Pre‐Administration of Akkermansia Muciniphila Prevents the Development of Severe Acute Graft‐Versus‐Host Disease in Systemic Organs

Akkermansia muciniphila, a next‐generation probiotic, alleviates acute graft‐versus‐host disease (aGvHD) following allogeneic hematopoietic stem cell transplantation (HSCT) by providing protective effects across multiple organs. Pre‐colonization with A. muciniphila improves survival and reduces disease severity by stabilizing the gut microbiome, preserving intestinal barrier integrity, restoring bile acid metabolism, and reprogramming disease‐associated transcriptomic and microRNA profiles. A. muciniphila enhances protective metabolites such as tauroursodeoxycholic acid (TUDCA) and suppresses intestinal miR‐155 expression, leading to reduced pro‐inflammatory cytokine production, improved immune homeostasis, and maintenance of gut barrier function. Abstract Acute graft‐versus‐host disease (aGvHD) remains a significant clinical challenge, with no optimal treatment despite advancements in medical science. This life‐threatening condition, characterized by multi‐organ involvement and high mortality, is increasingly linked to the gut microbiota. Therefore, this study investigates the protective effects of Akkermansia muciniphila on aGvHD, focusing on its capacity to modulate the gut microbiome and reduce disease symptoms. A. muciniphila is orally administered to mice prior to inducing aGvHD through allogeneic hematopoietic stem cell transplantation. The effects of A. muciniphila administration on the development of aGvHD are assessed through disease activity scoring, histological analysis, metabolite and immune profiling, and gut microbiota analyses. Pre‐administration of A. muciniphila significantly reduces aGvHD severity, particularly in the gastrointestinal tract, alleviates gut dysbiosis, and increases the levels of metabolites such as tauroursodeoxycholic acid and short‐chain fatty acids. These findings provide the basis for new therapeutic strategies for aGvHD and contribute to improving treatment outcomes for patients with intractable diseases. Akkermansia muciniphila, a next-generation probiotic, alleviates acute graft-versus-host disease (aGvHD) following allogeneic hematopoietic stem cell transplantation (HSCT) by providing protective effects across multiple organs. Pre-colonization with A. muciniphila improves survival and reduces disease severity by stabilizing the gut microbiome, preserving intestinal barrier integrity, restoring bile acid metabolism, and reprogramming disease-associated transcriptomic and microRNA profiles. A. muciniphila enhances protective metabolites such as tauroursodeoxycholic acid (TUDCA) and suppresses intestinal miR-155 expression, leading to reduced pro-inflammatory cytokine production, improved immune homeostasis, and maintenance of gut barrier function. Abstract Acute graft-versus-host disease (aGvHD) remains a significant clinical challenge, with no optimal treatment despite advancements in medical science. This life-threatening condition, characterized by multi-organ involvement and high mortality, is increasingly linked to the gut microbiota. Therefore, this study investigates the protective effects of Akkermansia muciniphila on aGvHD, focusing on its capacity to modulate the gut microbiome and reduce disease symptoms. A. muciniphila is orally administered to mice prior to inducing aGvHD through allogeneic hematopoietic stem cell transplantation. The effects of A. muciniphila administration on the development of aGvHD are assessed through disease activity scoring, histological analysis, metabolite and immune profiling, and gut microbiota analyses. Pre-administration of A. muciniphila significantly reduces aGvHD severity, particularly in the gastrointestinal tract, alleviates gut dysbiosis, and increases the levels of metabolites such as tauroursodeoxycholic acid and short-chain fatty acids. These findings provide the basis for new therapeutic strategies for aGvHD and contribute to improving treatment outcomes for patients with intractable diseases. Advanced Science, EarlyView.