Curr Gastroenterol Rep (2016) 18:8
DOI 10.1007/s11894-015-0482-9
NEUROGASTROENTEROLOGY AND MOTILITY DISORDERS OF THE GASTROINTESTINAL TRACT (S RAO, SECTION EDITOR)
How to Test and Treat Small Intestinal Bacterial Overgrowth:
an Evidence-Based Approach
Ali Rezaie 1,3 & Mark Pimentel 1 & Satish S. Rao 2
# Springer Science+Business Media New York 2016
Abstract Small intestinal bacterial overgrowth (SIBO) is
characterized by an excessive amount of bacteria in the small
intestine and a constellation of symptoms that include
bloating, pain, gas, and diarrhea. Although known for many
decades, there is a lack of consensus and clarity regarding the
natural history and methods for its diagnosis. Several tests
have been proposed, including the glucose breath test,
lactulose breath test, small intestinal aspiration and culture,
and others. However, there is a lack of standardization of these
tests and their interpretation. Treatment of SIBO remains empirical; generally, broad spectrum antibiotics are recommended for 2 weeks (amoxicillin, rifaximin, ciprofloxacin, etc.) but
evidence for their use is fair. Clearly, there is a strong need to
develop a systematic approach for the management of SIBO
and to perform multicenter clinical trials for the treatment of
SIBO. In this review, we will discuss the current evidence for
the diagnosis and treatment of SIBO, which includes (1)
elimination/modification of the underlying causes, (2) induction of remission (antibiotics and elemental diet), and (3)
This article is part of the Topical Collection on Neurogastroenterology
and Motility Disorders of the Gastrointestinal Tract
* Ali Rezaie
Ali.Rezaie@cshs.org
1
GI Motility Program, Division of Gastroenterology, Department of
Medicine, Cedars-Sinai Medical Center, 8730 Alden Drive, Thalians
Bldg, #E226, Los Angeles, CA 90048, USA
2
Division of Gastroenterology/Hepatology, Medical College of
Georgia, Augusta University, Augusta, GA, USA
3
David Geffen School of Medicine at University of California, Los
Angeles (UCLA), Los Angeles, USA
maintenance of remission (promotility drugs, dietary modifications, repeat or cyclical antibiotics).
Keywords Small intestinal bacterial overgrowth (SIBO) .
Glucose breath test . Lactulose breath test . Small intestinal
aspiration and culture . Antibiotics . Elemental diet .
Promotility drugs
Introduction
Small intestinal bacterial overgrowth (SIBO) is defined by the
presence of abnormal and excessive numbers of bacteria in the
small intestine [1] associated with a myriad of symptoms including bloating, flatulence, abdominal pain, nausea, dyspepsia, fatigue, diarrhea, and constipation [2]. Malabsorption,
weight loss, anemia, and deficiency of vitamins and iron are
less frequent but more serious manifestations of SIBO [3].
Multiple independent risk factors have been identified for
SIBO including [4]: (1) anatomical abnormalities such as
small intestinal diverticulosis; (2) postsurgical structural
changes such as ileocecal valve resection, gastric bypass,
and Roux-en-Y; (3) medications that slow the gut motility
such as narcotics, anticholinergics, and anti-diarrheals; (4)
hypo- or achlorhydria due to surgery, autoimmune gastritis,
or proton pump inhibitors [5••, 6]; and (5) small bowel
dysmotility irrespective of the cause (e.g., inflammatory bowel disease, celiac disease, radiation enteritis, small bowel adhesions, and systemic diseases associated with dysmotility
such as scleroderma, diabetes, and amyloidosis) [5••, 7].
In addition, SIBO has been associated with multiple conditions including irritable bowel syndrome [8], rosacea [9],
hepatic encephalopathy [11, 12], obesity [13], gastroparesis
[14], Parkinson’s disease [15], fibromyalgia [16], chronic
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pancreatitis [17], end-stage renal disease [18], and inflammatory bowel diseases [19].
