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.

[Assessment of the state of the small intestine microbiota in children on a long-term dairy-free diet].

An overview of recent outcomes of studies indicates an imbalance in the diet of children. Quantitative and qualitative malnutrition of children is the basis of a number of childhood diseases. The aim of the research was to study the prevalence of small intestine bacterial overgrowth syndrome (SIBO) in children on a long-term dairy-free diet. Material and methods. 40 children aged 7-11 years following a long-term dairy-free diet (average 3 years and 5 months, from 0.5 to 6.3 years) were examined (main group). 30 children who did not follow restrictive diets were consisted control group. In all children, SIBO was determined using a hydrogen breath test with a load of lactulose using a digital analyzer of exhaled hydrogen. Results. The proportion of children with intolerance to dairy products was 32.5%: 10.0% with allergy to cow's milk proteins, and 22.5% with lactose intolerance. 27.5% children followed a dairy-free diet according to an unjustified prescription by physician. 30.0% of children did not consume dairy products because of their unwillingness. 10.0% of children did not consume dairy products due to the unwillingness of their parents. An imbalance in the microbiota of the small intestine during the hydrogen breath test with lactulose loading was detected in 55.0% of children following a long-term dairy-free diet. 22.5% of children complained of recurrent abdominal pain, diarrhea was determined in 10.0%, constipation - in 7.5%, nausea - in 10.0%. In the control group, the SIBO during the hydrogen breath test with lactulose loading was found in 20.0%. Periodic abdominal pain was determined in 10.0%, nausea - in 6.7%, diarrhea - in 10.0%, constipation - in 3.3% children. Conclusion. Thus, among children of primary school age who follow a long-term dairyfree diet, SIBO is significantly more often recorded relative to children who are on a traditional type of diet.

[The importance of the bacterial overgrowth syndrome in the development of disorders metabolic functions of the liver in non-alcoholic fatty liver disease].

AIM: To study the basic metabolic functions of the liver in patients with non-alcoholic fatty liver disease and to assess the relationship of these disorders with the bacterial overgrowth syndrome. MATERIALS AND METHODS: 50 patients with non-alcoholic fatty liver disease at the stage of steatosis were examined. In the verification of the diagnosis, hepatobiliary system ultrasound and FibroMax test data were used. A study was conducted of indicators of lipid, carbohydrate, protein, pigment, mineral metabolism and the exchange of enzymes in the blood. The bacterial overgrowth syndrome was studied by the results of a hydrogen breath test with lactulose using a LactofаH2 analyzer. RESULTS: Patients with non-alcoholic fatty liver disease showed a significant increase in total cholesterol (median 5.9 mmol/l vs 5.0 mmol/l, p=0.000013), triglycerides (1.35 g/l vs 0.9 g/l, p=0.014), glucose (5.65 mmol/l against 5.1 mmol/l, p=0.000001) of blood serum compared with the control group. An increase in total protein and a tendency to decrease in albumin, an increase in serum sodium and calcium were detected. In patients with non-alcoholic fatty liver disease there is a significant increase in the markers of cytolysis and cholestasis compared with the control group. The bacterial overgrowth syndrome was detected in 72% of cases, with ileocecal valve function impaired in 50% of patients, gastrointestinal motility slowed down, or colon dysbiosis occurred. A correlation analysis revealed positive relationships between the bacterial overgrowth syndrome on the one hand and glucose (r=0.83, p0.05), total protein (r=0.35, p0.05), calcium (r=0.5, p0.05) on the other hand; negative relationship between the bacterial overgrowth syndrome and albumin (r=-0.8, p0.05). In this case, a positive relationship between the bacterial overgrowth syndrome and the increase in glycemia after glucose loading, that is, absorption in the small intestine, was revealed. CONCLUSION: The established violations of the metabolic functions of the liver with non-alcoholic fatty liver disease are closely related to the bacterial overgrowth syndrome.

[Chronic intestinal pseudoobstruction: difficulties in diagnosis and treatment. Case report].

The article presents a clinical case of a 23-year-old patient with an extremely severe congenital form of chronic intestinal pseudoobstruction coupled with a neuromyopathy,colon malrotation, malabsorption, bacterial overgrowth syndrome, cholelithiasis and gastrostasis, which excluded bowel transplantation. Long-term treatment in the intensive care unit with combined, mainly parenteral nutrition for 6 months, using antibiotics, prokinetics, intestinal decompression allowed to achieve partial stabilization of the patients condition and transfer to home treatment with the continuation of adequate complex therapy.

