Association of small intestinal bacterial overgrowth with nonalcoholic fatty liver disease in children: A meta-analysis.
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ABSTRACT:
SUBMITTER: Kuang L
PROVIDER: S-EPMC8638857 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) has been associated with small bowel bacterial overgrowth (SIBO) and cardiometabolic dysfunction. This cross-sectional study aimed to evaluate the cardio-metabolic parameters and SIBO in patients with different degrees of hepatic fibrosis estimated by NAFLD fibrosis score (NFS). METHODS:Subjects (n = 78) were allocated to three groups: Healthy control (n = 30), NAFLD with low risk of advanced fibrosis (NAFLD-LRAF, n = 17) and NAFLD with a high risk of advanced fibrosis (NAFLD-HRAF, n = 31). Anthropometrics, blood pressure, electrocardiogram and heart rate variability (HRV) were evaluated. Only the NAFLD-LRAF and NAFLD-HRAF groups were submitted to blood biochemical analysis and glucose hydrogen breath tests. RESULTS:The NAFLD-HRAF group had higher age and body mass index when compared to the control and NAFLD-LRAF groups. The prevalence of SIBO in the NAFLD group was 8.33%. The low frequency/high-frequency ratio (LF/HF ratio) was augmented in NAFLD-LRAF (p < 0.05) when compared with control group. NAFLD-HRAF group had a wide QRS complex (p < 0.05) and reduced LF/HF ratio (p < 0.05) compared to the control and NAFLD-LRAF groups. Serum levels of albumin and platelets were more reduced in the NAFLD-HRAF subjects (p < 0.05) than in the NAFLD-LRAF. CONCLUSIONS:NAFLD impairs cardiac autonomic function. Greater impairment was found in subjects with a worse degree of hepatic fibrosis estimated by NFS. Hypoalbuminemia and thrombocytopenia were higher in subjects with a worse degree of hepatic fibrosis, whereas prevalence of SIBO positive was similar between the groups.
| S-EPMC7449384 | biostudies-literature
Project description:Small intestinal bacterial overgrowth (SIBO) is an under-recognised diagnosis with important clinical implications when untreated. However, the optimal treatment regimen remains unclear.To perform a systematic review and meta-analysis comparing the clinical effectiveness of antibiotic therapies in the treatment of symptomatic patients with documented SIBO.Four databases were searched to identify clinical trials comparing effectiveness of: (i) different antibiotics, (ii) different doses of the same antibiotic and (iii) antibiotics compared with placebo. Data were independently extracted according to predetermined inclusion and exclusion criteria. Study quality was independently assessed. The primary outcome was normalisation of post-treatment breath testing. The secondary outcome was post-treatment clinical response.Of 1356 articles identified, 10 met inclusion criteria. Rifaximin was the most commonly studied antibiotic (eight studies) with overall breath test normalisation rate of 49.5% (95% confidence interval, CI 44.0-55.1) (44.0%-55.1%) then (46.7%-55.5%), then (4.6%-17.8%). Antibiotic efficacy varied by antibiotic regimen and dose. Antibiotics were more effective than placebo, with a combined breath test normalisation rate of 51.1% (95% CI 46.7-55.5) for antibiotics compared with 9.8% (95% CI 4.6-17.8) for placebo. Meta-analysis of four studies favoured antibiotics over placebo for breath test normalisation with an odds ratio of 2.55 (95% CI 1.29-5.04). Clinical response was heterogeneously evaluated among six studies, but tended to correlate with breath test normalisation.Antibiotics appear to be more effective than placebo for breath test normalisation in patients with symptoms attributable to SIBO, and breath test normalisation may correlate with clinical response. Studies were limited by modest quality, small sample size and heterogeneous design. Additional higher quality clinical trials of SIBO therapy are warranted.