Despite the high prevalence and importance of SIBO, there
is a lack of consensus and clarity regarding the optimal method for the diagnosis of this condition. Moreover, there is a
strong need to develop an evidence-based approach for the
management of SIBO including well-designed clinical trials
for its treatment of SIBO. In this review, we will discuss the
current methods for diagnosis of SIBO followed by a systematic approach for the treatment of this condition.
Diagnosis of SIBO
Numerous methods have been proposed and tested for the
diagnosis of SIBO [20, 21]. The most common diagnostic
tests include assessment of clinical symptom profiles, empirical treatments, breath tests, and small intestinal aspiration and
culture.
Clinical Symptoms
Several studies have assessed the clinical utility and predictive
value of symptoms associated with SIBO. These studies have
concluded that symptoms are non-specific and as such cannot
be used to accurately diagnose SIBO.
In one study, Jacobs et al. [5••] assessed 168 subjects with
SIBO (n = 38), small intestinal fungal overgrowth (SIFO,
n = 24), mixed SIFO/SIBO (n = 32), or no overgrowth proven
by aerobic/anaerobic/fungal small bowel cultures (n = 74).
There was no difference in the intensity, frequency, and duration of abdominal pain, bloating, fullness, belching, indigestion, nausea, vomiting diarrhea, and gas.
Recently, in a retrospective study, Baker et al. [22••]
assessed the symptom profiles of 5045 patients who
underwent glucose breath testing. Those with a positive breath
test (n = 1680) had similar prevalence of heartburn, regurgitation, chest pain, nausea, abdominal pain, bloating, gas, diarrhea, and constipation when compared to those with a negative test. These findings emphasize the inaccuracy of patients’
symptom profile in the diagnosis of SIBO among those patients with or without SIBO.
Clinical Response to Empirical Treatment with Antibiotics
Symptomatic response to antibiotics has been proposed as
a clinical tool for the diagnosis of SIBO [21]. However,
given the non-specific nature of symptom(s), the inability
to predict which antibiotic may be effective against which
constellation of symptoms or organisms, the potential for
misuse of antibiotics and development of drug resistance,
and the recent increase in the incidence of Clostridium
difficile colitis, empiric therapy with antibiotics may pose
unjustified risks to the patients. Also, there is no consensus
or an objective method of identifying symptom response to
antibiotics. Hence, this approach is not recommended.
Breath Testing
Quantification of hydrogen and methane gas in breath
samples remains the most inexpensive, non-invasive, and
widely available test for the diagnosis of SIBO [21].
Human cells are not capable of producing methane or
hydrogen gas [23]. The presence of these gases in the
human breath signifies the metabolism of carbohydrate
residues by gut, their absorption from the gut, and expiration through lungs. Based on this principle, when
lactulose or glucose is given to a patient with presumed
SIBO, the changes in hydrogen and methane concentrations in sequential breath samples will indicate the presence of SIBO (Fig. 1) [24]. Gas production in SIBO patients is clearly variable and depends on the concentration
and the types of colonizing bacteria in the small bowel, as
well as the availabilities of carbohydrate residue and the
absorptive capacity of the small bowel. Current commercially available gas chromatography equipment is unable
to detect hydrogen sulfide, which is another important gas
produced by gut microbiome, and its assessment may enhance the yield of breath tests.
In the absence of a universally acceptable gold-standard
test and cutoffs for an increase in hydrogen or methane concentration above baseline for a diagnosis of SIBO, exact determination of the test characteristics of breath testing is difficult to assess. In a systematic review, Khoshini et al. [21]
found 11 studies that have attempted to validate the accuracy
of lactulose breath testing for SIBO. The sensitivity ranged
from 31 to 68 % and specificity ranged from 44 to 100 %.
The sensitivity of glucose breath testing has varied from 20 to
93 % and specificity from 30 to 86 %. Multiple patterns of
hydrogen and methane production have also been described in
the literature, such as flat line (non-methane fixed-hydrogen
production), hydrogen-predominant, methane-predominant,
and mixed hydrogen/methane bacterial overgrowth [25•].
