Why does the same chemotherapy drug leave some patients struggling with side effects while others seem to get through treatment without them? A new Mayo Clinic study suggests part of the answer may lie in the gut, among the bacteria people carry before treatment begins.
Published online September 29, the study examined samples collected from people with cancer before they started a new treatment regimen. Researchers then linked those samples to clinical records on side effects, survival, and cancer type, looking for patterns that might explain why patients have different experiences.
Some findings pointed to particular cancers, while others challenged earlier studies’ suggestions about the relationship between gut bacteria and disease. The researchers also uncovered differences among younger patients, although not across every cancer they examined.
But one finding stood out for its potential practical value: a connection between specific gut bacteria, a widely used chemotherapy drug, and a side effect that can make treatment hard to tolerate.
The Chemo Clue Hiding in the Gut
It comes down to one drug and the bacteria that can break it down.
Among patients receiving intravenous 5-fluorouracil (5-FU), those who later developed diarrhea had fewer bacterial genes that break down the chemotherapy drug.
Much of that ability was traced to Anaerostipes hadrus, a gut bacterium carrying the gene for an enzyme called dihydropyrimidine dehydrogenase.
The researchers describe the bacterium as protective against 5-FU-associated diarrhea. However, that doesn’t mean giving patients more of it would prevent the side effect. The study didn’t test that possibility.
Interestingly, the same bacterial signal wasn’t associated with diarrhea in patients receiving carboplatin, another chemotherapy drug.
A Study Built for Comparisons
The team didn’t stick to one cancer, and that choice shaped what they could see.
The findings come from the Mayo Clinic Cancer Microbiome cohort, which included 1,364 patients with different cancers, stages, and treatments.
Participants were recruited at Mayo Clinic locations in Arizona, Florida, and Minnesota, representing 40 states. Another 287 people without cancer formed the comparison group. Researchers collected stool and blood samples.
That broad mix gave researchers an advantage. Rather than studying one cancer in isolation, they could compare patients with people without cancer and then examine differences among the cancer groups themselves.
The distinction matters because a bacterial pattern associated with one cancer might also appear in several others.
As Mars explained, identifying features genuinely specific to individual cancers could help researchers focus on microbial changes more likely to reflect their unique biology.
And when the team made those comparisons, some earlier assumptions didn’t hold up.
A Twist for Earlier Microbiome Research
Comparing cancers against each other exposed which signals were truly specific.
“We were surprised to find that many microbiome associations previously reported as specific to individual cancers were also present across multiple cancer types or were associated with common comorbidities,” Mars said.
In fact, some changes were remarkably widespread. One group of bacteria was elevated, and another was reduced, in 21 of the 22 cancer types examined.
After accounting for these shared patterns and other health conditions, the researchers identified 341 bacterial species associated with five cancer groups.
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The differences were particularly striking in certain cancers.
Neuroendocrine tumors showed a broad loss of common health-associated gut bacteria. Liver and bile duct cancers had higher levels of several bacteria, including Enterococcus faecalis.
Meanwhile, esophageal cancer was associated with higher levels of six bacterial species, several of which belong to the Streptococcus group. Lymphoid leukemia and multiple myeloma also displayed distinct patterns.
These findings help narrow the search for cancer-specific microbial signals. But they don’t establish that the bacteria cause the diseases.
Another part of the study raised a different question: Could the gut microbiome also help researchers understand cancers appearing earlier in life?
Related: Americans’ Gut-Healthy Eating Habits Stay Flat Even as Probiotic Use Soars 287%
Younger Patients Told a Different Story
Among colorectal cancer patients diagnosed at age 50 or younger, researchers found higher lactate levels and more Veillonella parvula, a bacterium that feeds on lactate, compared with patients diagnosed later.
Because tumors can produce substantial amounts of lactate, this connection gives scientists something to investigate. Whether it contributes to early-onset colorectal cancer remains unknown.
Breast cancer revealed another pattern. Younger patients had differences across 64 bacterial species, including lower levels of Clostridium scindens, which participates in bile acid and steroid metabolism.
They also had lower levels of primary bile acids, substances the liver produces that help digest fats. Yet the age-related pattern wasn’t universal. Researchers found no comparable differences in brain cancer.
These findings come as colorectal and breast cancers are becoming more common among younger adults. American Cancer Society figures show colorectal cancer incidence rising approximately 3% annually among adults ages 20 to 49, while breast cancer incidence is increasing about 1.4% annually among women younger than 50.
Survival Clues Come With Limits
The researchers also found associations between gut bacteria and survival in colorectal cancer, liver and bile duct cancers, melanoma, ovarian cancer and prostate cancer.
In liver and bile duct cancers, Bifidobacterium longum was associated with longer survival, while Blautia massiliensis was linked to shorter survival.
Those differences are intriguing, but they don’t establish that either bacterium changes how long someone lives.
Kashyap, who directs the Mayo Clinic Microbiome Program, described the microbiome as an underappreciated part of cancer care. It isn’t the sole driver of cancer or treatment outcomes, yet it hasn’t traditionally been considered when developing therapeutic approaches.
That is why the chemotherapy finding is particularly interesting. The 5-FU connection could prove that researchers might eventually identify why certain patients experience a specific side effect and find a target they can act on.
For now, however, identifying an association and demonstrating that changing the bacteria improves treatment are two very different things.
If a gut microbiome test could someday help predict which chemotherapy side effects you’re more likely to experience, would you want to know before treatment begins?
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