SIBO and GERD: The Relationship Revealed

What is GERD?

Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is a chronic gastrointestinal disorder where there is a reflux of stomach contents into the esophagus. GERD affects 18.1%–27.8% in North America, 8.8%–25.9% in Europe, 2.5%–7.8% in East Asia, 8.7%–33.1% in the Middle East, 11.6% in Australia and 23.0% in South America [1] and its prevalence continues to increase. Conditions like obesity may further increase the incidence of GERD [2].



GERD includes erosive reflux disease (ERD) and non-erosive reflux disease (NERD) as defined by the presence or absence of esophageal mucosal damage as observed by endoscopy. Chronic damage to the esophagus may further cause complications like esophagitis,  Barrett’s esophagus and esophageal cancer.

Typical symptoms of GERD include heartburn and acid regurgitation [3] and atypical symptoms include cough, asthma, hoarseness, chronic laryngitis, throat-clearing, chest pain, dyspepsia, and nausea. The most common factor responsible for GERD is the transient relaxation of lower esophageal sphincter (LES) and other LES pressure abnormalities such as reduction in resting lower esophageal sphincter (LES) pressure. The normal function of LES is to prevent reflux of stomach contents into the esophagus. Other factors that may contribute to GERD include hiatal hernia, ineffective esophageal acid and bolus clearance, delayed gastric emptying and impaired mucosal defensive factors.

GERD connection with SIBO?

  • The most common treatment for GERD is the use of proton pump inhibitors or PPI. Commonly used PPIs include omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole. PPIs work by suppressing the production of gastric acid thereby relieving the symptoms of GERD [4] and are generally considered safe to use. However, research studies show that long term use of PPIs may alter the gut microbiota including development of small intestinal bacterial overgrowth (SIBO) due to the suppression of gastric acids caused by these drugs. In one study, there was an increase in the symptoms of SIBO in NERD patients upon 8 weeks of PPI treatment. The percentage of patients reporting these symptoms further increased after 6 months of PPI treatment. Another study showed similar findings where 50% of patients with GERD receiving PPIs for 36 months had SIBO which further increased after 1 year of PPI treatment [5]. Several other clinical studies support the association between PPI use and SIBO [6], [7]. However, other studies that did not find a positive correlation between PPI and SIBO [8], [9]. This may be attributed to different methodology used in individual studies and warrants further investigation.




  • GERD, migrating motor complex (MMCs) and SIBO: Migrating Motor Complex (MMC) is a gut motility pattern that occurs in the stomach and small intestine in between meals and is controlled by the enteric nervous system. The MMC cycle consists of four phases. Phase I is a quiescent period of no contractions and is followed by irregular contractions in Phase II. Phase III is where contractions reach the maximum and occurs every 90-120 minutes and Phase IV represents decreasing contractions. A few studies have highlighted a connection between GERD and MMC activity where MMC gastric phase III shows lower amplitude in patients with reflux disease [10]. Gastric contents stay longer in the setting of dysfunctional Phase III MMC. Phase III of MMC performs an important housekeeping function of moving remnants of food and bacteria from small intestine into the colon. The lower amplitude of gastric phase III waves in GERD patients could reduce the housekeeping function of MMC and may lead to the development of SIBO. A study found that the MMC pattern were abnormal in 5/12 patients with SIBO [11]. Also, it was shown that in the presence of impaired MMC activity, there was a colonization of small bowel with gram negative bacteria [12]. Dysmotility, characterized by absence of phase III MMC activity as one of the criteria, was found to be a risk factor for small intestinal bacterial or fungal overgrowth in patients who had unexplained gastrointestinal symptoms [13]. In this study, it was found that 76% patients with dysmotility had small bowel bacterial and/or fungal overgrowth (SIBO and/or SIFO) when the criteria of >103 CFU/ml was used and 61% were positiv
    e for SIBO and/or SIFO based on bacteria count of >105 CFU/ml.Gut Microbiome and Gerd
  • It is possible that gases produced by colonic bacteria in the small intestine in the setting of SIBO may increase intra-abdominal pressure which may push the stomach contents into the esophagus leading to the complications of GERD. GERD may also be directly or indirectly connected to SIBO via it’s positively association with diseases such as IBS [14], [15], [16]  and obesity [2],[17].
  • Other possible association between GERD and SIBO may be determined by lifestyle factors. Western diet, alcohol use, smoking and stress may contribute to GERD. Interestingly, these are also risk factors for development of SIBO.
  • Also connected to SIBO and Gerd is the affect of emotional stress on gastrointestinal mechanism. Stress brings in a evident change in the gut microbiota, relocation of bacteria in our intestines, increase intestinal permeability and thereby cause GERD , depression, anxiety and skin conditions such as rosacea and acne.

