Effects of Fecal Microbiome Transfer in Adolescents With Obesity. The Gut Bugs Randomized Controlled Trial (Dec 2020, n=87) "FMT alone did not lead to weight loss at 6 weeks." FMT

[Michael Harrop]

Reposting this to add newer links from this study/group. Original posts in 2020 and 2021.

Articles:

• https://www.medpagetoday.com/pediatrics/obesity/90350
• https://www.lenscience.auckland.ac.nz/en/about/teaching-and-learning-resources/gut-bugs-exploring-the-human-microbiome/understanding-the-gut-bugs-trial-case-study.html

Study: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2774355

8 donors, delayed-release capsules. Each participant received 7 capsules from each of the 4 same-sex donors.

Participants therefore received 28 capsules, which equated to approximately 22 g (wet weight) of fecal material (approximately 14 mL of frozen microbial suspension or saline) over 2 consecutive days.

Donor and protocol info: Protocol for the Gut Bugs Trial: a randomised double-blind placebo-controlled trial of gut microbiome transfer for the treatment of obesity in adolescents https://bmjopen.bmj.com/content/9/4/e026174

Healthy lean donors (males and females, aged 18–28 years) will provide fresh stool samples from which bacteria will be isolated and double encapsulated.
Eligible donors will be identified by word of mouth, the internal email system at the University of Auckland and social media networks.
To eliminate the risks of transmission of infectious diseases, we will use screening procedures equivalent to those used for blood donation in New Zealand

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Table 1. Inclusion and exclusion criteria for donors in the Gut Bugs Trial https://bmjopen.bmj.com/content/9/4/e026174#T1

Totally inadequate donor criteria. No surprise they got no results.

No mention of stool type, only excluded antibiotic use in the past 3 months, they think they're going to cure obesity after only 2 days of FMT, etc.

I checked my emails for the listed study author contact and not only had I contacted them about FMT donor quality in 2019, and then again in early 2020, but a handful of the authors were also authors on the "super-donors" paper:

The Super-Donor Phenomenon in Fecal Microbiota Transplantation (Jan 2019) https://www.frontiersin.org/articles/10.3389/fcimb.2019.00002/full

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Fucking incredible. Even people who authored a major review arguing how critical donor quality is, did next to nothing different from the hundreds of other FMT studies that failed with inadequate donors & criteria, completely ignored vital donor quality criteria/metrics, and ignored advice & information on donor quality. This continued mind-boggling level of incompetence is insane.

 

[Michael Harrop]

Interesting 2021 docuseries covering the New Zealand "gut bugs" FMT clinical trial for obesity.

• Obese Teens Try Ground-Breaking Treatment That Could Change Lives | The Thin Pill E1 | Only Human https://www.youtube.com/watch?v=6n7R08Dfa64
• Would You Take Poo Pills To End Obesity? | The Thin Pill E2 | Only Human https://www.youtube.com/watch?v=MoTfNNBHpCE
• Can Ingesting the Faeces of Fit People Help Me Lose Weight? | The Thin Pill Ep3 | Only Human https://www.youtube.com/watch?v=gjMQMP7sG-I

They're trying to select super-donors but going about it very ignorantly it seems. For example, based on their stool types, many of the very fit donor applicants I got (with humanmicrobes.org) seemed to be slim because they're missing microbes, so their food isn't fully digested. If you could do a complete swap, like you can with germ-free mice, then yes it may work, but it's not going to work [with these stool types] like it's being tried in humans.

The stool quality they're collecting from their "super donors" is very poor. Their donor's physical traits are poor/unimpressive as well. None of their "super donors" would come close to passing my screening.

Even the 1 donor I've approved and started using out of 23,000+ applicants doesn't seem to be a highly effective donor. This should be extremely alarming to everyone. The fact that high-quality donors are this rare highlights what a dangerous path we've been going down, and how dystopian our current society is.

 

[Michael Harrop]

Their latest paper:

Fecal microbiota transplantation alters gut phage communities in a clinical trial for obesity https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-024-01833-w

Abstract​

Background​

Fecal microbiota transplantation (FMT) is a therapeutic intervention used to treat diseases associated with the gut microbiome. In the human gut microbiome, phages have been implicated in influencing human health, with successful engraftment of donor phages correlated with FMT treatment efficacy. The impact that gastrointestinal phages exert on human health has primarily been connected to their ability to modulate the bacterial communities in the gut. Nonetheless, how FMT affects recipients’ phage populations, and in turn, how this influences the gut environment, is not yet fully understood. In this study, we investigated the effects of FMT on the phageome composition of participants within the Gut Bugs Trial (GBT), a double-blind, randomized, placebo-controlled trial that investigated the efficacy of FMT in treating obesity and comorbidities in adolescents. Stool samples collected from donors at the time of treatment and recipients at four time points (i.e., baseline and 6 weeks, 12 weeks, and 26 weeks post-intervention), underwent shotgun metagenomic sequencing. Phage sequences were identified and characterized in silico to examine evidence of phage engraftment and to assess the extent of FMT-induced alterations in the recipients’ phageome composition.

Results​

Donor phages engrafted stably in recipients following FMT, composing a significant proportion of their phageome for the entire course of the study (33.8 ± 1.2% in females and 33.9 ± 3.7% in males). Phage engraftment varied between donors and donor engraftment efficacy was positively correlated with their phageome alpha diversity. FMT caused a shift in recipients’ phageome toward the donors’ composition and increased phageome alpha diversity and variability over time.

Conclusions​

FMT significantly altered recipients' phage and, overall, microbial populations. The increase in microbial diversity and variability is consistent with a shift in microbial population dynamics. This proposes that phages play a critical role in modulating the gut environment and suggests novel approaches to understanding the efficacy of FMT in altering the recipient’s microbiome.

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I didn't feel it was significant enough for its own thread, and thought it belonged here. But if someone disagrees, feel free to submit it as its own thread. "Trying to learn and publish as much as possible from a failed study", is my deduction.