Head and neck cancer patients have a high survival rate following treatment, but the various treatments which include surgery, radiation therapy and chemotherapy, can lead to a cluster of symptoms including fatigue, pain, disturbance in sleep, depression and cognitive dysfunction. These symptoms are referred to as psychoneurological symptoms (PNS) cluster. If not treated, these can significantly impair the patient’s quality of life. Several causes have been suggested including a pro-inflammatory response and dysregulation of the vagal nerve system. Also a deficiency in estrogen or hemoglobin levels may increase the risk of developing these symptoms.
The gut microbiome system is critical in regulating both pro-inflammatory cytokines and the nervous system. A balanced microbiome ecosystem is necessary for psychoneurological health. The human gut microbiome consists of tens of trillions of microbes belonging to on average 500 different species which act on neural, immune, metabolic and hormonal pathways. Cancer treatments can affect the composition of the microbiome leading to lower amounts of commensal microbes and increased quantities of pathogenic bacteria. Commensal microbes are bacteria that are fed by the body’s nutrients but do not invade or harm the body’s cells and act on the immune system to prevent invasion by pathogens and also inhibit the growth of the pathogens directly and compete for nutrients and binding sites. In other words, the “more of the good guys there are, the less room for the bad guys”. There is cross-talk between the gut and the brain linking emotional and cognitive centers of the brain with intestinal function.
The purpose of the study was to investigate the relation between various aspects of the microbiome and mechanisms underlying the development of the PNS cluster. Thirteen patients were enrolled and more than half had received radiation concomitantly with chemotherapy and more than 60% had undergone surgery. Gut microbiome composition was analyzed pre- and post-radiation therapy.
Prior to radiation, a higher presence of Proteobacteria, Firmicutes was correlated with fewer of the cluster symptoms, whereas with a higher concentration of Bacteroidetes and higher Bacteroidetes/Firmicutes ratio, there were more symptoms. One month following radiation therapy similarly a higher Bacteroidetes/Firmicutes ration and increased Bacillales were indication of inflammation leading to greater degree of PNS cluster symptoms, which continued to be true over time. In patients with PNS both pre- and post-radiation there were low levels of Bifidobacteriales. Bifidobacterium is a genus often included in conventional probiotics, especially for treating ulcerative colitis, which an inflammatory disease of the bowel. Higher levels of Phascolartobaterium and Subdoligranulum were correlated with fewer PNS – these produce short chain fatty acids which have been found to suppress inflammation. Short fatty chain acids are key to preventing the formation of the PNS cluster through hormonal and immune pathways.
Another important modulator is tryptophan which is produced by Proteobacteria, Actinobacteria and Firmicutes and cancer treatments can decrease these leading to a lower production of tryptophan. Tryptophan is an amino acid which helps produce melatonin which regulates the sleep-wake cycle and serotonin which regulates mood, appetite, sleep and pain. Tryptophan is also a cofactor for the production of vitamin B3 in the liver which is involved in the production of energy and DNA.
Another factor to be considered is nutrition. A typical Western diet high in protein and/or fat causes significant reduction in Bifidobacteria and short fatty acid-producing bacteria, which is correlated with more PNS. In contrast, a diet rich in fibers and high fat replenishes the depleted levels of these bacteria. Thus correcting the gut microbiome is directly related to improving mental health and reducing anxiety and depression. Patients with cancer can suffer from malnutrition and changes in diet thus affecting the microbiome and leading to the production of increased PNS.
The conclusion of the authors was the gut microbiome could be involved in affecting the severity of the PNS cluster through mechanisms such as modulation of the immune system, reduction of diversity of the flora constituting the microbiome and changing of the variability of the gut bacteria, and that supplementation with Bifidobacteriales and other short fatty acid-producing bacteria could help alleviate these symptoms in cancer patients.
Bai J, Bruner DW, Fedirko V, Beitler JJ, Zhou C, Gu J, Zhao H, Lin IH, Chico CE, Higgins KA, Shin DM, Saba NF, Miller AH, Xiao C. Gut Microbiome Associated with the Psychoneurological Symptom Cluster in Patients with Head and Neck Cancers. Cancers (Basel). 2020 Sep 6;12(9):2531. https://pubmed.ncbi.nlm.nih.gov/32899975/