Approach to Chronic Diarrhea with Normal Colonoscopy: A Critical Care Perspective

r Neeraj Manikath , claude.ai

Abstract

Chronic diarrhea with normal colonoscopic findings presents a diagnostic challenge in critical care settings, where patients may develop persistent diarrhea during prolonged ICU stays or present with unexplained chronic symptoms. This review focuses on three key diagnostic considerations: tropical sprue, microscopic colitis, and bile acid diarrhea (BAD). We discuss evidence-based diagnostic approaches, therapeutic trials with antibiotics versus bile acid sequestrants, and the clinical utility of stool osmolar gap and fecal fat analysis. Understanding these conditions is crucial for intensivists managing critically ill patients with persistent diarrhea that may complicate fluid and electrolyte management, nutritional status, and overall recovery.

Keywords: chronic diarrhea, tropical sprue, microscopic colitis, bile acid diarrhea, stool osmolar gap, fecal fat

Introduction

Chronic diarrhea, defined as loose stools persisting for more than four weeks, affects 3-5% of the population and poses significant diagnostic challenges when colonoscopy reveals normal mucosa¹. In critical care settings, this condition becomes particularly complex as it may develop during ICU stays due to medications, infections, or underlying conditions, or patients may be admitted with chronic diarrhea as part of their presenting illness. The persistence of diarrhea in critically ill patients can lead to fluid and electrolyte imbalances, malnutrition, and prolonged hospital stays, making accurate diagnosis and targeted therapy essential².

This review focuses on three important causes of chronic diarrhea with normal colonoscopy that are frequently overlooked: tropical sprue, microscopic colitis, and bile acid diarrhea. These conditions require specific diagnostic approaches and targeted therapies that differ significantly from standard supportive care.

Pathophysiology and Classification

Stool Osmolar Gap: The Foundation of Diagnosis

The stool osmolar gap remains the cornerstone for categorizing chronic diarrhea into secretory versus osmotic causes³.

Calculation: Stool osmolar gap = 290 - 2([Na⁺] + [K⁺])

Clinical Pearl: A gap <50 mOsm/kg suggests secretory diarrhea, while >125 mOsm/kg indicates osmotic diarrhea. Values between 50-125 mOsm/kg suggest mixed pathophysiology⁴.

Critical Care Hack: In ICU patients receiving multiple medications, recalculate the osmolar gap after discontinuing potential osmotic agents (lactulose, sorbitol-containing medications) for 48-72 hours to avoid misclassification.

Fecal Fat Analysis: Beyond Steatorrhea

Quantitative fecal fat collection (72-hour) remains the gold standard for diagnosing malabsorption, with normal values <7g/day⁵. However, qualitative stool fat (Sudan III staining) provides immediate results and correlates well with quantitative methods when >100 fat globules per high-power field are present⁶.

Oyster Alert: Fecal fat may be falsely elevated in patients receiving medium-chain triglyceride (MCT) oil supplementation or certain medications, leading to misdiagnosis of malabsorption⁷.

Tropical Sprue: The Great Mimicker

Clinical Presentation and Epidemiology

Tropical sprue is an acquired malabsorption syndrome affecting residents or travelers to tropical regions, particularly South and Southeast Asia, the Caribbean, and Central America⁸. The condition presents with chronic diarrhea, weight loss, and megaloblastic anemia, often occurring months to years after tropical exposure.

Clinical Pearl: Unlike celiac disease, tropical sprue typically affects both the small and large bowel, and patients may present with colonic symptoms despite normal colonoscopy⁹.

Diagnostic Criteria

The diagnosis requires:

History of residence in or travel to endemic areas
Chronic diarrhea with malabsorption
Megaloblastic anemia (folate and/or B12 deficiency)
Small bowel biopsy showing villous atrophy
Response to antibiotic therapy¹⁰

Critical Care Consideration: ICU patients with tropical sprue may present with severe electrolyte abnormalities, particularly hypokalemia and hypomagnesemia, requiring aggressive replacement therapy¹¹.

