The human body comprises a mixture of mammalian and microbial cells, with the latter exceeding the former by nearly tenfold. The microbial genetic repertoire is approximately 100-fold more abundant than that of the human host. Beyond bacteria, the human commensal microbiome consists of viruses, archaea, fungi, and other eukaryotic species. Commensal microbes inhabit at all mucosal barrier surfaces, with the distal gastrointestinal (GI) tract residing the most abundant population. The commensal microbiome is physiologically beneficial to the human host, but perturbed microbiota components or a disrupted mucosal environment could drive immune pathology and systemic inflammation that affects human health. Microbiome dysbiosis contributes to the development of enteritis, pneumonia, and cancer.

Cancer is a threat to human health worldwide owing to the high morbidity and mortality rates. All cancer cells are characterized by common hallmarks, including transformation, unrestricted growth, and progression. Various factors have been identified that contribute to cancer initiation and progression, including gene mutations, suppressed immune responses, and a complex tumor microenvironment (TME). The tumorigenic and immunomodulatory roles of abnormal microbiomes are now recognized. The existence of the microbiome in tumor sites has been widely validated and accepted, and their effects on oncogenesis and progression have been extensively studied. The interplay between the commensal microbiome and clinical treatment efficacy has also been proposed. The intimate interconnection between cancer and microbiota was documented as early as 1550 BCE when tumors were treated by incisions and poultices. However, early attempts to apply microbiota to cancer treatment failed. A limited mechanistic foundation might explain this, as technology that could detect low microbiome biomass was restricted. Current research into microbiota and cancer is supported by methods and technologies such as immunohistochemistry, quantitative PCR, immunofluorescence, fluorescence in situ hybridization, electron microscopy, and 16S rRNA sequencing.

The contribution of gut microbiota in cancer initiation, progression, and drug resistance has been thoroughly investigated. The gut microbiota can affect responses to chemo- and immunotherapeutic agents by modulating their efficacy or toxicity Therapeutic interventions to modulate microbiota composition to improve immunotherapy efficacy in mouse models have been promising. Subsequent endeavors have also translated preclinical findings into early-stage clinical tests with encouraging outcomes. Apart from the gut microbiota, the existence and functional importance of intratumor microbiota in cancer remain contentious. This review summarizes the roles of the intratumor microbiota in the tumor microenvironment, responses to therapies, and potential strategies that might facilitate better outcomes of cancer treatment.

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