Microbial Imbalance and IBS Symptoms

Many symptoms of IBS are now being connected to microbial imbalance and its impact on gut physiology.

Visceral pain perception

Preclinical studies suggest that the perception of visceral pain can be influenced by gut microbiota.20-23 In animal models of visceral pain induced by dysbiosis, interventions targeting the gut microbiome have been shown to improve pain responses.20,23 Moreover, one study reported visceral hypersensitivity development in rats that received fecal microbiota transplants from patients with IBS.22

Recent data have shown that gut dysbiosis may cause local or systemic immune activation, which can contribute to visceral hypersensitivity by disrupting epithelial barrier function.4,24 Altered fermentation due to microbial imbalance and gut bacteria modulation of intestinal sensory nerve endings may also contribute to visceral hypersensitivity.24

Altered Fermentation

Increased bacterial fermentation of poorly absorbable carbohydrates resulting from alterations in gut microbial composition contributes to the production of excessive intestinal gases. These gases can cause bloating, flatulence, abdominal pain, and distension.4-7 Additionally, increased production of methane gas has been associated with constipation in IBS-C and increased production of hydrogen gas has been associated with diarrhea in IBS-D.7

Altered GI Motility

The gut microbiota play a critical role in regulating serotonin (5-HT) levels in the colon and systemic circulation.25 Changes in microbial composition can increase the production of both short-chain fatty acids and 5-HT.1,6,7,25 The resulting colonic contraction, increased motility, accelerated intestinal transit, and changes in water and electrolyte transport contribute to the development of diarrhea.1,6,7 Certain intestinal bacteria can also suppress intestinal motility, resulting in constipation through the metabolites they produce.26

Altered Barrier Function and Immune System Activation

Microbial imbalance can contribute to increased intestinal permeability and immune system activation.1,4,27,28 These changes may lead to inflammatory cell infiltration and the release of cytokines or chemokines that interact with the intestinal environment to cause abdominal pain and diarrhea.1,4,29

Disrupted Signaling Along the Gut-Brain Axis

The microbiome-gut-brain axis enables bidirectional communication between the gut microbiota, enteric nervous system, and central nervous system. These neural pathways connect cognitive and emotional activity with peripheral intestinal functions.1,27,30

Changes in cognition and behavior have been observed as a result of disrupted communication between the gut and brain due to dysbiosis.1,25,27,31 According to animal studies, this disruption is caused by the release of inflammatory mediators and neuroactive substances into the systemic circulation. Psychological stress is thought to further influence mucosal immunity, gut microbiota, and gut barrier function, which may perpetuate symptoms similar to those experienced by patients with IBS.25,31,32

disrupted gut-brain axis signaling changes thoughts, behavior, pain perception, psychological stress, mental illness

Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Irritable bowel syndrome: a microbiome-gut-brain axis disorder? World J Gastroenterol. 2014;20(39):14105-14125.

 
 
TARGETING GUT MICROBIOTA IN IBS
IBS = irritable bowel syndrome
GI = gastrointestinal