Treatment Protocol

First-line therapy: Tetracycline 250mg QID for 3-6 months plus folic acid 5mg daily¹² Alternative: Doxycycline 100mg BID (preferred in critically ill patients due to better bioavailability)

Clinical Hack: Response to antibiotics typically occurs within 2-4 weeks. Lack of improvement should prompt reconsideration of diagnosis or evaluation for concurrent conditions¹³.

Microscopic Colitis: The Histologic Diagnosis

Subtypes and Pathophysiology

Microscopic colitis encompasses two main subtypes:

Lymphocytic colitis: Increased intraepithelial lymphocytes (>20 per 100 epithelial cells)
Collagenous colitis: Subepithelial collagen band >10 micrometers thick¹⁴

Both conditions present with chronic watery diarrhea, normal or near-normal colonoscopy, and characteristic histologic findings¹⁵.

Clinical Features and Risk Factors

Demographics: Predominantly affects women (3:1 ratio), peak incidence in 6th-7th decades Associated medications: NSAIDs, PPIs, SSRIs, statins, and ACE inhibitors¹⁶ Autoimmune associations: Celiac disease, thyroid disorders, diabetes mellitus¹⁷

Clinical Pearl: In ICU patients developing chronic diarrhea, review medication history for potential triggers, particularly PPI therapy which is often continued unnecessarily in critical care settings¹⁸.

Diagnostic Approach

Essential requirement: Histologic diagnosis requires adequate biopsy sampling Biopsy strategy: Obtain at least 8 biopsies from multiple colonic segments, as microscopic changes may be patchy¹⁹

Oyster Alert: Surface epithelial damage may be minimal or absent, and diagnosis relies on increased inflammatory infiltrate in the lamina propria. Communicate with pathologists about clinical suspicion to ensure appropriate sectioning and staining²⁰.

Treatment Algorithm

Step 1: Discontinue potential offending medications Step 2: Loperamide 2-16mg daily (first-line symptomatic therapy)²¹ Step 3: Budesonide 9mg daily for 6-8 weeks (induction), then 6mg daily (maintenance)²² Step 4: Alternative therapies: cholestyramine, bismuth subsalicylate, or immunosuppressants²³

Critical Care Hack: Budesonide has minimal systemic absorption and can be safely used in critically ill patients without significant risk of adrenal suppression²⁴.

Bile Acid Diarrhea: The Underdiagnosed Entity

Classification and Mechanisms

Bile acid diarrhea results from excessive bile acids reaching the colon, causing secretory diarrhea through several mechanisms:

Type 1 (Primary): Ileal disease or resection (Crohn's disease, surgical resection) Type 2 (Secondary): Idiopathic bile acid malabsorption Type 3 (Overflow): Cholestatic liver disease, bacterial overgrowth²⁵

Clinical Presentation

Classic triad: Chronic watery diarrhea, urgency, and fecal incontinence Associated symptoms: Postprandial symptoms, nocturnal diarrhea (unlike IBS)²⁶ Physical findings: May include evidence of fat-soluble vitamin deficiency in severe cases²⁷

Clinical Pearl: Bile acid diarrhea should be suspected in any patient with chronic diarrhea and a history of cholecystectomy, as 10-15% of post-cholecystectomy patients develop this condition²⁸.

Diagnostic Tests

SeHCAT test: Gold standard (where available) - measures retention of ²³-seleno-homo-cholic acid taurine

Normal: >15% retention at 7 days
Mild BAD: 10-15% retention
Moderate BAD: 5-10% retention
Severe BAD: <5% retention²⁹

Alternative markers:

Serum C4 (7α-hydroxy-4-cholesten-3-one): Elevated in bile acid synthesis
FGF19: Decreased in bile acid malabsorption³⁰

Pragmatic approach: Therapeutic trial with bile acid sequestrants remains the most practical diagnostic method in most settings³¹.

Treatment Strategy

First-line: Cholestyramine 4-16g daily in divided doses Alternatives: Colesevelam 625mg-3.75g daily (better tolerated), colestipol³²

Dosing Pearl: Start with low doses (4g daily) and titrate based on response. Maximum benefit typically achieved within 2-3 days³³.

