Primary Bile Acid Diarrhea: A Narrative Review of Pathophysiology, Diagnostic Challenges, and Emerging Therapeutic Strategies

Primary bile acid diarrhea (BAD) is a clinically relevant cause of persistent watery diarrhea caused by high bile acid production and poor enterohepatic feedback regulation. A growing body of evidence suggests that disrupting the farnesoid X receptor-fibroblast growth factor 19 (FXR-FGF19) signaling pathway contributes to aberrant bile acid metabolism and increased colonic output. Despite increased understanding of its link with diarrhea-predominant irritable bowel syndrome (IBS-D), primary BAD remains difficult to diagnose due to overlapping clinical symptoms and a scarcity of specialist diagnostic tools. This narrative review highlights current data on the pathogenesis, clinical presentation, diagnostic modalities, and evolving therapy approaches for primary BAD, with a focus on existing diagnostic limitations and unmet clinical needs. A thorough literature search was conducted using electronic databases such as PubMed, Scopus, Embase, and Google Scholar. BAD, bile acid malabsorption, IBS-D, FXR, FGF19, SeHCAT, serum C4, fecal bile acids, and bile acid sequestrants were all covered using both Medical Subject Headings (MeSH) and free-text phrases. A narrative synthesis was conducted on pertinent original research, reviews, clinical trials, and guidelines published in English. According to available data, a major mechanism underlying primary BAD is defective FXR-FGF19-mediated feedback inhibition. Nonspecific symptoms, overlap with functional gastrointestinal illnesses, and limited access to established diagnostic instruments, such as the SeHCAT retention scan, are the causes of persistent diagnostic difficulties. Alternative biomarkers, such as fecal bile acid measurement, FGF19, and blood 7α-hydroxy-4-cholesten-3-one (C4), show promise for diagnosis but are still unreliable and poorly standardized. The mainstay of treatment remains bile acid sequestrants, although there are no uniform management algorithms, and treatment response varies. Future therapy options may be enhanced by novel strategies targeting bile acid signaling pathways.