SIBO Tied to Higher Bile Acid Synthesis in Patients With Chronic Diarrhea

Patients with small intestinal bacterial overgrowth (SIBO) diagnosed by duodenal aspirate had significantly higher serum 7α-hydroxy-4-cholesten-3-one (7αC4), a marker of hepatic bile acid synthesis, than patients without SIBO, according to findings from a retrospective analysis presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee.1

Of note, the difference was significant at both SIBO thresholds evaluated: 10³ colony-forming units (cfu)/mL (P = .011) and 10⁵ cfu/mL (P = .036).1

Investigators described the findings as the first documentation of bile acid diarrhea (BAD) in patients with SIBO.¹ BAD has an estimated population prevalence of 1%, and prior work found it affects approximately a quarter of patients with irritable bowel syndrome with diarrhea (IBS-D), with a greater impact on bowel symptoms and quality of life.1,2

“It’s very important when it comes to chronic diarrhea to consider both bile acid diarrhea and SIBO,” said Ayah Matar, MD, in an interview with HCPLive. “They both present with very similar symptoms, which are chronic diarrhea, abdominal pain, and bloating.”

How Did Investigators Assess SIBO and Bile Acid Diarrhea?

The analysis included 1260 patients with chronic diarrhea and no history of intestinal surgery.¹ Of these, 584 had a fasting serum 7αC4 test (n = 26 with prior cholecystectomy), 584 underwent 48-hour stool collection for total and primary bile acids (n = 2 with prior cholecystectomy), and 92 underwent bile acid metabolic pattern (BAMP) testing (n = 5 with prior cholecystectomy).1

BAD was defined using 3 validated criteria sets: fasting serum 7αC4 > 52.5 ng/mL alone; 48-hour fecal excretion > 2337 µmol total bile acids, > 10% primary bile acids, or > 1000 µmol total bile acids with > 4% primary bile acids; or BAMP criteria combining 7αC4 > 52.5 ng/mL with single-stool primary bile acids > 10%. SIBO was diagnosed by duodenal aspirate obtained during endoscopy, and bile acid parameters were compared using the Mann-Whitney test.1,2,3

Matar explained SIBO produces bile salt hydrolase, an enzyme which deconjugates bile acids and prevents micelle formation. The resulting malabsorption and increased colonic secretion contribute to diarrhea, and the team set out to identify which biochemical changes accompany SIBO.1

What Did Bile Acid Biomarkers Show in Patients with SIBO?

Serum 7αC4 was significantly higher in SIBO-positive patients at both the 10³ and 10⁵ cfu/mL thresholds. The investigators attributed the increase to reduced negative feedback on hepatocytes, resulting from impaired ileal absorption of deconjugated bile acids.1

Fecal bile acid measures showed numerical but nonsignificant differences between groups. Median total fecal bile acid excretion over 48 hours was 1434 µmol in patients with SIBO > 10⁵ cfu/mL (n = 12), compared with 824 µmol in SIBO-negative patients (n = 24).1

Matar noted single-stool primary bile acid levels were numerically higher in SIBO-positive patients at the 10³ cfu/mL threshold. She said the BAMP subgroup of roughly 30 patients was likely underpowered to detect statistical significance, and larger studies are needed to confirm whether the increase is consistent at both thresholds.

What Should Clinicians Take From the SIBO and Bile Acid Findings?

Matar emphasized the retrospective study is hypothesis generating and did not evaluate treatment. She said it nonetheless supports considering both conditions when evaluating patients with chronic diarrhea.

“If a patient presents with abdominal pain, chronic diarrhea, bloating, two things have to come to mind, and it should be testing for SIBO and testing for bile acid diarrhea,” said Matar.

Future research should examine the mechanism behind the association and compare outcomes when clinicians treat SIBO, BAD, or both, according to Matar.

Editors’ note: Matar reports no relevant disclosures.

References:

1. Matar A, et al. Association between small intestinal bacterial overgrowth and bile acid diarrhea biomarkers in patients with chronic diarrhea. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 9-14, 2026; Nashville, TN.

2. BouSaba J, Sannaa W, McKinzie S, et al. Impact of bile acid diarrhea in patients with diarrhea-predominant irritable bowel syndrome on symptoms and quality of life. Clin Gastroenterol Hepatol. 2022;20(9):2083-2090.e1. doi:10.1016/j.cgh.2021.11.035

3. Vijayvargiya P, Camilleri M, Taylor A, et al. Combined fasting serum C4 and primary bile acids from a single stool sample to diagnose bile acid diarrhea. Gastroenterology. 2020;159(5):1952-1954.e2. doi:10.1053/j.gastro.2020.07.001