| S-EPMC3819138 | biostudies-literature
Project description:Small intestinal bacterial overgrowth (SIBO) is a heterogenous and poorly understood entity characterised by an excessive growth of select microorganisms within the small intestine. This excessive bacterial biomass, in turn, disrupts host physiology in a myriad of ways, leading to gastrointestinal and non-gastrointestinal symptoms and complications. SIBO is a common cause of non-specific gastrointestinal symptoms in children, such as chronic abdominal pain, abdominal distention, diarrhoea, and flatulence, amongst others. In addition, it has recently been implicated in the pathophysiology of stunting, a disease that affects millions of children worldwide. Risk factors such as acid-suppressive therapies, alterations in gastrointestinal motility and anatomy, as well as impoverished conditions, have been shown to predispose children to SIBO. SIBO can be diagnosed via culture-dependant or culture-independent approaches. SIBO's epidemiology is limited due to the lack of uniformity and consensus of its diagnostic criteria, as well as the paucity of literature available. Antibiotics remain the first-line treatment option for SIBO, although emerging modalities such as probiotics and diet manipulation could also have a role. Herein, we present a state-of-the-art-review which aims to comprehensively outline the most current information on SIBO in children, with particular emphasis on the gut microbiota.
| S-EPMC6737284 | biostudies-literature
Project description:BackgroundEvidence on small intestinal bacterial overgrowth (SIBO) in patients with chronic pancreatitis (CP) is conflicting.AimThe purpose of this study was to perform a systematic review and meta-analysis on the prevalence of SIBO in CP and to examine the relationship of SIBO with symptoms and nutritional status.MethodsCase-control and cross-sectional studies investigating SIBO in CP patients were analysed. The prevalence of positive tests was pooled across studies, and the rate of positivity between CP cases and controls was calculated.ResultsIn nine studies containing 336 CP patients, the pooled prevalence of SIBO was 36% (95% confidence interval (CI) 17-60%) with considerable heterogeneity (I2?=?91%). A sensitivity analysis excluding studies employing lactulose breath test gave a pooled prevalence of 21.7% (95% CI 12.7-34.5%) with lower heterogeneity (I2?=?56%). The odds ratio for a positive test in CP vs controls was 4.1 (95% CI 1.6-10.4) (I2?=?59.7%). The relationship between symptoms and SIBO in CP patients varied across studies, and the treatment of SIBO was associated with clinical improvement.ConclusionsOne-third of CP patients have SIBO, with a significantly increased risk over controls, although results are heterogeneous, and studies carry several limitations. The impact of SIBO and its treatment in CP patients deserve further investigation.
| S-EPMC5042309 | biostudies-literature
Project description:Overt hepatic encephalopathy (HE) is one of the complications of liver cirrhosis (LC), which negatively affects the prognosis and quality of life of patients. Small intestinal bacterial overgrowth (SIBO) is significantly associated with LC and its complications, including HE. We investigated the relationship between SIBO and LC, and the difference between hydrogen-producing and methane-producing SIBO (H-SIBO and M-SIBO, respectively). This is a prospective cohort study of 107 cases. Breath measurements of hydrogen and methane concentrations were performed for the diagnosis of SIBO. The study cohort included 81 males with a median age of 70 (40-86) years, and SIBO was detected in 31 cases (29.0%). There were no significant differences between the SIBO positive and SIBO negative groups. Reclassification into H-SIBO (16 cases) and others (91 cases) was performed, and the Child-Pugh score was only derived in the multivariate logistic analysis (P = 0.028, odds ratio 1.39, 95% confidence interval 1.04-1.85). Furthermore, H-SIBO was significantly associated with covert HE in chi-square test (50.0% vs. 24.2%, P = 0.034). In addition, we evaluated the therapeutic response on SIBO of rifaximin in eight covert HE patients. 20% patients with M-SIBO and 67% patients with H-SIBO showed an improvement of the breath test. In conclusion, H-SIBO, but not M-SIBO, is significantly associated with liver function, and rifaximin might be more effective for covert HE with H-SIBO. Therefore, the diagnosis of SIBO, including the classification as H-SIBO and M-SIBO, might help to determine the choice of treatment for HE.
