Dysmotility and Proton Pump Inhibitor Use Are Independent Risk Factors for Small Intestinal Bacterial and/or Fungal Overgrowth

C. Jacobs; E. Coss Adame; A. Attaluri; J. Valestin; S. S. C. Rao


Aliment Pharmacol Ther. 2013;37(11):1103-1111. 

In This Article

Abstract and Introduction


Background Whether intestinal dysmotility and the use of a proton pump inhibitor (PPI) either independently or together contributes to small intestinal bacterial overgrowth (SIBO), and/or small intestinal fungal overgrowth (SIFO) is not known.

Aim To investigate the role of dysmotility and PPI use in patients with persistent gastrointestinal complaints.

Methods Patients with unexplained gastrointestinal symptoms and negative endoscopy/radiology tests completed a validated symptom questionnaire and underwent 24-h ambulatory antro-duodeno-jejunal manometry (ADJM). Simultaneously, duodenal aspirate was obtained for aerobic, anaerobic and fungal culture. Dysmotility was diagnosed by (>2): absent phase III MMC, absent/diminished postprandial response, diminished amplitude of antral/intestinal phasic activity, impaired antro-duodenal coordination. Bacterial growth ≥103 CFU/mL or fungal growth was considered evidence for SIBO/SIFO. PPI use was documented. Correlation of symptoms with presence of SIBO or SIFO was assessed.

Results One hundred and fifty subjects (M/F = 47/103) were evaluated; 94/150 (63%) had overgrowth: 38/94 (40%) had SIBO, 24/94 (26%) had SIFO and 32/94 (34%) had mixed SIBO/SIFO. SIBO was predominately due to Streptococcus, Enterococcus, Klebsiella and E. coli. SIFO was due to Candida. Eighty of 150 (53%) patients had dysmotility and 65/150 (43%) used PPI. PPI use (P = 0.0063) and dysmotility (P = 0.0003) were independent significant risk factors (P < 0.05) for overgrowth, but together did not pose additional risk. Symptom profiles were similar between those with or without SIBO/SIFO.

Conclusions Dysmotility and PPI use were independent risk factors for SIBO or SIFO and were present in over 50% of subjects with unexplained gastrointestinal symptoms. Diagnosis of overgrowth requires testing because symptoms were poor predictors of overgrowth.


There is growing recognition that the intestinal microbiome could play an important role in the pathogenesis of gastrointestinal symptoms. In addition previous studies have implicated abnormal small bowel motility in the pathogenesis of small intestinal bacterial overgrowth (SIBO).[1,2]

The normal motility of the upper gut consists of organised, repetitive migrating movements (Migrating Motor Complexes – MMCs).[2,3] If the normal nerve and muscle function of the gut is disrupted, then two major subtypes of small intestinal dysmotility, notably myopathy (predominant muscle dysfunction) or neuropathy (predominant neuronal dysfunction) have been described.[2,3] Vantrappen et al. reported that the MMC patterns were abnormal in 5/12 patients with bacterial overgrowth[2] suggesting a relationship between altered microbiome and gut dysmotility. Furthermore, Husebye et al. reported that abnormal MMC and burst activity were strong predictors of gram-negative bacterial growth in the small bowel.[4]

Gastric acid is another important barrier for the prevention of bacterial colonisation of the stomach and proximal small intestine.[5] By increasing the gastric pH, PPIs may facilitate the survival and colonisation of bacteria.[6] Hypochlorhydria has also been shown to contribute to the proximal migration of more distally located bacteria in the GI tract.[7] Recently, Lombardo et al. reported that SIBO, as diagnosed by the glucose hydrogen breath test, occurs more frequently in PPI users than in healthy controls (50% vs. 6%), and in PPI non-users (25%) with IBS.[7] They further showed that the prevalence of SIBO and the severity of GI symptoms increased after 1 year of PPI use.[7] Husebye et al. suggested that an increase of one pH unit in the small intestine corresponded to a 13.8% increase in small bowel microbial counts.[4] These observations suggest that PPI therapy may have an effect on bacterial concentrations in the small bowel. Although PPI use and dysmotility have been suggested to be associated with SIBO, whether these factors independently or together contribute to the pathogenesis of chronic, unexplained GI symptoms and small intestinal bacterial overgrowth has not been systematically evaluated. Also, whether small intestinal fungal overgrowth (SIFO) may play a role in the pathogenesis of GI symptoms has been scarcely examined.

We tested the hypothesis that SIBO and/or SIFO are more likely to be prevalent in symptomatic patients with either small intestinal dysmotility and/or those taking PPIs. Our aim was to investigate the pathophysiological role of gastrointestinal dysmotility and PPI use in causing SIBO and/or SIFO in patients with chronic, unexplained GI symptoms by performing prolonged 24 h antro-duodenal-jejunal manometry and culture of duodenal aspirate, and by examining the relationship of symptoms to these factors.