The importance of food quality, gut motility, and microbiome in SIBO development and treatment.

The prevalence of small intestinal bacterial overgrowth (SIBO) is rising worldwide, particularly in nations with high rates of urbanization. Irritable bowel syndrome, inflammatory bowel illnesses, and nonspecific dysmotility are strongly linked to SIBO. Moreover, repeated antibiotic therapy promotes microorganisms' overgrowth through the development of antibiotic resistance. The primary cause of excessive fermentation in the small intestine is a malfunctioning gastrointestinal motor complex, which results in the gut's longer retention of food residues. There are anatomical and physiological factors affecting the functioning of the myoelectric motor complex. Except for them, diet conditions the activity of gastrointestinal transit. Indisputably, the Western type of nutrition is unfavorable. Some food components have greater importance in the functioning of the gastrointestinal motor complex than others. Tryptophan, an essential amino acid and precursor of the serotonin hormone, accelerates intestinal transit, and gastric emptying, similarly to fiber and polyphenols. Additionally, the effect of food on the microbiome is important, and diet should prevent bacterial overgrowth and exhibit antimicrobial effects against pathogens. Therefore, knowledge about proper nutrition is essential to prevent the development and recurrence of SIBO. Since the scientific world was unsure whether there was a long-term or potential solution for SIBO until quite recently, research on a number of the topics included in the article should be performed. The article aimed to summarize current knowledge about proper nutrition after SIBO eradication and the prevention of recurrent bacterial overgrowth. Moreover, a connection was found between diet, gut dysmotility, and SIBO.

Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the Stomach.

BACKGROUND & AIMS: Histamine in the stomach traditionally is considered to regulate acid secretion but also has been reported to participate in macrophage differentiation, which plays an important role in tissue homeostasis. Therefore, this study aimed to uncover the precise role of histamine in mediating macrophage differentiation and in maintaining stomach homeostasis. METHODS: Here, we expand on this role using histidine decarboxylase knockout (Hdc-/-) mice with hypertrophic gastropathy. In-depth in vivo studies were performed in Hdc-/- mice, germ-free Hdc-/- mice, and bone-marrow-transplanted Hdc-/- mice. The stomach macrophage populations and function were characterized by flow cytometry. To identify stomach macrophages and find the new macrophage population, we performed single-cell RNA sequencing analysis on Hdc+/+ and Hdc-/- stomach tissues. RESULTS: Single-cell RNA sequencing and flow cytometry of the stomach cells of Hdc-/- mice showed alterations in the ratios of 3 distinct tissue macrophage populations (F4/80+Il1bhigh, F4/80+CD93+, and F4/80-MHC class IIhighCD74high). Tissue macrophages of the stomachs of Hdc-/- mice showed impaired phagocytic activity, increasing the bacterial burden of the stomach and attenuating hypertrophic gastropathy in germ-free Hdc-/- mice. The transplantation of bone marrow cells of Hdc+/+ mice to Hdc-/- mice recovered the normal differentiation of stomach macrophages and relieved the hypertrophic gastropathy of Hdc-/- mice. CONCLUSIONS: This study showed the importance of histamine signaling in tissue macrophage differentiation and maintenance of gastric homeostasis through the suppression of bacterial overgrowth in the stomach.

Gastrointestinal toxicity of systemic oncology immunotherapy.