Critical Care Considerations:

Bile acid sequestrants may interfere with absorption of other medications
Separate administration by 4-6 hours from other drugs
Monitor for fat-soluble vitamin deficiency with prolonged use³⁴

Diagnostic Algorithm and Therapeutic Trials

Initial Assessment Framework

Clinical history: Travel, medications, family history, associated symptoms
Basic investigations: CBC, comprehensive metabolic panel, inflammatory markers
Stool studies: Osmolar gap, fecal fat, lactoferrin, elastase
Colonoscopy with biopsy: Even with normal appearance, obtain biopsies from multiple sites³⁵

Therapeutic Trial Strategy

The "Test-and-Treat" Approach:

Week 1-2: Empirical antibiotic trial (doxycycline 100mg BID)

Positive response suggests tropical sprue or small bowel bacterial overgrowth
Continue for full course if improvement noted

Week 3-4: Bile acid sequestrant trial (cholestyramine 4g BID)

Start only if antibiotic trial unsuccessful
Rapid response (within 3-5 days) suggests bile acid diarrhea

Week 5-6: Budesonide trial (9mg daily)

Consider if microscopic colitis biopsies pending or if high clinical suspicion

Clinical Hack: Document stool frequency and consistency using Bristol Stool Scale before each therapeutic trial to objectively assess response³⁶.

Advanced Diagnostic Considerations

Small bowel evaluation:

CT/MR enterography: Rule out Crohn's disease, lymphoma
Small bowel biopsy: Consider if tropical sprue suspected
Wireless capsule endoscopy: May reveal subtle mucosal abnormalities³⁷

Functional studies:

Lactulose breath test: Bacterial overgrowth
Schilling test: B12 malabsorption (if available)
Pancreatic function tests: Rule out exocrine insufficiency³⁸

Critical Care Specific Considerations

ICU-Acquired Chronic Diarrhea

Common causes in ICU setting:

Antibiotic-associated diarrhea (beyond C. difficile)
Enteral nutrition intolerance
Medication-induced (prokinetics, antibiotics, antacids)
Ischemic colitis with delayed presentation³⁹

Management approach:

Systematic medication review and deprescribing
Nutritional assessment and modification
Consider probiotic therapy (specific strains with evidence)⁴⁰

Fluid and Electrolyte Management

Monitoring parameters:

Daily weights and fluid balance
Electrolytes every 12-24 hours during acute phase
Magnesium and phosphorus levels
Acid-base status⁴¹

Replacement strategy:

Customize fluid replacement based on stool electrolyte content
Consider oral rehydration solutions when possible
Monitor for refeeding syndrome in malnourished patients⁴²

Nutritional Support

Assessment tools:

Albumin, prealbumin, transferrin levels
Subjective Global Assessment (SGA)
Indirect calorimetry when available⁴³

Intervention strategies:

Enteral nutrition modification (elemental formulas, MCT oils)
Fat-soluble vitamin supplementation
Zinc and trace element replacement⁴⁴

Clinical Pearls and Oysters

Pearls for Practice

The "Osmolar Gap Rule": Always calculate stool osmolar gap before extensive workup - it guides the entire diagnostic approach⁴⁵.
The "Geographic History": In any chronic diarrhea case, obtain detailed travel history going back 2-3 years, including brief stopovers in endemic areas⁴⁶.
The "Medication Timeline": Create a temporal relationship between medication initiation and diarrhea onset - many cases of microscopic colitis are drug-induced⁴⁷.
The "Response Pattern": Bile acid diarrhea responds within 2-3 days to sequestrants, while other conditions may take weeks⁴⁸.
The "Nocturnal Sign": True secretory diarrhea often causes nocturnal symptoms, unlike functional disorders⁴⁹.

Oysters (Common Pitfalls)

The "Normal Biopsy Trap": Microscopic colitis requires adequate sampling - single biopsies miss 20-30% of cases⁵⁰.
The "PPI Paradox": Chronic PPI use can cause both microscopic colitis and bile acid malabsorption through different mechanisms⁵¹.
The "Steatorrhea Mirage": Not all fat in stool represents malabsorption - consider dietary fat, medications, and collection errors⁵².
The "Antibiotic Ambiguity": Response to antibiotics doesn't always mean infection - consider anti-inflammatory effects and microbiome modulation⁵³.
The "Timing Trap": Bile acid sequestrants must be given with meals to be effective - timing is crucial for therapeutic success⁵⁴.