High Prevalence of Small Intestinal Bacterial Overgrowth among Functional Dyspepsia Patients.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO), characterized by either increased numbers or presence of colonic type bacteria in the small bowel has been previously described in functional dyspepsia (FD), based on breath testing. In this study, we aim to examine the prevalence of SIBO among FD patients using small bowel aspirate culture. METHODS: We prospectively enrolled outpatients fulfilling Rome IV criteria for FD. Severity of symptoms was graded using the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) questionnaire. Patients underwent upper gastrointestinal endoscopy and duodenal fluid was aspirated in sterile traps. SIBO was defined as ≥103 colony forming units/mL of duodenal aspirate and/or presence of colonic type bacteria. Patients undergoing gastroscopy due to gastroesophageal reflux symptoms - control group (CG) - and patients with irritable bowel syndrome (IBS) fulfilling Rome IV criteria were also recruited. RESULTS: We enrolled 227 FD subjects, 30 CG, and 90 IBS patients. Among FD patients, 144 (63.4%), 64 (28.2%), and 19 (8.4%) had postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and overlapping PDS-EPS syndrome, respectively. SIBO prevalence was 20.8%, 12.5%, and 31.6% among PDS, EPS, and overlapping PDS-EPS FD subtypes, respectively. Overall, SIBO prevalence was significantly higher in FD (44/227 [19.4%]) compared to CG (1/30 [3.3%]) (p = 0.037) and similar to IBS (44/227 [19.4%] vs. 15/90 [16.7%], p = 0.63) subjects. SIBO presence was associated neither with total nor with any subscale score of the PAGI-SYM questionnaire. CONCLUSION: In a cohort of Greek FD patients, SIBO prevalence was similar to that of IBS subjects and higher compared to that of controls.

[Innovative approaches to study food patterns in functional gastrointestinal disorders].

Dietary patterns play an important role in pathogenesis and treatment of functional gastrointestinal disorders. The aim - to perform literature review on modern approaches to perform nutritional assessment in functional gastrointestinal disorders and to summarize available data on its role in assessment of clinical manifestations and treatment of these conditions. Material and methods. A search was performed in the PubMed and Google scholar system with the use of keywords: "nutritional pattern", "dietary pattern", in combination with "methodology", "assessment", "functional gastrointestinal disorders", "GERD", "gastroesophageal reflux disease", "irritable bowel syndrome", "IBS", "small intestinal bacterial overgrowth", "treatment". The inclusion criteria were type of the paper (original study); they had to contain data on nutrition of patients with functional gastrointestinal disorders; main digital data should be present (sample size, design, diagnostic criteria, patients' eligibility criteria, control group characteristics, as well as results in quantitative characteristics and measure of dispersion of values). Results and discussion. Based on the data of 81 selected papers structured literature review was performed. We summarized the data on the methods of food patterns assessment, the knowledge on the food patterns in patients with functional gastrointestinal disorders (including gastroesophageal reflux disease and irritable bowel syndrome), clinical utility of the nutritional assessment with the use of food patterns. Assessment of nutritional patterns in patients with functional gastrointestinal disorders provides additional evidence that allows to correct the diet of these patients more effectively, to achieve better results of treatment in shorter time, to reduce the number of medications, and may be of use for the development of new functional foods.

[Association of thermal food processing methods and small intestinal bacterial overgrowth syndrome].