BACKGROUND: Systemic anti-cancer immunotherapy provides a substantial progress in options of current oncology treatment. Yet, this therapeutic approach is potentially associated with a significant gastrointestinal toxicity. AIM: The purpose of this paper is to provide a comprehensive review on pathogenesis, clinical features, dia gnostics and therapy of these toxicities. Review of current knowledge: Check-point inhibitors brought a major progress in anti-cancer immunotherapy and improved significantly prognosis of several malignancies (e. g. metastatic malignant melanoma, non-small-cell lung cancer, gastric and colorectal cancers in high-risk population associated with presence of pathogenic mutations, renal cell carcinoma, squamous cell carcinoma of the head and neck and urothelial carcinoma). They include monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4; e. g. ipilimumab, tremelimumab), programmed death-1 receptor (PD-1; e. g. pembrolizumab, nivolumab) and its ligand PD-L1 (e. gatezolizumab, avelumab). Chimeric antigen receptor (CAR) T-cell therapy is another new option for haematological malignancies and metastatic colorectal cancer. Major symptoms of gastrointestinal toxicity caused by systemic immunotherapy include diarrhoea (20-50%), entero-colitis (1-10%) and laboratory or clinical signs of hepatopathy (~10%). Anti-cancer immunotherapy can be also complicated by infections (Clostridium difficile, Mycoplasma and/ or cytomegalovirus). There is no data on other possible complications so far. However, it can be assumed that these will also include bile acid malabsorption as well as small intestinal bacterial overgrowth syndrome. Treatment of gastrointestinal complications of immunotherapy should be graded according to their severity. It includes symptomatic medications (e. g. loperamide), systemic glucocorticoids and anti-TNF monoclonal antibodies (alone or together with mycofenolate mofetil or tacrolimus in the most severe cases). CONCLUSIONS: Awareness of possible complications of systemic anti-cancer immunotherapy is crucial for patients safety. It is mandatory to consider immune-related adverse events, complicating infections, bile acids malabsorption and small intestinal bacterial overgrowth syndrome. Prompt proper dia gnostics and immediate vigorous therapy infl uence the outcome of patients signifi cantly. A strictly individualized approach is indispensable.

Severe small intestinal bacterial overgrowth syndrome after jejunal feeding requiring surgical intervention: a case report and review of the literature.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a condition of unknown prevalence characterized by an excessive amount of bacteria in the small bowel, typically resulting in vague gastrointestinal symptoms with bloating being most commonly reported. Here we describe a severe case of SIBO leading to small bowel necrosis requiring surgical intervention. CASE PRESENTATION: A 55-year-old Hispanic female with gastric outlet obstruction secondary to a newly diagnosed gastric adenocarcinoma, receiving neoadjuvant chemotherapy, developed bloody gastrostomy output and rapidly progressing nausea and abdominal distention 3 days after jejunostomy tube placement and initiation of jejunal enteral nutrition. Imaging revealed diffuse pneumatosis and portal venous gas. Surgical exploration confirmed segmental bowel necrosis requiring resection. Histologic findings were consistent with SIBO. CONCLUSIONS: Presentation of severe SIBO in the setting of intestinal stasis secondary to gastric outlet after initiation of enteral feeds is a rare phenomenon. Early recognition and diagnosis of SIBO is critical in minimizing patient morbidity and mortality.

A systematic review and meta-analysis on the prevalence of non-malignant, organic gastrointestinal disorders misdiagnosed as irritable bowel syndrome.

Treatable gastrointestinal disorders in patients with symptoms typical for irritable bowel syndrome (IBS) may be overlooked. The prevalence of five gastrointestinal conditions-bile acid diarrhoea (BAD), carbohydrate malabsorption (CM), microscopic colitis (MC), pancreatic exocrine insufficiency (PEI) and small intestinal bacterial overgrowth (SIBO) was systematically assessed from studies including consecutive patients meeting diagnostic criteria for IBS. 4 databases were searched from 1978 to 2020. Studies were included if they evaluated the prevalence of these conditions in secondary healthcare setting. Estimated pooled rates were calculated and statistical heterogeneity between studies was evaluated using Q and I2 statistics. Seven studies (n = 597) estimated the pooled prevalence for BAD as 41% (95% CI 29-54). 17 studies (n = 5068) estimated that of MC as 3% (95% CI 2-4%). Two studies (n = 478) suggested a rate of 4.6% (range: 1.8-6.1%) for PEI. Using breath testing, 26 studies (n = 6700) and 13 studies (n = 3415) estimated the prevalence of lactose and fructose malabsorption as 54% (95% CI 44-64%) and 43% (95% CI 23-62%); 36 studies (n = 4630) and 22 studies (n = 2149) estimated that of SIBO as 49% (95% CI 40-57%) with lactulose and 19% (95% CI 13-27%) with glucose. Rates of all conditions were significantly higher than in healthy controls. A significant proportion of patients presenting to secondary care with IBS have an organic condition which may account for their symptoms. Failure to exclude such conditions will deny patients effective treatment.

