Immune effects of faecal microbiota transplantation in amyotrophic lateral sclerosis: a pilot multicentre, randomised, masked, sham-controlled, proof-of concept trial.

@article{zucchi2026immune,
  title = {{Immune effects of faecal microbiota transplantation in amyotrophic lateral sclerosis: a pilot multicentre, randomised, masked, sham-controlled, proof-of concept trial.}},
  author = {Elisabetta Zucchi and Elena Niccolai and Flavio De Maio and Riccardo Cuoghi Costantini and Gianluca Quaranta and Alessandra Guarnaccia and Stefano Bibbò and Ilaria Martinelli and Giulia Gianferrari and Cecilia Simonini and Giulia Nannini and Matteo Lulli and Simone Baldi and Gianluca Bartolucci and Roberto Vicini and Margherita Capasso and Giulia Bisogni and Amelia Conte and Paola Brunori and Giovanni Cammarota and Sabrina Paganoni and Roberto D'Amico and Amedeo Amedei and Luca Masucci and Jessica Mandrioli and Elisabetta Zucchi and Riccardo Cuoghi Costantini and Ilaria Martinelli and Giulia Gianferrari and Cecilia Simonini and Andrea Ghezzi and Roberta Bedin and Roberto D'Amico and Nicola Fini and Roberto Vicini and Annalisa Gessani and Francesca Prompicai and Silvia Parisi and Jessica Mandrioli and Elena Niccolai and Amedeo Amedei and Giulia Nannini and Matteo Lulli and Simone Baldi and Gianluca Bartolucci and Gianluca Quaranta and Luca Masucci and Alessandra Guarnaccia and Flavio De Maio and Giovanni Fancello and Chiara Agrillo and Vanessa Di Pietro and Desy De Lorenzis and Roberto Rosato and Francesca Romana Monzo and Giovanni Cammarota and Stefano Bibbò and Irene Venturini and Debora Rondinella and Nausicaa Antonini},
  journal = {EBioMedicine},
  year = {2026},
  month = oct,
  doi = {10.1016/j.ebiom.2026.106509},
  url = {https://europepmc.org/article/MED/42849176},
  note = {CC BY},
}

TY  - JOUR
TI  - Immune effects of faecal microbiota transplantation in amyotrophic lateral sclerosis: a pilot multicentre, randomised, masked, sham-controlled, proof-of concept trial.
AU  - Elisabetta Zucchi
AU  - Elena Niccolai
AU  - Flavio De Maio
AU  - Riccardo Cuoghi Costantini
AU  - Gianluca Quaranta
AU  - Alessandra Guarnaccia
AU  - Stefano Bibbò
AU  - Ilaria Martinelli
AU  - Giulia Gianferrari
AU  - Cecilia Simonini
AU  - Giulia Nannini
AU  - Matteo Lulli
AU  - Simone Baldi
AU  - Gianluca Bartolucci
AU  - Roberto Vicini
AU  - Margherita Capasso
AU  - Giulia Bisogni
AU  - Amelia Conte
AU  - Paola Brunori
AU  - Giovanni Cammarota
AU  - Sabrina Paganoni
AU  - Roberto D'Amico
AU  - Amedeo Amedei
AU  - Luca Masucci
AU  - Jessica Mandrioli
AU  - Elisabetta Zucchi
AU  - Riccardo Cuoghi Costantini
AU  - Ilaria Martinelli
AU  - Giulia Gianferrari
AU  - Cecilia Simonini
AU  - Andrea Ghezzi
AU  - Roberta Bedin
AU  - Roberto D'Amico
AU  - Nicola Fini
AU  - Roberto Vicini
AU  - Annalisa Gessani
AU  - Francesca Prompicai
AU  - Silvia Parisi
AU  - Jessica Mandrioli
AU  - Elena Niccolai
AU  - Amedeo Amedei
AU  - Giulia Nannini
AU  - Matteo Lulli
AU  - Simone Baldi
AU  - Gianluca Bartolucci
AU  - Gianluca Quaranta
AU  - Luca Masucci
AU  - Alessandra Guarnaccia
AU  - Flavio De Maio
AU  - Giovanni Fancello
AU  - Chiara Agrillo
AU  - Vanessa Di Pietro
AU  - Desy De Lorenzis
AU  - Roberto Rosato
AU  - Francesca Romana Monzo
AU  - Giovanni Cammarota
AU  - Stefano Bibbò
AU  - Irene Venturini
AU  - Debora Rondinella
AU  - Nausicaa Antonini
PY  - 2026
DA  - 2026/10/08
JO  - EBioMedicine
DO  - 10.1016/j.ebiom.2026.106509
UR  - https://europepmc.org/article/MED/42849176
AB  - Background  The gut microbiota modulates peripheral immunity, which is altered in amyotrophic lateral sclerosis (ALS). Faecal microbiota transplantation (FMT) may exert immunological effects, but its impact in ALS remains unclear.Methods  FETR-ALS was a multicentre, randomised, masked, sham-controlled proof-of-concept trial conducted at four Italian ALS centres. Adults with ALS of 18 months duration or less and forced vital capacity of at least 70% predicted were randomly assigned (2:1) to receive FMT or a sham procedure (SP). The intervention consisted of two nasojejunal administrations of screened-donor faecal suspension at baseline and month 6, without antibiotic preconditioning. The primary endpoint was change in circulating Tregs among CD4⁺ T cells at 6 months. Secondary endpoints included safety, ALS Functional Rating Scale-Revised slope, respiratory and nutritional measures, survival, and exploratory biomarker profiles. Analyses followed the intention-to-treat principle.Clinicaltrials  gov identifier: NCT03766321.Findings  Between 2020 and 2024, 43 individuals were screened and 42 were enrolled and randomly assigned to FMT (n = 28; mean age 56.1 years [SD 8.2]; 14 [50%] male) or SP (n = 14; 59.6 years [9.1]; eight [57%] male). Overall, 29 participants completed the second procedure and 6-month follow-up, and Treg measurements were available for 28. The primary outcome was not met: at 6 months, 8/18 (44%) participant receiving FMT versus 2/10 (20%) receiving SP achieved a ≥20% increase in circulating Tregs (odds ratio [OR] 3.20, 95% CI 0.59-25.36; p = 0.21). Mean Treg increase was 2.36 percentage points higher with FMT (95% CI 0.19-4.55; p = 0.04). ALSFRS-R declined by -1.07 points/month in the SP group and -0.76 points/month in the FMT group, with a between-group difference in monthly decline of 0.31 points/month favouring FMT (95% CI 0.11-0.51; p = 0.002). Conversely, at month 6, the MRC score was lower in the FMT group than in the SP group (0.75 versus 0.89; mean difference -0.13, 95% CI -0.26 to 0.00; p = 0.042). FMT was associated with 32 adverse events (12.5% severe) versus 14 (28.6% severe) in SP, mostly gastrointestinal or infectious.Interpretation  In this exploratory trial, FMT was not associated with major safety concerns. Although the primary endpoint was not met, FMT was associated with a modest increase in circulating Tregs.Funding  Italian Ministry of Health.
SN  - 2352-3964
ER  -