“All disease begins in the gut” – Hippocrates

A patient, diagnosed with curable breast cancer, embarks on a treatment journey. She completes several cycles of chemotherapy, followed by surgery, radiation, and more chemotherapy. After months of stress and seemingly insurmountable challenges, she finishes therapy and returns to her life. Yet she continues to have bothersome side effects from treatment—brain fog, mild depression, fatigue, and persistent problems with diarrhea and constipation. She is exercising and getting enough sleep, but is struggling to return to a sense of normalcy.

The story is a common one. Up to 86% of patients experience side effects during chemotherapy, and these symptoms may persist long after completion of treatment. 1 While the cause of these effects is multifactorial, emerging data suggest that the gut may play an important role in their development and resolution.

How does this happen?

The digestive tract is one of the most densely packed ecosystems in the body, and the organisms present (including bacteria, fungi, viruses, and others) play an important role in immune, metabolic, psychological, and cognitive function.2 When this ecosystem is disrupted—called dysbiosis—a variety of changes can occur, including increased anxiety and depression, and increased systemic inflammation. These changes can lead to a number of downstream effects on important hormone pathways in the body, controlled by the hypothalamic, pituitary, and adrenal glands.3 

Recent studies suggest that both chemotherapy and immunotherapy can lead to drastic changes in the composition of the gut microbiota, which can lead to dysbiosis and alterations in immune and metabolic function.4–7 These interactions can lead to either increased or decreased side effects from therapy.8 One group has called this effect Chemotherapy Driven Dysbiosis of the Microbiota-Gut-Brain Axis. This model suggests that patients receiving chemotherapy can develop long-term gut dysbiosis. Furthermore, damage to the gut can lead to a condition called “leaky gut”, in which the barriers between the intestine and the body is disrupted, allowing bacterial toxins (such as lipopolysaccharide) to enter the blood stream. When this happens, the body reacts intensively, causing an inflammatory loop that can lead to pain, fatigue, anxiety, depression, weight gain, and changes in bowel habits.2 

What can be done to treat dysbiosis and restore the microbiota-gut-brain axis? While research is ongoing, there may be many approaches to employ. An anti-inflammatory diet—a diet rich in whole foods, emphasizing fruits, vegetables, and whole grains—may be beneficial. Many diets follow this model, with the Mediterranean diet being the most commonly cited. Anti-inflammatory diets contain a variety of natural plant fiber—called prebiotics—that serve as an important nutrient source for the microbiome.9  These also includes other healthful compounds such as polyphenols and omega-3 fatty acids, which can nourish the body while reducing inflammation. 10 We often incorporate other strategies, too, like targeted probiotics and herbal therapies that can support gut health and help recalibrate the makeup of the microbiome. While more details will emerge, it increasingly seems that Hippocrates was on to something—all disease begins in the gut.

1.         Pearce A, Haas M, Viney R, et al. Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study. PLoS ONE. 2017;12(10). doi:10.1371/journal.pone.0184360

2.         Deleemans JM, Chleilat F, Reimer RA, et al. The chemo-gut study: investigating the long-term effects of chemotherapy on gut microbiota, metabolic, immune, psychological and cognitive parameters in young adult Cancer survivors; study protocol. BMC Cancer. 2019;19(1):1243. doi:10.1186/s12885-019-6473-8

3.         Oh B, Boyle F, Pavlakis N, et al. Emerging Evidence of the Gut Microbiome in Chemotherapy: A Clinical Review. Front Oncol. 2021;11. Accessed June 20, 2022. https://www.frontiersin.org/article/10.3389/fonc.2021.706331

4.         Aarnoutse R, Ziemons J, Penders J, Rensen SS, de Vos-Geelen J, Smidt ML. The Clinical Link between Human Intestinal Microbiota and Systemic Cancer Therapy. Int J Mol Sci. 2019;20(17):4145. doi:10.3390/ijms20174145

5.         Bai J, Behera M, Bruner DW. The gut microbiome, symptoms, and targeted interventions in children with cancer: a systematic review. Support Care Cancer Off J Multinatl Assoc Support Care Cancer. 2018;26(2):427-439. doi:10.1007/s00520-017-3982-3

6.         Maes M, Kubera M, Leunis JC, Berk M, Geffard M, Bosmans E. In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS), and autoimmune responses directed against O&NS-damaged neoepitopes. Acta Psychiatr Scand. 2013;127(5):344-354. doi:10.1111/j.1600-0447.2012.01908.x

7.         Huang Y, Yang W, Liu H, et al. Effect of high-dose methotrexate chemotherapy on intestinal Bifidobacteria, Lactobacillus and Escherichia coli in children with acute lymphoblastic leukemia. Exp Biol Med Maywood NJ. 2012;237(3):305-311. doi:10.1258/ebm.2011.011297

8.         Chen J, Douglass J, Prasath V, et al. The microbiome and breast cancer: a review. Breast Cancer Res Treat. 2019;178(3):493-496. doi:10.1007/s10549-019-05407-5

9.         Strowski MZ, Wiedenmann B. Probiotic carbohydrates reduce intestinal permeability and inflammation in metabolic diseases. Gut. 2009;58(8):1044-1045. doi:10.1136/gut.2009.179325

10.       Román GC, Jackson RE, Gadhia R, Román AN, Reis J. Mediterranean diet: The role of long-chain ω-3 fatty acids in fish; polyphenols in fruits, vegetables, cereals, coffee, tea, cacao and wine; probiotics and vitamins in prevention of stroke, age-related cognitive decline, and Alzheimer disease. Rev Neurol (Paris). 2019;175(10):724-741. doi:10.1016/j.neurol.2019.08.005