The Effects of One Anastomosis Gastric Bypass Surgery on the Gastrointestinal Tract.

One anastomosis gastric bypass (OAGB) is an emerging bariatric procedure, yet data on its effect on the gastrointestinal tract are lacking. This study sought to evaluate the incidence of small-intestinal bacterial overgrowth (SIBO) following OAGB; explore its effect on nutritional, gastrointestinal, and weight outcomes; and assess post-OABG occurrence of pancreatic exocrine insufficiency (PEI) and altered gut microbiota composition. A prospective pilot cohort study of patients who underwent primary-OAGB surgery is here reported. The pre-surgical and 6-months-post-surgery measurements included anthropometrics, glucose breath-tests, biochemical tests, gastrointestinal symptoms, quality-of-life, dietary intake, and fecal sample collection. Thirty-two patients (50% females, 44.5 ± 12.3 years) participated in this study, and 29 attended the 6-month follow-up visit. The mean excess weight loss at 6 months post-OAGB was 67.8 ± 21.2%. The glucose breath-test was negative in all pre-surgery and positive in 37.0% at 6 months (p = 0.004). Positive glucose breath-test was associated with lower reported dietary intake and folate levels and higher vitamin A deficiency rates (p ≤ 0.036). Fecal elastase-1 test (FE1) was negative for all pre-surgery and positive in 26.1% at 6 months (p = 0.500). Both alpha and beta diversity decreased at 6 months post-surgery compared to pre-surgery (p ≤ 0.026). Relatively high incidences of SIBO and PEI were observed at 6 months post-OAGB, which may explain some gastrointestinal symptoms and nutritional deficiencies.

Effects of Proton Pump Inhibitors on the Small Bowel and Stool Microbiomes.

BACKGROUND: Proton pump inhibitor (PPI) use is extremely common. PPIs have been suggested to affect the gut microbiome, and increase risks of Clostridium difficile infection and small intestinal bacterial overgrowth (SIBO). However, existing data are based on stool analyses and PPIs act on the foregut. AIMS: To compare the duodenal and stool microbiomes in PPI and non-PPI users. METHODS: Consecutive subjects presenting for upper endoscopy without colonoscopy were recruited. Current antibiotic users were excluded. Subjects taking PPI were age- and gender-matched 1:2 to non-PPI controls. Subjects completed medical history questionnaires, and duodenal aspirates were collected using a validated protected catheter. A subset also provided stool samples. Duodenal and stool microbiomes were analyzed by 16S rRNA sequencing. RESULTS: The duodenal microbiome exhibited no phylum-level differences between PPI (N = 59) and non-PPI subjects (N = 118), but demonstrated significantly higher relative abundances of families Campylobacteraceae (3.13-fold, FDR P value < 0.01) and Bifidobacteriaceae (2.9-fold, FDR P value < 0.01), and lower relative abundance of Clostridiaceae (88.24-fold, FDR P value < 0.0001), in PPI subjects. SIBO rates were not significantly different between groups, whether defined by culture (> 103 CFU/ml) or 16S sequencing, nor between subjects taking different PPIs. The stool microbiome exhibited significantly higher abundance of family Streptococcaceae (2.14-fold, P = 0.003), and lower Clostridiaceae (2.60-fold, FDR P value = 8.61E-13), in PPI (N = 22) versus non-PPI (N = 47) subjects. CONCLUSIONS: These findings suggest that PPI use is not associated with higher rates of SIBO. Relative abundance of Clostridiaceae was reduced in both the duodenal and stool microbiomes, and Streptococcaceae was increased in stool. The clinical implications of these findings are unknown.

Diagnosing Small Intestinal Bacterial Overgrowth: A Comparison of Lactulose Breath Tests to Small Bowel Aspirates.