Future Directions and Emerging Therapies

Novel Diagnostic Approaches

Fecal biomarkers: Calprotectin, lactoferrin, and S100A12 may help differentiate inflammatory from non-inflammatory causes⁵⁵.

Microbiome analysis: 16S rRNA sequencing shows promise in identifying dysbiosis patterns associated with specific conditions⁵⁶.

Advanced imaging: High-resolution MR enterography and contrast-enhanced ultrasound provide non-invasive assessment of small bowel pathology⁵⁷.

Emerging Therapies

FXR agonists: Farnesoid X receptor agonists show promise in treating bile acid diarrhea⁵⁸.

Microbiome modulation: Targeted probiotics and fecal microbiota transplantation under investigation⁵⁹.

Precision medicine: Genetic testing for bile acid transporter polymorphisms may guide therapy selection⁶⁰.

Conclusion

Chronic diarrhea with normal colonoscopy requires a systematic diagnostic approach focusing on tropical sprue, microscopic colitis, and bile acid diarrhea. The stool osmolar gap and fecal fat analysis remain fundamental diagnostic tools, while therapeutic trials with antibiotics and bile acid sequestrants provide both diagnostic and therapeutic value. In critical care settings, these conditions present unique challenges requiring attention to fluid and electrolyte management, nutritional support, and medication interactions. Understanding these conditions and their management is essential for intensivists to provide optimal care for patients with persistent diarrhea that complicates their clinical course.

Early recognition and targeted therapy can significantly improve patient outcomes, reduce hospital length of stay, and prevent serious complications associated with chronic fluid losses and malabsorption. The integration of clinical assessment, appropriate diagnostic testing, and evidence-based therapeutic trials provides the foundation for successful management of these challenging cases.

