Does HFCS Feed the Wrong Bugs? A Reader Asks, We Dig In

A few days ago, this email came across my desk.

“I'm a regular reader of ACSH and have a question ... [I]am wondering about a possible connection between high fructose corn syrup (HFCS) and an intestinal issue known as SIBO (small intestinal bacterial overgrowth). Several years ago, my son was treated for this, and ... it cleared up with a couple of rounds of antibiotics and he has avoided HFCS ever since.

... is there something specific to HFCS that leads to SIBO that the other sweeteners don't have?” 

 – Julie Y

As it turns out, small intestinal bacterial overgrowth and fructose have a somewhat entangled and interesting relationship. To answer Julie’s question, we need to unpack what SIBO is and how it might relate to her son’s experience.

What exactly is Small intestinal bacterial overgrowth? 

Small intestinal bacterial overgrowth (SIBO) is not so much a well-defined disease as a cluster of signs and symptoms pointing to a poorly understood syndrome. It is relatively uncommon in the young and middle-aged, but can rise to as high as 15% in specific older populations. 

Typically, the small intestine contains roughly 1000 microbes per milliliter; in SIBO, the concentration increases by 100 to 1000-fold. The small intestinal microbiome is far denser compared to that of the colon (10³ vs. 10¹¹). However, it is the activity of these “misplaced” bacteria that is responsible for the symptoms of SIBO. Bacterial populations that metabolize bile salts may lead to fat malabsorption or diarrhea; those that metabolize carbohydrates can produce gas, causing bloating. The more classic “surgical presentation” of SIBO, which surgeons have termed “blind loop syndrome,” is a deficiency in Vitamin B₁₂, as microbes outcompete the small intestine's ability to absorb the vitamin and claim it for themselves, rather than allowing it to benefit their host. 

Gut Check: What Keeps Bacteria Where They Belong?

The level of bacteria in the small bowel is controlled primarily by the secretion of acid by the stomach in the initial phases of digestion and the motility, movement, of the small intestine itself as it propels and digests our meals. Gastric acid suppresses bacterial growth in the upper GI tract, so diminished production is a risk factor. Diminished production occurs with aging, but it can also be caused by Helicobacter pylori, the bacteria associated with stomach ulcers, as well as by the medications used to reduce “acid reflux,” such as Pepcid and Nexium. Of course, as with everything related to SIBO, there are conflicting reports in the literature regarding the impact of these medications. Beyond acid production, the movement of the intestine plays a key role in microbial control.

Our GI tract has a complex choreography moving what we have eaten from entry to exit. Studies indicate that a “migrating motor complex (MMC) develops approximately every 90–120 minutes to sweep residual debris through the GI tract.” Other causes of diminished motility, often associated with neural innervation impairment, are also risk factors for SIBO. In each instance, impaired motility predisposes for microbial “squatters.”

In the past, surgeons rearranging the stomach and small bowel, often for ulcers, created blind loops —dead ends of the small intestine — that allowed for microbial overgrowth. Individuals with impaired immunity of their intestinal mucosa appear to be at risk, while impaired cellular or humoral immunity carries no such burden. Lastly, the presence of these microbes in the small intestine seems to bring about an inflammatory response, exacerbating symptoms and implicating irritable bowel syndrome (IBS) and celiac disease as possible SIBO fellow travelers. In summary, several risks appear to be present, but no definitive evidence of a smoking gun has been found. 

When Bugs Go Rogue

Much like the risk factors, the symptoms of SIBO are nonspecific, ranging from bloating to abdominal pain, diarrhea, fatigue, and weakness. There are nutritional consequences, such as vitamin B₁₂ malabsorption. Symptoms seem to vary directly with the associated microbial “load.” 

As one might expect, diagnostic testing is fraught with controversy over the test to use, as well as the interpretation of the results. The most direct method is to culture the contents of the small intestine, but this is necessarily an invasive procedure requiring anesthesia. Unfortunately, the equipment used to culture the small bowel can become contaminated during the procedure as it traverses the mouth, esophagus, and stomach, and many of the microbes do not grow in routine culture media. 

