A number of studies have also shown that an imbalance in the gut microbiome can contribute to a wide range of diseases, including allergies, depression, inflammatory bowel disease, obesity, type 2 diabetes and certain cancers[4,5].
What is the Gut Microbiome?
We commonly associate microbes, such as bacteria and viruses, with causing infections. However, in contrast with microbes that can invade our bodies and cause infection, a huge number and diversity of microbes live in and on our bodies. These have a significant benefit to our health. The community of these microbes is thought to be just above the number of cells in our own body [1].
These ‘helpful’ microbes are found in many locations including the skin, gut, oral cavities, vaginal lining and respiratory airways, and help support our normal tissue and organ functions. By far the greatest amount are found in our gut, the majority of which are bacteria. Their collective name is the gut microbiota, and when talking about these and the environment they are in, it is referred to as the ‘gut microbiome’.
Over the last two decades, there has been a huge increase in research to try and understand the relationship between the gut microbiome and us. Studies have shown that the microbes in the gut are essential for maintaining good health, including protection against disease, digestion, metabolism, and blood glucose regulation[2,3].
What constitutes a healthy adult gut microbiome?
The make-up of a healthy adult’s microbe population can be very different between individuals. Therefore, there is no single blueprint. However, we do know that certain bacteria categories have beneficial effects in the gut, whilst others are detrimental.
Diversity in the bacteria in the gut microbiome is beneficial and diet is a significant factor that can increase this diversity[6,7].
“There is no single blueprint for a healthy gut microbiome…. a dominance of beneficial bacterial categories, where there is lots of diversity in the different types present, is considered best”.
How do I gain a healthy gut microbiome?
Many studies have shown that a high-fibre diet is hugely beneficial (>30g fibre a day)[7,8]. The fibre acts as food for the good bacteria. Fibre-rich foods include: whole-grain foods such as wholemeal bread, whole-wheat cereal, brown rice, oats, plain popcorn; fibrous vegetables including peas, broccoli, baked potatoes with skin on; fruit rich in fibre for example pears, apples, raspberries and bananas; pulses like brown lentils, baked beans, black beans and chick peas; nuts such as raw brazil nuts and raw almonds.
Another suggestion is trying to eat at least thirty different types of plant products a week — ‘Thirty for Diversity,’ including as many different varieties of fruit, vegetables, pulses, nuts, spices and herbs as possible[9]. Herbs and spices count as a ¼ point towards your quota of 30 and 1 portion of fruits, vegetables, beans, pulses, seeds and nuts count as 1 point. In essence, variety is key and one study has shown that eating 30 different plant points or more compared to those who eat 10 per week had a far more diverse microbiome.
Brightly coloured plant products often contain polyphenols that are also thought to be beneficial, for example turmeric and berries. Tea and coffee also contain a type of polyphenol known as flavonoids.
Prebiotics are foods which help feed the good bacteria. Examples include raw garlic, chicory, onion, asparagus, bananas and apples.
Probiotics are different. These introduce beneficial bacteria into the gut. Examples of these include fermented foods like kimchi, sauerkraut, miso and also live yoghurts such as kefir. Some yoghurt drinks that mention they contain a ‘good bacteria’ should be avoided as they contain a single strain and lower diversity.
High levels of saturated fats (e.g butter, animal fats) and animal proteins have been shown to have a unhelpful effect on the human gut microbiome. Alcohol also has a negative impact [10].
“A high-fibre diet is hugely beneficial. Another good rule is eating at least thirty different types of plant products a week — sometimes called ‘Thirty for Diversity.’ These can include as many different varieties of fruit, vegetables, pulses, nuts, spices and herbs as possible”.
Immunotherapy response in melanoma
Some patients with a diagnosis of melanoma are offered treatment with immunotherapy. In two separate studies in melanoma patients the best responses to immunotherapy were seen in patients who had a gut microbiome with a good diversity of healthy bacteria. Patients with a disrupted or unhealthy gut microbiome had a lower response [11,12,13]. This was further corroborated in a recent trial from a 2022 study by same research group[14] .