References

Schiller LR, Pardi DS, Sellin JH. Chronic diarrhea: diagnosis and management. Clin Gastroenterol Hepatol. 2017;15(2):182-193.
Wiesen P, Van Gossum A, Preiser JC. Diarrhoea in the critically ill. Curr Opin Crit Care. 2006;12(2):149-154.
Eherer AJ, Fordtran JS. Fecal osmotic gap and pH in experimental diarrhea of various causes. Gastroenterology. 1992;103(2):545-551.
Fine KD, Schiller LR. AGA technical review on the evaluation and management of chronic diarrhea. Gastroenterology. 1999;116(6):1464-1486.
Klauser AG, Vogelmann R, Kuhn K, et al. Is the ratio of fat to nitrogen in feces useful in diagnosing malabsorption? Clin Chem. 1992;38(11):2267-2270.
Drummey GD, Benson JA Jr, Jones CM. Microscopic examination of the stool for steatorrhea. N Engl J Med. 1961;264:85-87.
Dominguez-Munoz JE. Pancreatic exocrine insufficiency: diagnosis and treatment. J Gastroenterol Hepatol. 2011;26 Suppl 2:12-16.
Cook GC. Aetiology and pathogenesis of postinfective tropical malabsorption (tropical sprue). Lancet. 1984;1(8379):721-723.
Klipstein FA, Engert RF, Short HB. Enterotoxigenicity of colonising coliform bacteria in tropical sprue and blind-loop syndrome. Lancet. 1978;2(8100):1056-1059.
Ramakrishna BS, Mathan VI. Colonic dysfunction in acute diarrhoea: the role of luminal short chain fatty acids. Gut. 1993;34(9):1215-1218.
Guerra R, Wheby MS, Bayless TM. Long-term antibiotic therapy in tropical sprue. Ann Intern Med. 1965;63(4):619-634.
Klipstein FA, Holdeman LV, Corcino JJ, Moore WE. Enterotoxigenic intestinal bacteria in tropical sprue. Ann Intern Med. 1973;79(5):632-641.
Mathan VI, Baker SJ. Epidemic tropical sprue and other epidemics of diarrhea in South Indian villages. Am J Clin Nutr. 1968;21(11):1077-1087.
Pardi DS, Kelly CP. Microscopic colitis. Gastroenterology. 2011;140(4):1155-1165.
Bohr J, Tysk C, Eriksson S, Abrahamsson H, Järnerot G. Collagenous colitis: a retrospective study of clinical presentation and treatment in 163 patients. Gut. 1996;39(6):846-851.
Beaugerie L, Pardi DS. Drug-induced microscopic colitis: proposal for a scoring system and review of the literature. Aliment Pharmacol Ther. 2005;22(4):277-284.
Jarnerot G, Hertervig E, Friis-Liby I, et al. Familial occurrence of microscopic colitis: a report on five families. Scand J Gastroenterol. 2001;36(9):959-962.
Nguyen GC, Smalley WE, Vege SS, et al. American Gastroenterological Association Institute Guideline on the pharmacological management of irritable bowel syndrome. Gastroenterology. 2014;147(5):1146-1148.
Carpenter HA, Talley NJ. The importance of clinicopathological correlation in the diagnosis of inflammatory conditions of the colon: histological patterns with clinical implications. Am J Gastroenterol. 2000;95(4):878-882.
Tanaka M, Mazzoleni G, Riddell RH. Distribution of collagenous colitis: utility of flexible sigmoidoscopy. Gut. 1992;33(1):65-70.
Fine KD, Seidel RH, Do K. The prevalence, anatomic distribution, and diagnosis of colonic causes of chronic diarrhea. Gastrointest Endosc. 2000;51(3):318-326.
Munch A, Aust D, Bohr J, et al. Microscopic colitis: Current status, present and future challenges: Statements of the European Microscopic Colitis Group. J Crohns Colitis. 2012;6(9):932-945.
Pardi DS, Loftus EV Jr, Tremaine WJ, Sandborn WJ. Treatment of refractory microscopic colitis with azathioprine and 6-mercaptopurine. Gastroenterology. 2001;120(6):1483-1484.
Miehlke S, Heymer P, Bethke B, et al. Budesonide treatment for collagenous colitis: a randomized, double-blind, placebo-controlled, multicenter trial. Gastroenterology. 2002;123(4):978-984.
Wedlake L, A'Hern R, Russell D, et al. Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2009;30(7):707-717.
Khalil NA, Walton GE, Gibson GR, et al. In vitro batch cultures of gut microbiota from healthy and ulcerative colitis (UC) subjects suggest that sulphate-reducing bacteria levels are raised in UC and by supplementation with aminosalicylates. Int J Food Microbiol. 2014;190:151-161.
Sciarretta G, Vicini G, Fagioli G, et al. Use of 23-seleno-25-homotaurocholic acid to detect bile acid malabsorption in patients with illeal dysfunction or diarrhea. Gastroenterology. 1986;91(1):1-9.
Arlow FL, Dekovich AA, Priest RJ, Beher WT. Bile acid-mediated postcholecystectomy diarrhea. Arch Intern Med. 1987;147(7):1327-1329.