Conclusion: GERD and SIBO may be more tightly related then we can envision.

Detailed studies are needed to understand the potential relationship between GERD and SIBO which may aid in the development of novel treatment options for GERD.




References:

  1. El-Serag HB, Sweet S, Winchester CC, et al. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2014;63:871–80. Available at: /pmc/articles/PMC4046948/?report=abstract [Accessed October 22, 2015].
  2. Anand G, Katz PO. Gastroesophageal reflux disease and obesity. Rev. Gastroenterol. Disord. 2008;8:233–9. Available at: [http://www.ncbi.nlm.nih.gov/pubmed/19107097 [Accessed January 10, 2016].
  3. Klauser AG, Schindlbeck NE, Müller-Lissner SA. Symptoms in gastro-oesophageal reflux disease. Lancet (London, England) 1990;335:205–8. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1967675 [Accessed January 8, 2016].
  4. Huang JQ, Hunt RH. Pharmacological and pharmacodynamic essentials of H(2)-receptor antagonists and proton pump inhibitors for the practising physician. Best Pract. Res. Clin. Gastroenterol. 2001;15:355–70. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11403532 [Accessed January 10, 2016].
  5. Lombardo L, Foti M, Ruggia O, et al. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy. Clin. Gastroenterol. Hepatol. 2010;8:504–8. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20060064 [Accessed January 10, 2016].
  6. Lo W-K, Chan WW. Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis. Clin. Gastroenterol. Hepatol. 2013;11:483–90. Available at: http://www.sciencedirect.com/science/article/pii/S154235651201511X [Accessed January 10, 2016].
  7. Franco DL, Disbrow MB, Kahn A, et al. Duodenal Aspirates for Small Intestine Bacterial Overgrowth: Yield, PPIs, and Outcomes after Treatment at a Tertiary Academic Medical Center. Gastroenterol. Res. Pract. 2015;2015:1–5. Available at: /pmc/articles/PMC4324922/?report=abstract [Accessed January 10, 2016].
  8. Fujiwara Y, Watanabe T, Muraki M, et al. Association between chronic use of proton pump inhibitors and small- intestinal bacterial overgrowth assessed using lactulose hydrogen breath tests. Hepatogastroenterology. 62:268–72. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25916046 [Accessed January 10, 2016].
  9. Ratuapli SK, Ellington TG, O’Neill M-T, et al. Proton pump inhibitor therapy use does not predispose to small intestinal bacterial overgrowth. Am. J. Gastroenterol. 2012;107:730–5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22334250 [Accessed January 10, 2016].
  10. Anon. Swallows, oesophageal and gastric motility in normal subjects and in patients with gastro-oesophageal reflux disease: a 24-h pH-manometric study. Neurogastroenterol. Motil. 1998;10:115–121. Available at: http://doi.wiley.com/10.1046/j.1365-2982.1998.00094.x [Accessed January 10, 2016].
  11. Vantrappen G, Janssens J, Hellemans J, et al. The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J. Clin. Invest. 1977;59:1158–66. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=372329&tool=pmcentrez&rendertype=abstract [Accessed January 10, 2016].
  12. Husebye E, Skar V, Høverstad T, et al. Abnormal intestinal motor patterns explain enteric colonization with gram-negative bacilli in late radiation enteropathy. Gastroenterology 1995;109:1078–1089. Available at: http://www.sciencedirect.com/science/article/pii/0016508595905650 [Accessed January 10, 2016].
  13. Jacobs C, Coss Adame E, Attaluri A, et al. Dysmotility and proton pump inhibitor use are independent risk factors for small intestinal bacterial and/or fungal overgrowth. Aliment. Pharmacol. Ther. 2013;37:1103–11. Available at: /pmc/articles/PMC3764612/?report=abstract [Accessed January 10, 2016].
  14. Bortoli N de. Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome. World J. Gastroenterol. 2013;19:5787. Available at: /pmc/articles/PMC3793133/?report=abstract [Accessed January 10, 2016].
  15. Jung H-K, Halder S, McNally M, et al. Overlap of gastro-oesophageal reflux disease and irritable bowel syndrome: prevalence and risk factors in the general population. Aliment. Pharmacol. Ther. 2007;26:453–61. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17635380 [Accessed January 10, 2016].
  16. Nastaskin I, Mehdikhani E, Conklin J, et al. Studying the overlap between IBS and GERD: a systematic review of the literature. Dig. Dis. Sci. 2006;51:2113–20. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17080246 [Accessed December 13, 2015].
  17. Eusebi LH, Fuccio L, Bazzoli F. The role of obesity in gastroesophageal reflux disease and Barrett’s esophagus. Dig. Dis. 2012;30:154–7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22722430 [Accessed January 10, 2016].

 

 

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