Cited by 777Gut microbiota and healthAnimal Nutrition and PhysiologyNutritional Studies and Diet

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Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- N -Oxide

Open access

Romano, Kymberleigh A., Vivas, Eugenio I., Amador-Noguez, Daniel, Rey, Federico E.·2015·mBio

DOI 10.1128/mbio.02481-14PMC PMC4453578

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Abstract

Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which upon absorption by the host is converted in the liver to trimethylamine- N -oxide (TMAO). Recent studies revealed that TMAO exacerbates atherosclerosis in mice and positively correlates with the severity of this disease in humans. However, which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., genotype) and diet affect TMA production and colonization of these microbes, and the effects TMA-producing microbes have on the bioavailability of dietary choline remain largely unknown. We screened a collection of 79 sequenced human intestinal isolates encompassing the major phyla found in the human gut and identified nine strains capable of producing TMA from choline in vitro . Gnotobiotic mouse studies showed that TMAO accumulates in the serum of animals colonized with TMA-producing species, but not in the serum of animals colonized with intestinal isolates that do not generate TMA from choline in vitro . Remarkably, low levels of colonization by TMA-producing bacteria significantly reduced choline levels available to the host. This effect was more pronounced as the abundance of TMA-producing bacteria increased. Our findings provide a framework for designing strategies aimed at changing the representation or activity of TMA-producing bacteria in the human gut and suggest that the TMA-producing status of the gut microbiota should be considered when making recommendations about choline intake requirements for humans. IMPORTANCE Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and increased trimethylamine N -oxide (TMAO) levels have been causally linked with CVD development. This work identifies members of the human gut microbiota responsible for both the accumulation of trimethylamine (TMA), the precursor of the proatherogenic compound TMAO, and subsequent decreased choline bioavailability to the host. Understanding how to manipulate the representation and function of choline-consuming, TMA-producing species in the intestinal microbiota could potentially lead to novel means for preventing or treating atherosclerosis and choline deficiency-associated diseases.

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Written from the paper’s full text.

TL;DR

Gut microbial conversion of dietary choline to trimethylamine (TMA) drives serum trimethylamine-N-oxide (TMAO) accumulation in gnotobiotic mice, and TMA-producing bacteria reduce host-available choline. Host gender, genotype, and community composition also modulate TMAO levels via hepatic flavin monooxygenase (FMO) activity.

Key findings

Screening 79 sequenced human intestinal isolates across six phyla identified TMA-producing strains from choline; the Results list eight species, including *Anaerococcus hydrogenalis*, *Clostridium asparagiforme*, *Clostridium hathewayi*, *Clostridium sporogenes*, *Escherichia fergusonii*, *Proteus penneri*, *Providencia rettgeri*, and *Edwardsiella tarda*. These consumed more than 60% of provided choline, and none generated TMA from l-carnitine under the same conditions.
In gnotobiotic mice, a five-species “core” community that did not produce TMA in vitro yielded no detectable cecal TMA or serum TMAO. Adding *C. sporogenes*, representing only 0.15% ± 0.01% of the cecal community, reduced fecal choline, increased cecal TMA, and produced serum TMAO.
A “core plus all” community had >100-fold higher relative abundance of TMA-producing bacteria than “core plus *C. sporogenes*,” but cecal TMA, fecal choline, and serum TMAO were not significantly different between the two groups. Serum choline decreased significantly as TMA-producer abundance increased.
Female mice accumulated significantly more serum TMAO than males despite similar cecal TMA, with higher hepatic FMO activity in females. NMRI females showed 2-fold higher serum TMAO than C57BL/6J females. Mice on a choline-deficient diet had no detectable serum TMAO, while total TMA-producing bacteria did not differ significantly (24.7% ± 2.2% vs. 24.1% ± 1.8%).

Methods

In vitro screen: 79 human intestinal isolates representing Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, Verrucomicrobia, and Lentisphaerae were grown anaerobically with 15 mM choline; supernatants were analyzed by uHPLC-MS/MS for choline, TMA, and TMAO.
Gnotobiotic mouse experiments: germ-free C57BL/6J and NMRI mice were colonized with defined communities (“core,” “core plus *C. sporogenes*,” or “core plus all”) and fed a 1% (wt/wt) choline diet or choline-deficient diet; serum, feces, cecal contents, and liver were collected for metabolite, microbial community (COPRO-Seq), and FMO activity analyses.
Main analysis: metabolite quantification by uHPLC-MS/MS, community profiling by COPRO-Seq, hepatic FMO activity assays, and unpaired two-tailed Student’s t tests.

