI
  16. 10.1096/fj.15-276840 · DOI · Paper page
  17. 10.3945/jn.111.148643 · DOI
  18. 10.1038/nature24299 · DOI
  19. Esquilin-Lebron, K. , Dubrac, S. , Barras, F. , and Boyd, J.M. (2021). Bacterial Approaches for Assembling Iron-Sulfur Proteins. MBio e0242521. · DOI
  20. 10.1093/femsre/fuw004 · DOI
  21. 10.1126/science.1238328 · DOI
  22. 10.1038/nature03104 · DOI · Paper page
  23. 10.3181/00379727-111-27718 · DOI
  24. 10.1016/j.micres.2014.08.004 · DOI
  25. 10.1111/mmi.12052 · DOI
  26. 10.1016/S1097-2765(02)00708-6 · DOI · Paper page
  27. 2018, Topical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner, Nat Microbiol, 3, 611, 10.1038/s41564-018-0138-2 · DOI
  28. 10.1038/nature02744 · DOI · Paper page
  29. 10.1146/annurev.mi.48.100194.003523 · DOI · Paper page
  30. 10.1093/molbev/mst187 · DOI · Paper page
  31. 10.1126/science.1188454 · DOI · Paper page
  32. 10.1136/gutjnl-2014-307720 · DOI · Paper page
  33. 2020, Consensus Finder web tool to predict stabilizing substitutions in proteins, Methods Enzymol, 643, 129, 10.1016/bs.mie.2020.07.010 · DOI
  34. 10.4014/jmb.0906.06028 · DOI
  35. 10.1111/1574-6976.12086 · DOI · Paper page
  36. 2020, Dysbiosis individualizes the fitness effect of antibiotic resistance in the mammalian gut, Nat Ecol Evol, 4, 1268, 10.1038/s41559-020-1235-1 · DOI
  37. 10.1038/ncomms9292 · DOI · Paper page
  38. 10.1128/IAI.01141-13 · DOI
  39. 10.1016/j.molcel.2012.10.001 · DOI
  40. 2019, Functions and regulation of lipocalin-2 in gut-origin sepsis: a narrative review, Crit Care, 23, 269, 10.1186/s13054-019-2550-2 · DOI · Paper page
  41. 10.1016/j.chom.2007.06.010 · DOI
  42. 10.1038/srep15211 · DOI
  43. 10.1007/BF02013651 · DOI · Paper page
  44. 10.1371/journal.ppat.1004194 · DOI
  45. 2021, The role of iron homeostasis in remodeling immune function and regulating inflammatory disease, Science Bulletin, 66, 1806, 10.1016/j.scib.2021.02.010 · DOI
  46. 10.1111/j.1462-5822.2010.01529.x · DOI · Paper page
  47. 10.1016/j.jmb.2009.01.055 · DOI
  48. 10.1016/j.chom.2019.10.011 · DOI
  49. Nguyen, J. , Lara-Gutiérrez, J. , and Stocker, R. (2020). Environmental fluctuations and their effects on microbial communities, populations, and individuals. FEMS Microbiol Rev. · DOI
  50. 2021, A distinct growth physiology enhances bacterial growth under rapid nutrient fluctuations, Nat Commun, 12, 3662, 10.1038/s41467-021-23439-8 · DOI
  51. 10.1136/gut.38.3.414 · DOI
  52. 10.1534/genetics.117.300129 · DOI
  53. 10.1016/j.cub.2018.04.093 · DOI
  54. 1972, Effect of intestinal microflora on iron and zinc metabolism, and on activities of metalloenzymes in rats, J Nutr, 102, 101, 10.1093/jn/102.1.101 · DOI
  55. 10.1016/j.tree.2015.03.007 · DOI
  56. Sandberg, T.E. , Lloyd, C.J. , Palsson, B.O. , and Feist, A.M. (2017). Laboratory Evolution to Alternating Substrate Environments Yields Distinct Phenotypic and Genetic Adaptive Strategies. Appl Environ Microbiol 83. · DOI
  57. 10.1073/pnas.1322728111 · DOI
  58. 2015, What a difference a cluster makes: The multifaceted roles of IscR in gene regulation and DNA recognition, Biochim Biophys Acta, 1854, 1101, 10.1016/j.bbapap.2015.01.010 · DOI
  59. 10.1038/nrmicro1046 · DOI · Paper page
  60. 10.1073/pnas.251550898 · DOI