| S-EPMC8880851 | biostudies-literature
Project description:BackgroundReliable non-invasive markers to characterize inflammation, hepatocellular ballooning, and fibrosis in nonalcoholic fatty liver disease (NAFLD) are lacking. We investigated the relationship between plasma cytokine levels and features of NAFLD histology to gain insight into cellular pathways driving NASH and to identify potential non-invasive discriminators of NAFLD severity and pattern.MethodsCytokines were measured from plasma obtained at enrollment in pediatric participants in NASH Clinical Research Network studies with liver biopsy-proven NAFLD. Cytokines were chosen a priori as possible discriminators of NASH and its components. Minimization of Akaike Information Criterion (AIC) was used to determine cytokines retained in multivariable models.ResultsOf 235 subjects, 31% had "Definite NASH" on liver histology, 43% had "Borderline NASH", and 25% had NAFLD but not NASH. Total plasminogen activator inhibitor 1 (PAI1) and activated PAI1 levels were higher in pediatric participants with Definite NASH and with lobular inflammation. Interleukin-8 (IL-8) was higher in those with stage 3-4 fibrosis and lobular inflammation. sIL-2rα was higher in children with stage 3-4 fibrosis and portal inflammation. In multivariable analysis, PAI1 variables were discriminators of Borderline/Definite NASH, definite NASH, lobular inflammation and ballooning. IL-8 increased with steatosis and fibrosis severity; sIL-2rα increased with fibrosis severity and portal inflammation. IL-7 decreased with portal inflammation and fibrosis severity.ConclusionsPlasma cytokines associated with histology varied considerably among NASH features, suggesting promising avenues for investigation. Future, more targeted analysis is needed to identify the role of these markers in NAFLD and to evaluate their potential as non-invasive discriminators of disease severity.
| S-EPMC5679472 | biostudies-literature
Project description:Small Intestinal Bacterial Overgrowth (SIBO) is a form of dysbiosis that involves increased bacterial colonization of the small intestine with some of the bacteria more characteristic of the colon microbiota. The prevalence of SIBO over recent decades has been estimated to range from 2.5 to 22% (depending on the source) and to increase with age and among individuals with comorbidities. Recently, an increase in the number of diagnosed SIBO cases has been observed, which is primarily due to the availability of noninvasive breath tests that facilitate the diagnostic process. However, SIBO is still both a diagnostic and a therapeutic problem. This review presents the pathophysiology, manifestations, diagnostics, and recommended management of SIBO.
| S-EPMC9604644 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It represents a spectrum of disease from simple hepatic steatosis to steatohepatitis that may develop into progressive hepatic fibrosis and even cirrhosis. NAFLD is the most rapidly increasing indication for liver transplantation in adults. In children, the incidence of NAFLD has also increased over the past decade. Although the majority of children with NAFLD are overweight or obese, there is an increasing subset of children with normal body mass index with so-called lean NAFLD. NAFLD in children is associated with several extrahepatic manifestations, including hyperlipidemia, insulin resistance, and obstructive sleep apnea. The pathogenesis of NAFLD in children involves a multifactorial interaction among genetics, in utero exposures, early childhood exposures, and ongoing nutritional exposures. Although there are some similarities between pediatric NAFLD and adult NAFLD, liver biopsies in children show histologic differences between the two. The current standard-of-care treatment of NAFLD in children is lifestyle change to decrease caloric intake and increase physical activity. There are no medications currently approved for the treatment of NAFLD in children. This article aims to summarize the current understanding of pediatric NAFLD and future directions for intervention and therapeutic aims.
