SIBO Pathology Risk In Intestinal Failure Patients
Overview
Patients with intestinal failure (IF) often experience abnormal intestinal anatomy, secretion issues, and dysmotility, which can disrupt intestinal homeostasis and lead to small intestinal bacterial overgrowth (SIBO). To understand the prevalence of SIBO in IF patients and identify associated risk factors, a systematic review and meta-analysis were conducted.
The study involved searching the MEDLINE (PubMed) and Embase databases, covering all records until December 2023, to identify studies reporting the prevalence of SIBO in IF patients. The prevalence rates, odds ratios (OR), and 95% confidence intervals (CI) were calculated using a random-effects model to assess SIBO prevalence and related risk factors in these patients.
The final analysis included nine studies encompassing 407 IF patients. The overall prevalence of SIBO in this population was found to be 57.5% (95% CI 44.6–69.4). The analysis showed significant heterogeneity (I² = 80.9, P = 0.0001). Notably, SIBO prevalence was significantly higher in IF patients receiving parenteral nutrition (PN), with a sixfold increase compared to those not on PN (OR = 6.0, 95% CI 3.0–11.9, P = 0.0001). Additionally, IF patients using proton pump inhibitors (PPI) or acid-suppressing agents had a higher prevalence of SIBO (72.0%, 95% CI 57.5–83.8) compared to those not using these agents (47.6%, 95% CI 25.7–70.2).
This systematic review and meta-analysis suggest that patients with IF are at an increased risk of developing SIBO, particularly those receiving PN or using PPI/acid-suppressing agents. However, the evidence quality is low, largely due to the lack of case-control studies and the clinical heterogeneity observed in the analyzed studies. Further research is necessary to better understand these associations and improve clinical outcomes for IF patients.
Introduction
Intestinal failure (IF) is characterized by the inability of the gut to function adequately, necessitating intravenous supplementation to sustain health and growth. IF can result from various conditions, including short bowel syndrome, intestinal fistula, intestinal dysmotility, mechanical obstruction, and mucosal disease, with short bowel syndrome being the most common cause. Parenteral nutrition (PN) and home PN are essential treatments for IF, regardless of its nature, but they increase the risk of catheter-related bloodstream infections (CRBSI).
Patients with IF often experience abnormal intestinal anatomy, secretion, and motility, which can disrupt intestinal homeostasis and lead to small intestinal bacterial overgrowth (SIBO). SIBO is a well-recognized form of gut microbial dysbiosis and is associated with a broad range of gastrointestinal symptoms. It may cause structural changes in the small intestine, such as villous atrophy, which impairs absorption. Traditionally, SIBO has been diagnosed by culturing jejunal aspirates with ≥10^5 colony-forming units (CFU) per milliliter, but more recent data suggest that a threshold of ≥10^3 CFU/mL in duodenal aspirates may be more accurate. While duodenal aspirate cultures are the gold standard for SIBO diagnosis, breath tests are often used in practice due to their ease, despite their limited accuracy.
SIBO and CRBSI are common and significant complications in IF patients, directly affecting both morbidity and mortality. SIBO has been linked to an increased risk of CRBSI due to bacterial translocation and subsequent intestinal mucosal inflammation, which complicates the initiation of enteral feeding and the transition from PN. Therefore, understanding and mitigating risk factors is crucial for the long-term health of IF patients. Antimicrobial therapy is a frequent treatment for SIBO, often improving symptoms and test results, though SIBO frequently recurs, necessitating empirical treatment strategies like intermittent or cycling antibiotic regimens. However, this approach raises concerns about antibiotic misuse, adverse effects, and the development of drug resistance.
In this context, a systematic review and meta-analysis were conducted to determine the prevalence of SIBO in IF patients. The study also explored the relationship between PN (and its complications) and SIBO, the etiology of IF and SIBO, the impact of diagnostic methods and acid-suppressing medications on SIBO prevalence, the association between SIBO and anatomical changes in IF patients, and the effectiveness of antibiotic therapy in alleviating symptoms in IF patients with SIBO.
Method
This systematic review and meta-analysis adheres to the PRISMA guidelines and was registered prospectively with PROSPERO (CRD42023414010). The review included a comprehensive search of electronic databases such as PUBMED, MEDLINE, and EMBASE from 1966 to December 2023, focusing on studies that examined the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with intestinal failure (IF) and/or short gut syndrome (SGS)/short bowel syndrome (SBS). The search strategy, which was conducted with assistance from a librarian, is detailed in the PRISMA flow diagram. The search was not restricted by language, and additional searches were conducted using gray literature sources and the “Snowball” method to ensure all relevant studies were captured.
The selection process involved two independent reviewers who screened titles and abstracts to identify studies that explored the relationship between SIBO and IF or SBS. Eligible studies included case-control and cohort studies that reported the prevalence of SIBO using validated methods. Studies that did not present original data, such as reviews, case reports, or series, as well as those without relevant SIBO data in IF patients, were excluded. Conference abstracts with available data were included.
Data extraction was carried out independently by two authors, with any discrepancies resolved by referring to the original publications. Extracted data included details on study design, diagnosis methods, demographic characteristics, and treatment outcomes. The quality of the included cohort studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. The risk of bias was categorized as high, moderate, or low based on the proportion of “yes” scores achieved.
