The journal JGH Open recently published a critical review of small intestinal bacterial overgrowth (SIBO), highlighting the need for accurate diagnosis, which remains a challenge. As outlined in this review, the diagnosis of SIBO is quite controversial, with two main approaches: the culture of small intestinal fluid and breath testing. While traditionally considered the “gold standard,” jejunal/duodenal aspirates are prone to multiple types of errors, and it is this lack of a reliable objective standard that has plagued diagnostic efforts.
Traditionally, a standard of ≥10⁵ CFU/mL for jejunal aspirate was used, though more recently a lower threshold of ≥10³ CFU/mL has been suggested. Yet this gold standard is fraught with challenges, including the potential need for saline during endoscopy (diluting the sample) and introduction of air during the procedure (consequential for an accurate anaerobe count), as well as the challenge of bacteria that do not culture well (potentially the majority), and important distinctions between luminal and mucosal bacterial populations, along with lack of standardization in both the methods used to collect (e.g., location, volume, etc.) and culture bacteria, cost, contamination, and invasiveness of the procedure.
Thus, breath testing emerged as a less invasive alternative, based on the principle that excessive fermentation of carbohydrates, including hydrogen and methane, signifies the presence of an abnormal small bowel microbiome. But both lactulose and glucose-based breath tests are problematic; lactulose is not absorbed in the gastrointestinal tract, so in theory, any hydrogen measured on a breath test represents fermentation by bacteria followed by absorption of hydrogen, ultimately into the bloodstream, and an increase of 20ppm from baseline by 90 minutes after lactulose administration has been used to diagnose SIBO. However, the assumption that lactulose doesn’t reach the large intestine before 20 minutes (which would rapidly ferment it) has been shown to be mistaken, as scintigraphy reveals it may reach the large intestine in as few as 10 minutes. Additionally, doses as small as 0.5g were enough to trigger a rise in hydrogen once lactulose reached the large intestine, proving yet another assumption false and raising significant potential for false positives.
A systematic review and meta-analysis published in 2020 found that lactulose testing has a sensitivity of only 42% and a specificity 70.6%. Using glucose as the carbohydrate is only slightly better; the same meta-analysis found a sensitivity of 54.5% and specificity of 83.2% for glucose. Keep in mind, this is in comparison to the jejunal aspirate, which itself is prone to many errors and inconsistencies. Additionally, while SIBO refers to bacterial overgrowth, other organisms, such as fungi (SIFO) and methanogens (intestinal methanogen overgrowth, IMO) present diagnostic challenges.
Culture-independent omics (e.g., metagenomics, metatranscriptomics, metaproteomics), 16S ribosomal RNA amplification, and swallowable capsules that transmit intraluminal gas data (e.g., the Atmo Capsule) are emerging technologies that offer promise for understanding the complexity of the microbiome, but there are still substantial knowledge gaps. At present, there are many challenges with SIBO diagnosis, emphasizing the need for broad-based intestinal support that targets the many possible contributors to associated symptoms, e.g., promoting gut motility, supporting gastric acid and exocrine pancreatic function, etc., while awaiting more precise and individualized diagnostic testing.