The relationship between small intestinal bacterial overgrowth and constipation in children - a comprehensive review.

Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the bacterial population of the small intestine due to an imbalance between the amount of bacteria and the intestinal barrier. Pediatric SIBO presents with a wide spectrum of symptoms, ranging from mild gastrointestinal complaints to malabsorption or malnutrition. Breath tests are commonly used as noninvasive diagnostic tools for SIBO, but a standardized methodology is currently unavailable. Intestinal flora produces methane which slows intestinal transit and increases the contractile activity of small intestine. Emerging literature suggests a correlation between overgrowth of methanogenic bacteria in the intestines and constipation. Treatment of SIBO involves administration of antibacterial therapy in addition to management of underlying conditions and optimal dietary adjustments. However, research on antibiotic treatment for pediatric patients with constipation and SIBO is limited and has yielded conflicting results. In the current review, we summarize the state-of-the-art of the field and discuss previous treatment attempts and currently used regimens for SIBO patients with constipation, with a focus on pediatric populations.

Liquid Thyroxine Improves Outcomes in Hypothyroid Patients With Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome.

OBJECTIVE: Malabsorption of levothyroxine (LT4) is often seen in patients with hypothyroidism and gastrointestinal (GI) conditions. Our study was designed to establish the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with hypothyroidism and irritable bowel syndrome (IBS), and to demonstrate that liquid LT4 is more consistently absorbed vs tablet, leading to improvement in thyroid and GI symptoms. METHODS: This was a single-center, open label, prospective cohort study of liquid LT4 in 75 adult patients with hypothyroidism and IBS. Patients were transitioned from LT4 tablets to solution at equivalent dosing. Patients returned at 6 and 12 weeks for repeat thyroid levels and completion of validated questionnaires. A standard 2-hour SIBO breath test was administered at Week 6. Patients recorded daily stool appearance and frequency. RESULTS: Prevalence of SIBO was 65.3%. Liquid LT4 normalized thyroid stimulating hormone (TSH) in a higher percentage of patients vs tablet (77.55% vs 57.14%); significantly decreased TSH in subjects with SIBO; improved hypothyroid symptoms, IBS symptoms, stool appearance in all groups, and significantly altered bowel frequency among those with SIBO. CONCLUSION: Small intestinal bacterial overgrowth (SIBO) is common in patients with hypothyroidism and IBS. Among SIBO patients, LT4 tablets were inefficiently absorbed, leading to suboptimal thyroid control; however, transitioning from LT4 tablets to solution normalized TSH and improved hypothyroid symptoms. Liquid LT4 also significantly improved GI symptoms in all patients with hypothyroidism and IBS, regardless of SIBO status. Additionally, 1 in 5 patients had complete resolution of IBS symptoms after switching from LT4 tablets to solution, independent of changes in TSH.

Alternative Treatment Approaches to Small Intestinal Bacterial Overgrowth: A Systematic Review.

Background: Broad-spectrum antibiotics are the first-line treatment for small intestinal bacterial overgrowth (SIBO). However, many antibiotics have a considerable side-effect profile and SIBO commonly reoccurs after successful eradication with antibiotics. Alternative therapies such as probiotics, therapeutic diets, and herbal medicines have been used to individualize SIBO management, particularly in recalcitrant cases. Objectives: The objective of this review is to evaluate the role of alternative therapies in SIBO treatment. Data Sources: EMBASE, MEDLINE, and the Cochrane Central Register were systematically searched for clinical studies evaluating alternative therapies in the management of SIBO. Study Eligibility Criteria: Human studies in which an alternative intervention was used to treat SIBO were included. Alternative interventions were defined as an intervention that included a probiotic supplement, herbal preparation, or a dietary change. Randomized controlled trials (RCTs), nonrandomized clinical trials with or without a control, and crossover studies were included. Study Appraisal: The following information was extracted from the selected studies: study type, study participants, SIBO subtype, intervention, comparison, outcome measures, relevant results, relevant side effects, and Jadad score. Results: Eight studies met inclusion criteria. The studies evaluated probiotics (n = 5), therapeutic diet (n = 1), and herbal medicines (n = 2). Among these studies, there were four RCTs, two open-label single-arm studies, one randomized, double-blind crossover study, and one two-arm open-label study with crossover. Main results are summarized. Limitations: There may be studies not captured by the defined search criteria. Additionally, studies used different methodologies in both breath testing and measurement of clinical symptoms, making it difficult to draw conclusions on SIBO eradication and symptom improvement across studies. Conclusions and Implications: Our findings suggest preliminary evidence for a role of alternative therapies in the treatment of SIBO. However, robust clinical trials are generally lacking. Existing studies tend to be small and lack standardized formulations of treatment. Breath testing protocols and clinical symptom measurement greatly varied between studies. Large-scale, randomized, placebo-controlled trials are needed to further evaluate the best way to utilize alternative therapies in the treatment of SIBO.

