Advancements in cancer treatments, especially cytotoxic chemotherapy, have heightened patients' risks of opportunistic infections due to weakened immune systems. Often originating from the gut, these infections can sometimes prove more detrimental than the cancer itself. To counteract this, antibiotic prophylaxis is employed, which, unfortunately, can damage the healthy microbiome and potentially worsen outcomes.
During our analysis of microbiome data from bone marrow transplantation patients at Memorial Sloan Kettering Cancer Center, we made a striking discovery. Streptococcus bacteria, usually confined to the oral cavity and not found in healthy gut environments, were predominant in the feces of patients showing extensive microbiome damage. This association with lower gut microbiome loads and stool consistency issues led us to investigate further the role of oral bacteria in gut microbiota depletion and its impact on patient outcomes.
Employing a multidisciplinary approach that included microbiome sequencing and clinical data analysis, we explored how oral bacteria end up in feces and what this indicates about gut health. Experiments using mouse models paralleled the findings in human patients, showing antibiotic treatments increased the relative—but not absolute—amount of oral bacteria in feces, suggesting a method to detect microbiota damage.
.jpg "Oral bacteria in feces. The relative abundance of oral bacteria increases after the depletion of native gut bacteria under different conditions. The left gut microbiota shows a healthy balance with low oral bacteria and high gut bacteria. The right gut microbiota depicts a condition of high oral bacteria and low gut bacteria in relative abundance. Symbols: green represents oral bacteria, and brown represents gut bacteria.")
Oral bacteria in feces. The relative abundance of oral bacteria increases after the depletion of native gut bacteria under different conditions. The left gut microbiota shows a healthy balance with low oral bacteria and high gut bacteria. The right gut microbiota depicts a condition of high oral bacteria and low gut bacteria in relative abundance. Symbols: green represents oral bacteria, and brown represents gut bacteria.
We faced challenges in quantifying oral bacteria in our patient dataset due to the absence of paired oral samples. Overcoming these obstacles enriched our understanding, indicating that the proportion of oral bacteria rises following treatments that impair gut microbiota, correlating with poorer patient outcomes.
Further validation came from a study published subsequently on bioRxiv, which confirmed that oral bacteria like Streptococcus and Veillonella spp. in feces could indicate reduced gut bacterial populations. This supports the potential therapeutic benefit of restoring healthy gut bacteria over targeting oral bacteria, offering a new perspective on enhancing cancer treatment outcomes.
Our paper "Oral bacteria relative abundance in faeces increases due to gut microbiota depletion and is linked with patient outcomes" is available at:
https://www.nature.com/articles/s41564-024-01680-3
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