For years, a condition called small intestinal bacterial overgrowth—or SIBO—has attracted growing attention from both patients and doctors. Once considered a rare issue in people with specific structural or motility disorders of the gut, SIBO is now frequently implicated in individuals with vague or unexplained gastrointestinal symptoms, especially those with irritable bowel syndrome (IBS). But how reliable is this diagnosis in today’s clinical practice? A major review by Kashyap and a group of leading experts in disorders of brain gut interactions questions the scientific foundations of the SIBO-IBS connection and the tests used to support it, calling for a reassessment of our diagnostic and treatment strategies.
I have voiced the same skepticism about the SIBO diagnosis and its implication in IBS pathophysiology, a cleverly marketed myth which has spawned the widespread use of questionable breath tests and of rifaximin, a non-absorbable antibiotic in patients without evidence for a bacterial infection. This is particularly troublesome at a time when we are increasingly aware of the harmful effects of antibiotic intake on the health of our gut microbiome.
A Historical Perspective: What Is SIBO Really?
Traditionally, SIBO referred to a very specific medical problem: when too many bacteria accumulate in the proximal small intestine, often due to anatomical or functional issues like prior gut surgery, scleroderma, or chronic intestinal stasis. In these cases, bacterial overgrowth interfered with digestion and nutrient absorption, leading to malnutrition, diarrhea, and vitamin deficiencies. The diagnosis relied on both clear clinical signs and laboratory findings, like bacterial cultures from the jejunum or evidence of malabsorption. These were well-defined and measurable issues.
However, starting around 20 years ago, a new hypothesis emerged: perhaps SIBO was far more common and could help explain symptoms in people with IBS, even in the absence of malabsorption. This idea—that bacterial overgrowth could cause gas, bloating, and discomfort in IBS—was an attractive new mechanism in the never ending search for a gut-based cause of IBS. Not surprisingly, the concept sparked a wave of enthusiasm and research in the IBS research community. At a time when IBS was still considered a pure gut disorder, the idea was compelling, but according to the recent opinion article it has not held up under scientific scrutiny.
“Breath tests, especially the lactulose hydrogen breath test (LHBT), were never originally designed to detect SIBO”
A cornerstone of the modern SIBO diagnosis is breath testing, which is used as a non-invasive way to detect bacterial fermentation in the gut. Patients ingest a sugar solution (usually glucose or lactulose), and their breath is analyzed over time for hydrogen or methane, gases that bacteria produce when they ferment carbohydrates.
These breath tests, especially the lactulose hydrogen breath test (LHBT), were never originally designed to detect SIBO. In fact, they were developed to measure gut transit time—how fast food moves from the mouth to the colon. As such, they are highly influenced by how quickly the test sugar reaches the colon, where bacteria are naturally abundant. If the sugar gets there fast, as it often does in people with diarrhea-predominant IBS, gas production can begin early and falsely suggest SIBO.
Multiple studies, including those using radioactive tracers, have shown that breath gas increases are often due to early fermentation in the colon—not the small intestine. This means many people are being told they have SIBO when what they really have is rapid gut transit, a much more common abnormality than true SIBO. The test isn’t measuring bacterial overgrowth where it’s supposed to.
Even the glucose breath test (GHBT), while slightly more reliable, has its own flaws. Glucose is absorbed earlier in the small intestine, but in people with abnormal gut anatomy or fast transit, it can still reach the colon and lead to false positives. Moreover, studies comparing breath tests to bacterial cultures from the small intestine show poor agreement—suggesting breath test results don’t accurately reflect what’s happening in the gut and its microbiome.
“Are Breath Tests Reliable in Guiding Treatment?”
Clinically, a key question is whether breath tests can predict who will benefit from treatment—especially antibiotics like rifaximin. The evidence is mixed at best. Some early studies showed symptom improvements in IBS patients who had “positive” breath tests, but these studies often lacked placebo controls or consistent test criteria. Later, more rigorous trials found only a modest benefit of antibiotics over placebo—approximately 10% on average.
Even in the landmark TARGET trials that led to rifaximin’s FDA approval for IBS, breath testing was performed in only a small subset of participants. Among those who improved, many had normal breath tests, and many with abnormal tests did not improve. This undermines the notion that breath tests are useful for selecting patients who will benefit from antibiotic treatment.
Furthermore, the symptoms that improve most consistently with antibiotics are bloating and gas—symptoms that could stem from bacterial fermentation in the colon rather than the small intestine. In fact, some evidence suggests that antibiotics may reduce colon-based fermentation, thereby reducing gas and decreasing the stimulation of hypersensitive nerves in IBS patients, rather than treating any true overgrowth in the small intestine.
“The disagreement [in guidelines] highlights just how shaky the science behind SIBO breath testing really is.”
Professional guidelines reflect the confusion in this area. North American recommendations suggest that breath tests are simple and useful for diagnosing SIBO, despite acknowledging their low accuracy. They recommend either glucose or lactulose as test sugars. In contrast, European and Asian guidelines are more cautious. They advise using glucose, not lactulose, and only in select cases with high suspicion of true SIBO. Some even suggest adding imaging to reduce false positives. Meanwhile, British and Canadian guidelines go further, explicitly advising against breath testing for IBS. This disagreement highlights just how shaky the science behind SIBO breath testing really is.
Meta-analyses and Misinterpretations
Meta-analyses have shown that people with IBS are more likely to have positive breath tests than healthy controls. But this doesn’t prove that SIBO causes IBS. Many other digestive conditions also show positive breath tests—including dyspepsia, reflux, and ulcerative colitis—where SIBO is not considered central. It’s more likely that a positive breath test reflects general gut dysfunction rather than true bacterial overgrowth.
What Should We Focus on Instead of Breath tests?
Kashyap and colleagues argue that it’s time to move beyond simplistic ideas like “too many bacteria” and toward a more nuanced view of the gut microbiome’s function. Instead of fixating on bacterial numbers, researchers should study what the bacteria are doing—their metabolism, interactions with the host immune and nervous systems, and how they respond to dietary changes.
They highlight that the distal ileum has a dynamic microbial environment shaped by bile, immune defenses, motility, and nutrient flow. These factors make the small intestine very different from the colon. The microbes here are more sensitive to shifts in diet and stress and may influence symptoms via complex mechanisms we are only beginning to understand.
Emerging research suggests that in IBS, it’s not just the presence of bacteria but how they behave that matters—what chemicals they produce, how they affect gut nerves, and how they interact with the brain and the immune system. This is where future therapies should be aimed.
Time for a Paradigm Shift in Understanding Brain Gut Microbiome Interactions
The authors make a strong case that the widespread use of breath testing for diagnosing SIBO in IBS patients is not supported by solid evidence. The tests are flawed, their results are hard to interpret, and they don’t reliably guide treatment. Meanwhile, the overuse of antibiotics carries risks and may provide only marginal benefits.
Instead, the field should invest in understanding the deeper relationships between gut microbes, the nervous system, and diet—especially in the small intestine. Until then, clinicians are urged to stop relying on breath tests to diagnose IBS or justify repeated antibiotic treatments.
This article represents a call for caution, and scientific rigor in the evolving field of gut microbiome research—and a plea to replace outdated assumptions that primarily benefit the pharmaceutical industry with more meaningful exploration of the bidirectional interactions between the brain, the gut and its microbiome.

Emeran Mayer, MD Is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.