BACKGROUND: Duodenal aspiration (DA) and lactulose breath tests (LBT) are commonly performed to diagnose small intestinal bacterial overgrowth (SIBO). There are no data directly comparing these tests. AIMS: To investigate the agreement between DA and LBT for the diagnosis of SIBO. METHODS: A retrospective cohort study of adult patients who underwent a LBT and a DA at a tertiary care center over 9 years was assembled. LBT was considered positive if the hydrogen baseline or peak change measurement was ≥ 20 ppm, and/or if the methane baseline or peak change was ≥ 10 ppm. DA was considered positive if > 100,000 cfu/mL of gram-negative flora was identified on culture, and contaminated if > 100,000 cfu/mL of gram-positive flora was identified. RESULTS: A total of 106 patients were evaluated; 81 (76.4%) were female; the mean age was 53.4 ± 15.9 years. 21 patients (19.8%) had evidence of contamination on DA. 14 (16.5%) patients had a positive DA result. Patients with diabetes mellitus and those with PPI use were more likely to have a positive DA (94.4% vs. 71.4%, p = 0.007; 62% vs. 28.6%, p = 0.021, respectively). 33 (31.1%) patients had a positive LBT. Patients with a history of small bowel resection were more likely to have a positive LBT (12.1% vs. 1.4%, p = 0.016). DA and LBT results agreed in 54 patients (63.5%; kappa = - 0.02), indicating poor agreement. CONCLUSIONS: The agreement between LBT and DA in evaluation for SIBO was poor. LBT may be favorable to DA, as LBT is safer, cheaper, and less likely to yield a contaminant result.

The overlap between irritable bowel syndrome and organic gastrointestinal diseases.

Irritable bowel syndrome (IBS) is a common functional bowel disorder characterised by symptoms of recurrent abdominal pain associated with a change in bowel habit. This condition is one of the most frequent reasons to seek a gastroenterology consultation in primary and secondary care. The diagnosis of IBS is made by identifying characteristic symptoms, as defined by the Rome criteria, and excluding organic gastrointestinal diseases that might otherwise explain these symptoms. Organic conditions that can be mistaken for IBS include coeliac disease, inflammatory bowel disease (IBD), colorectal cancer, and, in those with diarrhoea-predominant symptoms, chronic gastrointestinal infections, microscopic colitis, and primary bile acid diarrhoea. The concept of small intestinal bacterial overgrowth being associated with IBS is shrouded with controversy and uncertainty, mainly because of invalid tests due to poor sensitivity and specificity, potentially leading to incorrect assumptions. There is insufficient evidence to link IBS-type symptoms with exocrine pancreatic insufficiency or with symptomatic uncomplicated diverticular disease, since both are hampered by conflicting data. Finally, there is growing appreciation that IBS can present in patients with known but stable organic gastrointestinal diseases, such as quiescent IBD or coeliac disease. Recognising functional gut symptoms in these individuals is paramount so that potentially harmful escalations in immunosuppressive therapy can be avoided and attention can be focused on addressing disorders of gut-brain interaction. This Review endeavours to aid clinicians who practise adult gastroenterology in recognising the potential overlap between IBS and organic gastrointestinal diseases and highlights areas in need of further research and clarity.

Acute gastric injury after ingestion of substrate with hyperosmolar glucose and benzoate inversely related with small intestinal bacterial overgrowth.

BACKGROUND/AIMS: The occurrence of gastrointestinal symptoms and the presence of small intestinal bacterial overgrowth (SIBO) could be determined after ingestion of substrate with highly concentrated glucose for glucose breath test (GBT), after which endoscopic images for acute gastric injury have not been clarified. The aims of this study were to investigate the prevalence and relationship of acute gastric injury with SIBO after GBT. MATERIALS AND METHODS: A cohort of 235 patients with functional gastrointestinal symptoms undergoing breath test with 50 g glucose solution, immediately followed by upper endoscopy were surveyed. The acute gastric injury in endoscopic images and the GBT for hydrogen (H2) or methane (CH4) were assessed. RESULTS: The prevalence of acute gastric injury was 28.1% (66/235) after GBT. There were significant differences in GBT positivity (+) with and without gastric injury (25.8% vs 40.8%, p=0.03). In subtypes, GBT (H2) + was significantly lower in group with gastric injury than in the group without. No differences were seen in GBT (CH4) + between two groups. On multivariate analysis, the subtype of GBT (H2) + (Odds ratio (OR)=0.42; 95% Confidence interval (CI)=0.20-0.90; p=0.03) inversely and female (OR=2.11; 95% CI=1.11-4.00; p=0.02) were significantly related with gastric injury. Whereas gastric injury was the only independent related factor for GBT + inversely (OR=0.51; 95% CI=0.27-0.97; p=0.04). CONCLUSION: Highly concentrated glucose might provoke acute gastric injury, which could predict the absence of SIBO.