However, hydrogen-predominant overgrowth and
methane-predominant bacterial overgrowth are the two patterns that have been more widely studied. Although patients
with either pattern share similar symptoms such as bloating
Fig. 1 Examples of common patterns with glucose breath test. After 12 h„
of fasting, exhaled methane and hydrogen are measured at baseline (i.e.,
minute 0). Patients ingest 75 g of glucose mixed with 100 cm3 of water,
and measurements are repeated every 15 min for a total of 3 h. Lack of
excessive methane production or an early rise in hydrogen excretion
within 90 min of the test is considered normal (a). Hydrogen production
rises by more than 20 ppm within 90 min of the test which suggest
hydrogen-predominant bacterial overgrowth (b). Methane levels of more
than 10 ppm are suggestive of overgrowth of methane-producing bacteria (c)
Curr Gastroenterol Rep (2016) 18:8
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Curr Gastroenterol Rep (2016) 18:8
Fig. 1 (continued).
and abdominal distension, those with excessive methane production are five times more likely to have constipation [26].
Moreover, the severity of constipation directly correlates with
the methane level [27] and the choice of antibiotics for the
treatment of SIBO differs between these two groups.
There is also a great degree of heterogeneity in defining a
positive breath test, underlining the need for large-scale validation studies and expert consensus reviews [28••]. In one
recent study that compared glucose breath hydrogen testing
with duodenal aspiration/culture, a cutoff value of ≥20 ppm
hydrogen above baseline had a sensitivity and specificity of
77 and 66 %, respectively [28••, 29].
Small Bowel Aspiration/Culture for Identifying SIBO
Although not fully validated, currently, the accepted gold standard for diagnosis of SIBO is the aspiration of small bowel
fluid, followed by culture and bacterial count [5••, 14, 28••,
29]. As opposed to breath testing, small bowel aspiration is
time-consuming, costly, and invasive, often requiring endoscopy with sedation, although fluoroscopic-assisted small bowel tube placement has been described [24]. Proximal small
bowel culture may be falsely negative as it can miss overgrowth of bacteria in the mid and distal small bowel, which
is beyond the reach of a regular endoscope [4]. Moreover,
given the current sample collection techniques, contamination
with oral and esophageal flora may lead to false-positive results [5••], although use of aseptic technique could minimize
this [5••, 28••, 29].
Historically, a bacterial concentration ≥105 colony forming
units (CFU)/mL has been used for identifying any bacterial
infection including a diagnosis of SIBO. However, this cutoff
is debatable, especially in the context of SIBO, and has not
been well validated [5••, 28••]. A systematic review of literature on the diagnosis of SIBO found that healthy controls have
≤103 CFU/mL, and concentrations ≥105 CFU are mostly seen
in patients with Billroth II patients [21]. Currently, a bacterial
concentration of ≥103 CFU/mL is generally considered significant [5••, 6]. In a recent comparative study, duodenal culture
was positive in 62/139 (45 %) patients whereas glucose breath
test was positive in 38/139 (27 %) patients. The sensitivity and
specificity of GBT were 42 and 84 %, respectively [28••].
Further research regarding bacterial concentrations in various small bowel segments in healthy subjects using sterile
and anaerobic techniques is urgently needed. Moreover, these
studies should consider integrating deep sequencing techniques for further assessment of bacterial diversity in SIBO
patients [9, 10].
Curr Gastroenterol Rep (2016) 18:8
Treatment
Treatment of SIBO is comprised of three broad strategies: (1)
induction of remission, (2) maintenance of remission, and (3)
treatment/modification of the underlying cause of SIBO
(Fig. 2).
Induction of Remission
Antibiotics are the mainstay of therapy for SIBO. However,
given the limited qualitative and quantitative assessment of
the bacteria that are causing the symptoms, the choice, dosing,
and duration of antibiotic therapy have not been fully
understood.