Limitations

Stated: further experimentation is required to determine whether the observed reduction in choline bioavailability recapitulates the biochemical and pathological manifestations of choline deficiency; the gnotobiotic mouse model is a simplified representation of the human gut ecosystem.
Stated: future studies are needed to understand how to manipulate TMA-producing bacteria or identify species that modulate host TMA-to-TMAO conversion.
Evident from the text: experiments used low-complexity defined communities and small group sizes (often 3–6 animals per group); *A. hydrogenalis* was not detected in cecal samples of “core plus all” mice; and in vitro TMA production may not fully predict in vivo activity.

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Crossref · 10.1128/mbio.02481-14

Cites

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In the paper
“None of the identified TMA-producing strains generated TMA from l-carnitine, another quaternary amine linked to TMAO accumulation, under the same test conditions (Table 1) (10).”
§ Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide > RESULTS AND DISCUSSION > In vitro screening reveals human gut isolates able to generate TMA from choline.
What the sources say
- Not checked yetcites [10] Koeth RA, Wang Z, Levison BS, Buffa JA, Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WHW, Bushman FD, Lusis AJ, Hazen SL 2013 Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19: 576– 585. doi: 10.1038/nm.3145. 23563705 PMC3650111 source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
In the paper
“Genome analysis for members of the “core plus all” community, using the curated database for metabolic pathways MetaCyc, disclosed that Clostridium hathewayi carries genes that encode proteins (3-α-hydroxysteroid dehydrogenase/carbonyl reductase and 3-oxo-cholyl-coenzyme A [CoA] oxidoreductase) predicted to be involved in the metabolism of cholic acid that were not detected in members of the “core”
§ Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide > RESULTS AND DISCUSSION > Host genotype and community composition modulate FMO activity and TMAO accumulation in female mice.
What the sources say
- Not checked yetcites [28] Caspi R, Altman T, Billington R, Dreher K, Foerster H, Fulcher CA, Holland TA, Keseler IM, Kothari A, Kubo A, Krummenacker M, Latendresse M, Mueller LA, Ong Q, Paley S, Subhraveti P, Weaver DS, Weerasinghe D, Zhang P, Karp PD 2014 The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res 42: D459– D471. doi: 10.1093/nar/gkt1103. 24225315 PMC3964957 source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes

