<i>Holdemanella biformis</i> augments washed microbiota transplantation for the treatment of radiation enteritis
Weihong Wang, You Yu, Rui Wang, Yaxue Wang, Xiao Ding, Gaochen Lu, Lu Chen, Chenchen Liang, Sheng Zhang, Bo Yi, Jianling Bai, Lizhen Zhang, Pan Li, Quan Wen, Bota Cui, Faming Zhang
Abstract
BACKGROUND: Current microbiome-based therapeutics face two prominent issues: the limited clinical efficacy of probiotics and the significant variability in the efficacy of microbiota transplantation across different diseases. Although washed microbiota transplantation (WMT) is a new faecal microbiota transplantation, a single therapeutic agent cannot be universally effective for multiple dysbiosis-related diseases. OBJECTIVE: We introduced a new therapeutic concept, X-augmented WMT (X-auWMT), which combines a disease-specific beneficial microbe, 'X', with WMT to enhance its effectiveness. Our goal was to identify a candidate 'X' bacterium to augment WMT efficacy and examine the efficacy of X-auWMT in animal models of radiation enteritis (RE). DESIGN: We conducted a prospective, non-randomised cohort study on a cohort of abdominal or pelvic cancer patients who developed RE after radiotherapy to identify a potential beneficial microbe. We used RE mouse models to evaluate the efficacy of X-auWMT compared with WMT. Multiomics analyses and experiments were undertaken to elucidate the underlying mechanisms. RESULTS: as a candidate 'X' bacterium within the RE cohort and developed Hb-auWMT. Hb-auWMT significantly mitigated radiation-induced injury compared with WMT, exhibiting enhanced anti-apoptotic effects, improved maintenance of epithelial hypoxia, increased Treg cell levels and elevated butyrate and valerate levels in the RE mouse model. PPAR-γ is an essential pathway for the therapeutic efficacy of Hb-auWMT. CONCLUSIONS: This study overcomes the aforementioned recognised limitations with probiotics and microbiota transplantation and provides a new research paradigm in the concept of microbiome-based therapeutics.