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Faecal phageome transplantation alleviates intermittent intestinal inflammation in IBD and the timing of transplantation matters: a preclinical proof-of-concept study in mice
  1. Nengneng Li1,2,3,
  2. Yue Li1,2,3,
  3. Ziyu Huang1,2,3,
  4. Zhirui Cao1,2,
  5. Cha Cao4,
  6. Xiang Gao2,5,
  7. Tao Zuo1,2,3,6
  1. 1Key Laboratory of Human Microbiome and Chronic Diseases, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, China
  2. 2Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
  3. 3Centre for Fecal Microbiota Transplantation Research, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
  4. 4College of Life Science and Technology, Department of Food Science and Engineering, Jinan University, Guangzhou, Guangdong, China
  5. 5Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
  6. 6Biomedical Innovation Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong, China
  1. Correspondence to Professor Tao Zuo; zuot{at}mail.sysu.edu.cn

https://doi.org/10.1136/gutjnl-2024-333598

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    We read with interest the Rome Consensus paper on faecal microbiota transplantation (FMT) in IBD (a refractory disease with intermittent flare-ups and remissions of intestinal inflammation) by Lopetuso et al.1 It highlights modest efficacies of FMT in treating IBD and adverse event risks caused by bacteria transplantation, according to data from clinical trials.1 Hence, further refinement of FMT is warranted for IBD treatment.2 3 Our prior study found that FMT can simultaneously reconfigure the gut bacteriome and phageome in patients with Clostridioides difficile infection; however, the reconfiguration of phageome was associated more with a long-term intestinal inflammation amelioration, suggesting a prominent role for gut bacteriophages in combating intestinal pathologies.4–6 Our more recent studies discovered a critically perturbed gut phageome in the intestinal mucosa of patients with IBD.7 8 Surprisingly, the distortion in the phageome-bacteriome ecology was even more pronounced in patients in remission compared with those in flare-up, implying the perturbed mucosal phageome during remission might be ‘quiescently’ fuelling disease flare-up.7 These findings together led us to hypothesise that targeting the perturbed gut phageome by faecal phageome transplantation (FPT), during the remission phase rather than the flare-up phase, might be a viable strategy for treating IBD.

    Inspired by this hypothesis, we conducted a preclinical proof-of-concept study in an IBD mouse model with intermittent, step-up dextran sulfate sodium (DSS) challenges (to mimic the relapsing and remitting disease courses of IBD), whereby we transplanted healthy faecal phageome at different intervention timings on the first round of DSS challenge (FPT administered during remission (FPT-r) vs flare-up (FPT-f)) and then evaluated treatment …

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    Footnotes

    • X @Tao_Zuo_

    • Contributors TZ conceived and devised the study and drafted the manuscript. NL conducted the experiments, performed data analyses and jointly drafted the manuscript. YL, ZH, ZC, CC and XG assisted in performing the experiments and data analysis. TZ is the guarantor.

    • Funding This work was jointly supported by National Natural Science Foundation of China (NSFC grant nos. 82172323, 32100134, 823B2010), Guangdong Provincial Natural Science Foundation (grant no. 2024A1515010533), National Key Research and Development Programme of China, Guangzhou Key R&D programme (grant no. 202206010014), a seed fund from the Sixth Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University (2022JBGS03).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.