Chinese herbal medicine for the treatment of small intestinal bacterial overgrowth (SIBO): A protocol for systematic review and meta-analysis.

BACKGROUND: Chinese medicine has a unique theory and the Chinese herbal medicine treatment is based on the integral concepts and syndrome differentiation of the Traditional Chinese Medicine system. Although antibiotics remain the mainstay of SIBO treatment, various alternative or adjunctive therapies are available, including prokinetic agents, dietary interventions, probiotics, and herbal combinations. There is accumulating evidence demonstrating the antimicrobial properties of a growing number of herbs including garlic, black cumin, cloves, cinnamon, thyme, all-spices, bay leaves, mustard, and rosemary. This has prompted an interest in herbal therapy for the treatment of SIBO. Currently, there is no systematic review focusing on efficacy of CHM in the treatment of SIBO with PCOS, so our meta-analysis aims to comprehensively explore it. Meanwhile we will provide high-quality evidence to help patients, clinicians as well as health policymakers select better treatment strategy of PCOS. METHODS: We will search the following sources without restrictions for date, language, or publication status: PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) Cochrane Library, EMBASE and China National Knowledge Infrastructure. We will apply a combination of Medical Subject Heading (MeSH) and free-text terms incorporating database-specific controlled vocabularies and text words to implement search strategies. We will also search the ongoing trials registered in the World Health Organization's International Clinical Trials Registry Platform. Besides, the previous relevant reviews conducted on CHM for SIBO and reference lists of included studies will also be searched. RESULTS: This study will provide a reliable basis for the treatment of SIBO with CHM. CONCLUSIONS: The findings will be an available reference to evaluate the efficacy and safety of CHM in the treatment of SIBO. REGISTRATION NUMBER: INPLASY202080004.

Short-course Rifaximin therapy efficacy and lactulose hydrogen breath test in Chinese patients with diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Gut microbiota alterations including small intestinal bacterial overgrowth (SIBO) might play a role in pathogenesis of irritable bowel syndrome (IBS). Rifaximin could effectively and safely improve IBS symptoms. The aim of this study was to investigate the effect of rifaximin on Gastrointestinal (GI) symptoms, quality of life (QOL) and SIBO eradication in Chinese IBS-D patients. METHODS: This study included 78 IBS-D patients defined by the Rome IV criteria. Patients received 400 mg rifaximin twice daily for 2 weeks and 10-week follow-up. GI symptoms were assessed at week 0, 2, 4, 8 and 12. QOL and lactulose hydrogen breath test (LHBT) results were estimated at week 0 and 4. RESULTS: All participants showed significant improvements in GI symptom subdomains after rifaximin treatment (all P < 0.05), which could maintain at least 10 weeks of follow-up. Additionally, QOL scores were increased with concomitant improvement of clinical symptoms (all P < 0.05). The 45 rifaximin-responsive patients (57.7%) achieved significantly greater GI-symptom improvement than non-responders (all P < 0.05). No GI symptoms were associated with SIBO (all P > 0.05). SIBO normalization after rifaximin treatment measured by LHBT was found in 44.4% (20/45) of patients with SIBO before treatment. CONCLUSION: A short course (2 weeks) of rifaximin improved GI symptoms and QOL in Chinese IBS-D patients whether they had SIBO or not. However, the efficacy of rifaximin could not be explained by the successful eradication of SIBO. Further studies on the therapeutic mechanisms of rifaximin in IBS are urgently needed.