Oxidative stress and inflammatory markers in type 2 diabetic patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is most demanding public health problem of 21st century. Uncontrolled diabetes may cause complications affecting any part of gut from mouth to rectum presenting as vomiting, nausea, bloating, abdominal pain, constipation and diarrhoea. The aim of this study was to compare levels of oxidative stress and inflammatory markers in small intestinal bacterial overgrowth (SIBO)-positive and negative diabetic patients. SUBJECTS AND METHODS: An observational analytical study was conducted on 300 T2DM (>5 years' duration) attending Diabetic Clinic. A total of 200 age- and sex-matched healthy individuals were enrolled as controls. Noninvasive glucose hydrogen breath test was used to diagnose SIBO. A total of 5 mL blood was taken. Plasma was used for measurement of inflammatory cytokines (TNF-α, IL-6 and IL-10) by ELISA. Hemolysate was used for measurement of lipid peroxidation, reduced GSH, superoxide dismutase and catalase. RESULTS: It was observed that constipation was present in 59.6% T2DM patients. SIBO was observed significantly higher (P < .0001) in T2DM patients than controls. Inflammatory and oxidative stress markers were significantly (P < .001) higher in diabetic and SIBO-positive patients than controls and SIBO negative. Reduced GSH was significantly (P < .05) lower whereas superoxide dismutase (SOD) and catalase antioxidant enzymes were significantly (<.05) higher in diabetic and SIBO-positive patients than controls and SIBO-negative patients. CONCLUSION: From this study, it could be concluded that SIBO in T2DM patients can cause oxidative stress and inflammation. Therefore, SIBO should be taken care to prevent further damage to intestine.

Vague abdominal pain after Roux-en-Y gastric bypass: not always an internal herniation: case report and literature review.

Background: Roux-en-Y gastric bypass is a frequently carried out bariatric procedure, proven to be effective in the management of obesity and its accompanying health issues. Following its popularity, admission to the emergency department for abdominal pain is often seen with known early and late onset causes. We present a case of a young woman with vague abdominal pain years after her gastric bypass, who eventually underwent a resection of a 'candy cane' like biliopancreatic blind loop.Methods: A healthy 23-year-old woman has been suffering of vague abdominal complaints after a gastric bypass procedure 4 years earlier. Postprandial pain, diarrhoea and abdominal distension were present at a daily to weekly basis. Several investigations and management options were administered by surgeons, gastroenterologists as well as endocrinologists. On a performed explorative laparoscopy, a large blind loop at the entero-enteric anastomosis was seen and resected.Results: At current follow-up of 15 months the resection of the candy cane like blind end of the biliopancreatic loop resulted in a complete withdrawal of our patient's symptoms. A tentative diagnosis of bacterial overgrowth in the blind loop was made.Conclusions: Abdominal pain after gastric bypass is a frequent cause of admission to the emergency department. Besides the more serious complications, internal hernia is often withheld as possible diagnosis in the differential diagnosis of late onset, postprandial epigastric pain. This case report highlights another possibility. At initial surgery, a candy cane shaped blind loop should be avoided both at the gastro-jejunal as well as the entero-enteric anastomosis.

Blind Pouch Syndrome-associated Anastomotic Ulcer Diagnosed with Capsule and Double-balloon Endoscopy.

Blind pouch syndrome-associated anastomotic ulcer is rare, and its endoscopic features remain poorly described. A 79-year-old man was referred to our hospital for melena. Capsule endoscopy revealed multiple ulcers in the small intestine. Double-balloon endoscopy (DBE) and a gastrografin examination through DBE revealed a potential anastomotic ulcer, a blind pouch, and a side-to-side anastomosis in the middle of the small intestine. Laparoscopic partial resection of the small intestine with anastomosis was performed on the suspected blind pouch syndrome-associated anastomotic ulcer. To our knowledge, this is the first report describing the endoscopic features of a blind pouch syndrome-associated anastomotic ulcer.

Systematic review with meta-analysis: the prevalence of small intestinal bacterial overgrowth in inflammatory bowel disease.