“the best responses to immunotherapy were seen in those who had a gut microbiome with a good diversity of healthy bacteria”
Antibiotic treatment during melanoma cancer treatment
Antibiotics cannot distinguish between the good bacteria in your gut microbiome, and the harmful bacteria that cause infection. This means that taking antibiotics for an infection can upset the balance in your gut microbiome.
There is some very early research to suggest that taking antibiotics before immunotherapy may be associated with less benefit from immunotherapy – it has been proposed that this could be because the antibiotics have disrupted the gut microbiome [15]. However, antibiotics can be an important part of treatment for bacterial infection and not enough research has happened yet for doctors to understand the possible impact of antibiotics on treatment for melanoma.
Until more evidence is available, it is worth bearing in mind that many infections are caused by viruses and will not not benefit from treatment with antibiotics[16]. If you have any concern about whether antibiotics are needed in your case, you can discuss this with your medical team.
Use of Proton-pump Inhibitors (PPIs) during melanoma cancer treatment
Proton-pump inhibitors (PPIs), such as omeprazole or lansoprazole, are a commonly used medicine in the general population. They are used to reduce the acid produced by the stomach to stop the symptoms of heartburn/acid-reflux. It can also be used in combination with other common medicines to protect the stomach lining from being damaged while taking them, for example, aspirin or steroid treatment.
In some new studies, there appears to be a theoretical risk of immunotherapy treatment being less effective if a patient also takes a PPI. [17,18,19,20] This may be because the PPI reduces the amount of acid in the stomach, therefore changing the environment of the gut (gastrointestinal tract) and affecting the healthy make-up of the gut microbiome.
There is strong evidence in other cancer patients having immunotherapy treatment, and less strong in melanoma patients. However, until more evidence becomes available, if you are regularly taking a PPI, or if during your immunotherapy treatment you are prescribed a PPI, please discuss this with your medical team to see if there is an alternative option available, such as famotidine.
Further information:
Dr Heather Shaw. Presentation 2021. Melanoma Patient conference.
Diet and Cancer
Why is it important to eat well during cancer treatment?
Cancer treatments disrupt the way cancer cells grow and divide but they can also affect normal cells. This can cause you to feel unwell. It is therefore very important to have a healthy balanced diet appropriate to your specific needs during your treatment to keep you as well as possible. This can help you recover faster and support your body during your treatment.
Why is it important for me to keep my weight stable during my treatment?
Research has shown that people who maintain a stable weight through cancer treatment live longer and have better quality of life. It is therefore important not to lose weight during your cancer treatment even if you are overweight.
Why should I eat a healthy diet?
You should follow a healthy diet if:
You are coping well with treatment
You are not suffering with side effects or symptoms that are affecting your food intake
If you have not lost weight
If you have gained weight during your treatment
If you are managing well with your cancer treatment and are not having problems with eating and do not have a poor appetite you should aim to have a healthy balanced diet and keep your weight stable.
What should I do if I’m losing weight or struggling to eat properly?
When you are having cancer treatment you should aim to stay a stable weight. If you are losing weight you may need to make some changes to your diet. If your appetite is reduced it is important to make the most of each mouthful of food. There are several ways you can do this. Foods high in fat, protein and sugar provide lots of energy in small portions, making it easier for you to eat what you need.
More information and videos
The St Luke’s Cancer dietitians in Guildford have a wealth of information on their webpages including a series of short videos which will provide you with evidence-based advice to support you during your cancer treatment. Please visit www.royalsurrey.nhs.uk/dietandcancer.
British Dietetic Association page on Challenging cancer myths and diet
https://www.bda.uk.com/resource/challenging-cancer-diets-myths.html
Relevant References:
[1] Sender R., Fuchs S., Milo R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell. 2016;164:337–340. doi:10.1016/j.cell.2016.01.013
[2] Hou, K., Wu, ZX., Chen, XY. et al. Microbiota in health and diseases. Sig Transduct Target Ther 7, 135 (2022). https://doi.org/10.1038/s41392-022-00974-4
[3] Durack J, Lynch SV. The gut microbiome: Relationships with disease and opportunities for therapy. J Exp Med. 2019 Jan 7;216(1):20-40. doi: 10.1084/jem.20180448.
