Determine independent gut microbiota-diseases association by eliminating the effects of human lifestyle factors

Lifestyle and physiological variables on human disease risk have been revealed to be mediated by gut microbiota. Low concordance between case-control studies for detecting disease-associated microbe existed due to limited sample size and population-wide bias in lifestyle and physiological variables. To infer gut microbiota-disease associations accurately, we propose to build machine learning models by including both human variables and gut microbiota. When the model’s performance with both gut microbiota and human variables is better than the model with just human variables, the independent gut microbiota -disease associations will be confirmed. By building models on the American Gut Project dataset, we found that gut microbiota showed distinct association strengths with different diseases. Adding gut microbiota into human variables enhanced the classification performance of IBD significantly; independent associations between occurrence information of gut microbiota and irritable bowel syndrome, C. difficile infection, and unhealthy status were found; adding gut microbiota showed no improvement on models’ performance for diabetes, small intestinal bacterial overgrowth, lactose intolerance, cardiovascular disease. Our results suggested that although gut microbiota was reported to be associated with many diseases, a considerable proportion of these associations may be very weak. We proposed a list of microbes as biomarkers to classify IBD and unhealthy status. Further functional investigations of these microbes will improve understanding of the molecular mechanism of human diseases.

Association of small intestinal bacterial overgrowth with nonalcoholic fatty liver disease in children: A meta-analysis

It has been suggested that small intestinal bacterial overgrowth (SIBO) could cause nonalcoholic fatty liver disease (NAFLD), but this association was not examined in children by meta-analysis. This meta-analysis aimed to determine the association between SIBO and NAFLD in children. The electronic databases PubMed, Embase, and Cochrane Library were searched for studies published before April 22, 2021. The outcome was the association between SIBO and NAFLD. Three studies and 205 children were included. All three studies reported the association between SIBO and NAFLD. Children with SIBO were more likely to have NAFLD (odds ratio = 5.27, 95% confidence interval (CI): 1.66–16.68, P<0.001; I2 = 63.5%, Pheterogeneity = 0.065). When directly pooling the reported relative risks (RR) from two studies, children with NAFLD had an over 2-fold increased relative risk of developing SIBO (RR = 2.17, 05%CI: 1.66–2.82, P<0.001; I2 = 0.0%, Pheterogeneity = 0.837). This meta-analysis reports a possible association between SIBO and NAFLD in children.

Small intestinal bacterial overgrowth in Alzheimer’s disease

The results of animal studies and clinical data support the gut microbiota contribution to the pathogenesis of Alzheimer’s disease (AD). The aim of this pilot study was to evaluate the prevalence of small intestinal bacterial overgrowth (SIBO) and fecal markers of intestinal inflammation and permeability in AD patients. The study was conducted in 45 AD patients and 27 controls. Data on comorbidities, pharmacotherapy, and gastrointestinal symptoms were acquired from medical records and a questionnaire. SIBO was evaluated using lactulose hydrogen breath test. Fecal calprotectin and zonulin levels were assessed by ELISA assays. The positive result of SIBO breath test was found in 49% of the AD patients and 22% of the controls (p = 0.025). The comparative analysis between SIBO-positive and SIBO-negative AD patients with respect to the degree of cognitive impairment, comorbidities and used medications did not reveal any statistically significant difference, except for less common heartburn in SIBO-positive AD patients than in SIBO-negative ones (9 vs 35%, p = 0.038). The median fecal calprotectin and zonulin levels in the AD group compared to the control group amounted to 43.1 vs 64.2 µg/g (p = 0.846) and 73.5 vs 49.0 ng/ml (p = 0.177), respectively. In the AD patients there was no association between the presence of SIBO and fecal calprotectin level. Patients with AD are characterized by higher prevalence of SIBO not associated with increased fecal calprotectin level that may be related to anti-inflammatory effect of cholinergic drugs used in the treatment of AD.

Prevalence of Small Intestinal Bacterial Overgrowth (SIBO) In Type 2 Diabetes Mellitus: A Systematic Review

Purpose: Gastrointestinal symptoms affect 50-70% of diabetic patients, resulting in a microbiota composition imbalance. Autonomic neuropathy is irreversible, resulting in diabetic enteropathy and sometimes even small intestine bacterial overgrowth (SIBO). SIBO can result in bile acid deconjugation, diarrhea, steatorrhea, vitamin and micronutrient malabsorption, weight loss, mucosal injury, bacterial translocation, and worsened intestinal motility. Carbohydrate malabsorption is related to the pathogenesis of diabetic macrovascular complications. The goal of this study is to find out how prevalent SIBO is in type 2 diabetes patients. Methods: "Small intestinal bacterial overgrowth," "small bowel bacterial overgrowth," “SIBO,” "type 2 diabetes mellitus," and "type 2 DM," are the keywords used. We searched Proquest, CINAHL, SCOPUS, ScienceDirect, PubMed/MEDLINE, and manual searches through world diabetes associations such as ADA, EASD, EFSD, IDF, FASEB, and PERKENI using the keywords. We use the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for bias risk assessment, and for data analysis, we use STATA 16. Results: Six articles covered 1072 type 2 diabetes patients in clinics and hospitals. With a minimum score of 7.42% and a maximum value of 53.85%, 95% CI 9.97-38.86, and an I2 of 97.17%, the pooled prevalence was 24.39% SD 15.31. HbA1c levels were higher (p=0.02) in type 2 DM patients with SIBO, and blood insulin levels were lower (p=0.001) in type 2 DM patients with SIBO. Each study was pretty varied, and there was evidence of publication bias. Assessment of findings based on GRADE is moderate. Conclusion: According to this study, SIBO is present in 24.39% of type 2 diabetes patients. SIBO conditions exacerbate the morbidity of patients with type 2 diabetes, as indicated by lower insulin levels and a higher HbA1c. In type 2 diabetes patients, a hydrogen breath test (HBT) is recommended to be performed regularly, especially in those who have had DM for more than 5 years.

Quantitative sequencing clarifies the role of disruptor taxa, oral microbiota, and strict anaerobes in the human small-intestine microbiome

Background Upper gastrointestinal (GI) disorders and abdominal pain afflict between 12 and 30% of the worldwide population and research suggests these conditions are linked to the gut microbiome. Although large-intestine microbiota have been linked to several GI diseases, the microbiota of the human small intestine and its relation to human disease has been understudied. The small intestine is the major site for immune surveillance in the gut, and compared with the large intestine, it has greater than 100 times the surface area and a thinner and more permeable mucus layer. Results Using quantitative sequencing, we evaluated total and taxon-specific absolute microbial loads from 250 duodenal-aspirate samples and 21 paired duodenum-saliva samples from participants in the REIMAGINE study. Log-transformed total microbial loads spanned 5 logs and were normally distributed. Paired saliva-duodenum samples suggested potential transmission of oral microbes to the duodenum, including organisms from the HACEK group. Several taxa, including Klebsiella, Escherichia, Enterococcus, and Clostridium, seemed to displace strict anaerobes common in the duodenum, so we refer to these taxa as disruptors. Disruptor taxa were enriched in samples with high total microbial loads and in individuals with small intestinal bacterial overgrowth (SIBO). Absolute loads of disruptors were associated with more severe GI symptoms, highlighting the value of absolute taxon quantification when studying small-intestine health and function. Conclusion This study provides the largest dataset of the absolute abundance of microbiota from the human duodenum to date. The results reveal a clear relationship between the oral microbiota and the duodenal microbiota and suggest an association between the absolute abundance of disruptor taxa, SIBO, and the prevalence of severe GI symptoms.