Oral microbes form a complex and dynamic biofilm community, which is subjected to daily host and environmental challenges. Dysbiosis of the oral biofilm is correlated with local and distal infections and postulating a baseline for the healthy core oral microbiota provides an opportunity to examine such shifts during the onset and recurrence of disease. Here we quantified the daily, weekly, and monthly variability of the oral microbiome by sequencing the largest oral microbiota time-series to date, covering multiple oral sites in ten healthy individuals. Temporal dynamics of salivary, dental, and tongue consortia were examined by high-throughput 16S rRNA gene sequencing over 90 days, with four individuals sampled additionally 1 year later. Distinct communities were observed between dental, tongue, and salivary samples, with high levels of similarity observed between the tongue and salivary communities. Twenty-six core OTUs that classified within Streptococcus, Fusobacterium, Haemophilus, Neisseria, Prevotella, and Rothia genera were present in ≥95% samples and accounted for ~65% of the total sequence data. Phylogenetic diversity varied from person to person, but remained relatively stable within individuals over time compared to inter-individual variation. In contrast, the composition of rare microorganisms was highly variable over time, within most individuals. Using machine learning, an individual's oral microbial assemblage could be correctly assigned to them with 88–97% accuracy, depending on the sample site; 83% of samples taken a year after initial sampling could be confidently traced back to the source subject.
Cancers often cause excruciating pain and rapid weight loss, severely reducing quality of life in cancer patients. Cancer-induced pain and cachexia are often studied and treated independently, although both symptoms are strongly linked with chronic inflammation and sustained production of pro-inflammatory cytokines. Since nerve growth factor (NGF) plays a cardinal role in inflammation, and pain, and because it interacts with multiple pro-inflammatory cytokines, we hypothesized that NGF acts as a key endogenous molecule involved in the orchestration of cancer-related inflammation. NGF might be a molecule common to the mechanisms responsible for clinically distinctive cancer symptoms such as pain and cachexia as well as cancer progression.
Here we reported that NGF was highly elevated in human oral squamous cell carcinoma tumors and cell cultures. Using two validated mouse cancer models, we further demonstrated that NGF blockade decreased tumor proliferation, nociception, and weight loss by orchestrating pro-inflammatory cytokines and leptin production. NGF blockade also decreased expression levels of nociceptive receptors TRPV1, TRPA1, and PAR-2. Together, these results identified NGF as a common link among proliferation, pain, and cachexia in oral cancer. Anti-NGF could be an important mechanism-based therapy for oral cancer and its related symptoms.
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