Gut Dysbiosis

Studies show that many patients with IBS-D have a bacterial imbalance1-3

In a US clinical trial, the majority of patients with IBS-D had an abnormal composition of bacteria in the gut4,*

gut dysbiosis

What is gut dysbiosis? Alterations in specific bacterial groups and microbial community diversity are known as gut dysbiosis. It is an imbalance in the ratio of harmful and helpful bacterial groups5

*Data from 93 patients with IBS-D in a prospective TARGET 3 substudy that used lactulose breath testing to predict response to XIFAXAN.4

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Dr. Sayuk discuss IBS-D and treatment with XIFAXAN

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Bacterial imbalance has been linked to multiple symptoms of IBS-D1,6,7

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Altered
fermentation8,9

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Associated change in intestinal environment

Production of excessive
intestinal gases9,10

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Potential resulting symptoms

Abdominal pain
and bloating11,12

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Increased production of SCFAs
and release of 5-HT13-15

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Associated change in intestinal environment

Colonic contraction increased
motility16-18

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Potential resulting symptoms

Diarrhea and urgency14,17,19

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Activation of intestinal immune
system and inflammation20-22

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Associated change in intestinal environment

Impaired barrier function,
intestinal permeability23,24

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Potential resulting symptoms

Abdominal pain, diarrhea,
bloating, and urgency17,20,21,23-25

Target 1 and Target 2 Target 1 and Target 2

5-HT, serotonin; SCFA, short-chain fatty acid.

Additional studies are needed to further clarify the role of gut microbiota in IBS.

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Dr. Pimentel and Dr. Brenner discuss the gut microbiota and IBS-D

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THE FUTURE

As the body of evidence continues to grow in support of the link between gut dysbiosis and IBS-D, so too does the need for compatible pharmacologic therapies.5

IBS-D, irritable bowel syndrome with diarrhea.

