Nurturing the non-human
Research on the ‘human microbiome’ continues to explore the complex interactions between our population of resident and transient microbes, and a plethora of functions and aspects of health. Influencing immune function, metabolic health, inflammation and even mental health, have all been described as effects of microbiome – host interactions (1).
The nature and effects of the microbiome – technically the sum of the DNA of our microbiota – offer a wealth of opportunity for research and potentially for clinically interventions, particularly in the context of cancer. This topic has moved gradually from a theoretical and even ‘fringe’ interest, to the scientific mainstream, and today the microbiome attracts considerable popular interest. As any good research topic should, it offers more questions than answers, but in our forthcoming BSIO webinar, we will attempt to address some common questions that arise in applying evidence to some aspects of the integrative nutritional care of people affected by cancer.
As a microbiologist and nutritionist, I have a long-standing interest in this field, from which some very significant findings have recently emerged. When I started my first microbiology lab post in the 1980’s, I could not have imagined either the toolkit of today’s microbiologists, nor the wealth of knowledge that would emerge on the complexities of the relationships with our non-human inhabitants. Microbiome research in the cancer field now spans almost the entire spectrum of interest from primary cancer biology and understanding of disease mechanisms, through public health and cancer prevention, to treatment optimisation and patient activation.
Changes in the intestinal microbiome and colorectal carcinogenesis are now well documented, with certain pro-inflammatory species such as Fusobacterium nucleatum implicated (2). Exploration of the microbiome in other cancers reveals that this particular species, and others that also appear implicated in periodontal disease, may also be implicated in malignancy of the pancreas (3). Although the search for specific ‘causative’ species continues, more complex and dynamic disturbances in the gut microbiome in various disease states are now evident (4).
It has been suggested that different patterns of microbiome disturbance appear associated with different cancers, for example considerable differences are reported between liver and colorectal cancer (5). However, there is no clear proof that these changes are causative, or even contributory, but may merely represent the exquisite ability of microbes to adapt to a changing environment and utilising whatever nutrients are present. To add a further layer of complexity, the aforementioned cancer microbiome studies focus solely on bacterial species, whereas the ‘microbiome’ in its entirety includes the fungal species comprising the mycobiome, as well as viruses, helminths and assorted other microscopic species6, which themselves interact with the bacterial microbiome. Relationships between microbiome species and with the host are highly dynamic, with nutrients shuttling between neighbours in networks within the intestinal lumen. Incidentally, the intestinal mycobiome also appears perturbed in malignancy (6).
Beyond intestinal microbiome interactions that may impinge on the development of malignancy in the gastrointestinal and biliary tracts, interactions also take place in the respiratory (7) and urogenital (8) microbiome niches. In all of these niches, local immunity may be influenced by the microbiome, although the gut microbiome appears to predominates in interactions that influence systemic immunity (9).
Despite some pockets of resistance, it is now widely accepted that the most powerful influence on the human microbiome is what we put on our plates (10). It is also now apparent that microbiome response to dietary intake is also highly individual (11), variable over time, and has a considerable influence on immunity (12). This also implies that a ‘one-size-fits-all’ diet may not reflect best practice for microbiome ‘optimisation’.
A handful of milestone studies (13) illustrating an association between response to immunotherapy and patients’ intestinal microbiome, marked the start of a journey. A number of studies now in progress are exploring the effects of microbiome manipulation on treatment outcomes. Faecal microbiome transplantation, probiotics (supplements of living microbes), prebiotics (supplements of nutrients for microbes) and dietary interventions are potential tools being studied (13). Some surprising results so far illustrate how little certainty there is for some very narrow interventions. For example, questions have emerged on the choice of probiotic supplements, and whether they may have negative effects on microbiome diversity; in one study in melanoma patients, probiotics compared unfavourably with improved dietary diversity (14). The influence of nutritional intake on obesity also implicates a role for the microbiome and may have immunotherapy implications (15).
If the early data are confirmed, and a direct impact of dietary intake on some cancer treatment outcomes is demonstrated, this moves nutritional interventions to centre-stage. However, we don’t need to wait for the evidence that diet matters to immunotherapy outcomes - with the evidence already in hand, we know that patient well-being improves with better nutritional intake. Integrative clinicians can support patients with appropriate advice that supports a ‘healthier’ microbiome and empowers patients to play an active part in their treatment and recovery.
Moving beyond nutritional considerations, some useful areas of knowledge are emerging about use of antimicrobials and colorectal cancer risk, with a Swedish cancer registry study published this month (16) suggesting a positive association, concurring with other observational studies (17). These may inform future practice and will be interesting to see future data on the impact of antimicrobial use on CRC recurrence. Life-saving antimicrobials are indispensable in immunocompromised patients, so evidence that informs their efficacious use will be particularly welcome, especially in the age of widespread antibiotic resistance.
Author
Dr Carol Granger, DProf MSc MRSB CBiol FBANT
Carol is a registered nutrition practitioner with an honours degree in biochemistry and a Master’s in microbiology. As a Chartered Biologist she had two decades in bioscience research, diagnostics and medical technology before retraining in nutrition. Carol is one of the company directors and an Executive Committee member of the British Society for Integrative Oncology (BSIO), Co-Chair of the Research Council for Complementary Medicine, and contributes to the NIHR research collaboration on nutrition and cancer
References
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14. Spencer, C.N., Gopalakrishnan, V., McQuade, J., Andrews, M.C., Helmink, B., Khan, M.W., Sirmans, E., Haydu, L., Cogdill, A., Burton, E. and Amaria, R., 2019. The gut microbiome (GM) and immunotherapy response are influenced by host lifestyle factors.
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