Bakteria Akkermansia muciniphila zwiększa skuteczność przeszczepu oczyszczonej mikrobioty jelitowej w leczeniu epilepsji
Akkermansia muciniphila enhances washed microbiota transplantation in the treatment of epilepsy
W skrócie
Badanie wykazało, że przeszczep oczyszczonej mikrobioty jelitowej (специфicznych bakterii z jelit) może pomóc pacjentom z epilepsją, szczególnie gdy zawiera wystarczającą ilość bakterii Akkermansia muciniphila. U ponad połowy pacjentów leczonych tą metodą zmniejszyła się liczba napadów padaczkowych, a powtórzenie zabiegu po trzech miesiącach dało jeszcze lepsze rezultaty. Badania na myszach potwierdziły, że właśnie ta szczególna bakteria jest odpowiedzialna za zmniejszenie napadów padaczkowych.
Oryginalny abstract (angielski)
BACKGROUND: Refractory epilepsy remains a global clinical challenge. This first-in-human cohort study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT) in the treatment of epilepsy. METHODS: A prospective, single-center, open-label study of WMT in patients with epilepsy was conducted at the Second Affiliated Hospital of Nanjing Medical University from November 2016 to November 2023. The primary outcome was the clinical response rate (≥50% reduction in seizure frequency) at one month post-WMT. Parallel experiments using a pentylenetetrazole-induced epileptic mouse model were performed to validate clinical findings and investigate the role of specific core bacterial species. RESULTS: Among 21 patients (mean age, 18.9 years), including 18 with refractory epilepsy, the clinical response rates were 43% (9/21), 57% (12/21), and 38% (8/21) at one, three, and six months post-WMT, respectively. A second maintenance WMT course at three months was associated with a higher response rate at six months compared to no maintenance therapy (odds ratio [OR] >999, 95% confidence interval [CI]: [1.12, +infinity], P = 0.080). WMT significantly increased Akkermansia muciniphila (A. muciniphila) levels in responders (P = 0.038). A higher baseline A. muciniphila abundance was associated with improved clinical outcomes (Z = 3.28, P = 0.001). The preclinical study confirmed that A. muciniphila augmented the effects of WMT against seizures, significantly reducing seizure severity and duration, and prolonging seizure latency. CONCLUSIONS: Integrating clinical and preclinical findings, this study demonstrates that A. muciniphila synergistically enhances the effects of WMT against epileptic seizures. This study provides evidence for a new concept of microbiome-based therapeutics in epilepsy treatment. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02889627.