Gut Microbiome Associated with the Psychoneurological Symptom Cluster in Patients with Head and Neck Cancers

SIMPLE SUMMARY: Patients with head and neck cancers (HNCs) report a cluster of psychoneurological symptoms (i.e., the PNS cluster), including pain, fatigue, sleep disturbance, depressive symptoms, and cognitive dysfunction across different treatments. The aim of this longitudinal study was to examine associations between the gut microbiome and the PNS cluster in 13 patients with HNCs pre- and post-radiotherapy. Patients with the high PNS cluster showed a greater decrease in microbial evenness than those with the low PNS cluster from pre- to post-radiotherapy. The high and low PNS clusters showed significant gut microbiome dissimilarities. Patients with the high PNS cluster had higher abundances of Bacteroidetes, Ruminiclostridium9, Tyzzerella, Eubacterium_fissicatena, and DTU089. Patients with the low PNS cluster had higher abundances in Lactococcus, Phascolarctobacterium, and Desulfovibrio. Glycan metabolism and vitamin metabolism were different between the high and low PNS clusters pre- and post-radiotherapy. ABSTRACT: Cancer patients experience a cluster of co-occurring psychoneurological symptoms (PNS) related to cancer treatments. The gut microbiome may affect severity of the PNS via neural, immune, and endocrine signaling pathways. However, the link between the gut microbiome and PNS has not been well investigated in cancer patients, including those with head and neck cancers (HNCs). This pilot study enrolled 13 patients with HNCs, who reported PNS using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (CTCAEs). Stool specimens were collected to analyze patients’ gut microbiome. All data were collected pre- and post-radiation therapy (RT). Associations between the bacterial abundances and the PNS clusters were analyzed using the linear discriminant analysis effect size; functional pathway analyses of 16S rRNA V3-V4 bacterial communities were conducted using Tax4fun. The high PNS cluster had a greater decrease in microbial evenness than the low PNS cluster from pre- to post-RT. The high and low PNS clusters showed significant differences using weighted UniFrac distance. Those individuals with the high PNS cluster were more likely to have higher abundances in phylum Bacteroidetes, order Bacteroidales, class Bacteroidia, and four genera (Ruminiclostridium9, Tyzzerella, Eubacterium_fissicatena, and DTU089), while the low PNS cluster had higher abundances in family Acidaminococcaceae and three genera (Lactococcus, Phascolarctobacterium, and Desulfovibrio). Both glycan metabolism (Lipopolysaccharide biosynthesis) and vitamin metabolism (folate biosynthesis and lipoic acid metabolism) were significantly different between the high and low PNS clusters pre- and post-RT. Our preliminary data suggest that the diversity and abundance of the gut microbiome play a potential role in developing PNS among cancer patients.