Reporting on a Study of One with Flagellin Immunization to Adjust the Gut Microbiome

This post is a report on a self-experiment with flagellin immunization, tested as an approach to adjust the gut microbiome in a favorable direction. Flagellin is the protein that makes up bacterial flagellae, and it is hypothesized that there is a sizable overlap between populations of gut microbes that possess flagellae and populations of gut microbes that are harmful rather than helpful. The harmful microbes are largely a problem because they contribute to chronic inflammation, while helpful microbes are largely beneficial due to the metabolites that they produce. The gut microbiome changes with age, shifting towards more harmful and fewer helpful microbes.

If the immune system can be roused to do a better job of eliminating the problem microbes, then perhaps this could lead to improved health. Flagellin immunization has been trialed in humans as a vaccine adjuvant, and shown to be safe in the small studies conducted to date. Recently, researchers tested its ability to adjust the gut microbiome in mice, with favorable results. Last year I posted a study outline for a self-experiment in flagellin immunization, and this year I have a report from one adventurous self-experimenter.

Setting Expectations

The motivation for this self-experiment was curiosity: would human data be similar to the mouse data? The results here were on balance positive. This is a self-experiment in which there is an unusually clear readout for the outcome of interest, in the form of the Viome gut microbiome assay. This is nonetheless a study population of one. The results should be taken as interesting, but not supportive of any particular conclusion beyond the desire to run a larger and more formal study.

Schedule for the Self-Experiment

The self-experiment ran for ten weeks. Weekly intramuscular injections of 10 μg flagellin in 0.5ml phosphate-buffered saline were used, with Viome gut microbiome assays performed beforehand, at 10 weeks, and six months later.

  • Day 0: Perform a Viome gut microbiome assessment.
  • Day 1: Intramuscular injection of 10 μg of flagellin.
  • Day 8: Intramuscular injection of 10 μg of flagellin.
  • Day 15: Intramuscular injection of 10 μg of flagellin.
  • Day 22: Intramuscular injection of 10 μg of flagellin.
  • Day 29: Intramuscular injection of 10 μg of flagellin.
  • Day 36: Intramuscular injection of 10 μg of flagellin.
  • Day 43: Intramuscular injection of 10 μg of flagellin.
  • Day 50: Intramuscular injection of 10 μg of flagellin.
  • Day 57: Intramuscular injection of 10 μg of flagellin.
  • Day 64: Intramuscular injection of 10 μg of flagellin.
  • Day 65: Perform a Viome gut microbiome assessment.
  • Day 225: Perform a Viome gut microbiome assessment.

Subject Details

The subject for the self-experiment was in the 45-50 age range, healthy and without chronic conditions, with a BMI of ~22 throughout the duration of the experiment. Diet and exercise were described as "relatively consistent" across this time, including the six month follow up assessment. I feel that one should always be relatively skeptical of that sort of claim, however, no matter how formal or informal the study.

Summary of Results

Viome does not provide raw data on species and prevalence of gut microbes and their biochemistry, but rather a set of scores derived from that raw data. The algorithm used isn't public, meaning that one can't really dispute any of their choices or the studies used to support those choices, unfortunately. The algorithm is, nonetheless, consistent between assays at different times, and so can be used as a point of comparison for the purposes of a self-experiment, at least.

Over the course of the self-experiment, Viome summary scores improved for Inflammatory Activity, Digestive Efficiency, Gut Lining Health, Protein Fermentation, and Gas Production. The summary scores declined for Metabolic Fitness and Active Microbial Diversity. The gains (largely bad scores transforming into good scores) were larger than the declines (bad scores becoming worse scores).