BACKGROUND: Current data on small intestinal bacterial overgrowth (SIBO) in patients with inflammatory bowel diseases (IBD) are controversial. AIM: To conduct a systematic review and meta-analysis to determine the prevalence of SIBO in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Electronic databases were searched up to May 2018 for studies reporting prevalence of SIBO in IBD patients. The prevalence rate of SIBO among IBD patients and the odds ratio (OR) and 95% CI of SIBO in IBD patients compared with controls were calculated. RESULTS: The final dataset included 11 studies (1175 adult patients with IBD and 407 controls), all utilising breath test for diagnosis of SIBO. The proportion of SIBO in IBD patients was 22.3% (95% CI 19.92-24.68). The OR for SIBO in IBD patients was 9.51 (95% CI 3.39-26.68) compared to non-IBD controls, and high in both CD (OR = 10.86; 95% CI 2.76-42.69) and UC (OR = 7.96; 95% CI 1.66-38.35). In patients with CD, subgroup analysis showed the presence of fibrostenosing disease (OR = 7.47; 95% CI 2.51-22.20) and prior bowel surgery (OR = 2.38; 95% CI 1.65-3.44), especially resection of the ileocecal valve, increased the odds of SIBO. Individual studies suggest that combined small and large bowel disease but not disease activity may be associated with SIBO. CONCLUSIONS: Overall, there is a substantial increase in the prevalence of SIBO in IBD patients compared to controls. Prior surgery and the presence of fibrostenosing disease are risk factors for SIBO in IBD.

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.

Association between small intestinal bacterial overgrowth and toll-like receptor 4 in patients with pancreatic carcinoma and cholangiocarcinoma.

BACKGROUND/AIMS: Multiple factors have been linked to pathogenesis of pancreatic cancer and cholangiocarcinoma. Until now, few studies have investigated the role of small intestinal bacterial overgrowth (SIBO) and toll-like receptor 4 (TLR-4) signaling in these diseases. This study aimed to examine the relationship between the prevalence of SIBO and the TLR-4 expression in patients with pancreatic carcinoma and cholangiocarcinoma. MATERIALS AND METHODS: A total of 90 human subjects suffering from pancreatic carcinoma (n=30), cholangiocarcinoma (n=30), and healthy controls (n=30) were enrolled in the study. A glucose hydrogen breath test (GHBT) was used to evaluate SIBO. The TLR4 protein expression was measured by immunohistochemistry (IHC). RESULTS: The positive rate of SIBO was 63.3% in the pancreatic cancer group and 46.7% in patients with cholangiocarcinoma, which was significantly greater than 13.3% in the healthy control group (p<0.05). An IHC analysis revealed that the TLR-4 protein expression in the SIBO-positive pancreatic carcinoma patients was significantly higher than that in the SIBO-negative patients (p<0.05), and the same result was in the cholangiocarcinoma subjects. In addition, a correlation analysis identified the positive relationship between the prevalence of SIBO and the TLR-4 protein expression in pancreatic carcinoma (r=0.489), and the same result was in the cholangiocarcinoma subjects. CONCLUSION: Our findings indicate a high prevalence of SIBO in pancreatic carcinoma and cholangiocarcinoma, and SIBO displays a positive correlation with the TLR-4 expression, suggesting that SIBO could be a risk factor for the pathogenesis of pancreatic carcinoma and cholangiocarcinoma, in which the TLR4 signaling may be involved.

Fecal microbiota analysis of children with small intestinal bacterial overgrowth among residents of an urban slum in Brazil / Análise da microbiota fecal de crianças com sobrecrescimento bacteriano no intestino delgado de moradoras de uma favela urbana no Brasil

