Unravelling the role of intratumoral bacteria in digestive system cancers: current insights and future perspectives

Abstract

Recently, research on the human microbiome, especially concerning the bacteria within the digestive system, has substantially advanced. This exploration has unveiled a complex interplay between microbiota and health, particularly in the context of disease. Evidence suggests that the gut microbiome plays vital roles in digestion, immunity and the synthesis of vitamins and neurotransmitters, highlighting its significance in maintaining overall health. Conversely, disruptions in these microbial communities, termed dysbiosis, have been linked to the pathogenesis of various diseases, including digestive system cancers. These bacteria can influence cancer progression through mechanisms such as DNA damage, modulation of the tumour microenvironment, and effects on the host's immune response. Changes in the composition and function within the tumours can also impact inflammation, immune response and cancer therapy effectiveness. These findings offer promising avenues for the clinical application of intratumoral bacteria for digestive system cancer treatment, including the potential use of microbial markers for early cancer detection, prognostication and the development of microbiome-targeted therapies to enhance treatment outcomes. This review aims to provide a comprehensive overview of the pivotal roles played by gut microbiome bacteria in the development of digestive system cancers. Additionally, we delve into the specific contributions of intratumoral bacteria to digestive system cancer development, elucidating potential mechanisms and clinical implications. Ultimately, this review underscores the intricate interplay between intratumoral bacteria and digestive system cancers, underscoring the pivotal role of microbiome research in transforming diagnostic, prognostic and therapeutic paradigms for digestive system cancers.

Keywords: Digestive system cancers; Functions; Intratumoral bacteria; Mechanisms; Therapeutic strategy.

Fig. 1

The pivotal roles of intratumoral bacteria in the pathogenesis of gastrointestinal cancers. Diverse gastrointestinal cancers exhibit significant alterations in the diversity and abundance of bacterial communities, with strong links to cancer progression. The enrichment and colonisation of specific bacterial populations within tumour tissues lead to significant reshaping of the tumour microenvironment. Through various direct and indirect mechanisms, these bacteria contribute to cancer development by promoting chronic inflammation, inducing DNA damage and enhancing cellular proliferation and invasion. Moreover, the bacteria associated with digestive system cancers exert a dual role in cancer dynamics, capable of both driving and impeding tumour progression. Their influence extends across multiple malignant processes, including immune system evasion, persistent inflammation stimulation and genetic instability promotion within host cells

Fig. 2

Major characteristic alterations and molecular mechanisms of intratumoral bacteria in digestive system cancers. In digestive system cancers, significant changes in the diversity and abundance of bacterial communities underscore an abnormal bacterial landscape, highlighting their significant roles in cancer development. These aberrant bacterial communities influence cancer progression through a myriad of mechanisms, engaging in both direct and indirect interactions. Directly, bacteria interact with cancer cells or modulate the tumour microenvironment, whereas indirectly, they exert effects through the secretion of virulence factors or the generation of metabolic byproducts. Such interactions significantly affect cancer-associated molecular pathways and cellular processes, thereby playing a critical role in the regulation of tumour progression. Therefore, these altered bacteria are implicated in various malignant processes. They contribute to the proliferation and invasion of tumour cells, facilitate the epithelial-mesenchymal transition (EMT) and regulate inflammation, apoptosis, immune evasion and bile acid metabolism. Furthermore, they influence oxidative stress and DNA damage, underscoring their comprehensive impact on the pathogenesis of digestive system cancers

Fig. 3

Clinical potential of intratumoral bacteria in digestive system cancers The unique bacterial signatures correlated with various stages and types of digestive system cancers offer novel avenues for utilising certain bacterial species as non-invasive biomarkers, with promise potential as early detection and accurate diagnostic markers of digestive system cancers. In terms of prognosis, the composition of bacterial communities within tumours is intricately linked to a range of clinicopathological features and can profoundly influence survival outcomes. Therapeutically, innovative approaches targeting these bacterial populations and their metabolic outputs have shown promising results. The strategic application of antibiotics, probiotics and faecal microbiota transplantation has been found to significantly inhibit tumour growth. Furthermore, these microbial-based therapies enhance the sensitivity of tumours to conventional chemotherapies and immunotherapies