References

  1. Ringel Y. The gut microbiome in irritable bowel syndrome and other functional bowel disorders. Gastroenterol Clin North Am. 2017;46(1):91-101.
  2. Klem F, Wadhwa A, Prokop LJ, et al. Prevalence, risk factors, and outcomes of irritable bowel syndrome after infectious enteritis: a systematic review and meta-analysis. Gastroenterology. 2017;152(5):1042-1054.
  3. DuPont HL. Review article: evidence for the role of gut microbiota in irritable bowel syndrome and its potential influence on therapeutic targets. Aliment Pharmacol Ther. 2014;39(10):1033-1042.
  4. Lee KN, Lee OY. Intestinal microbiota in pathophysiology and management of irritable bowel syndrome. World J Gastroenterol. 2014;20(27):8886-8897.
  5. Zhuang X, Xiong L, Li L, Li M, Chen M. Alterations of gut microbiota in patients with irritable bowel syndrome: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2017;32(1):28-38.
  6. Passos MDCF, Moraes-Filho JP. Intestinal microbiota in digestive diseases. Arq Gastroenterol. 2017;54(3):255-262.
  7. Ghoshal UC, Shukla R, Ghoshal U, Gwee KA, Ng SC, Quigley EM. The gut microbiota and irritable bowel syndrome: friend or foe? Int J Inflam. 2012;2012:151085.
  8. Stern EK, Brenner DM. Gut microbiota-based therapies for irritable bowel syndrome. Clin Transl Gastroenterol. 2018;9(2):e-134.
  9. Posserud I, Stotzer PO, Björnsson ES, Abrahamsson H, Simrén M. Small intestinal bacterial overgrowth in patients with irritable bowel syndrome. Gut. 2007;56(6):802-808.
  10. Giamarellos-Bouboulis E, Tang J, Pyleris E, et al. Molecular assessment of differences in duodenal microbiome in subjects with irritable bowel syndrome. Scand J Gastroenterol. 2015;50(9):1076-1087.
  11. Pimentel M, Morales W, Pokkunuri V et al. Autoimmunity links vinculin to the pathophysiology of chronic functional bowel changes following campylobacter jejuni infection in a rat model. Dig Dis Sci. 2015;60:1195-1205.
  12. Menees S, Chey W. The gut microbiome and irritable bowel syndrome. F1000Res. 2018;7(F1000 Faculty Rev):1029.
  13. Harris LA, Baffy N. Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome. Postgrad Med. 2017;129(8):872-888.
  14. Kassinen A, Krogius-Kurikka L, Mäkivuokko H, et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology. 2007;133(1):24-33.
  15. Carroll IM, Ringel-Kulka T, Keku TO, et al. Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2011;301(5):G799-G807.
  16. Carroll IM, Ringel-Kulka T, Siddle JP, Ringel Y. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012;24(6):521-530.
  17. Tap J, Derrien M, Törnblom H, et al. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology. 2017;152(1):111-123.
  18. Pyleris E, Giamarellos-Bourboulis EJ, Tzivras D, Koussoulas V, Barbatzas C, Pimentel M. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci. 2012;57(5):1321-1329.
  19. König J, Brummer RJ. Alteration of the intestinal microbiota as a cause of and a potential therapeutic option in irritable bowel syndrome. Benef Microbes. 2014;5(3):247-261.
  20. Luczynski P, Tramullas M, Viola M, et al. Microbiota regulates visceral pain in the mouse. Elife. 2017;6:e25887.
  21. O’Mahoney SM, Felice VD, Nally K, et al. Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats. Neuroscience. 2014;277:885-901.
  22. Crouzet L, Gaultier E, Del’Homme C, et al. The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota. Neurogastroenterol Motil. 2013;25(4):e272-e282.
  23. Verdu EF, Bercik P, Verma-Gandhu M, et al. Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice. Gut. 2006;55(2):182-190.
  24. Distrutti E, Monaldi L, Ricci P, Fiorucci S. Gut microbiota role in irritable bowel syndrome: new therapeutic targets. World J Gastroenterol. 2016;22(7):2219-2241.
  25. Raskov H, Burcharth J, Pommergaard HC, Rosenberg J. Irritable bowel syndrome, the microbiota and the gut-brain axis. Gut Microbes. 2016;7(5):365-383.
  26. Ohkusa T, Koldo S, Nishikawa Y, Sato N. Gut microbiota and chronic constipation: a review and update. Front Med. 2019;6:19.
  27. Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Irritable bowel syndrome: a microbiome-gut-brain axis disorder? World J Gastroenterol. 2014;20(39):14105-14125.
  28. Quigley EMM. Gut bacteria in health and disease. Gastroenterol Hepatol. 2013;9(9):560-569.
  29. Fan WT, Ding C, Xu NN, Zong S, Ma P, Gu B. Close association between intestinal microbiota and irritable bowel syndrome. Eur J Clin Microbiol Infect Dis. 2017;36(12):2303-2317.
  30. Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota. J Clin Invest. 2015;125(3):926-938.
  31. Quigley EMM. The gut-brain axis and the microbiome: clues to pathophysiology and opportunities for novel management strategies in irritable bowel syndrome (IBS). J Clin Med. 2018;7(1):6.
  32. Skonieczna-Zydecka K, Marlicz W, Misera A, Koulaouzidis A, Loniewski I. Microbiome – the missing link in the gut-brain axis: focus on its role in gastrointestinal mental health. J Clin Med. 2018;7(12):521.
  33. Vazquez-Roque MI, Camilleri M, Smyrk T, et al. A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology. 2013;144(5):903-911.
  34. Altobelli E, Del Negro V, Angeletti PM, Latella G. Low-FODMAP diet improves irritable bowel syndrome symptoms: a meta-analysis. Nutrients. 2017;9(9):940.
  35. Zhou SY, Gillilland M III, Wu X, et al. FODMAP diet modulates visceral nociception by lipopolysaccharide-mediated intestinal inflammation and barrier dysfunction. J Clin Invest. 2018;128(1):267-280.
  36. Ford AC, Moayyedi P, Chey WD, et al. American College of Gastroenterology monograph on management of irritable bowel syndrome. Am J Gastroenterol. 2018;113(suppl 2):1-18.
  37. Ford AC, Quigley EMM, Lacy BE, et al. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol. 2014;109(10):1547-1561.
  38. O’Mahoney L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128(3):541-551.
  39. Moser AM, Spindelboeck W, Halwachs B, et al. Effects of an oral synbiotic on the gastrointestinal immune system and microbiota in patients with diarrhea-predominant irritable bowel syndrome. Eur J Nutr. 2019;58(7):2767-2778.
  40. Lembo A, Pimentel M, Rao SS, et al. Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2016;151(6):1113-1121.
  41. EnteraGam (serum-derived bovine immunoglobulin/protein isolate) [product information]. Ankeny, IA: Entera Health, Inc.; 2017.
  42. El-Salhy M, Hatlebakk JG, Gilja OH, Kristoffersen AB, Hausken T. Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut. 2020;69(5):859-867.
  43. Mizuno S, Masaoka T, Naganuma M, et al. Bifidobacterium-rich fecal donor may be a positive predictor for successful fecal microbiota transplantation in patients with irritable bowel syndrome. Digestion. 2017;96(1):29-38.
  44. Mazzawi T, Lied GA, Sangnes DA, et al. The kinetics of gut microbial community composition in patients with irritable bowel syndrome following fecal microbiota transplantation. PLoS One. 2018;13(11):e0194904.
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