Show all 61 claims

It may state two separate claims as one. 11
Probably not a substantial claim. 12

None of the sources cited for this claim have been checked yet.
In the paper
“Recent human studies have established that the levels of TMAO in serum are positively correlated with impaired renal function, colorectal cancer, and cardiovascular disease (CVD) (8, 10, 17, 18).”
§ Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide > INTRODUCTION
What the sources say
- Not checked yetcites [8] Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, Feldstein AE, Britt EB, Fu X, Chung Y-M, Wu Y, Schauer P, Smith JD, Allayee H, Tang WHW, DiDonato JA, Lusis AJ, Hazen SL 2011 Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472: 57– 63. doi: 10.1038/nature09922. 21475195 PMC3086762 source
- Not checked yetcites [10] Koeth RA, Wang Z, Levison BS, Buffa JA, Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WHW, Bushman FD, Lusis AJ, Hazen SL 2013 Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19: 576– 585. doi: 10.1038/nm.3145. 23563705 PMC3650111 source
- Not checked yetcites [17] Tang WHW, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, Li XS, Levison BS, Hazen SL 2015 Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res 116: 448– 455. doi: 10.1161/CIRCRESAHA.116.305360. 25599331 PMC4312512 source
- Not checked yetcites [18] Bae S, Ulrich CM, Neuhouser ML, Malysheva O, Bailey LB, Xiao L, Brown EC, Cushing-Haugen KL, Zheng Y, Cheng T-YD, Miller JW, Green R, Lane DS, Beresford SAA, Caudill MA 2014 Plasma choline metabolites and colorectal cancer risk in the women’s health initiative observational study. Cancer Res 74: 7442– 7452. doi: 10.1158/0008-5472.CAN-14-1835. 25336191 PMC4268282 source
Strength:boosted· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“TMAO exacerbates atherosclerosis in a genetic knockout mouse model, in part by promoting forward cholesterol transport and by inhibiting reverse cholesterol transport (8, 10, 19, 20).”
§ Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide > INTRODUCTION
What the sources say
- Not checked yetcites [8] Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, Feldstein AE, Britt EB, Fu X, Chung Y-M, Wu Y, Schauer P, Smith JD, Allayee H, Tang WHW, DiDonato JA, Lusis AJ, Hazen SL 2011 Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472: 57– 63. doi: 10.1038/nature09922. 21475195 PMC3086762 source
- Not checked yetcites [10] Koeth RA, Wang Z, Levison BS, Buffa JA, Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WHW, Bushman FD, Lusis AJ, Hazen SL 2013 Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19: 576– 585. doi: 10.1038/nm.3145. 23563705 PMC3650111 source
- Not checked yetcites [19] Trøseid M, Ueland T, Hov JR, Svardal A, Gregersen I, Dahl CP, Aakhus S, Gude E, Bjørndal B, Halvorsen B, Karlsen TH, Aukrust P, Gullestad L, Berge RK, Yndestad A 1 12 2014 Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure. J Intern Med doi: 10.1111/joim.12328. 25382824 source
- Not checked yetcites [20] Wang Z, Tang WHW, Buffa JA, Fu X, Britt EB, Koeth RA, Levison BS, Fan Y, Wu Y, Hazen SL 2014 Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Heart J 35: 904– 910. doi: 10.1093/eurheartj/ehu002. 24497336 PMC3977137 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Recent human studies have established that the levels of TMAO in serum are positively correlated with impaired renal function, colorectal cancer, and cardiovascular disease (CVD) (8, 10, 17, 18).”
§ Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide > INTRODUCTION
What the sources say
- Not checked yetcites [8] Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, Feldstein AE, Britt EB, Fu X, Chung Y-M, Wu Y, Schauer P, Smith JD, Allayee H, Tang WHW, DiDonato JA, Lusis AJ, Hazen SL 2011 Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472: 57– 63. doi: 10.1038/nature09922. 21475195 PMC3086762 source
- Not checked yetcites [10] Koeth RA, Wang Z, Levison BS, Buffa JA, Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WHW, Bushman FD, Lusis AJ, Hazen SL 2013 Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19: 576– 585. doi: 10.1038/nm.3145. 23563705 PMC3650111 source
- Not checked yetcites [17] Tang WHW, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, Li XS, Levison BS, Hazen SL 2015 Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res 116: 448– 455. doi: 10.1161/CIRCRESAHA.116.305360. 25599331 PMC4312512 source
- Not checked yetcites [18] Bae S, Ulrich CM, Neuhouser ML, Malysheva O, Bailey LB, Xiao L, Brown EC, Cushing-Haugen KL, Zheng Y, Cheng T-YD, Miller JW, Green R, Lane DS, Beresford SAA, Caudill MA 2014 Plasma choline metabolites and colorectal cancer risk in the women’s health initiative observational study. Cancer Res 74: 7442– 7452. doi: 10.1158/0008-5472.CAN-14-1835. 25336191 PMC4268282 source
Strength:boosted· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“This cluster includes cutC, which encodes a glycyl radical enzyme with choline trimethylamine-lyase activity; cutD, which encodes a glycyl radical-activating protein; and genes encoding proteins involved in the assembly of microcompartments which may sequester the acetaldehyde generated as a by-product during TMA production (22, 23).”
§ Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide > INTRODUCTION
What the sources say
- Not checked yetcites [22] Craciun S, Balskus EP 2012 Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. Proc Natl Acad Sci U S A 109: 21307– 21312. doi: 10.1073/pnas.1215689109. 23151509 PMC3535645 source
- Not checked yetcites [23] Thibodeaux CJ, van der Donk WA 2012 Converging on a mechanism for choline degradation. Proc Natl Acad Sci U S A 109: 21184– 21185. doi: 10.1073/pnas.1219534110. 23243142 PMC3535664 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“TMAO exacerbates atherosclerosis in a genetic knockout mouse model, in part by promoting forward cholesterol transport and by inhibiting reverse cholesterol transport (8, 10, 19, 20).”
§ Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide > INTRODUCTION
What the sources say
- Not checked yetcites [8] Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, Feldstein AE, Britt EB, Fu X, Chung Y-M, Wu Y, Schauer P, Smith JD, Allayee H, Tang WHW, DiDonato JA, Lusis AJ, Hazen SL 2011 Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472: 57– 63. doi: 10.1038/nature09922. 21475195 PMC3086762 source
- Not checked yetcites [10] Koeth RA, Wang Z, Levison BS, Buffa JA, Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WHW, Bushman FD, Lusis AJ, Hazen SL 2013 Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19: 576– 585. doi: 10.1038/nm.3145. 23563705 PMC3650111 source
- Not checked yetcites [19] Trøseid M, Ueland T, Hov JR, Svardal A, Gregersen I, Dahl CP, Aakhus S, Gude E, Bjørndal B, Halvorsen B, Karlsen TH, Aukrust P, Gullestad L, Berge RK, Yndestad A 1 12 2014 Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure. J Intern Med doi: 10.1111/joim.12328. 25382824 source
- Not checked yetcites [20] Wang Z, Tang WHW, Buffa JA, Fu X, Britt EB, Koeth RA, Levison BS, Fan Y, Wu Y, Hazen SL 2014 Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Heart J 35: 904– 910. doi: 10.1093/eurheartj/ehu002. 24497336 PMC3977137 source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim.
In the paper
“Choline is a water-soluble nutrient essential for human life.”
§ Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide > Abstract
What the sources say
- Not checked yetcites [11] Zeisel SH, da Costa K-A 2009 Choline: an essential nutrient for public health. Nutr Rev 67: 615– 623. doi: 10.1111/j.1753-4887.2009.00246.x. 19906248 PMC2782876 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Significant reduction in choline consumption leads to organ dysfunction and failure along with an increased risk of the development of heart disease, cancer, and liver disease (11, 26).”
§ Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide > RESULTS AND DISCUSSION > Colonization with TMA-producing bacteria decreases levels of choline available to the host.
What the sources say
- Not checked yetcites [11] Zeisel SH, da Costa K-A 2009 Choline: an essential nutrient for public health. Nutr Rev 67: 615– 623. doi: 10.1111/j.1753-4887.2009.00246.x. 19906248 PMC2782876 source
- Not checked yetcites [26] Strilakou AA, Lazaris AC, Perelas AI, Mourouzis IS, Douzis IC, Karkalousos PL, Stylianaki AT, Pantos CI, Liapi CA 2013 Heart dysfunction induced by choline-deficiency in adult rats: the protective role of l-carnitine. Eur J Pharmacol 709: 20– 27. doi: 10.1016/j.ejphar.2013.03.025. 23562624 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“consistent with previous studies in conventionally raised mice which demonstrated that FMO3 is expressed at higher levels in females than in males (8, 27).”
§ Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide > RESULTS AND DISCUSSION > Host gender affects FMO activity and TMAO accumulation in gnotobiotic mice colonized with the same microbiota.
What the sources say
- Not checked yetcites [8] Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, Feldstein AE, Britt EB, Fu X, Chung Y-M, Wu Y, Schauer P, Smith JD, Allayee H, Tang WHW, DiDonato JA, Lusis AJ, Hazen SL 2011 Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472: 57– 63. doi: 10.1038/nature09922. 21475195 PMC3086762 source
- Not checked yetcites [27] Bennett BJ, de Aguiar Vallim TQ, Wang Z, Shih DM, Meng Y, Gregory J, Allayee H, Lee R, Graham M, Crooke R, Edwards PA, Hazen SL, Lusis AJ 2013 Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab 17: 49– 60. doi: 10.1016/j.cmet.2012.12.011. 23312283 PMC3771112 source
Strength:boosted· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.