[4] Vijay, A., Valdes, A.M. RETRACTED ARTICLE: Role of the gut microbiome in chronic diseases: a narrative review. Eur J Clin Nutr 76, 489–501 (2022). https://doi.org/10.1038/s41430-021-00991-6
[5] Baohong Wang, Mingfei Yao, Longxian Lv, Zongxin Ling, Lanjuan Li, The Human Microbiota in Health and Disease, Engineering, Volume 3, Issue 1, 2017, Pages 71-82, ISSN 2095-8099, https://doi.org/10.1016/J.ENG.2017.01.008
[6] Zhang P. Influence of Foods and Nutrition on the Gut Microbiome and Implications for Intestinal Health. Int J Mol Sci. 2022 Aug 24;23(17):9588. doi: 10.3390/ijms23179588
[7] Yang Q, Liang Q, Balakrishnan B, Belobrajdic DP, Feng QJ, Zhang W. Role of Dietary Nutrients in the Modulation of Gut Microbiota: A Narrative Review. Nutrients. 2020;12(2):381. Published 2020 Jan 31. doi:10.3390/nu12020381
[8] Tap J, et al. Gut microbiota richness promotes its stability upon increased dietary fibre intake in healthy adults. Environ Microbiol. 2015 Dec;17(12):4954-64. doi: 10.1111/1462-2920.13006
[9] https://zoe.com/learn/30-plants-per-week
[10] Purohit V, Bode JC, Bode C, et al. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Alcohol. 2008;42(5):349-361. doi:10.1016/j.alcohol.2008.03.131
[11] Lee KA, Shaw HM, Bataille V, Nathan P, Spector TD. Role of the gut microbiome for cancer patients receiving immunotherapy: Dietary and treatment implications. Eur J Cancer. 2020 Oct;138:149-155. doi: 10.1016/j.ejca.2020.07.026. Epub 2020 Sep 2. PMID: 32889369
[12] Gopalakrishnan et al., Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018 Jan 5; 359(6371):97-103
[13] Matson et al., The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018 Jan 5;359(6371):104-108. doi: 10.1126/science.aao3290. PMID: 29302014; PMCID: PMC6707353
[14] Lee, K.A., Thomas, A.M., Bolte, L.A. et al. Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma. Nat Med (2022). https://doi.org/10.1038/s41591-022-01695-5
[15] Pinato DJ, Howlett S, Ottaviani D, et al. Association of Prior Antibiotic Treatment With Survival and Response to Immune Checkpoint Inhibitor Therapy in Patients With Cancer. JAMA Oncol. 2019;5(12):1774–1778. doi:10.1001/jamaoncol.2019.2785
[16] Hicks, LA et al 2019. Improving outpatient antibiotic prescribing. BMJ 2019; 364 doi: https://doi.org/10.1136/bmj.l289
[17] Lee KA, Shaw HM, Bataille V, Nathan P, Spector TD. Role of the gut microbiome for cancer patients receiving immunotherapy: Dietary and treatment implications. Eur J Cancer. 2020 Oct;138:149-155. https://doi.org/10.1016/j.ejca.2020.07.026 Epub 2020 Sep 2. PMID: 32889369
[18] Wada A, et al. Proton pump inhibitors and antibiotics adversely effect the efficacy of nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Eur J Cancer. 2023 May;184:30-38. https://doi.org/10.1016/j.ejca.2023.02.011 Epub 2023 Feb 15. PMID: 36898232.
[19] Kawachi H, et al. Concomitant Proton Pump Inhibitor Use With Pembrolizumab Monotherapy vs Immune Checkpoint Inhibitor Plus Chemotherapy in Patients With Non-Small Cell Lung Cancer. JAMA Netw Open. 2023 Jul 3;6(7):e2322915. https://doi.org/10.1001/jamanetworkopen.2023.22915 PMID: 37432682; PMCID: PMC10336622.
[20] Homicsko K, et al.Proton Pump Inhibitor Use and Efficacy of Nivolumab and Ipilimumab in Advanced Melanoma. Cancers (Basel). 2022 May 5;14(9):2300. https://doi.org/10.3390/cancers14092300 PMID: 35565428; PMCID: PMC9103038.