The Effect of Ursodeoxycholic Acid on Small Intestinal Bacterial Overgrowth in Patients with Functional Dyspepsia: A Pilot Randomized Controlled Trial.

Functional dyspepsia (FD) is associated with small intestinal bacterial overgrowth (SIBO). Several animal studies have reported that ursodeoxycholic acid (UDCA) has antibacterial and anti-inflammatory effects in the intestine. We hypothesized that UDCA may be effective against dyspeptic symptoms and SIBO in patients with FD. We conducted this randomized controlled trial to investigate the effects of UDCA in FD patients with SIBO. Twenty-four patients diagnosed with FD and SIBO based on lactulose breath test (LBT) were randomly assigned to either a UDCA treatment group or an untreated group. The treatment group received 100 mg of UDCA three times per day for two months; the untreated group was monitored for two months without intervention. After two months in both groups, we reevaluated LBT and FD symptoms using the Nepean dyspepsia index-K. FD symptoms in the UDCA-treated group were significantly reduced after two months compared with baseline and FD symptom scores between the UDCA-treated and untreated groups showed statistically significant differences after two months. In addition, the total methane gas levels for 90 minutes in LBT were significantly decreased after two months compared with baseline in the UDCA-treated group. In this preliminary exploratory study, we found that two months of UDCA treatment resulted in FD symptom improvement and reduced methane values during 90 minutes on the LBT, suggesting that methane-producing SIBO were associated with symptoms of dyspepsia and that UDCA was helpful in these patients. These findings need to be validated via large-scale controlled and well-designed studies.

Small Intestinal Bacterial Overgrowth Diagnosed by a Breath Test and Improved by Rifaximin in a Patient with Hepatic Encephalopathy and Alcoholic Liver Cirrhosis.

A 66-year-old Japanese man was admitted to our hospital with grade 2 hepatic encephalopathy (HE). Abdominal computed tomography and laboratory examinations revealed decompensated liver cirrhosis. Intravenous administration of branched-chain amino acids immediately ameliorated the HE, and lactulose was initiated. However, a breath test revealed small intestinal bacterial overgrowth (SIBO); therefore, rifaximin was additionally initiated. The breath test was repeated after discharge, when no evidence of SIBO or overt HE was identified. This case suggested that a breath test is effective for the identification of SIBO and that the administration of a poorly absorbed antibiotic should be considered in SIBO-positive HE patients taking lactulose.

Small Intestinal Bacterial Overgrowth in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Case-Control Studies.

INTRODUCTION: We conducted a systematic review and meta-analysis to compare the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with irritable bowel syndrome (IBS) and controls. METHODS: Electronic databases were searched up to December 2018 for studies reporting SIBO prevalence in patients with IBS. Prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) of SIBO in patients with IBS and controls were calculated. RESULTS: We included 25 studies with 3,192 patients with IBS and 3,320 controls. SIBO prevalence in patients with IBS was significantly increased compared with controls (OR = 3.7, 95% CI 2.3-6.0). In studies using only healthy controls, the OR for SIBO in patients with IBS was 4.9 (95% CI 2.8-8.6). With breath testing, SIBO prevalence in patients with IBS was 35.5% (95% CI 33.6-37.4) vs 29.7% (95% CI 27.6-31.8) in controls. Culture-based studies yielded a SIBO prevalence of 13.9% (95% CI 11.5-16.4) in patients with IBS and 5.0% (95% CI 3.9-6.2) in controls with a cutoff value of 10 colony-forming units per milliliter vs 33.5% (95% CI 30.1-36.9) in patients with IBS and 8.2% (95% CI 6.8-9.6) in controls with a cutoff value of 10 colony-forming unit per milliliter, respectively. SIBO prevalence diagnosed by lactulose breath test is much greater in both patients with IBS (3.6-fold) and controls (7.6-fold) compared with glucose breath test. Similar difference is seen when lactulose breath test is compared with culture methods. OR for SIBO in patients with IBS-diarrhea compared with IBS-constipation was 1.86 (95% CI 1.83-2.8). Methane-positive breath tests were significantly more prevalent in IBS-constipation compared with IBS-diarrhea (OR = 2.3, 95% CI 1.2-4.2). In patients with IBS, proton pump inhibitor was not associated with SIBO (OR = 0.8, 95% CI 0.5-1.5, P = 0.55). DISCUSSION: This systematic review and meta-analysis suggests a link between IBS and SIBO. However, the overall quality of the evidence is low. This is mainly due to substantial "clinical heterogeneity" due to lack of uniform selection criteria for cases and controls and limited sensitivity and specificity of the available diagnostic tests.

