Faecal microbiota transplantation for sleep disturbance in post-acute COVID-19 syndrome, 2024, Lau et al

Faecal microbiota transplantation for sleep disturbance in post-acute COVID-19 syndrome
Raphaela I. Lau, Qi Su, Jessica Y.L. Ching, Rashid N. Lui, Ting Ting Chan, Marc T.L. Wong, Louis H.S. Lau, Yun Kwok Wing, Rachel N.Y. Chan, Hanson Y.H. Kwok, Agnes H.Y. Ho, Yee Kit Tse, Chun Pan Cheung, Moses K.T. Li, Wan Ying Siu, Chengyu Liu, Wenqi Lu, Yun Wang, Emily O.L. Chiu, Pui Kuan Cheong, Francis K.L. Chan, Siew C. Ng

Abstract
Background & Aims
Post-acute COVID-19 syndrome (PACS) is associated with sleep disturbance but treatment options are limited. The aetiology of PACS may be secondary to alterations in the gut microbiome. Here, we report the efficacy of faecal microbiota transplantation (FMT) in alleviating post-COVID insomnia symptoms in a non-randomised, open-label prospective interventional study.
Methods
Between September 22, 2022 and May 22, 2023, we recruited 60 PACS patients with insomnia defined as Insomnia Severity Index (ISI) ≥ 8 and assigned them to the FMT group (FMT at weeks 0, 2, 4 and 8; n=30) or the control group (n=30). The primary outcome was clinical remission defined by an ISI of less than eight at 12 weeks. Secondary outcomes included changes in the Pittsburgh Sleep Quality Index (PSQI), Generalised Anxiety Disorder-7 scale (GAD-7), Epworth Sleepiness Scale (ESS), Multidimensional Fatigue Inventory (MFI), blood cortisol and melatonin, and gut microbiome analysis on metagenomic sequencing.
Results
At week 12, more patients in the FMT than the control group had insomnia remission (37.9% vs 10.0%; p=0.018). The FMT group showed a decrease in ISI score (p<0.0001), PSQI (p<0.0001), GAD-7 (p=0.0019), ESS (p=0.0057) and blood cortisol concentration (p=0.035) from baseline to week 12, but there was no significant change in the control group. There was enrichment of bacteria such as Gemmiger formicilis and depletion of microbial pathways producing menaquinol derivatives after FMT. Gut microbiome profile resembled that of the donor in FMT responders but not in non-responders at week 12. There was no serious adverse event.
Conclusion
This pilot study showed that FMT could be effective and safe in alleviating post-COVID insomnia and further clinical trials are warranted. ClinicalTrials.gov identifier: NCT05556733.

Competing interests
All authors have completed the Unified Competing Interest form (available on request from the corresponding author). FKLC is Board Member of CUHK Medical Centre. He is a co-founder, non-executive Board Chairman, non-executive scientific advisor, Chief Medical Officer and shareholder of GenieBiome Ltd. He receives patent royalties through his affiliated institutions. He has received fees as an advisor and honoraria as a speaker for Eisai Co. Ltd., AstraZeneca, Pfizer Inc., Takeda Pharmaceutical Co., and Takeda (China) Holdings Co. Ltd. SCN has served as an advisory board member for Pfizer, Ferring, Janssen, and Abbvie and received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, Abbvie, and Takeda. SCN has received research grants through her affiliated institutions from Olympus, Ferring, and Abbvie. SCN is a founder member, non-executive director, non-executive scientific advisor and shareholder of GenieBiome Ltd. SCN receives patent royalties through her affiliated institutions. QS, FKLC and SCN are named inventors of patent applications held by the CUHK and MagIC that cover the therapeutic and diagnostic use of microbiome. No other potential conflict of interest relevant to this article was reported.

Link (Clinical Gastroenterology and Hepatology, Paywall)