A systematic review found 23 trials in the literature that
addressed the role of antibiotics in SIBO [21]. The majority
of these trials were uncontrolled, and 17 studies included less
than 20 subjects. Study endpoints were variable, with
investigator-defined clinical response being the most common
primary endpoint which ranged from 35 to 100 %. While the
most common antibiotics were clindamycin, metronidazole,
neomycin, rifaximin, and tetracycline, other antimicrobial
compounds such as ampicillin, amoxicillin, chloramphenicol,
ciprofloxacin, erythromycin, and trimethoprim/
sulfamethoxazole have been used in smaller numbers of
Page 5 of 11 8
subjects. The duration of therapy has varied from 5 days to
1 month, and the frequency of repeat therapy has ranged from
none to monthly and for 4–6 months. In a meta-analysis of 10
placebo-controlled trials, antibiotics were shown to be superior to placebo with a combined normalization rate of 51 %
(95 % confidence interval (CI), 47–56 %) for antibiotics compared with 10 % (95 % CI, 5–18 %) for placebo [30].
In an uncontrolled open-label trial, Pimentel et al. [31]
assessed 157 IBS patients with hydrogen-predominant bacterial overgrowth diagnosed by lactulose breath test. All patients
underwent treatment with neomycin, ciprofloxacin, metronidazole, or doxycycline as per discretion of managing physicians and patients’ preference. Of 157 subjects, 47 had a
follow-up breath testing 7–10 days after antibiotic therapy.
There was significant improvement in symptoms of diarrhea
and abdominal pain in those who showed eradication of bacterial overgrowth on the repeat breath testing (n = 22, 47 %).
In a double-blind randomized placebo-controlled study
[32], 111 IBS patients (84 % had a positive lactulose breath
test) were randomized to neomycin 500 mg twice daily or
placebo for a total of 10 days. Clinical response was defined
as a 50 % reduction in a composite score calculated from the
three symptoms of abdominal pain, diarrhea, and constipation
each on a scale of 0–5. In subjects with abnormal breath test,
21 of 46 (46 %) receiving neomycin had a clinical response,
a
LES
Antrum
Pylorus
Duodenum
b
LES
Antrum
Pylorus
Duodenum
Jejunum
Fig. 2 A high-resolution solid-state catheter with 36 pressure sensors
(Given Imaging Inc.) was used to measure intraluminal pressures from
lower esophageal sphincter to proximal jejunum in a 22-year-old patient
with myogenic chronic intestinal pseudo-obstruction (CIPO). During the
first 4 h of the fasting phase, patient only had a 2-min MMC-like contraction compatible with his known diagnosis of myogenic CIPO. One
hour after oral administration of prucalopride 2 mg, patient had a 3-min
MMC-like contraction originating from proximal duodenum (a). Subsequently, 50 mg of intravenous erythromycin was administered which after
10 min, led to a 6-min-long MMC phase III contraction originating from
antrum (b)
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compared with seven of 47 (15 %) in the placebo group
(P < 0.01). Only one out of 43 patients with an abnormal
breath test who received placebo had a normal breath test at
the end of the study. No severe adverse events were reported.
Rifaximin is one of the most extensively studied antibiotics
in functional bowel disorders. It has been approved by Food
and Drug Association (FDA) for traveler’s diarrhea, hepatic
encephalopathy, and IBS with diarrhea. In the largest study
that specifically addressed the effect of rifaximin on SIBO,
Lauritano et al. [33] randomized 142 SIBO patients diagnosed
by glucose breath test to rifaximin 400 mg thrice daily or
metronidazole 250 mg thrice daily for 7 days. After 1 month,
breath test normalized in 63 % of patients in the rifaximin
group versus 44 % in the metronidazole group (P < 0.05).
The number of dropouts was significantly greater in the metronidazole group. Clinical response was not reported in this
study.