Total Bilirubin Is Associated with Small Intestinal Bacterial Overgrowth in Diarrhea Predominant Irritable Bowel Syndrome.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) associated with irritable bowel syndrome (IBS) can cause microscopic mucosal inflammation and oxidative damage. Bilirubin is a marker of oxidant stress that is responsible for anti-oxidative activities. The objective of this research was to determine whether or not total bilirubin is associated with SIBO according to IBS subtypes. MATERIALS AND METHODS: We retrospectively reviewed the charts of patients who showed IBS symptoms with documented results of lactulose breath test for SIBO. Multivariate models were used in order to assess the relationship of total bilirubin with SIBO according to IBS subtypes. In addition, we observed changes in total bilirubin when SIBO was treated with rifaximin in the relevant IBS subtype. RESULTS: The total bilirubin level of subjects with SIBO was significantly higher than it was in those without. An examination according to IBS subtype groups showed that total bilirubin was independently associated with SIBO only in the subjects with diarrhea-predominant IBS subtype (OR: 2.723, 95% CI: [1.303-5.692], p<0.001). Additionally, a decrease in total bilirubin level and overall improvement of abdominal symptoms were observed following rifaximin treatment. CONCLUSIONS: These findings suggest that total bilirubin levels may provide additional information regarding the presence of SIBO in diarrhea-predominant IBS patients.

The role of small intestinal bacterial overgrowth in cystic fibrosis: a randomized case-controlled clinical trial with rifaximin.

BACKGROUND: Scientific literature shows a high prevalence of Small Intestinal Bacterial Overgrowth (SIBO) in patients with Cystic Fibrosis (CF). The role of SIBO in nutritional status and gastrointestinal symptoms in CF is not known. Our aim was to study epidemiology and clinical impact of SIBO while assessing the efficacy of rifaximin in eradicating SIBO in CF patients. METHODS: Symptoms questionnaire and Glucose Breath Test (GBT) were given to 79 CF patients (median age 19.6 years; 9.2-36.9). Subjects with a positive GBT were enrolled in a randomized controlled trial and received rifaximin 1200 mg for 14 days or no treatment. Questionnaire and GBT were repeated 1 month after the end of treatment or 45 days after the first negative GBT. RESULTS: Out of 79 patients, 25 were affected by SIBO (31.6%) with a significant correlation with lower BMI, SDS-BMI (p < 0.05) and serum albumin levels (p < 0.05), independently from pancreas insufficiency. Twenty-three patients took part in the randomized trial, 13 patients (56.5%) in rifaximin group and 10 patients (43.5%) in control group. Eradication rate of SIBO was 9/10 (90%) in rifaximin group and 2/6 (33.3%) in control group (p < 0.05). In the rifaximin group, gastrointestinal symptom improvement was observed in 4/5 patients aged ≤ 14 years and in 0/5 patients aged > 14 years (p < 0.05); in 2/6 patients in the control group. CONCLUSIONS: CF patients show a high prevalence of SIBO, related to a poorer nutritional status. Rifaximin therapy is well tolerated and the results are promising in terms of efficacy in eradicating small intestinal bacterial overgrowth in CF.