Viome Data

Gut Microbiome Health (overall score):
   Before: 27
   After: 43
   +6 months: 49

Inflammatory Activity (lower is better):
   Before: 50
   After: 45
   +6 months: 28
Metabolic Fitness (higher is better):
   Before: 25
   After: 29
   +6 months: 21
Digestive Efficency (higher is better):
   Before: 0
   After: 57
   +6 months: 68
Gut Lining Health (higher is better):
   Before: 12
   After: 64
   +6 months: 69
Protein Fermentation (lower is better):
   Before: 87
   After: 49
   +6 months: 33
Gas Production (lower is better):
   Before: 83
   After: 48
   +6 months: 35
Active Microbial Diversity (higher is better):
   Before: 34
   After: 15
   +6 months: 15

Ammonia Production Pathways
   Before: Not Optimal
   After: Average
   +6 months: Good
Bile Acid Metabolism Pathways
   Before: Average
   After: Good
   +6 months: Good
Biofilm, Chemotaxis, and Virulence Pathways
   Before: Not Optimal
   After: Not Optimal
   +6 months: Good
Butyrate Production Pathways
   Before: Average
   After: Average
   +6 months: Not Optimal
Flagellar Assembly Pathways
   Before: Not Optimal
   After: Not Optimal
   +6 months: Average
LPS Biosynthesis Pathways
   Before: Average
   After: Average
   +6 months: Average
Methane Gas Production Pathways
   Before: Good
   After: Not Optimal
   +6 months: Good
Oxylate Metabolism Pathways
   Before: Average
   After: Not Optimal
   +6 months: Not Optimal
Putrescine Production Pathways
   Before: Not Optimal
   After: Not Optimal
   +6 months: Average
Salt Stress Pathways
   Before: Average
   After: Average
   +6 months: Average
Sulfide Gas Production Pathways
   Before: Not Optimal
   After: Average
   +6 months: Average
TMA Production Pathways
   Before: Good
   After: Good
   +6 months: Good
Uric Acid Production Pathways
   Before: Not Optimal
   After: Not Optimal
   +6 months: Not Optimal

Anecdotal Notes

The first few injections of flagellin produced a minor injection site reaction that lasted a few days: red and tender. That was reduced with each injection, and later injections produced no reaction. Beyond that, no perceptible change in health or digestion, positive or negative, was observed as a result of the self-experiment.

Conclusion

Coupled with the animal data, and the existing human trial data for safety, the results here suggests that someone should run a formal, controlled trial of flagellin immunization in older people, 65 and over. The goal would be to see whether (a) this sort of outcome holds up in a larger group of people, and (b) there is a meaningful impact on chronic inflammation and other parameters of health that are known to be affected by the aging of the gut microbiome.

Comments

These are all interesting biomarkers, but why did the subject do the study? Did they have a condition which drove their interest?

Obviously the IBD community will be very interested in this due to recent research, but if they were a patient suffering from a chronic condition I'd be very interested in the subjective biomarkers as well - did they feel better, and better in ways that matched up with the Viome scores?

Posted by: R at March 3rd, 2021 4:26 PM

Good job Reason!

Was it inactivated salmonella flagellin? I have read along the way that sublingual flagellin worked too. I think I would like to try that.

Andrei Gudkov used Entolimod which is a flagellin therapy in mice and found that it eliminated age related frailty. You probably just added some time back to your life.

Posted by: Lee at March 4th, 2021 4:29 AM

Flagellin is pretty obscure. Guessing there is one grey market source for this in like Australia. Did Viome recommend Flagellin after preliminary testing?

Posted by: JohnD at March 4th, 2021 4:31 AM

@R: This was a curiosity-driven self-experiment to see whether sizable effects on the microbiome composition in mice translated to sizable effects on the microbiome composition in humans, justifying formal studies. Only the gut microbiome was measured. There was no subjective change. In any case we should always be skeptical of any subjective description of outcomes.

Posted by: Reason at March 4th, 2021 7:15 AM

Just thinking about the pattern of 'single promising result' prompting additional self-experiments with the intent of replicating. If one was curious about reproducing the study, would it make sense to share the sourcing of the buy list? Do you think it would be possible to anonymously connect the original subject and us? Maybe a group buy or something would be worth discussing if there was enough interest.

Posted by: dentalperson at March 8th, 2021 3:26 PM

It is awesome you did this and shared the results. I was unaware of Viome but will set the wife up for Gut Intelligence ASAP. I wonder how your results would compare to a straight forward regime of high-fiber and probiotics, and compare to a stringent regime of calorie restriction, monthly 4 day fasts, and last fast day enemas with the last rinse being a probiotic soup. I'll do Viome Gut Intelligence after I see my wife's test results and the effectiveness of their recommendations.

Posted by: Thomas Mark Schaefer at March 10th, 2021 10:57 AM

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