In Adolescents With Obesity, FMT Shows No Negative Impact on Horizontal Gene Transfer

Horizontal gene transfer was not adversely affected by fecal microbiota transplantation (FMT) among a study population of 87 adolescents classified as obese, according to new research published in Microbiome.¹

FMT | Image credit: TopMicrobialStock - stock.adobe.com

During horizontal gene transfer, a process by which genetic information moves between organisms, the genetic material of the donor cells is replicated completely or partially by those cells, which then use a self-generated sex pilus to move over to the recipient cell.^2,3 Advantages of the process include the spreading of beneficial genes and larger fitter genomes, while disadvantages include introduction of genetic parasites, genes incompatible with the new host, and spread of human-related infections.^4-6

“New paradigms that incorporate pivotal roles for the microbiome in complex phenotypes are leading to research into further treatment indications,” the study authors wrote. “These include small trials that have demonstrated potential for treating obesity by FMT.”

Using metagenomic sequencing files from the Gut Bugs trial, a double-blinded, randomized, placebo-controlled multidonor FMT trial out of Auckland, New Zealand, the study authors analyzed 381 FMT samples from 87 recipient patients at 4 time points: baseline and 6, 12, and 26 weeks post FMT. Also, at each donation, 9 donors were sampled, for 58 FMT donor samples collected over a year-long donation period. WAAFLE, a bioinformatics application, quantified all putative HGT events.

Overall, at the 6-week mark, no effect on weight loss was seen, and there were highly variable rates of strain engraftment. Metagenomic sequencing data were available on all 381 trial samples, and each sample contained an average 96,604 (range, 27,729-202,760) contigs with a minimum length of 500 bp.

There were 2.9 million genes collected across these samples, and they accounted for 20,941 metagenome-assembled genomes, of which 20% were considered high quality. In addition, genetic segments implicated in horizontal gene transfer were seen in 0.15% (range, 0.074%-0.26%) of assembled contigs.

Species richness was used to normalize horizontal gene transfer event counts in the microbiomes of each participant, and the investigators did not see an adverse effect from the FMT on HGT overall (P = .90), based on sex (P = .060), or from baseline to week 6 (P = .96) or week 12 (P = .71). However, there was a noticeable longitudinal effect from baseline to week 26 (P < .001).

The investigators also found 57,590 putative horizontal gene transfer events post FMT in 39 recipients and 111,273 in those who received placebo. No percentage difference was found between genes involved in horizontal gene transfer for those who received FMT and placebo, including when they conducted a subanalysis considering sex of the patient (male patients, P = .84; female patients, P = .63).

No increase was seen for FMT-specific horizontal gene transfer events compared with the placebo group’s background rate of horizontal gene transfer, and at the 26-week mark post FMT, horizontally transferred gene clusters were maintained.

“In conclusion,” the authors wrote, “FMT does not increase rates of horizontal gene transfer in human subject. “However, donated strains do participate in horizontal gene transfer and evidence for these events is retained for at least 6 months following the FMT treatment itself.”

References

1. Behling AH, Wilson BC, Ho D, Cutfield WS, Vatanen T, O’Sullivan JM. Horizontal gene transfer after faecal microbiota transplantation in adolescents with obesity. Microbiome. 2024;12(1):26. doi:10.1186/s40168-024-01748-6
2. Burmeister AR. Horizontal gene transfer. Evol Med Public Health. 2015;2015(1):193-194. doi:10.1093/emph/eov018
3. Horizontal gene transfer. University of Colorado Denver. Accessed February 14, 2024. http://tinyurl.com/29439wmf
4. Hall RJ, Whelan FJ, McInerney JO, Ou Y, Domingo-Sananes MR. Horizontal gene transfer as a source of conflict and cooperation in prokaryotes. Front Microbiol. 2020;11:1569. doi:10/.3389/fmicb.2020.01569
5. Vogan AA, Higgs PG. The advantages and disadvantages of horizontal gene transfer and the emergence of the first species. Biol Direct. 2011;6:1. doi:10.1186/1745-6150-6-1
6. Emamalipour M, Seidi K, VAhed SZ, et al. Horizontal gene transfer: from evolutionary flexibility to disease progression. Front Cell Dev Biol. 2020;8:229. doi:10.3389/fcell.2020.00229