Incremental Diagnostic Value of Fecal Microbial Biomarkers Added to Quantitative Fecal Immunochemical Testing for Colorectal Neoplasia: A Systematic Review
This systematic review concludes that while adding fecal microbial biomarkers to quantitative fecal immunochemical testing (qFIT) may improve the detection of advanced colorectal neoplasia, particularly advanced adenomas, the magnitude of this benefit remains uncertain due to high risks of bias and substantial heterogeneity across studies, necessitating further prospective external validation before routine clinical implementation.
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Every year, millions of people around the world are diagnosed with colorectal cancer, a disease that often begins as a small, precancerous growth called an adenoma before turning into something far more dangerous. For decades, doctors have relied on a simple, non-invasive test to catch these problems early: a stool test that looks for tiny amounts of blood. This test, known as a quantitative fecal immunochemical test, is excellent at spotting cancer because cancers tend to bleed. However, it is much worse at finding those early adenomas, which often do not bleed at all. This leaves a gap in our safety net: we might miss the very lesions we need to remove to prevent the disease entirely. Scientists have long suspected that the trillions of bacteria living in our gut, known as the microbiome, change in specific ways when these growths are present. The big question has been whether adding a test for these bacteria to the standard blood test could help us find more of these hidden dangers without causing too many false alarms.
A team of researchers recently set out to answer this question by gathering and analyzing every available study that compared the standard blood test alone against a combination of that blood test plus a bacterial test. They looked for evidence in adults who had undergone colonoscopy, the gold-standard procedure where a doctor visually examines the entire colon to confirm whether growths are present. The researchers were careful to distinguish between two different ways these tests could be used. One approach tries to catch every possible lesion by flagging a person as positive if either the blood test or the bacterial test shows a problem. This strategy aims to find as many growths as possible, even if it means more healthy people get sent for unnecessary colonoscopies. The other approach uses the bacterial test only for people who already tested positive on the blood test, hoping to filter out false alarms and reduce the number of unnecessary procedures.
The researchers found thirteen studies that directly compared these methods, but they discovered that the results were too varied to simply add them all up into a single average number. The studies differed in the specific bacteria they looked for, the equipment they used, and the populations they tested. Despite this variety, a clear pattern emerged regarding the first strategy: adding a bacterial test to the standard blood test does appear to help find more advanced growths that the blood test alone would have missed. In several early studies, this combination dramatically increased the detection of advanced adenomas, with some reports showing the test finding between twenty-three and forty-one percent more of these growths than the blood test could find on its own. One large, prospective study involving thousands of participants across the Asia-Pacific region found that the combination increased the detection of advanced neoplasia by ten percentage points. This suggests that the bacterial signal is indeed picking up something the blood test is missing, likely because these early growths do not bleed enough to trigger the standard test.
However, the researchers also found that this benefit comes with a cost. When the tests are combined to catch more growths, they also flag more healthy people as having a problem, which leads to more colonoscopies. In the large Asia-Pacific study, while the combination found ten percentage points more growths, the overall specificity—the ability to correctly identify healthy people—dropped to about eighty-five percent. This means that for every ten extra growths found, a significant number of healthy people would undergo an invasive procedure they did not need. The second strategy, using bacteria to filter out false alarms, showed a different trade-off. In one study, using a bacterial signature to re-evaluate people who tested positive on the blood test successfully reduced the number of false alarms, but it also meant missing some actual growths that the blood test had correctly identified.
The authors of this review are careful to note that while the idea is promising, the current evidence is not yet strong enough to change medical practice. Most of the studies they analyzed were at high risk of bias, meaning they were often designed in ways that could exaggerate the results, such as testing the bacteria and the blood test on the same group of people who were already known to have the disease. The few studies that followed a more rigorous, prospective design showed smaller, more modest improvements than the early, enthusiastic reports. The researchers conclude that while fecal microbial biomarkers hold real potential to complement the standard stool test, we cannot yet say exactly how much better they will work in the real world. Before this combination becomes a routine part of screening, scientists need to run new, large-scale studies that use fixed rules and test the method on diverse populations to see if the extra detection is worth the extra procedures. Until then, the standard blood test remains the primary tool, with the bacterial test serving as a powerful but unproven partner waiting for its final validation.
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