Abstract Objective: To analyze the fecal microbiota composition of children living in an urban slum in Brazil, with or without small intestinal bacterial overgrowth, and to investigate the occurrence of stunting and anemia. Methods: A total of 100 children were studied, aged 5-11 years, from the municipality of Osasco, São Paulo. Small intestinal bacterial overgrowth was screened through hydrogen and methane breath test with lactulose. Weight and height were measured, and the height-for-age and body mass-for-age anthropometric indexes were calculated. The occurrence of anemia was investigated by capillary hemoglobin. Analysis of bacterial phylum, genus, and species was performed by real-time polymerase chain reaction in fecal samples. Results: Small intestinal bacterial overgrowth was identified in 61.0% of the children. A lower mean of height-for-age Z-score ([−0.48 ± 0.90] vs. [−0.11 ± 0.97]; p = 0.027), as well as capillary hemoglobin ([12.61 ± 1.03 g/dL] vs. [13.44 ± 1.19 g/dL]; p < 0.001) was demonstrated in children with SIBO when compared with children without small intestinal bacterial overgrowth. Children with small intestinal bacterial overgrowth presented a higher frequency of Salmonella spp., when compared to those without small intestinal bacterial overgrowth (37.7% vs. 10.3%; p = 0.002). Higher counts of total Eubacteria (p = 0.014) and Firmicutes (p = 0.038) were observed in children without small intestinal bacterial overgrowth; however, a higher count of Salmonella (p = 0.002) was found in children with small intestinal bacterial overgrowth. Conclusion: Children who lived in a slum and were diagnosed with small intestinal bacterial overgrowth showed lower H/A Z-scores and hemoglobin levels. Furthermore, differences were observed in the fecal microbiota of children with small intestinal bacterial overgrowth, when compared to those without it; specifically, a higher frequency and count of Salmonella, and lower counts of Firmicutes and total Eubacteria.

Resumo Objetivo: Analisar a composição da microbiota fecal de crianças moradoras de uma favela urbana no Brasil, com e sem sobrecrescimento bacteriano no intestino delgado, e investigar a ocorrência de déficit de crescimento e anemia. Métodos: Foram estudadas 100 crianças, com idade entre 5 e 11 anos, na cidade de Osasco, São Paulo. Sobrecrescimento bacteriano no intestino delgado foi pesquisado por teste respiratório do hidrogênio e metano no ar expirado com lactulose. Foram mensurados peso, estatura e calculados os índices antropométricos estatura para idade e índice de massa corporal para idade. Foi investigada a ocorrência de anemia, pela avaliação da hemoglobina capilar. A análise dos filos, gêneros e espécies bacterianas em amostras de fezes foi realizada por polymerase chain reaction em tempo real. Resultados: Sobrecrescimento bacteriano no intestino delgado foi diagnosticado em 61,0% das crianças avaliadas. Foi verificada menor média do escore Z do índice estatura para idade (-0,48±0,90 vs.-0,11±0,97 DP) e de hemoglobina capilar (12,61±1,03 vs. 13,44±1,19 g/dL) no grupo de crianças com sobrecrescimento bacteriano no intestino delgado, quando comparadas àquelas sem sobrecrescimento bacteriano no intestino delgado (p < 0,05). Nas crianças com sobrecrescimento bacteriano no intestino delgado foi observada maior frequência de Salmonella spp., quando comparadas àquelas sem sobrecrescimento bacteriano no intestino delgado (37,7% vs. 10,3%; p = 0,002). Maior contagem de Eubactérias totais (p = 0,014) e Firmicutes (p = 0,038) foi observada nas crianças sem sobrecrescimento bacteriano no intestino delgado, enquanto que as crianças com sobrecrescimento bacteriano no intestino delgado apresentaram maior contagem de Salmonella (p = 0,002). Conclusão: Nas crianças com diagnóstico de sobrecrescimento bacteriano no intestino delgado verificaram-se menores valores de estatura para idade e de hemoglobina. Foram constatadas diferenças na microbiota fecal das crianças com sobrecrescimento bacteriano no intestino delgado, especificamente, maior frequência e contagem de Salmonella spp. e menores contagens de Firmicutes e Eubactérias totais.

Blind Pouch Syndrome in Gastrojejunostomy.

Blind pouch syndrome is a rare complication of a gastrojejunostomy. Its presentation may differ from blind pouches at other locations in that a small pouch can cause significant symptoms of mechanical obstruction before it is large enough to develop bacterial overgrowth. The effect of a small pouch may be overlooked at endoscopy and a high clinical index of suspicion is required. Here we present a case report of Gastrojejunostomy Blind Pouch Syndrome to highlight this clinically distinct entity.

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.

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.