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Stress, Bile Acids, and IBS Symptoms

Functional Medicine doctor examining patient.

Research is still uncovering the causes of and triggers for irritable bowel syndrome (IBS), many of which are lifestyle-related. In the past two years, increasing evidence has been found relating structural and biochemical factors to IBS development. Australian researchers note that low-grade mucosal inflammation, altered intestinal permeability, and altered bile salt metabolism (in diarrhea-dominant IBS) can be factors, as well as abnormal metabolism.1

Gut-brain dysfunction leading to depression and anxiety are also commonly found in IBS patients.1 A meta-analysis found patients who had anxiety or depression were twice as likely to develop new-onset IBS.2 Polish researchers found that biochemical markers of stress and anxiety (activation of the autonomic nervous system and an increase in cortisol levels and proinflammatory cytokines) weaken gut tight junctions, with a resulting increase of bacterial translocation.3

Bacterial families in the microbiome may help to tailor treatment by IBS type.4 For example, Bacteroides bacterium have been found to be prominent in IBS-C (constipation-predominant) patients, while Escherichia coli was prominent in IBS-D (diarrhea-predominant) patients.4

Bile acids (BA) have a significant effect on gut motility, sensory, and secretory functions, intestinal permeability, and inflammatory response regulation. In one study, over a quarter of patients with IBS-D had BA malabsorption.5 Even in IBS patients without overt bile acid malabsorption, bile acids affect colonic transit time and fecal weight, strengthening the hypothesis that bile acids play an important role in IBS symptomotology.6 In one study, a 75SeHCAT scan found abnormal (<10%) BA levels in IBS patients. They also experienced more frequent stools, a faster colonic transit time, and rectal hyposensitivity.7 Treatments that alter bile acid production (like colestipol) also alter colonic transit time and fecal weight.6 Colestipol also improved severity symptom scores, providing adequate relief of IBS symptoms.7

The impact on gut function and a predisposition to diarrhea by malabsorption of BA are being examined as both a cause and a treatment path.8 In one study, patients with IBS-C had high levels of serum and amino-conjugated BA levels but decreased BA deconjugation activity compared to healthy volunteers.4 IBS-D patients had increased fecal primary, sera primary, and amino-conjugated BA levels but decreased BA deconjugation activity.4 Serum and fecal primary BA was associated with abdominal pain in all IBS patients.4

Increasingly, BA is being used as a biomarker for identifying and directing treatment.8 Serum and fecal primary BA have been associated with abdominal pain in all types of IBS patients.4 One review article concluded that elevated bile acid in the stool and altered colonic transit were the most promising actionable markers.9 More effective, individualized treatment paths can be developed based on IBS type, acid balance, and motility.

A variety of lifestyle interventions to restore a healthy microbiome and reduce gut permeability are known to be crucial for treating IBS.10-12 In IBS, the gut-brain connection is a little-realized factor in symptom severity. Cognitive behavioral, nutritional, and other therapies can reduce symptoms driven by psychological factors. A treatment plan addressing both gut and brain has proven successful in managing stress and relieving IBS symptoms.13

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References

  1. Holtmann G, Shah A, Morrison M. Pathophysiology of functional gastrointestinal disorders: a holistic overview. Dig Dis. 2017;35(Suppl 1):5-13. doi:1159/000485409.
  2. Sibelli A, Chalder T, Everitt H, Workman P, Windgassen S, Moss-Morris R. A systematic review with meta-analysis of the role of anxiety and depression in irritable bowel syndrome onset. Psychol Med. 2016;46(15):3065-3080. doi:1017/S0033291716001987.
  3. Brzozowski B, Mazur-Bialy A, Pajdo R, et al. Mechanisms by which stress affects the experimental and clinical inflammatory bowel disease (IBD): role of brain-gut axis. Curr Neuropharmacol. 2016;14(8):892-900. doi:2174/1570159X14666160404124127.
  4. Dior M, Delagrèverie H, Duboc H, et al. Interplay between bile acid metabolism and microbiota in irritable bowel syndrome. Neurogastroenterol Motil. 2016;28(9):1330-1340. doi:1111/nmo.12829.
  5. Slattery SA, Niaz O, Aziz Q, Ford AC, Farmer AD. Systematic review with meta-analysis: the prevalence of bile acid malabsorption in the irritable bowel syndrome with diarrhoea. Aliment Pharmacol Ther. 2015;42(1):3-11. doi:1111/apt.13227.
  6. Peleman C, Camilleri M, Busciglio I, Burton D, Donato L, Zinsmeister AR. Colonic transit and bile acid synthesis or excretion in patients with irritable bowel syndrome-diarrhea without bile acid malabsorption. Clin Gastroenterol Hepatol. 2017;15(5):720-727.e1. doi:1016/j.cgh.2016.11.012.
  7. Bajor A, Törnblom H, Rudling M, Ung KA, Simrén M. Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS. Gut. 2015;64(1):84-92. doi:1136/gutjnl-2013-305965.
  8. Panek-Jeziorna M, Mulak A. The role of bile acids in the pathogenesis of bowel diseases. Postepy Hig Med Dosw (Online). 2017;71(1):737-746. doi:5604/01.3001.0010.3852.
  9. Camilleri M, Halawi H, Oduyebo I. Biomarkers as a diagnostic tool for irritable bowel syndrome: where are we? Expert Rev Gastroenterol Hepatol. 2017;11(4):303-316. doi:1080/17474124.2017.1288096.
  10. Leventogiannis K, Gkolfakis P, Spithakis G, et al. Effect of a preparation of four probiotics on symptoms of patients with irritable bowel syndrome: association with intestinal bacterial overgrowth [published online March 5, 2018]. Probiotics Antimicrob Proteins. doi:1007/s12602-018-9401-3.
  11. Francavilla R, Piccolo M, Francavilla A, et al. Clinical and microbiological effect of a multispecies probiotic supplementation in celiac patients with persistent IBS-type symptoms: a randomized, double-blind, placebo-controlled, multicenter trial [published online April 23, 2018]. J Clin Gastroenterol. doi:1097/MCG.0000000000001023.
  12. Pusceddu MM, Murray K, Gareau MG. Targeting the microbiota, from irritable bowel syndrome to mood disorders: focus on probiotics and prebiotics. Curr Pathobiol Rep. 2018;6(1):1-13. doi:1007/s40139-018-0160-3.
  13. Edebol-Carlman H, Ljótsson B, Linton SJ, et al. Face-to-face cognitive-behavioral therapy for irritable bowel syndrome: the effects on gastrointestinal and psychiatric symptoms. Gastroenterol Res Pract. 2017;2017:8915872. doi:10.1155/2017/8915872.

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