Diagnosis by Microbial Culture, Breath Tests and Urinary Excretion Tests, and Treatments of Small Intestinal Bacterial Overgrowth

Yorinobu Maeda, Teruo Murakami, Yorinobu Maeda, Teruo Murakami

Abstract

Small intestinal bacterial overgrowth (SIBO) is characterized as the increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract and accompanies various bowel symptoms such as abdominal pain, bloating, gases, diarrhea, and so on. Clinically, SIBO is diagnosed by microbial culture in duodenum/jejunum fluid aspirates and/or the breath tests (BT) of hydrogen/methane gases after ingestion of carbohydrates such as glucose. The cultural analysis of aspirates is regarded as the golden standard for the diagnosis of SIBO; however, this is invasive and is not without risk to the patients. BT is an inexpensive and safe diagnostic test but lacks diagnostic sensitivity and specificity depending on the disease states of patients. Additionally, the urinary excretion tests are used for the SIBO diagnosis using chemically synthesized bile acid conjugates such as cholic acid (CA) conjugated with para-aminobenzoic acid (PABA-CA), ursodeoxycholic acid (UDCA) conjugated with PABA (PABA-UDCA) or conjugated with 5-aminosalicylic acid (5-ASA-UDCA). These conjugates are split by bacterial bile acid (cholylglycine) hydrolase. In the tests, the time courses of the urinary excretion rates of PABA or 5-ASA, including their metabolites, are determined as the measure of hydrolytic activity of intestinal bacteria. Although the number of clinical trials with this urinary excretion tests is small, results demonstrated the usefulness of bile acid conjugates as SIBO diagnostic substrates. PABA-UDCA disulfate, a single-pass type unabsorbable compound without the hydrolysis of conjugates, was likely to offer a simple and rapid method for the evaluation of SIBO without the use of radioisotopes or expensive special apparatus. Treatments of SIBO with antibiotics, probiotics, therapeutic diets, herbal medicines, and/or fecal microbiota transplantation are also reviewed.

Keywords: 5-aminosalicylic acid; conjugated bile acids; diagnosis of SIBO; para-aminobenzoic acid; small intestinal bacterial overgrowth; treatments of SIBO; ursodeoxycholic acid.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of (A) ursodeoxycholic acid (UDCA), (B) UDCA conju gated with para-aminobenzoic acid (PABA-UDCA), (C) UDCA disulfate conjugated with PABA (PABA-UDCA disulfate), and (D) UDCA monophosphate conjugated with 5-aminosalycilic acid (5-ASAUDCA monophosphate.
Figure 2
Figure 2
Schematic representation for the fate of (A) PABA-UDCA and (B) 5-ASA-UDCA mono-phosphate in the proximal small intestine. (A): A part of orally ingested PABA-UDPA is deconjugated by intestinal bacterial bile salt (cholylglycine) hydrolase. The released PABA and UDCA are absorbed by passive diffusion. A part of PABA is metabolized to N-acetyl-PABA (Ac-PABA) by N-acetyltransferase in the intestine and liver. These PABA and Ac-PABA are efficiently excreted into the urine. UDCA and a part of intact PABA-UDPA are absorbed by passive diffusion in the proximal intestine and UDCA is conjugated with taurine and/or glycine in the liver. These UDCA, UDCA-amino acids conjugates and PABA-UDCA are subjected to enterohepatic circulation. (B): A part of orally ingested 5-ASA-UDPA monophosphate (5-ASA-UDCA-mP) is deconjugated by intestinal bacterial bile salt (cholylglycine) hydrolase. The released 5-ASA is absorbed by carrier-mediated transport at a low concentration and passive diffusion at a higher concentration and is metabolized to N-acetyl-5-ASA (Ac-5ASA) by N-acetyltransferase. Ac-5ASA is effluxed into the intestinal lumen by apical MRP2 or into a portal vein by basolateral MRP3. Un-metabolized, 5-ASA and Ac-5ASA absorbed into blood circulation are excreted into the urine. Intact 5-ASA-UDCA monophosphate (5-ASA-mP) and UDCA-monophosphate (UDCA-mP) are hardly absorbed in the small intestine (single-pass type substance). Solid arrows represent the transport and/or metabolism of the compound in the intestinal membrane. The dotted arrows represent small transport in the membrane. Open arrows represent the metabolism and/or migration toward the distal intestinal lumen.

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