References: 1. Zhong W, Lu X, Shi H, et al. Distinct microbial populations exist in the mucosa associated microbiota of diarrhea predominant irritable bowel syndrome and ulcerative colitis. J Clin Gastroenterol. 2019;53(9):660-672. doi:10.1097/MCG.0000000000000961 2. Casén C, Vebø HC, Sekelja M, et al. Deviations in human gut microbiota: a novel diagnostic test for determining dysbiosis in patients with IBS or IBD. Aliment Pharmacol Ther. 2015;42(1):71-83. doi:10.1111/apt.13236 3. 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. doi:10.1053/j.gastro.2007.04.005 4. Rezaie A, Heimanson Z, McCallum R, Pimentel M. Lactulose breath testing as a predictor of response to rifaximin in patients with irritable bowel syndrome with diarrhea. Am J Gastroenterol. 2019;114(12):1886-1893. doi:10.14309/ajg.0000000000000444 5. 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. 6. Pimentel M, Lembo A, Chey WD, et al; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364(1):22-32. doi:10.1056/NEJMoa1004409 7. Sundin J, Aziz I, Nordlander S, et al. Evidence of altered mucosa-associated and fecal microbiota composition in patients with irritable bowel syndrome. Sci Rep. 2020;10(1):593. doi:10.1038/s41598-020-57468-y 8. Serra J, Azpiroz F, Malagelada JR. Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome. Gut. 2001;48(1):14-19. doi:10.1136/gut.48.1.14 9. Houghton LA, Lea R, Agrawal A, Reilly B, Whorwell PJ. Relationship of abdominal bloating to distention in irritable bowel syndrome and effect of bowel habit. Gastroenterology. 2006;131(4):1003-1010. doi:10.1053/j.gastro.2006.07.015 10. Ong DK, Mitchell SB, Barrett JS, et al. Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome. J Gastroenterol Hepatol. 2010;25(8):1366-1373. doi:10.1111/j.1440-1746.2010.06370.x 11. King TS, Elia M, Hunter JO. Abnormal colonic fermentation in irritable bowel syndrome. Lancet. 1998;352(9135):1187-1189. doi:10.1016/s0140-6736(98)02146-1 12. Ringel-Kulka T, Choi CH, Temas D, et al. Altered colonic bacterial fermentation as a potential pathophysiological factor in irritable bowel syndrome. Am J Gastroenterol. 2015;110(9):1339-1346. doi:10.1038/ajg.2015.220 13. Törnblom H, Van Oudenhove L, Sadik R, Abrahamsson H, Tack J, Simrén M. Colonic transit time and IBS symptoms: what’s the link? Am J Gastroenterol. 2012;107(5):754-760. doi:10.1038/ajg.2012.5 14. Chey WY, Jin HO, Lee MH, Sun SW, Lee KY. Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea. Am J Gastroenterol. 2001;96(5):1499-1506. doi:10.1111/j.1572-0241.2001.03804.x 15. Tack J, Broekaert D, Corsetti M, Fischler B, Janssens J. Influence of acute serotonin reuptake inhibition on colonic sensorimotor function in man. Aliment Pharmacol Ther. 2006;23(2):265-274. doi:10.1111/j.1365-2036.2006.02724.x 16. Houghton LA, Atkinson W, Lockhart C, Whorwell PJ, Keevil B. Sigmoid-colonic motility in health and irritable bowel syndrome: a role for 5-hydroxytryptamine. Neurogastroenterol Motil. 2007;19(9):724-731. doi:10.1111/j.1365-2982.2007.00943.x 17. Atkinson W, Lockhart S, Whorwell PJ, Keevil B, Houghton LA. Altered 5-hydroxytryptamine signaling in patients with constipation- and diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2006;130(1):34-43. doi:10.1053/j.gastro.2005.09.031 18. Gargari G, Taverniti V, Gardana C, et al. Fecal clostridiales distribution and short-chain fatty acids reflect bowel habits in irritable bowel syndrome. Environ Microbiol. 2018;20(9):3201-3213. doi:10.1111/1462-2920.14271 19. Shulman RJ, Jarrett ME, Cain KC, Broussard EK, Heitkemper MM. Associations among gut permeability, inflammatory markers, and symptoms in patients with irritable bowel syndrome. J Gastroenterol. 2014;49(11):1467-1476. doi:10.1007/s00535-013-0919-6 20. Cremon C, Gargano L, Morselli-Labate AM, et al. Mucosal immune activation in irritable bowel syndrome: gender-dependence and association with digestive symptoms. Am J Gastroenterol. 2009;104(2):392-400. doi:10.1038/ajg.2008.94 21. Piche T, Barbara G, Aubert P, et al. Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut. 2009;58(2):196-201. doi:10.1136/gut.2007.140806 22. Liebregts T, Adam B, Bredack C, et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology. 2007;132(3):913-920. doi:10.1053/j.gastro.2007.01.046 23. Zhou Q, Zhang B, Verne GN. Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome. Pain. 2009;146(1-2):41-46. doi:10.1016/j.pain.2009.06.017 24. Guilarte M, Santos J, de Torres I, et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut. 2007;56(2):203-209. doi:10.1136/gut.2006.100594 25. Lacy BE, Pimentel M, Brenner DM, et al. ACG clinical guideline: management of irritable bowel syndrome. Am J Gastroenterol. 2021;116(1):17-44. doi:10.14309/ajg.0000000000001036 26. Lacy BE, Patel NK. Rome criteria and a diagnostic approach to irritable bowel syndrome. J Clin Med. 2017;6(11):99. doi:10.3390/jcm6110099 27. Lembo A, Sultan S, Chang L, Heidelbaugh JJ, Smalley W, Verne GN. AGA clinical practice guideline on the pharmacological management of irritable bowel syndrome with diarrhea. Gastroenterology. 2022;163(1):137-151. doi:10.1053/j.gastro.2022.04.017

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INDICATIONS

XIFAXAN® (rifaximin) 550 mg tablets are indicated for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults and for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

XIFAXAN® (rifaximin) 550 mg tablets are indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

IMPORTANT SAFETY INFORMATION

  • XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis.
  • Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
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INDICATIONS

XIFAXAN® (rifaximin) 550 mg tablets are indicated for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults and for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

IMPORTANT SAFETY INFORMATION

  • XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema, and anaphylaxis.
  • Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
  • There is an increased systemic exposure in patients with severe (Child-Pugh Class C) hepatic impairment. Caution should be exercised when administering XIFAXAN to these patients.
  • Caution should be exercised when concomitant use of XIFAXAN and P-glycoprotein (P-gp) and/or OATPs inhibitors is needed. Concomitant administration of cyclosporine, an inhibitor of P-gp and OATPs, significantly increased the systemic exposure of rifaximin. In patients with hepatic impairment, a potential additive effect of reduced metabolism and concomitant P-gp inhibitors may further increase the systemic exposure to rifaximin.
  • In clinical studies, the most common adverse reactions for XIFAXAN (alone or in combination with lactulose) were:
    HE (≥10%): Peripheral edema (17%), constipation (16%), nausea (15%), fatigue (14%), insomnia (14%), ascites (13%), dizziness (13%), urinary tract infection (12%), anemia (10%), and pruritus (10%)
    IBS-D (≥2%): Nausea (3%), ALT increased (2%)
  • INR changes have been reported in patients receiving rifaximin and warfarin concomitantly. Monitor INR and prothrombin time. Dose adjustment of warfarin may be required.
  • XIFAXAN may cause fetal harm. Advise pregnant women of the potential risk to a fetus.

To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please click here for full Prescribing Information.

XIFI.0122.USA.23V2.0