Treatment of small intestinal bacterial overgrowth in systemic sclerosis: a systematic review.

Objectives: Almost all patients with SSc have gastrointestinal manifestations. Small intestinal bacterial overgrowth (SIBO) occurs in 30-60% of patients and leads to malnutrition and impaired quality of life. Recent systematic reviews have reported efficacy of treatments for SIBO, but these are not specific to patients with SSc. We conducted a systematic review of the evidence for all possible SIBO treatments in the SSc population. Methods: The following databases were searched: MEDLINE, EMBASE and the Cochrane Library, from database inception to 1 January 2017. All evidence for all possible SIBO treatments including antibiotics, prokinetics, probiotics and alternative treatments was included. Treatment outcomes included symptomatic relief or demonstrated SIBO eradication. Results: Of 5295 articles, five non-randomized studies were reviewed with a total of 78 SSc patients with SIBO. One trial assessed octreotide while the remaining four trials investigated the effectiveness of ciprofloxacin, rifaximin, norfloxacin and metronidazole, and the combination of amoxicillin, ciprofloxacin and metronidazole. Studies were generally of low quality and most were un-controlled. Conclusion: Data indicate that, for some SSc patients, antibiotics can eradicate SIBO. There is a paucity of data reporting the effectiveness of either prokinetics or probiotics in SSc.

Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis.

BACKGROUND: D-lactic acidosis is characterized by brain fogginess (BF) and elevated D-lactate and occurs in short bowel syndrome. Whether it occurs in patients with an intact gut and unexplained gas and bloating is unknown. We aimed to determine if BF, gas and bloating is associated with D-lactic acidosis and small intestinal bacterial overgrowth (SIBO). METHODS: Patients with gas, bloating, BF, intact gut, and negative endoscopic and radiological tests, and those without BF were evaluated. SIBO was assessed with glucose breath test (GBT) and duodenal aspiration/culture. Metabolic assessments included urinary D-lactic acid and blood L-lactic acid, and ammonia levels. Bowel symptoms, and gastrointestinal transit were assessed. RESULTS: Thirty patients with BF and 8 without BF were evaluated. Abdominal bloating, pain, distension and gas were the most severe symptoms and their prevalence was similar between groups. In BF group, all consumed probiotics. SIBO was more prevalent in BF than non-BF group (68 vs. 28%, p = 0.05). D-lactic acidosis was more prevalent in BF compared to non-BF group (77 vs. 25%, p = 0.006). BF was reproduced in 20/30 (66%) patients. Gastrointestinal transit was slow in 10/30 (33%) patients with BF and 2/8 (25%) without. Other metabolic tests were unremarkable. After discontinuation of probiotics and a course of antibiotics, BF resolved and gastrointestinal symptoms improved significantly (p = 0.005) in 23/30 (77%). CONCLUSIONS: We describe a syndrome of BF, gas and bloating, possibly related to probiotic use, SIBO, and D-lactic acidosis in a cohort without short bowel. Patients with BF exhibited higher prevalence of SIBO and D-lactic acidosis. Symptoms improved with antibiotics and stopping probiotics. Clinicians should recognize and treat this condition.

Nutritional Interventions in Chronic Intestinal Pseudoobstruction.

Although chronic intestinal pseudo-obstruction (CIPO) is a rare disorder, it presents a wide spectrum of severity that ranges from abdominal bloating to severe gastrointestinal dysfunction. In the worst cases, patients may become dependent upon artificial nutrition via parenteral nutrition or choose to have an intestinal transplant. However, whatever the severity, a patient's quality of life can be seriously compromised. This article defines the disorder and discusses the spectrum of disease and challenges to providing adequate nutrition to help improve a patient's quality of life.

Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment.

A patient with severe postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS) received immunotherapy with low-dose naltrexone (LDN) and intravenous immunoglobulin (IVIg) and antibiotic therapy for small intestinal bacterial overgrowth (SIBO). A dramatic and sustained response was documented. The utility of IVIg in autoimmune neuromuscular diseases has been published, but clinical experience with POTS is relatively unknown and has not been reported in MCAS. As a short-acting mu-opioid antagonist, LDN paradoxically increases endorphins which then bind to regulatory T cells which regulate T-lymphocyte and B-lymphocyte production and this reduces cytokine and antibody production. IVIg is emerging as a promising therapy for POTS. Diagnosis and treatment of SIBO in POTS is a new concept and appears to play an important role.

