It’s a curious place, the small intestine.
It occupies around 24-feet of the entire 30-foot long gastrointestinal (GI) tract, yet it is the least explored, least investigated segment of the human GI system. This is because it is relatively inaccessible to endoscopy from above that can rarely reach much beyond the duodenum, leaving the 24-feet of jejunum and ileum untouched. Likewise, a colonoscope can reach the ascending colon but cannot navigate the ileum. This is a major practical challenge. Imagine someone is hemorrhaging from the small intestine, 8 feet down from the duodenum, 16 or so feet feet up the colon—how do you identify, then cauterize or otherwise stop the hemorrhage? This has been a perennial challenge in clinical practice.
It also means that, because we commonly make judgements about the intestinal microbiome by examining stool, we are making judgements based on colonic contents, not small intestinal contents, since the contents of the small intestine have to pass through the colon before exiting the body. A stool sample is a reflection of the composition of the sigmoid colon and rectum, i.e., the last few inches of colon, and less representative of, say, the ascending colon. The colon therefore introduces substantial change to the material passing through, obscuring what happens in the small intestine.
Yet it’s the small intestine that is responsible for about 90% of nutrient absorption and the majority of the intestinal immune response. Diseases such as Crohn’s disease, celiac disease, malabsorption (steatorrhea), irritable bowel syndrome (IBS), and small intestinal bacterial overgrowth (SIBO) are small intestinal, not colon, processes. The small intestine, not the colon, is therefore the center of the GI microbiome universe. But the small intestine remains the most elusive, most shadowy, segment of the human GI tract.
So how do you obtain a sample of ileal fluid to assess its microbiome composition? As a practical matter, you simply cannot. We are therefore left with making indirect observations about small intestinal physiology and microbiome composition.
Among the indirect ways to assess small intestinal physiology and microbiome include:
- Vitamin B12 absorption occurs in the ileum, a processed that is impaired when the Proteobacteria species of SIBO have proliferated. In other words, vitamin B12 deficiency can indicate SIBO (as well as impairment of the parietal cells of the stomach that produce the intrinsic factor necessary for B12 absorption).
- Fat malabsorption, e.g., seeing fat droplets in the toilet with a bowel movement, occurs when the species of SIBO interfere with the action of pancreatic enzymes in the duodenum and jejunum.
- Intolerances to any prebiotic fiber or polysaccharide (e.g., inulin, legumes, fruit, etc.) within the first 90 minutes of consumption suggests that unhealthy microbial species have ascended up the small bowel, i.e., SIBO. In other words, it typically takes an absolute minimum of 90 minutes after ingesting something for it to traverse the entire 24-feet of small bowel before it reaches the colon where fermentation normally occurs. If it occurs within the first 90 minutes after ingestion, fermenting bacteria must be in the small intestine.
- Food intolerances—Because it requires a minimum of 90 minutes for anything you ingest to reach the colon, a food intolerance to, say, FODMAPS, histamine-containing foods, legumes, fruit, nighthshades, etc. that occurs within the first 90 minutes of consumption is indicative of dysbiosis in the small intestine, i.e., SIBO.
- H2-breath testing, as with the AIRE device, is a way to map whether H2-producing microbes have colonized the small intestine and ferment sugars or prebiotic fibers to H2 gas within the first 90 minutes of ingestion, parallel to prebiotic fiber intolerances.
- Serum lipopolysaccharide (LPS)–This can serve as an index of intestinal permeability and endotoxemia. Unfortunately, it does not identify the LPS of all small intestinal species and remains a research tool, not yet clinically available.
- Serum zonulin—First identified as an index of increased intestinal permeability due to exposure to the gliadin protein of wheat, it may also serve as a gauge of increased intestinal permeability due to dysbiosis/SIBO. However, there are some methodological details that need to be worked out before it reliably reflects this process.
The issues unique to the small intestine mean that the insights we draw from stool testing may be largely incorrect or incomplete. Given current methods, we can therefore only piece together a glimpse into what is going on in the small intestine from indirect pieces of information. Until we have better methods, we need to take information such as H2 breath testing or the presence of food intolerances seriously as indicators of small intestinal dysbiosis.