21 of 21

The paper relies on this without support.
The diversity of gut microbes that contribute to TMA production in humans and the impact of these species on serum TMAO levels and choline bioavailability remain unknown.
“However, the diversity of gut microbes that contribute to TMA production in humans and the impact of these species on serum TMAO levels and choline bioavailability remain unknown.”

1 of 1

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In vitro screening incubation time differs between Results and Methods
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The Results state that the strains were incubated for 24 hours in the 96-well choline screen, while the Methods describe a 48-hour incubation for that screen.

1 of 1

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Authors: Romano, K. A., Vivas, E. I., Amador-Noguez, D., & Rey, F. E.
Affiliations: University of Wisconsin–Madison (US)
Department of Bacteriology, University of Wisconsin—Madison, Madison, Wisconsin, USA
Corresponding author: Rey, Federico E.
ORCID: Rey, Federico E.
Venue: mBio
Publisher: American Society for Microbiology
Published: 2015-05
Volume: 6
Issue: 2
Pages: e02481-e02481
ISSN: 2150-7511 (ISSN-L)
2161-2129
DOI: 10.1128/mbio.02481-14
PMC: PMC4453578
OpenAlex: W2119343060
Cited by: 777
References: 31
Citations by year: 2026: 55 · 2025: 87 · 2024: 77 · 2023: 85 · 2022: 79 · 2021: 109 · 2020: 78 · 2019: 56 · 2018: 75 · 2017: 32 · 2016: 32 · 2015: 11
FWCI: 21.69
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/3.0/ (vor)
journals.asm.org/non-commercial-tdm-license (tdm)
Locations: mBio (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health (KL2TR000428, UL1TR000427)
National Center for Advancing Translational Sciences
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P2CHD047873)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords: trimethylamine, trimethylamine N-oxide, gut microbiota, atherosclerosis, cardiovascular disease, choline deficiency, gnotobiotic mice, dietary choline, host-microbe interactions
MeSH terms: Gastrointestinal Microbiome, Animals, Choline, Diet, Germ-Free Life, Humans, Methylamines, Molecular Sequence Data, Sequence Analysis, DNA, Mice, Microbiota

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Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- N -Oxide

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