Small intestinal bacterial overgrowth as a cause for irritable bowel syndrome: guilty or not guilty?

PURPOSE OF REVIEW: Small intestinal bacterial overgrowth (SIBO) has been proposed as a cause of irritable bowel syndrome (IBS). However, this relationship has been subject to controversy. This review aims to provide a current perspective on the SIBO-IBS hypothesis. RECENT FINDINGS: Case-control studies evaluating the prevalence of SIBO in IBS and healthy individuals have shown conflicting results. Moreover, the tests available in routine clinical practice to diagnose SIBO are not valid and lack both sensitivity and specificity. Hence, interpreting the effect of interventions based on these tests is fraught with uncertainty. Furthermore, the SIBO-IBS hypothesis has paved the way to assess antibiotic therapy in nonconstipated IBS, with rifaximin, a nonabsorbable antibiotic, showing modest but significant clinical benefit. However, individuals were not tested for SIBO and the mechanism of action of rifaximin in IBS remains to be elucidated. Preliminary data suggest that rifaximin decreases microbial richness and previous studies have noted antibacterial interventions in IBS to reduce colonic fermentation and improve symptoms. The advent of rapid culture-independent molecular techniques is a promising tool that will seek to clarify and advance our understanding of the gut microbial function. SUMMARY: The SIBO-IBS hypothesis lacks convincing evidence but remains under scrutiny. The mechanism resulting in symptom improvement after rifaximin treatment in some IBS individuals requires exploration. Novel molecular techniques provide an exciting and challenging opportunity to explore the host-gut microbiota interaction.

Identification and Treatment of New Inflammatory Triggers for Complex Regional Pain Syndrome: Small Intestinal Bacterial Overgrowth and Obstructive Sleep Apnea.

Complex regional pain syndrome (CRPS) is evoked by conditions that may be associated with local and/or systemic inflammation. We present a case of long-standing CRPS in a patient with Ehlers-Danlos syndrome in which prolonged remission was attained by directing therapy toward concomitant small intestinal bacterial overgrowth, obstructive sleep apnea, and potential increased microglia activity. We theorize that cytokine production produced by small intestinal bacterial overgrowth and obstructive sleep apnea may act as stimuli for ongoing CRPS symptoms. CRPS may also benefit from the properties of low-dose naltrexone that blocks microglia Toll-like receptors and induces production of endorphins that regulate and reduce inflammation.

The treatment of gastroparesis, constipation and small intestinal bacterial overgrowth syndrome in patients with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) affects the nerves of the entire gastrointestinal (GI) tract and may result in profound gastrointestinal (GI) dysfunction leading to poor patient outcomes. Common GI disturbances in patients with PD include gastroparesis (GP), constipation and small intestinal bacterial overgrowth syndrome (SIBO). In particular, GP is difficult to treat due to the limited options available and precautions, contraindications and adverse effects associated with the approved treatments. Moreover, some commonly used medications can worsen pre-existing PD. AREAS COVERED: Our review will focus on treatment options for GP and SIBO with motilin agonists, dopamine receptor antagonists, Ghrelin agonists muscarinic agonists, 5-HT4 receptor agonists, antibiotics, probiotics and herbal formulation such as iberogast. Constipation occurs in the majority of patients with PD and fortunately many treatments are now available. Our review is based on original papers or reviews selected from PUBMED search and Cochrane reviews. EXPERT OPINION: Motility disorders of the GI tract are found frequently in patients with PD and treating the underlying GI disorders caused by PD with various prokinetics and laxatives is paramount in achieving improvements in patient's motor function. Various prokinetics and laxatives are now available to provide some relief of the GI morbidity caused by PD leading even to better absorption of even the PD treatments.