  61. 10.1080/19490976.2020.1854008 · DOI
  62. 10.1016/0092-8674(92)90029-C · DOI
  63. 2016, Microbiota-inducible Innate Immune, Siderophore Binding Protein Lipocalin 2 is Critical for Intestinal Homeostasis, Cell Mol Gastroenterol Hepatol, 2, 482, 10.1016/j.jcmgh.2016.03.007 · DOI · Paper page
  64. 2017, Regulation of life span by the gut microbiota in the short-lived African turquoise killifish, Elife, 6, e27014, 10.7554/eLife.27014 · DOI · Paper page
  65. 10.4049/jimmunol.1200892 · DOI
  66. 1954, [The problem of iron resorption], Experientia, 10, 227
  67. 10.1126/science.1154456 · DOI · Paper page
  68. 10.1016/j.chom.2017.03.002 · DOI · Paper page
  69. 10.1007/s002840010257 · DOI
  70. 2020, Negative frequency-dependent selection maintains coexisting genotypes during fluctuating selection, Mol Ecol, 29, 138, 10.1111/mec.15307 · DOI
  71. 10.1016/j.arr.2017.01.001 · DOI · Paper page
  72. 10.1146/annurev.nutr.012809.104804 · DOI · Paper page
  73. 10.1073/pnas.95.12.6578 · DOI · Paper page
  74. Wickham, H. (2016). ggplot2: elegant graphics for data analysis (Cham: Springer). · DOI
  75. 10.1111/j.1365-2958.2006.05220.x · DOI
  76. Yilmaz, B. , and Li, H. (2018). Gut Microbiota and Iron: The Crucial Actors in Health and Disease. Pharmaceuticals (Basel) 11. · DOI · Paper page
  77. 10.1016/S0140-6736(07)61235-5 · DOI · Paper page
  78. 10.3945/ajcn.110.004564 · DOI · Paper page

Metadata

Authors
Barreto, H. C., Abreu, B., & Gordo, I.
Affiliations
Instituto Gulbenkian de Ciência (PT)
Corresponding author
  • Barreto, Hugo C.
  • Gordo, Isabel
ORCID
Venue
Current Biology
Publisher
openRxiv
Published
2021-12-30
Volume
32
Issue
15
Pages
3261-3275.e4
ISSN
0960-9822 (ISSN-L)
DOI
10.1101/2021.12.30.474527
OpenAlex
W4284691909
Cited by
12
References
1
Citations by year
2026: 2 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 1
FWCI
1.51
Type
journal article
Language
en
Open access
Locations
  • Current Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Yakult Bio-Science Foundation
  • Fundação para a Ciência e a Tecnologia (0145-FEDER-022170, 01-0145, LISBOA‐01‐0145‐FEDER‐022170, PORTUGAL 2020, LISBOA-01-0145-FEDER- 016417, /2017, PD/BD/128429/2017, PTDC/BIA-EVL/7546/2020, LISBOA-01-0145-FEDER)
  • European Regional Development Fund (LISBOA-01-0145-FEDER- 016417, LISBOA-01-0145-FEDER-022170, 01-0145, PORTUGAL2020)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
fluctuating selection, iron homeostasis, IscR, Escherichia coli, gut microbiota, host-microbe interactions, neutrophil gelatinase-associated lipocalin, antibiotic effects on gut microbiota, immune system, germ-free mice, adaptive alleles, fitness costs and benefits
MeSH terms
Lipocalin-2, Animals, Anti-Bacterial Agents, Escherichia coli, Iron, Mammals, Transcription Factors, Gene Expression Regulation, Bacterial, Escherichia coli Proteins, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Gut mélange à trois: fluctuating selection modulated by microbiota, host immune system, and antibiotics. https://app.cochat.ai/papers/10.1101/2021.12.30.474527
The paper
Barreto, H. C., Abreu, B., & Gordo, I. (2021). Gut mélange à trois: fluctuating selection modulated by microbiota, host immune system, and antibiotics. Current Biology. https://doi.org/10.1101/2021.12.30.474527