Abstract

Simple SummaryPatients 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.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.

Highlights

  • Head and neck cancers (HNCs) account for approximately 4% of all cancer diagnosed in the UnitedStates [1]

  • About half of the participants were diagnosed with oropharyngeal cancer, and 64% of them were HPV-related head and neck cancers (HNCs)

  • At the phylum level, we found positive trend of association between Bacteroidetes and the psychoneurological symptoms (PNS) cluster, and there was a negative trend or association between Proteobacteria, Firmicutes, and the PNS cluster prior to radiation therapy (RT)

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Summary

Introduction

Head and neck cancers (HNCs) account for approximately 4% of all cancer diagnosed in the UnitedStates [1]. The primary treatments for HNCs include surgery, radiation therapy (RT), and chemotherapy, which is often combined with RT [2]. Patients with HNCs have a high survival rate after RT, especially RT following surgeries [2]. Patients report an array of co-occurring symptoms across different treatments, including pain, fatigue, sleep disturbance, depressive symptoms, and cognitive dysfunction [4,5]. These co-occurring symptoms are defined as the psychoneurological symptoms (PNS) cluster, which potentially have common underlying biological mechanisms [6]. Poor treatment management of the PNS cluster could lead to adverse effects on a patient’s functional performance and may decrease their overall quality of life (QOL) [6]

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