1. Introduction
Small intestinal bacterial overgrowth (SIBO) is characterized by the presence of excessive bacteria in the small intestine. SIBO can be associated with a variety of different clinical conditions and is often found in patients with irritable bowel syndrome (IBS) [
1]. Recently, the presence of SIBO was described in patients with inflammatory bowel disease (IBD) [
2,
3,
4].
Clinical symptoms can be nonspecific, such as abdominal pain, changes in stool frequency and formation, diarrhea or bloating, and psychological disorders therefore also mimicking a flare of IBD. Simultaneously, there is no diagnostic gold standard for SIBO. As a consequence, the true prevalence and connection to other diseases still remain unclear and is definitely underrecognized so far.
In diseases with gut stasis such as constipation predominant IBS, the prevalence of SIBO is high [
1,
3].
IBD includes both ulcerative colitis (UC) and Crohn’s disease (CD). Both diseases occur with periods of activity interrupted by times of complete remission [
5]. Despite remission and disease control, many patients with IBD still suffer from symptoms mimicking irritable bowel syndrome with consecutive reduced quality of life [
6,
7,
8,
9]. According to the literature, about 40% of patients with IBD suffer from IBS-associated symptoms [
9,
10].
Not only in gastrointestinal disorders such as IBD but also in patients with liver diseases, an increased prevalence of SIBO is found compared to control patients. In these patients, SIBO is found independently of the stage of the liver disease (e.g., early or advanced liver disease) [
11]. The use of proton pump inhibitors was found to be another risk factor for SIBO [
12].
Different diets and supplements have been shown to improve the symptoms of IBS patients as well as IBD patients with IBS symptoms (e.g., low-FODMAP, vitamin D, or probiotics) [
13,
14,
15,
16,
17,
18]. Treatment of SIBO includes antibiotics, probiotics, and prokinetics, while in recent years therapy with rifaximin is regarded as the standard of care for SIBO [
12]. The impact of SBIO in IBD patients still remains unclear, while clinical symptoms are similar for both diseases. Therefore, it is important to differentiate between patients with IBD having a flare from those having SIBO because treatments are completely different for both diseases.
In our study, we investigated the prevalence and impact of SIBO in our patient cohort, with a focus on patients with both UC and CD in accordance with their IBD activity status (remission or active disease) and their clinical symptoms and provide a review of the literature for this topic.
4. Discussion
In our single center retrospective study, SIBO was more often found in patients with CD than in those with UC. Furthermore, SIBO was more often positive in patients with IBD when they were not in clinical remission. SIBO rates were similar in patients with UC, infectious colitis, and collagenous colitis, as well as those with IBS. Older age in patients with CD was associated with a significantly higher risk of SIBO.
The numerical higher rate of positive SIBO tests in 17.3% CD patients might be due to several predisposing factors in these patients. It is well known that, in general, patients with IBD suffer from gut dysbiosis [
16] with a small intestinal bacterial overgrowth, mainly due to chronic intestinal inflammation in the small intestine, while in UC inflammation is mostly limited to the colon. In patients with IBS, small intestinal inflammation is a risk factor for SIBO [
17].
In addition, ileocecal resection can lead to increased intestinal permeability due to the lack of the ileocecal valve and dysmotility [
2,
18,
19,
20]. Consequently, these factors might contribute to reduced digestion and absorption of nutrients and the production of osmotically active metabolites in the lumen, leading to clinical symptoms such as discomfort, bloating, and diarrhea [
21,
22]. In our cohort, patients were suffering from similar symptoms to those described in the literature, with mainly abdominal pain, diarrhea, and weight loss or bloating.
The exact prevalence of SIBO is unknown. Our incidences of positive SIBO, especially in CD, is in accordance with other studies published [
23,
24,
25], while some studies report even higher rates of positive SIBO. Only in one meta-analysis was the prevalence of methane-positive SIBO in IBD patients lower, with 5.3% for CD as compared to those with UC (20.2%). In general, literature data indicate a frequency of overlap of SIBO in patients with inflammatory bowel disease of 18–30% for CD and 14–17.8% for UC [
26,
27]. In our cohort, we had similar results to those described in the literature for patients with CD, having a positive SIBO test in 21.1% of our cases. In contrast, positive SIBO was rather low in UC in our cohort (9.1%) compared to the literature; however, the rate of positive SIBO was similar for patients with IBS (7.7%).
IBD compromising CD and UC are clinical heterogeneous diseases. While patients with an acute flare suffer from symptoms such as abdominal pain, diarrhea, and weight loss, it is well known that patients with IBD in remission can still suffer from ongoing “flare like” symptoms despite adequate control of the inflammation in the gut [
28,
29]. SIBO can present with similar symptoms to a flare in IBD patients. However, treatment is different for both diseases [
30]. Therefore, careful medical history and testing is key to differentiate an acute flare in IBD from other reasons such as SIBO. In general, non-invasive glucose or lactulose breath testing are methods to diagnose SIBO, while invasive testing is not practical in everyday routines [
27]. A breath test is easy to offer to the patient, with a high acceptance, and should always be performed in IBD patients with suspicion of SIBO.
In the treatment of SIBO, rifaximin is effective and safe and is associated with a rapid improvement of gastrointestinal symptoms [
31]. So far, evidence of specific diets in the treatment of SIBO is still rare, resulting in no clear dietician recommendations [
32], e.g., low-FODMAP diets might help to improve symptoms of SIBO. However, recurrence rates of SIBO after treatment are still high [
33]. Concerning further treatment, the standard of care in our hospital is treatment with rifaximin as recommended [
34,
35,
36,
37]. However, due to its retrospective character, further treatment could not be analyzed for all patients included.
In our study, we could show that older patients with CD have a higher risk for SIBO. So far, to our knowledge, no other study could show older age as a risk factor for SIBO in IBD. In one meta-analysis, older age was also a risk factor for SIBO in patients with IBS [
38], which was confirmed in another study [
39].
Our study has some limitations. First, its retrospective analysis, regarding the current clinical symptoms of all IBD patients provided at the time of testing, has no objective confirmation of the current activity status in IBD patients (e.g., missing biomarker or endoscopy). Furthermore, due to the limited number of patients, the statistical analysis was not elusive for all questions raised.
In addition, concurrent medication or former surgery as potential risk factors in patients with IBD were not included in our analysis. In addition, patients were only screened for gastrointestinal disorders with a focus on IBD. Other concomitant diseases that might have additional influence on the diagnosis of SIBO, such as liver diseases, were not analyzed in our study [
11].