TARGET 1, 2 [34], and 3 [35] assessed the efficacy and
safety of rifaximin in large number of IBS patients without
constipation; however, the presence or absence of SIBO was
not fully assessed in these studies. TARGET 1 and 2 were two
identically designed double-blind placebo-controlled trials
that randomized 1258 IBS patients without constipation to
placebo or rifaximin 550 mg twice daily for 14 days. By week
4, more patients in the treatment arm had achieved a relief
from global IBS symptoms as compared to placebo (40.7 vs.
31.7 %, P < 0.001). Adequate relief from bloating was also
achieved more frequently in the rifaximin group (40.2 vs.
30.3 %, P < 0.001). In addition, significantly more patients
in the rifaximin arm had a positive response as assessed by
daily ratings of IBS symptoms, bloating, abdominal pain, and
stool consistency. Adverse events were similar in both groups,
and there were no cases of C. difficile infection (CDI).
TARGET 3 was designed to assess the efficacy and safety
of repeated courses of rifaximin in IBS-D patients whose
symptoms recurred after an open-label course of rifaximin.
Of 2579 patients who received open-label rifaximin, 1074
patients showed a clinical response within 4 weeks of therapy
and were followed up for a maximum of 18 weeks for signs
and symptoms of relapse. Of the initial responders, 636 relapsed and were randomized to receive rifaximin 550 mg or
placebo twice daily for 2 weeks with a 4-week follow-up
post-therapy. Subsequently, patients received a second blinded
treatment with placebo or rifaximin and were followed for
four more weeks. Based on FDA guidelines, response was
defined as ≥30 % decrease in mean abdominal pain score from
baseline and ≥50 % decrease in the stool consistency score of
type 6/7 from baseline in a given week for at least 2 weeks of a
month. In the open-label phase of the study, 46 % of patients
had a response while 72 % had improvement on at least one
component of response (i.e., abdominal pain or stool consistency). Significantly, more patients had a clinical response
(32.5 %) after the first round of repeat treatment with rifaximin
Curr Gastroenterol Rep (2016) 18:8
as compared to placebo (25.0 %). Similar pattern was observed in the second repeat treatment phase. Adverse events
were similar among both groups. There was one case of CDI
in the treatment arm during maintenance phase; however, this
patient was being treated with a cephalosporin for urinary tract
infection.
While the exact mechanism of action of rifaximin in IBS is
unknown, given the high prevalence of SIBO in IBS patients
[6, 36], the safety profile of rifaximin, and the size and quality
of TARGET trials, we suggest that a similar regimen may be
useful for induction of remission in SIBO although this merits
a further assessment in a randomized controlled trial.
When there is excess methane production, rifaximin alone
may not have the expected efficacy. Methanobrevibacter
smithii is an archaeon that is responsible for methane production in humans and is resistant to many antibiotics. In a retros p e c t i v e s t u d y, L o w e t a l . [ 3 7 ] o b s e r v e d t h a t
methane-producing subjects receiving either neomycin or
rifaximin did not have a substantial benefit. However, a combination of neomycin and rifaximin appeared to decrease
methane production in greater than 80 % of subjects with
similar outcome in constipation-related symptoms.
There has been only one randomized controlled trial that
addressed the effect of antibiotics on methane productivity.
Pimentel et al. [38••] randomized 31 patients with C-IBS
and methane levels >3 ppm to neomycin (500 mg twice daily)
plus placebo or neomycin plus rifaximin (550 mg thrice daily)
for 14 days and followed patients for 4 weeks after antibiotic
therapy. Constipation severity, bloating, and straining were
significantly less in the rifaximin plus neomycin group as
compared to the neomycin-alone group. Abdominal pain
was not different between the groups. The main determinant
of clinical response in the neomycin plus rifaximin group was
a decrease in methane production to below 3 ppm, which
occurred in two thirds of patients. Similar rates of adverse
events were seen in the two groups. Based on this, we advocate 2 weeks of therapy with neomycin and rifaximin for
treatment of patients with methane-predominant bacterial
overgrowth. Although antibiotic trials have not been performed in this population; anecdotally, neomycin alone, metronidazole (500 mg thrice daily), or amoxicillin-clavulanic
acid may be considered. It should be noted that in patients
who have a blind loop and SIBO, systemic antibiotic therapy
rather than non-absorbable antibiotics such as neomycin and
rifaximin should be considered.