| S-EPMC9021174 | biostudies-literature
Project description:Nonalcoholic steatohepatitis (NASH) is considered the hepatic manifestation of metabolic syndrome (MetS) among adults. Emerging data suggest that MetS may be associated with nonalcoholic fatty liver disease (NAFLD) in children as well. We sought to determine whether MetS or its component features are associated with specific histological features or severity of NAFLD.Children and adolescents aged 6-17 years enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) with clinical data obtained within 6 months of liver biopsy were included. MetS was defined as the presence of three or more of the following features as determined by application of age-adjusted normative values: central obesity, dyslipidemia, impaired fasting glucose, and elevated blood pressure. Liver biopsies were evaluated by the Pathology Committee of the NASH CRN.Two hundred fifty four children were included in the analysis, of whom 65 (26%) met specified criteria for MetS. Among children with MetS, there is a higher proportion of females who were on average older in age and pubertal. The risk of MetS was greatest among those with severe steatosis (odds ratio (OR)=2.58 for grade 3 vs. grade 1 steatosis, P=0.001). The presence of hepatocellular ballooning was also significantly associated with MetS (OR=2.10, P=0.03). Those with advanced fibrosis (stage 3/4) had an OR for MetS of 3.21 (P=0.04) vs. those without fibrosis (stage 0). Borderline zone 1 or definite NASH patterns compared with "not NASH" were strongly associated with MetS (OR=4.44, P=0.005 and OR=4.07, P=0.002, respectively). The mean NAFLD Activity Score (NAS) was greater among children with MetS vs. those without (4.8 +/- 1.4 vs. 4.3 +/- 1.4, P=0.01). Central obesity was significantly associated with steatosis, fibrosis, hepatocellular ballooning, and NAFLD pattern. Insulin resistance was significantly associated with steatosis, fibrosis, hepatocellular ballooning, NAS, and NAFLD pattern.MetS is common among children with NAFLD and is associated with severity of steatosis, hepatocellular ballooning, NAS, NAFLD pattern, and the presence of advanced fibrosis. Individual MetS features, particularly central obesity and insulin resistance, were also associated with severity of NAFLD. MetS features should be considered in children with NAFLD as individually and collectively they help identify children with more advanced disease.
| S-EPMC3070291 | biostudies-literature
Project description:Small intestinal bacterial overgrowth (SIBO) is highly prevalent and is associated with numerous gastrointestinal disorders, but the microbes involved remain poorly defined. Moreover, existing studies of microbiome alterations in SIBO have utilized stool samples, which are not representative of the entire gastrointestinal tract. Therefore, we aimed to determine and compare the duodenal microbiome composition in SIBO and non-SIBO subjects, using duodenal aspirates from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Using the recently-redefined cutoff for SIBO of >103 colony forming units per milliliter (CFU/mL), 42 SIBO and 98 non-SIBO subjects were identified. Duodenal samples from SIBO subjects had 4x103-fold higher counts than non-SIBO subjects when plated on MacConkey agar (P<0.0001), and 3.8-fold higher counts when plated on blood agar (P<0.0001). Twenty subjects had also undergone lactulose hydrogen breath tests (LHBTs), of whom 7/20 had SIBO. At the 90-minute timepoint, 4/7 SIBO subjects had positive LHBTs (rise in hydrogen (H2) ??20 ppm above baseline), as compared to 2/13 non-SIBO subjects. 16S ribosomal RNA (rRNA) sequencing revealed that SIBO subjects had 4.31-fold higher relative abundance of Proteobacteria (FDR P<0.0001) and 1.64-fold lower Firmicutes (P<0.0003) than non-SIBO subjects. This increased relative abundance of Proteobacteria correlated with decreased ?-diversity in SIBO subjects (Spearman R = 0.4866, P<0.0001) Specific increases in class Gammaproteobacteria correlated with the area-under-the-curve for H2 for 0-90 mins during LHBT (R = 0.630, P = 0.002). Increases in Gammaproteobacteria resulted primarily from higher relative abundances of the family Enterobacteriaceae (FDR P<0.0001), which correlated with the symptom of bloating (Spearman R = 0.185, 2-tailed P = 0.028). Increases in family Aeromonadaceae correlated with urgency with bowel movement (Spearman R = 0.186, 2-tailed P = 0.028). These results validate the >103 CFU/mL cutoff for the definition of SIBO, and also reveal specific overgrowth of Proteobacteria in SIBO vs. non-SIBO subjects, coupled with an altered Proteobacterial profile that correlates with symptom severity. Future research may elucidate host-microbiome interactions underlying these symptoms in SIBO patients.
| S-EPMC7347122 | biostudies-literature