The gut-immune axis in primary immune thrombocytopenia (ITP): a paradigm shifts in treatment approaches

Abstract

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet destruction and impaired production, leading to bleeding risk. While immunosuppressive therapies are standard, many patients experience relapses or refractory disease, highlighting the need for novel approaches. Emerging evidence suggests the gut microbiota plays a role in immune regulation, yet its impact on ITP remains unclear. Dysbiosis has been linked to immune dysfunction in other autoimmune diseases, but whether it drives or results from immune dysregulation in ITP is debated. This review explores the gut-immune axis in ITP, focusing on microbiota-driven immune modulation, cytokine signaling, and platelet homeostasis. We assess microbiota-targeted interventions, including fecal microbiota transplantation (FMT), probiotics, and dietary modifications, while addressing key controversies and knowledge gaps. Advances in microbiome sequencing and artificial intelligence may facilitate personalized interventions. Standardizing microbiota-based diagnostics and validating their efficacy in clinical trials are crucial for their integration into ITP management. Bridging these gaps may lead to microbiota-driven strategies that enhance immune regulation and improve patient outcomes.

Keywords: gut-immune axis; immune dysregulation; microbiota-based therapy; platelet homeostasis; primary immune thrombocytopenia (ITP).

Figure 1

Interactions between gut microbiota, systemic organs and the immune system. The gut microbiota plays a central role in regulating immune function, metabolism, and overall systemic health through interactions with multiple organ systems. This schematic illustration depicts how bacteria, viruses, fungi, and archaea influence host physiology by modulating immune responses, metabolic processes, and disease development. Dysbiosis has been implicated in various conditions, including autoimmune diseases, neurodegenerative disorders, metabolic syndromes, and inflammatory diseases. Key organ systems affected by alterations in microbiota include the immune system, colon, liver, and pancreas. In immune system, the gut microbiota regulates Tregs, Th1/Th17 responses, and inflammation. In the colon, microbial communities influence gut barrier integrity and are associated with inflammatory bowel diseases. In the liver, the gut-derived metabolites affect metabolic conditions such as non-alcoholic fatty liver disease (NAFLD). In the pancreas, microbiota alterations have been associated with type 2 diabetes and other metabolic disorders. In the bloodstream, microbial dysbiosis is linked to hematologic conditions, including immune thrombocytopenia (ITP). In the brain, microbiota-derived metabolites have been implicated in neurological conditions such as Alzheimer’s disease, depression, and neuroinflammation. By modulating microbial composition and function, the gut microbiota exerts local and systemic effects that contribute to immune homeostasis, disease pathogenesis, and potential therapeutic interventions.

Figure 2

Gut microbiota balance and immune modulation. (A) In a normal gut microbiota environment, commensal bacteria such as Vibrio and Bacillus interact with intestinal epithelial cells to maintain immune homeostasis. This balance promotes the differentiation of regulatory T cells (Treg) and immune tolerance while preventing excessive inflammation driven by Th1 and Th17 cells. A balanced gut microbiota contributes to a well-regulated immune system by enhancing gut barrier integrity and modulating host immune responses. (B) In a state of gut microbiota imbalance (known as dysbiosis), there is an overrepresentation of pathogenic bacteria and viruses, along with a reduction in beneficial microbial populations. This microbial shift disrupts gut barrier function, leading to increased bacterial translocation and heightened immune activation. Dysbiosis skews immune regulation by reducing Treg activity and increasing Th1 and Th17 responses, promoting systemic inflammation and immune dysregulation. Such alterations in the gut microbiota may contribute to autoimmune conditions, including ITP, by exacerbating inflammatory pathways and impairing immune tolerance.

Figure 3

Overview of microbiota-based biomarkers and diagnostic approaches in ITP. This figure illustrates the role of microbiota profiling in the diagnosis and management of immune thrombocytopenia (ITP). (A) Microbial signatures in ITP highlight key alterations in bacterial taxa, including decreased Bacteroides and Firmicutes, and increased Enterobacteriaceae, which are associated with immune dysregulation and platelet destruction. (B) A comparison of diagnostic tools—metagenomic sequencing, 16S rRNA sequencing, microbiota biomarker panels, and multi-omics integration—highlighting their benefits and limitations for clinical application in ITP. (C) Clinical applications and future perspectives include predictive models for early detection, personalized treatment strategies integrating probiotics and dietary interventions, and longitudinal monitoring to assess disease progression and therapeutic responses. This schematic underscores the potential of microbiota-based diagnostics in improving precision medicine approaches for ITP management.