Recently, there has been interest in the use of statins as
a treatment for methane production in humans. Statins
have been shown to inhibit growth and production of
methane in several Methanobrevibacter isolates, presumably by interfering with mevalonate synthesis needed for
isoprenoid lipid synthesis in methanogens [39]. The clinical use of this warrants further study in the treatment of
constipation [40].
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Elemental Diet
Watchful Observation and Retreatment as Needed
Therapeutic options for the induction of remission in patients
with SIBO with allergies to antibiotics or those who do not
respond to optimal doses of antibiotics are very limited.
Elemental diets may be an extremely safe and effective alternative to antibiotics. These formulations are believed to be
absorbed within the first few feet of small bowel and potentially limiting the delivery of nutrients to the bacteria residing
in distal portion of small bowel [41]. In a retrospective study,
124 patients with methane- or hydrogen-predominant SIBO
were treated exclusively with elemental diet (Vivonex Plus,
Novartis Nutrition Corp., Minneapolis, MN) for at least
2 weeks. If breath test did not normalize by week 2, patients
continued the diet for a total of 3 weeks. Fourteen patients
could not tolerate the diet and dropped out. By day 15, 80 %
of subjects normalized their breath test. Of 19 subjects who
did not normalize their breath test, only five had a normal
breath test by day 22 for a cumulative response of 85 %.
Patients who normalized their breath test showed 66 % improvement in symptoms as opposed to 12 % improvement in
patients with persistently abnormal breath tests [42]. While the
cost and palatability of elemental formulations can be a limiting factor in their use, this strategy may be effective in the
induction of remission of SIBO and merits randomized clinical trials.
Watchful observation is a reasonable option after induction of
remission of SIBO, although most experts believe that patients
will eventually relapse. In the recent TARGET 3 study of
IBS-D patients, 36 % of responders in the open phase of the
trial did not experience a relapse for at least 22 weeks after
treatment with rifaximin. In addition, approximately one third
of patients who relapsed after open-label therapy responded to
retreatment with rifaximin. Although this study did not address SIBO, clinical experience suggests that SIBO patients
are at higher risk of relapse and may require a more rigorous
management plan for maintenance of remission.
Herbal Antibiotics
There is a growing interest among patients in the use of complementary and alternative medicine. In a recent
non-randomized open-label trial, of 37 breath test-positive
SIBO patients who received a mixture of over 10 herbal therapies for 4 weeks, 17 (46 %) had a negative lactulose breath
test at follow-up, compared to 23/67 (34 %) in the rifaximin
(400 mg thrice daily) group (P = 0.24). No data was provided
regarding clinical response [43].
Although the use of herbal medications with antibiotic
properties such as peppermint oil [44] in the treatment of
SIBO is intriguing, these compounds need to undergo robust
clinical trials for assessment of their efficacy, correct dosing,
and safety profiles before widespread clinical use.
Maintenance of Remission
SIBO is a relapsing disease, especially when there are predisposing factors. Lauritano et al. [45] showed that 13, 28, and
44 % of SIBO patients experience a relapse of their symptoms
and breath test positivity at 3, 6, and 9 months after induction
of remission with rifaximin, respectively. Therefore, following induction of remission, one should consider implementing
appropriate therapeutic interventions to decrease the chance of
recurrence (i.e., maintenance of remission).