For data analysis, case numbers for patients with IF were determined, and pooled prevalence rates and confidence intervals for SIBO in IF patients were calculated. Subgroup analyses were conducted to assess the impact of diagnostic modalities, etiology of IF, and treatments like parenteral nutrition (PN) and antibiotics. The Comprehensive Meta-Analysis Software (CMA) was used for statistical analyses, employing a random effects model to account for variability between studies. Potential publication biases were assessed using standard methods such as Egger’s test and funnel plots.
In summary, this systematic review and meta-analysis followed rigorous protocols to assess the prevalence of SIBO in patients with IF, utilizing a comprehensive search strategy, thorough data extraction, and robust statistical analysis to provide reliable findings on the association between SIBO and IF.
Results
The initial literature search identified 305 publications, with 184 deemed relevant for the study. After further evaluation, 175 articles were excluded, leaving nine eligible studies. These included three case-control studies and six cohort studies. It is noteworthy that in the case-control studies, only cases were analyzed for small intestinal bacterial overgrowth (SIBO) as controls were not assessed for SIBO.
The meta-analysis encompassed data from 407 patients with intestinal failure (IF), revealing a SIBO prevalence of 57.5%. Significant heterogeneity was observed across the studies. The methods for diagnosing SIBO varied, with some studies using duodenal aspirate and culture, others employing breath tests, and one study relying solely on clinical symptoms. Due to the variability in diagnostic methods, subgroup analyses to evaluate their impact on SIBO prevalence were not feasible.
Regarding risk of bias, four of the nine studies were classified as having a high risk of bias, while four were considered low risk, and one had a moderate risk. A higher prevalence of SIBO was observed in high-quality studies at 66.1%, though moderate heterogeneity was present.
The analysis also examined SIBO prevalence in patients with IF who were on parenteral nutrition (PN). Among 105 patients, the prevalence was 74.9%, significantly higher than in those not on PN. This finding suggests a sixfold increase in SIBO risk for IF patients on PN.
The link between SIBO and catheter-related bloodstream infections (CRBSI) was assessed in two studies, but no significant difference was found in CRBSI prevalence between patients with and without SIBO. Additionally, the studies provided data on the types of microbes cultured from small bowel aspirates, with *Streptococcus viridans* and *Enterococcus* species being the most common Gram-positive bacteria, and *Escherichia coli* and *Klebsiella pneumoniae* the most common Gram-negative bacteria.
Further analysis explored the relationship between SIBO and the etiology of IF, such as short bowel syndrome (SBS), but substantial heterogeneity prevented clear conclusions. The effect of acid-suppressive therapy on SIBO prevalence was also investigated, but no statistically significant differences were found.
Lastly, the relationship between SIBO and anatomical factors, such as the presence of an ileocecal valve (ICV) and remnant bowel length, was explored. While SIBO prevalence was higher in patients without an ICV, the difference was not statistically significant. Similarly, no significant relationship was found between SIBO and the length of the remnant small or large bowel.
In summary, this analysis highlights the substantial prevalence of SIBO among patients with IF, particularly those on PN, and underscores the variability in diagnostic methods and study quality. Further research is needed to clarify the relationships between SIBO, anatomical changes, and treatment modalities in IF patients.
Conclusion
This systematic review and meta-analysis is the first to explore the prevalence of Small Intestinal Bacterial Overgrowth (SIBO) in patients with Intestinal Failure (IF). The study analyzed data from nine studies across four countries, including a total of 407 patients with IF. The findings indicate a high prevalence of SIBO among these patients, with an overall rate of 57.5%. A notable risk factor identified was dependence on Parenteral Nutrition (PN), which increased the likelihood of SIBO sixfold. Moreover, patients with both SIBO and IF were found to require PN for a significantly longer period than those without SIBO, though the difference was not statistically significant due to the small sample size.
The analysis revealed significant heterogeneity in the studies, attributed to variations in study design, populations, and diagnostic methods. Efforts to reduce this heterogeneity by focusing on higher-quality studies did not yield substantial improvements. The studies reviewed had several limitations, including a lack of standardized diagnostic criteria for SIBO, reliance on retrospective data, and inadequate control of potential confounding factors. Furthermore, the majority of the studies included pediatric populations, and the diagnosis of SIBO was often based on clinical suspicion rather than validated diagnostic tests.
The review also highlighted the challenges in diagnosing SIBO, given the limitations of available tests, including the invasive nature and potential inaccuracies of small bowel aspirates and the lack of standardization in breath tests. Moreover, it was noted that the specific bacterial taxa associated with SIBO in IF patients remain unclear, as it is uncertain whether these bacteria are a cause or a consequence of the condition. Additionally, none of the included studies assessed methane positivity during breath testing, despite its suggested significance in diagnosing intestinal dysbiosis.
One of the key findings was the strong association between PN dependence and an increased risk of SIBO, possibly due to structural changes in the small intestine that impair absorption. This association could explain the prolonged need for PN in patients with SIBO. However, the link between SIBO and other potential risk factors, such as the absence of the ileocecal valve, shorter residual bowel length, and the use of acid-suppressing agents, remains uncertain and warrants further investigation.
The review underscores the need for more robust and standardized research in this area. It calls for collaboration among centers involved in IF management to create a joint clinical database, which would facilitate more comprehensive and impactful research. Despite its limitations, this review provides valuable insights into the prevalence and risk factors of SIBO in patients with IF, but its findings should be interpreted with caution due to the low quality of evidence and substantial heterogeneity among the included studies.
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