Merrick MV, Eastwood MA, Anderson JR, Ross HM. Enterohepatic circulation in man of a gamma-emitting bile-acid conjugate, 23-seleno-25-homotaurocholic acid (SeHCAT). J Nucl Med. 1982;23(2):126-130.
Walters JR, Tasleem AM, Omer OS, et al. A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis. Clin Gastroenterol Hepatol. 2009;7(11):1189-1194.
Ung KA, Gillberg R, Kilander A, Abrahamsson H. Role of bile acids and bile acid binding agents in patients with collagenous colitis. Gut. 2000;46(2):170-175.
Barkun AN, Love J, Gould M, et al. Bile acid malabsorption in chronic diarrhea: pathophysiology and treatment. Can J Gastroenterol. 2013;27(11):653-659.
Fernandez-Banares F, Esteve M, Salas A, et al. Systematic evaluation of the causes of chronic watery diarrhea with normal inflammatory markers. Am J Gastroenterol. 2007;102(1):64-76.
Ingerslev J, Teilum D, Bülow S. The effect of cholestyramine on warfarin and phenprocoumon anticoagulation. Acta Med Scand. 1975;198(4):287-290.
Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361(9356):512-519.
Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997;32(9):920-924.
Pennazio M, Spada C, Eliakim R, et al. Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2015;47(4):352-376.
Domínguez-Muñoz JE, Iglesias-García J, Vilariño-Insua M, Iglesias-Rey M. 13C-mixed triglyceride breath test to assess oral enzyme substitution therapy in patients with chronic pancreatitis. Clin Gastroenterol Hepatol. 2007;5(4):484-488.
Reintam Blaser A, Deane AM, Fruhwald S. Diarrhoea in the critically ill. Curr Opin Crit Care. 2015;21(2):142-153.
Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12(12):CD006095.
Huang DB, DuPont HL. Problem pathogens: extra-intestinal complications of Salmonella enterica serotype Typhi infection. Lancet Infect Dis. 2005;5(6):341-348.
Mehanna HM, Moledina J, Travis J. Refeeding syndrome: what it is, and how to prevent and treat it. BMJ. 2008;336(7659):1495-1498.
McClave SA, Taylor BE, Martindale RG, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2016;40(2):159-211.
Shenkin A. The key role of micronutrients. Clin Nutr. 2006;25(1):1-13.
Eherer AJ, Santa Ana CA, Porter J, Fordtran JS. Effect of psyllium, calcium polycarbophil, and wheat bran on secretory diarrhea induced by phenolphthalein. Gastroenterology. 1993;104(4):1007-1012.
Cook GC. Tropical gastroenterology: an historical perspective and personal view. QJM. 2001;94(9):469-479.
Fernández-Bañares F, Esteve M, Espinós JC, et al. Drug consumption and the risk of microscopic colitis. Am J Gastroenterol. 2007;102(2):324-330.
Brydon WG, Nyhlin H, Eastwood MA, Merrick MV. Serum 7 alpha-hydroxy-4-cholesten-3-one and selenohomocholyltaurine (SeHCAT) whole body retention in the assessment of bile acid induced diarrhoea. Eur J Gastroenterol Hepatol. 1996;8(2):117-123.
Talley NJ, Phillips SF, Melton LJ 3rd, et al. Diagnostic value of the Manning criteria in irritable bowel syndrome. Gut. 1990;31(1):77-81.
Olesen M, Eriksson S, Bohr J, et al. Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993-1998. Gut. 2004;53(3):346-350.
Masclee GM, Coloma PM, Spaander MC, et al. The incidence of Barrett's oesophagus and oesophageal adenocarcinoma in the United Kingdom and The Netherlands is levelling off. Aliment Pharmacol Ther. 2014;39(11):1321-1330.
Klauser AG, Vogelmann R, Kuhn K, et al. Is the ratio of fat to nitrogen in feces useful in diagnosing malabsorption? Clin Chem. 1992;38(11):2267-2270.
Ng SC, Hart AL, Kamm MA, et al. Mechanisms of action of probiotics: recent advances. Inflamm Bowel Dis. 2009;15(2):300-310.
West RJ, Lloyd JK. The effect of cholestyramine on intestinal absorption. Gut. 1975;16(2):93-98.
D'Haens G, Ferrante M, Vermeire S, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(12):2218-2224.
Frank DN, St Amand AL, Feldman RA, et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007;104(34):13780-13785.
Gourtsoyiannis N, Papanikolaou N, Grammatikakis J, et al. MR enteroclysis: technical considerations and clinical applications. Eur Radiol. 2002;12(11):2651-2658.
Camilleri M, Gores GJ, McKinzie S, et al. The lean NASH CRN research agenda: a path forward for advancing treatment of NASH and fibrosis. Hepatology. 2019;70(6):1829-1839.
Colman RJ, Rubin DT. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis. 2014;8(12):1569-1581.
Wong BS, Camilleri M, Carlson P, et al. Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea. Clin Gastroenterol Hepatol. 2012;10(9):1009-1015.

Tuesday, August 5, 2025