Use of Promotility Drugs
Motility is an important determinant of gut flow and stasis. It
is therefore intuitive that improving motility might have a
benefit in maintaining remission in SIBO patients. During
the fasting state (i.e., inter-digestive period), every 90–
120 min, phase III migrating motor complexes (MMCs) repetitively sweep through the foregut [46]. These so-called
housekeeper waves are vital to maintain balanced gut floral
populations and to clear residual food particles and secretions
from the small bowel [5••, 47]. Patients with IBS-like symptoms have abnormal intensity and frequency of phase III
MMCs [48]. In addition, many of the disease states that can
lead to SIBO are associated with abnormal MMC patterns
including opioid-induced gut dysmotility, partial obstructive
disease, and diabetes [48]. Neuronal and hormonal control of
MMCs is complex. Motilin, ghrelin, and serotonin have been
shown to induce phase III-like MMCs [49]. Hence,
promotility drugs such as motilin receptor agonists (e.g.,
erythromycin and azithromycin) and 5-HT4 agonists (e.g.,
tegaserod, cisapride, and prucalopride) can induce phase III
MMCs in a fasting state [50] and potentially decrease the
recurrence of bacterial overgrowth (Fig. 3).
In an open-label trial [51], 34 cirrhotic patients were randomized to alternating antibiotics, cisapride and placebo for
6 months. At 6 months, cisapride was superior to placebo and
non-inferior to antibiotics in normalization of the breath test.
In a retrospective study, patients who underwent maintenance
of remission with tegaserod experienced less relapse when
compared to those who underwent no treatment, and there
was a trend towards benefit with erythromycin [52].
Diet Restriction
A low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet significantly affects
the gut microbiota [53]. However, to date, no study has systematically addressed the role of diet in SIBO patients.
Carbohydrate intolerance (e.g., lactose, fructose, and fructan)
8
Curr Gastroenterol Rep (2016) 18:8
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Fig. 3 Proposed management of
SIBO that includes induction and
maintenance of remission
is very common among SIBO patients [54], and dietary restrictions can lead to symptomatic improvement.
Table 1
Theoretically, a diet with low fermentable foods can decrease
the chance of bacterial overgrowth by creating a less favorable
Disease states that lead to SIBO and can be potentially treated or modified
Disease states leading to SIBO
Diagnosis
Potential treatment
Gut dysmotility (idiopathic, scleroderma, pseudo-obstruction, -History, transit studies,
post-infectious, and opioid-induced constipation)
antroduodenal manometry
-Temporal correlation of opioid
use and symptoms
-Symptomatic response to partial
μ-receptor antagonists
-Prokinetics (erythromycin, domperidone,
and prucalopride)
-Decreasing or stopping the opioids
-Partial μ-receptor antagonists
(e.g., methylnaltrexone [56] and naloxegol [57]
-Prucalopride [58]
-Lubiprostone [59]
Adhesive diseasea
-Sharp bowel angulations on SBFT
or enterographic studies
-Exploratory laparotomy
-Enterographic studies
-Wireless capsule endoscopy
-Enteroscopy
-Lysis of adhesions with possible use
of bioabsorbable membranes [60]
-Enterographic studies
-Wireless capsule endoscopy
-Enteroscopy
- Small bowel follow through
and enterographic studies
-Anti-inflammatory drugs
-Strict gluten-free diet
Small bowel stricturing disease (Crohn’s disease, NSAIDs,
anastomosis narrowing and radiation)
Active inflammation in the small bowel (e.g. CD, celiac
disease, radiation enteritis)
Small bowel diverticular disease
-Enteroscopic dilatation
-Surgical repair
-NSAIDs avoidance
-Treating active CD
-Promotility drugs
-Long-term low-dose antibiotic therapy
Collagen vascular disease (hypermobility joint syndrome,
scleroderma, SLE)
-Clinical history and physical examination -Promotility drugs
-Visceroptosis in standing position
-Pyridostigmine in patients with concomitant postural
on SBFT [61]
orthostatic tachycardia syndrome [62]
Diabetic enteropathy
-Clinical history
-Promotility drugs
-Strict control of blood glucose levels
-Avoiding diabetic drugs known to slow gut motility
(e.g., GLP1 agonists) [63]
SBFT small bowel follow through, CD Crohn’s disease, POTS postural orthostatic tachycardia syndrome, GLP-1 glucagon-like peptide-1, NSAIDs nonsteroidal anti-inflammatory drugs
a
Adhesive disease can be seen even in virgin abdomen (e.g., Fitz-Hugh-Curtis disease, endometriosis, and contained or missed appendicitis/
diverticulitis)
Curr Gastroenterol Rep (2016) 18:8
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luminal environment for overgrown bacteria. In a systematic
review, Rao et al. [55] found that a low FODMAP diet improved overall IBS symptoms in 6/6 trials, but the key principle in its success was dependent on dietary education. This
was confirmed by a recent multicenter single-blind trial that
showed similar rate of improvement in severity of IBS symptoms with FODMAP vs. traditional IBS diet (i.e., regular meal
pattern; avoidance of large meals; and reduced intake of fat,
fiber, and gas-producing foods).
