Amino AcidsGlycine

Engineered probiotic Escherichia coli Nissle produces sustained guanidinoacetic acid titers that may mitigate cognitive effects of sleep deprivation

The study engineered the human probiotic Escherichia coli Nissle to continuously produce guanidinoacetic acid (GAA), which is converted to creatine in the liver. Under laboratory conditions, a standard dose of 10^12 cells produced 41 ± 7 mg GAA per hour, potentially providing a sustained creatine source to improve cognitive performance during sleep deprivation.

Last updated: Aug 25, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score24/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Design of a Continuous GAA-Producing Probiotic as a Potential Mitigator of the Effects of Sleep Deprivation.

observational

Fields BD, Pascal DG, Rando OK, Huddleston ME, Ingram K, Hopton R, Grogg MW, Nelson MT, Voigt CA · ACS synthetic biology (2025)

Participants: N/A
Duration: N/A
Intervention: Engineered probiotic Escherichia coli Nissle expressing three copies of arginine:glycine amidinotransferase (AGAT) from Actinokineospora terrae, with genomic edits to improve substrate availability
Outcome: Guanidinoacetic acid production rate (mg per hour) under laboratory conditions
Effect Size: N/A
Population: Not applicable (in vitro laboratory study)

Result:

PubMed: 40378286DOI: 10.1021/acssynbio.4c00690

Mechanism Graph

Engineered probiotic expresses arginine:glycine amidinotransferase (AGAT) from Actinokineospora terrae
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Genomic edits (gcvP, argR, argA) improve substrate availability without reducing cell viability
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Probiotic continuously produces guanidinoacetic acid (GAA) in the gastrointestinal tract
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GAA is converted to creatine in the liver, potentially mitigating cognitive effects of sleep deprivation

Limitations

  • ⚠GAA production was measured only under laboratory conditions, not in vivo
  • ⚠The study does not directly test cognitive performance improvements in sleep-deprived humans
  • ⚠Potential variability in GAA production within the human gut environment is unaddressed

Frequently Asked Questions

What is guanidinoacetic acid (GAA)?▼

GAA is a precursor to creatine that is naturally converted to creatine in the liver. It is produced by engineered probiotics in this study to provide a sustained creatine source.

How does this probiotic compare to taking creatine supplements?▼

Unlike oral creatine supplements that are rapidly cleared from the gastrointestinal tract within hours, this engineered probiotic is designed to continuously produce GAA, potentially providing a more persistent creatine dose.

Is this probiotic safe for human consumption?▼

The study uses Escherichia coli Nissle (EcN), a well-known human probiotic strain, and reports that genetic edits did not negatively impact cell viability. However, human safety trials have not been conducted.

What cognitive benefits are expected from this approach?▼

Creatine has been shown to improve cognitive performance upon sleep deprivation. By providing sustained GAA for creatine production, this probiotic may help mitigate cognitive decline during sleep loss, though direct cognitive testing was not performed in this study.

Products

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References

  1. 1.Fields BD, Pascal DG, Rando OK, Huddleston ME, Ingram K, Hopton R, Grogg MW, Nelson MT, Voigt CA. "Design of a Continuous GAA-Producing Probiotic as a Potential Mitigator of the Effects of Sleep Deprivation.." ACS synthetic biology, 2025. PMID: 40378286 DOI: 10.1021/acssynbio.4c00690
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.