Interference of human microbiome with cancer therapeutics

Kanikah Mehndiratta, MSc, University of Glasgow

Human microbiome constitutes various microorganisms and their genomes, residing on the skin or inside organ systems. Inside the body, these microbes are known to be involved in many intricate metabolic pathways. This automatically gives them an opportunity to interfere in different diseases and their treatments.

Devising successful therapeutics against cancer has been a challenge for scientists. Studies have also reported association between response of a patient to a cancer treatment with his microbiome. Specific bacteria, fungi, viruses, and protozoans could be responsible for cancer treatment-related toxicity. However, not much is known about the kind of interaction that interferes with treatment efficacy/toxicity. To find answers in this field, a recent study published in the BMC Cancer journal is found to review the association of gut microbiome with different cancer therapies.

The gut microbiome

Trillions of microbes are interacting with host cells constantly at various sites in the body. The gut microbiome is an essential part of this community and is involved in modulation of various metabolic pathways. Residing in the gastrointestinal tract, an abnormality in their type or number, called Dysbiosis could result in various illnesses. That is why, many people emphasize the use of probiotics to maintain a healthy gut environment. These health issues do not pertain only to the digestive tract but also include neurological, respiratory, and metabolic illnesses.

Cancer has led to millions of deaths every year globally. Several researchers have identified the dominant role of the host’s immune system in carcinogenesis, cancer control, progression, and therapeutic responses. Mutational load, tumour metabolism, and sensitivity of tumour to immune effectors are considered tumour-centric markers when discussing the host’s response to treatment. But many other factors could be involved in a therapeutic response such as overall immune status and tumour microenvironment. An infiltration of immune cells with tumour cells could potentially be stimulatory or inhibitory in generation of immune responses. New studies are demonstrating mediation of treatment-related toxicity by changing constituents of the gut microbiome.

Interference of intra-tumour microbiota with immunity

Techniques such as NGS have helped identify specific microbial species and their abundance in patients undergoing cancer therapies. The study of interest here used PubMed, Embase and various other databases to review interference of the gut microbiota in tumour associated host’s immunity. It emphasizes on the utilization of immune checkpoint inhibitors (ICIs) while devising therapeutics against cancer. Monoclonal antibodies that target programmed death receptors, associated ligands, and cytotoxic T lymphocyte receptors could prove revolutionary in improving cancer prognosis.

Impact of gut microbiota in specific tumour response to ICIs has been reported in various preclinical mouse models. Same mouse strains but purchased from different sources, thus with different gut microbiomes, respond differently to ICI therapy against melanoma. Gut dysbiosis can also induce resistance to ICI therapy, affect its efficacy and potentially cause side-effects. Mice with healthier gut microbiomes exhibit better treatment efficacy.

The basis of interference in cancer therapy

The study concludes that interaction between the gut microbiome and the patient’s immune system could be the basis of interference with his cancer therapy. The review also concludes that in metastatic melanomas, Bacteriodetes act as biomarkers against ICI therapy. They can attenuate immunity against tumour and may decrease response rate. This could lead to lesser risk of ICI-induced colon inflammation. Other bacterial species such as Bacteroides caccae and B. thetaiotamicron would rather improve the effectiveness of an immune response. Much more substantial research is needed in the area in order to improve efficacy of treatments and counter associated side-effects.

Also read: Fetal membranes can heal themselves

References:

Yu, Z.-K., Xie, R.-L., You, R., Liu, Y.-P., Chen, X.-Y., Chen, M.-Y., & Huang, P.-Y. (2021). The role of the bacterial microbiome in the treatment of cancer. BMC Cancer, 21(1), 934. https://doi.org/10.1186/s12885-021-08664-0

2. Gopalakrishnan, V., Helmink, B. A., Spencer, C. N., Reuben, A., & Wargo, J. A. (2018). The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy. Cancer Cell, 33(4), 570–580. https://doi.org/10.1016/j.ccell.2018.03.015

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Author info:

Kanikah Mehndiratta is an avid researcher in the field of Genetics with a background in Biotechnology. She is a postgraduate from the University of Glasgow in their Medical Genetics and Genomics program. Currently, based in Chandigarh as a scientific writer, she involves herself mainly in projects related to neurological disorders. Outside of academics, she likes to read novels, travel and is involved in volunteer work mostly.

LinkedIn profile- https://www.linkedin.com/in/kanikah-mehndiratta-301830171

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