Overall, it appears that dietary education and avoidance of
fermentable foods have favorable effects on symptom control;
however, the role of dietary intervention in objective outcomes of induction and maintenance of treatment of SIBO
needs further evaluation.
Alternatively, glucose or lactulose breath tests are widely
available, non-invasive, safe, and useful for diagnosis of
SIBO.
Induction of remission for SIBO can be achieved with antibiotics. The choice of antibiotics is dependent on the type of
bacteria (aerobic or anaerobic, especially when cultures are
performed) as well as the presence of excessive methane on
breath test. Elemental diet may be an alternative to antibiotic
therapy. Prokinetic drugs, peppermint oil, and dietary carbohydrate restriction may serve as useful adjuncts to the management and maintenance of remission. Where possible, attempts should be made to eliminate or modify the underlying
causes of SIBO.
Treatment of the Underlying Cause of SIBO
Compliance with Ethical Standards
SIBO is often a secondary disease, and unless the underlying
problem is addressed and well controlled, the chance of recurrence remains high. However, in the majority of cases, elimination of the underlying cause is not possible. In Table 1,
specific strategies are presented that may be helpful in the
modification of the underlying cause.
Role of Probiotics, Prebiotics, and Symbiotics
The role of probiotics/prebiotics/symbiotics in the management of SIBO remains to be clarified. While the concept of
Breplacement of bad bacteria with good bacteria^ in the treatment of SIBO is intriguing, there is little objective evidence to
support this. In a retrospective study of 10 children with abdominal pain and SIBO who were treated with
bifidobacterium and lactobacillus strains, four had symptomatic improvement by 15 months [64]. The PLACIDE trial (the
largest placebo-controlled randomized study in the field of
probiotics to date, with over 3000 subjects) examined the role
of bifidobacterium and lactobacillus strains in the prevention
of antibiotic-associated diarrhea and C. difficile infection. The
rates of diarrhea and C. difficile infection were similar in the
placebo and probiotic arms [65, 66]. However, patients on
probiotics experienced significantly more bloating and
flatulence.
Until further data is available regarding the benefit and
safety of probiotics/prebiotics/symbiotics in the management
of SIBO, one should exercise caution with their use in clinical
practice.
Conflict of Interest Ali Rezaie reports support from the following
sources for teaching, research, and consultation, outside the submitted
work: Commonwealth Laboratories, Actavis, and Salix
Pharmaceuticals. Mark Pimentel reports support from the following
sources for teaching, research, and consultation, outside the submitted
work: Commonwealth Laboratories, Salix Pharmaceuticals, Entera
Health, Synthetic Biologics, Synthetic Biologics, Micropharma, and
Naia Pharmaceuticals. Satish Rao reports support from the following
sources for teaching, research, and consultation, outside the submitted
work: Forest Laboratories, Hollister, Ironwood Pharmaceuticals,
Sucampo Pharmaceuticals, In Control Medical, Vibrant, American
Medical Systems, Sun Sweet Corporation, Synergy Pharmaceuticals,
Salix Pharmaceuticals, and Ventrus Laboratories.
Human and Animal Rights and Informed Consent With regard to
the authors’ research cited in this paper, all procedures performed in
studies involving human participants were in accordance with the ethical
standards of the institutional and/or national research committee and with
the 1964 Helsinki Declaration and its later amendments or comparable
ethical standards.
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