"This study shows for the first time that patients with biochemically proven BAD have greater intestinal permeability (measured by validated non-invasive testing) than patients with IBS-diarrhea, reinforcing the need to positively diagnose and specifically treat BAD," Dr. Michael Camilleri of Mayo Clinic in Rochester, Minnesota, told Reuters Health by email.
"Among patients with IBS-D, about 30% have increased hepatic synthesis or malabsorption of bile acids, resulting in increased colonic bile acid concentrations," he explained. "It is well established that some bile acids cause colonic secretion and stimulate colonic motility. This reduced barrier function may predispose to further water and electrolyte secretion or facilitate mucosal inflammation."
Dr. Camilleri and his colleagues at Mayo Clinic compared the lactulose:mannitol-test results of 44 patients with IBS-D with BAD, 161 IBS-D patients without BAD, and 60 healthy volunteers. IBS-D patients with BAD had significantly higher body mass index (BMI) than patients without BAD.
Participants with IBS-D and normal healthy volunteers were tested for fasting (before 9 am) serum 7 alpha C4 and fibroblast growth factor-19, and for the percentage of primary bile acids in a random stool sample. Participants with serum 7 alpha C4 over >52 ng/mL were considered to have BAD, the researchers explain in Gastroenterology.
After an overnight fast, participants drank 100 mg 13C-mannitol and 1g lactulose in a 240mL glass of water. They fasted for 2 hours and drank another 500mL of water 30 minutes after ingesting the sugars.
Urine samples were collected and mass urinary excretion of mannitol and lactulose were calculated at 0-2 hours (indicating small-intestinal permeability), 2-8 hours (indicating combined small-bowel and colonic permeability), and 8-24 hours (indicating colonic permeability). The ratio of excreted lactulose to mannitol was calculated.
For the normal healthy volunteers, a measurement of intestinal permeability from an earlier study was used.
There were no significant differences in urinary excretion of 13C-mannitol and lactulose over 2-24 hours between normal healthy volunteers and patients with IBS-D without BAD.
Urinary excretions of the sugars during this period, corresponding to small-intestinal and colonic permeability, were increased in patients with BAD compared with those with IBS-D without BAD (P<0.05). By contrast, 0-2-hour urine excretion of 13C-mannitol, corresponding to selective small-intestinal permeability, was not increased, suggesting higher colonic permeability in BAD.
"The study's strengths are the relatively large number of participants," Dr. Lin Chang, a professor and vice-chief of the Division of Digestive Diseases of the David Geffen School of Medicine at UCLA in Los Angeles, told Reuters Health by email. "Also, it was conducted by a senior investigator who is an expert in IBS and bile acid diarrhea."
"Limitations are that diagnosing BAD can be challenging because it typically requires a two-day stool collection while on a specific diet," added Dr. Chang, who was not involved in the study. "To me, the main weakness is that the IBS-D group with BAD had a significantly higher BMI than the IBS-D group without BAD and the healthy volunteers."
"Higher BMI has been associated with increased intestinal permeability," she noted. "The authors acknowledge this but it doesn't seem that they controlled or adjusted for the high BMI in the IBS-D group with BAD. It is possible that the increased intestinal permeability is due to the higher BMI and not specifically to BAD, or that both factors can contribute to increased intestinal permeability."
"Bile acid diarrhea has recently been identified as cause of diarrhea in up to 25% of IBS-D patients," said Dr. Greg S. Cohen, a clinical associate professor of medicine at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.
"This study creates great hope that the pool of patients with IBS-D could potentially shrink by up to 25% with the availability of more precise diagnostic tools that would allow clinicians to identify patients with BAD, and treat them more specifically, rather than treating them like all other IBS-D patients," Dr. Cohen, who also was not involved in the study, told Reuters Health by email.
SOURCE: https://bit.ly/3FUDDVH Gastroenterology, online December 16, 2021.
By Lorraine L. Janeczko
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