Scientists at NYU Langone Health's Perlmutter Cancer Center say that at least three kinds of bacteria in the mouths of Americans may heighten or lower their risk of developing esophageal cancer. Their study (“Oral Microbiome Composition Reflects Prospective Risk for Esophageal Cancers”), which appears in Cancer Research, analyzes data from two national studies involving more than 120,000 patients.

“Bacteria may play a role in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), although evidence is limited to cross-sectional studies. In this study, we examined the relationship of oral microbiota with EAC and ESCC risk in a prospective study nested in two cohorts. Oral bacteria were assessed using 16S rRNA gene sequencing in prediagnostic mouthwash samples from n = 81/160 EAC and n = 25/50 ESCC cases/matched controls. Findings were largely consistent across both cohorts. Metagenome content was predicted using PiCRUST. We examined associations between centered log-ratio transformed taxon or functional pathway abundances and risk using conditional logistic regression adjusting for BMI [body mass index], smoking, and alcohol,” write the investigators.

“We found the periodontal pathogen Tannerella forsythia to be associated with higher risk [21%] of EAC. Furthermore, we found that depletion of the commensal genus Neisseria and the species Streptococcus pneumoniae was associated with lower [24%] EAC risk. Bacterial biosynthesis of carotenoids was also associated with protection against EAC. Finally, the abundance of the periodontal pathogen Porphyromonas gingivalis trended with higher risk of ESCC. Overall, our findings have potential implications for the early detection and prevention of EAC and ESCC.”

The mouth's overall bacterial makeup, which can be changed by smoking, heavy drinking, diet, and gum disease or gastric reflux, has long been thought to influence risk of esophageal adenocarcinoma or squamous cell carcinoma, according to the scientists. But they add that the new study, which monitored healthy patients for as long as 10 years, is the first to identify which among nearly 300 kinds of bacteria commonly found in the mouth are statistically linked to the risk of getting either of the two most common forms of the disease. 

“Our study brings us much closer to identifying the underlying causes of these cancers because we now know that at least in some cases disease appears consistently linked to the presence of specific bacteria in the upper digestive tract,” says study senior investigator and epidemiologist Jiyoung Ahn, Ph.D. “Conversely, we have more evidence that the absence or loss of other bacteria in the mouth may lead to these cancers, or to gut diseases that trigger these cancers.”

That said, the researchers emphasized that their findings do not demonstrate that the bacteria directly cause or prevent esophageal cancer. Study participants were men and women already enrolled in the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, and the American Cancer Society Cancer Prevention Study II Nutrition Cohort. All were between the ages of 50 and 75 and were considered healthy and cancer free when they enrolled in either study and had the bacteria in their mouths sampled.

Among study participants, 106 developed esophageal cancer. The bacteria in the mouth of each of these patients at the beginning of these studies were compared to those of another study participant of similar age, sex, and race who remained cancer free. 

Dr. Ahn, who says the latest findings may lead to guidelines to help physicians in the risk assessment and early detection of esophageal cancers, is an associate director of population science at Perlmutter and an associate professor in the departments of population health and environmental medicine at NYU School of Medicine.

“Early diagnosis could really help because esophageal cancers are often diagnosed in the later stages when the disease is harder to treat,” adds Dr. Ahn.

Postdoctoral fellow and study lead investigator Brandilyn Peters, Ph.D, notes that the team next will study whether use of probiotic pill supplements could be used to alter the oral microbiome and possibly decrease esophageal cancer risk. She says there are also plans to analyze the main biological functions of some bacteria in the mouth to see how these metabolic pathways may influence cancer risk. Further studies are planned to look at fungi and various viruses in the mouth to see if they also may influence who does and does not get esophageal cancer.








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