The hydrogen breath test (HBT) is a non-invasive alternative that analyzes the gases you exhale after consuming a specific sugar. While under normal conditions, carbohydrates like glucose and fructose are absorbed, in SIBO, those sugars are fermented by bacteria, producing hydrogen and, in some instances, methane gases that enter the bloodstream and can be measured in exhaled breath. There are no established protocols or guidelines for challenge doses or types of sugar to be used, making consistent interpretation difficult. That said, HBT is the predominant diagnostic test because it is far easier than direct cultures. 

Treatment aims to address the underlying cause, provide essential nutritional support, and alleviate bacterial overgrowth. As with all things SIBO, treatment goals are more definitive than outcomes. Iatrogenic motility disorders, from the Nexiums and Pepcids, can be stopped by discontinuing the medications. But motility disorders from underlying neurologic impairment remain a challenge to treat successfully. Nutritional support is straightforward, so the mainstay of therapy remains antibiotic therapy. Unfortunately, rational therapy based on culture-identified bacteria is rare, and the necessary length of treatment is more a matter of belief than a fact. The success of treatment also remains unclear. 

The Fructose Factor: A Tangled Web with SIBO

Fructose malabsorption (FM) has a distinct underlying cause from SIBO, but they share several processes and symptoms that leave them entangled and physicians confused. Fructose, like glucose, is a monosaccharide, but unlike glucose, it has limited absorption in the small bowel. When dietary fructose intake exceeds capacity, the unabsorbed fructose then passes into the colon, where it is fermented by the normal microbiome, producing bloating, gas, and diarrhea. Sound familiar? SIBO also has “abnormal” metabolism of fructose and glucose primarily because the microbiome is in the wrong place, resulting in excess metabolic capacity that outcompetes the small bowel’s mucosa for absorption. FM may even promote SIBO, as excess fructose provides fuel for bacteria that shouldn’t be there.

One Test, Many Questions

This entanglement of FM and SIBO, further complicated by routine hydrogen breath testing (HBT), means that both problems may be falsely attributed to one another. The lack of a standard protocol for HBT’s carbohydrate of choice, as well as the correct “challenging” dose, further muddies the diagnostic waters. A Korean study sheds light on the difficulty in distinguishing SIBO from FM, particularly when using breath testing.

The study began by enlisting individuals with IBS along with a group of asymptomatic control patients. All patients were screened for SIBO using a 75-gram glucose challenge, and 48.5% of these participants were found to have SIBO and were subsequently excluded. Thirty-five patients were identified in the treatment arm. But here is where the entanglement grows. When these patients underwent HBT with 15 grams of fructose, 20% were identified as having fructose malabsorption. When the dose was increased to 25 grams, the number identified as having fructose malabsorption increased to 45.7%. Interestingly, this was the case for 22.9% of the asymptomatic controls. The takeaway? When fructose, rather than glucose, is used in HBT, it may falsely suggest SIBO in approximately 17% of patients who actually have FM. Moreover, the true incidence of SIBO and FM can never be known because there may be a large group of asymptomatic individuals. 

Julie’s Son: A Clinical Success, A Diagnostic Shrug

Julie, it appears that in this case, antibiotics and avoiding HFCS resolved the problem, but the underlying diagnostic cause remains unresolved. HFCS can accentuate both SIBO and FM. It could be that the antibiotics removed the errantly placed small bowel microbes. Or that avoiding HFCS prevented an excess of fructose in the face of fructose malabsorption. As a clinician, I would take this as a win.

Source:  Small Intestinal Bacterial Overgrowth: A Comprehensive Review  Gastroenterology & Hepatology PMID: 21960820

Prevalence Of Fructose Malabsorption In Patients With Irritable Bowel Syndrome After Excluding Small Intestinal Bacterial Overgrowth Journal of Neuroenterology Motility PMID: 29433301