Lymphoid neoplasms encompass a heterogeneous group of malignancies with a predilection for immunocompromised individuals, and the disease burden of lymphoid neoplasms has been rising globally over the last decade. At the same time, mounting studies delineated a crucial role of the gut microbiome in the aetiopathogenesis of various diseases. Orchestrated interactions between myriad microorganisms and the gastrointestinal mucosa establish a defensive barrier for a range of physiological processes, especially immunity and metabolism. These findings provide new perspectives to harness our knowledge of the gut microbiota for preclinical and clinical studies of lymphoma. Here, we review recent findings that support a role for the gut microbiota in the development of lymphoid neoplasms and pinpoint relevant molecular mechanisms. Accordingly, we propose the microbiota-gut-lymphoma axis as a promising target for clinical translation, including auxiliary diagnosis, novel prevention and treatment strategies, and predicting clinical outcomes and treatment-related adverse effects of the disease in the future. This review will reveal a fascinating avenue of research in the microbiota-mediated lymphoma field.

Gut microbiota represents a hidden treasure vault encompassing trillions of microorganisms that inhabit the intestinal epithelial barrier of the host. In the past decade, numerous in-vitro, animal and clinical studies have revealed the profound roles of gut microbiota in maintaining the homeostasis of various physiological functions, especially immune modulation, and remarkable differences in the configuration of microbial communities between cancers and healthy individuals. In addition, although considerable efforts have been devoted to cancer treatments, there remain many patients succumb to their disease with the incremental cancer burden worldwide. Nevertheless, compared with the stability of human genome, the plasticity of gut microbiota renders it a promising opportunity for individualized treatment. Meanwhile, burgeoning findings indicate that gut microbiota is involved in close interactions with the outcomes of diverse cancer immunotherapy protocols, including immune checkpoint blockade therapy, allogeneic hematopoietic stem cell transplantation, and chimeric antigen receptor T cell therapy. Here, we reviewed the evidence for the capacity of gut microflora to modulate cancer immunotherapies, and highlighted the opportunities of microbiota-based prognostic prediction, as well as microbiotherapy by targeting the microflora to potentiate anticancer efficacy while attenuating toxicity, which will be pivotal to the development of personalized cancer treatment strategies.

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