Small intestinal bacterial overgrowth (SIBO) is a widespread disease which antibiotic therapy is not effective enough and the relapse rate is high. Microbiota is dependent on dietary pattern of the patient and specific nutrients, therefore the diversity of dietary patterns may be one of the major factor promoting SIBO or its relapses after treatment. The aim: to compare the patterns of thermal food processing methods in patients with and without SIBO. Material and methods. We performed retrospective single center database search to identify unique depersonalized records of patients with SIBO and the data of lactulose breath test and nutritional assessment with the use of 24-hours dietary recall. Inclusion criteria were complete data on patient's demography, adequate data of nutritional assessment and the lactulose breath test, absence of previous history of SIBO treatment in a special form of the database. In accordance with the results of lactulose breath test, patients were assigned into groups with the presence of SIBO with excess production of hydrogen (H2), methane (CH4), both gases (CH4-H2) or without SIBO (control group). According to the data of 24 h dietary recall, we divided all dishes and products consumed by a patient to 6 categories (Cat) depending on thermal food processing method: those that were not processed (raw) (Cat-r), boiled (Cat-bl), fried (Cat-f), stewed (Cat-s), baked in the oven (Cat-bk) or grilled (Cat-g). To analyze the structure of thermal food processing, we divided the weight of all products or dishes that underwent specific method of processing to the total weight of the food eaten. We did not take into the account the weight of thermally stable components like water and salt. The pattern of thermal food processing within each patients group was obtained as a quotient of the total percentage (by weight) of the food processed with the certain method by the number of patients in the group. Results and discussion. The data of 1108 patients were available for the final analysis: 602 patients in the SIBO-H2 group, 140 in the SIBO-CH4 group, 248 in the SIBO-CH4-H2 group, and 118 patients in the control group. The distribution of thermal food processing categories was in patients with SIBO-H2 as follows: Cat-r - 45.8±17.3%, Cat-bl - 31.9±15.7%, Cat-s - 3.5±7.7%, Cat-f - 6.3±10.4%, Cat-bk - 12.2±10.2%, Cat-g - 0.3±3.3%); in patients with SIBO-CH4: Cat-r - 47.9±17.4%, Cat-bl - 29.6±15.6%, Cat-s - 4.4±7.6%, Cat-f - 5.8±9.8%, Cat-bk - 12.3±10.4%, Cat-g - 0,2±2,7%; in patients with SIBO-CH4-H2: Cat-r - 45.6±16.3%, Catbl - 31.5±16.2%, Cat-s - 4.0±8.0%, Cat-f - 5.1±9.3%, Cat-bk - 13.4±10.8%, Cat-g - 0.4±2.3%. Similar results were obtained in the control group (Cat-r - 44.7±17.0%, Cat-bl - 32.6±16.5%, Cat-s - 2.7±6.0%, Cat-f - 5.5±8.0%, Cat-bk - 14.2±10.6%, Cat-g - 0.3±2.0%). There were no significant differences between the SIBO and control groups by mean percentage of raw, boiled, stewed, fried, baked and grilled food intake. Conclusion. We found no association between thermal food processing patterns and SIBO. It seems that thermal food processing patterns has no influence on SIBO and its variants.

[Evaluation of the effectiveness of differentiated therapy of non-alcoholic fatty liver disease].

AIM: Study of the effectiveness of differentiated therapy of non-alcoholic fatty liver disease taking into account the clinical and pathogenetic features of its course. MATERIALS AND METHODS: 168 patients with non-alcoholic fatty liver disease were examined, 108 of them were women and 60 men aged from 30 to 70 years. For treatment, depending on the characteristics of the course of the disease, 3 groups of patients were formed. The first group included patients (n=47) with liver steatosis with a high content of lipids in the blood and an increased atherogenic coefficient; they received therapy with ursodeoxycholic acid with atorvastatin. The second group consisted of patients (n=65) with liver steatosis with an increased level of glycemia, insulin and insulin resistance, they were prescribed therapy with ursodeoxycholic acid and metformin. Patients of the third group (n=56) with steatohepatitis with concomitant bacterial overgrowth received еssentiale forte H therapy with rioflora immuno. Clinical data, blood biochemical parameters, insulin and HOMA-IR levels, intestinal microbiota status, as well as regression of liver steatosis and steatohepatitis were evaluated in the dynamics of treatment. RESULTS: In the dynamics of treatment, there was a decrease in the clinical manifestations of the disease in all observed groups of patients, an improvement in lipid metabolism and indicators of the functional state of the liver, a decrease in excessive bacterial growth. On the basis of ultrasound, elastography and fibrotest, the reverse development of liver steatosis was found in 20% and steatohepatitis in 66.6% of patients. CONCLUSION: The data obtained indicate the feasibility of differentiated treatment of patients with non-alcoholic fatty liver disease depending on thecharacteristics of its course and stage.

[Prevalence of small bowel bacterial overgrowth in patients with functional dyspepsia: a meta-analysis].

AIM: Systematization of data on the frequency of detection of the syndrome of bacterial overgrowth in the small intestine (SIBO) in patients with functional dyspepsia (FD). MATERIALS AND METHODS: MEDLINE/PubMed, EMBASE, Cochrane, Google Scholar, the Russian Science Citation Index (RSCI) through July 2020 were searched to identify studies evaluating the prevalence of SIBO in FD. In addition, a search for relevant abstracts was carried out in the electronic databases of the United European Gastroenterology Week (UEG), American College of Gastroenterology (ACG), International Conference on Nutrition and Food (ICNF). For the final analysis, publications were selected that used validated tests for the assessment of SIBO (hydrogen breath test using glucose or lactulose) with detailed descriptive statistics, allowing the resulting data to be included in the meta-analysis. RESULTS: The final analysis included 7 studies with 1248 patients with FD. Overall pooled prevalence of SIBO in patients with FD was 34.73% (95% CI 24.80745.383). There was significant heterogeneity between the results (p0.0001; I2=89.91%). When excluded from the meta-analysis of a study in which the incidence of SIBO was studied in patients with refractory FD, the pooled prevalence was 38.98% (95% CI 28.96449.490). CONCLUSION: This meta-analysis has demonstrated that SIBO is often associated with FD and is observed in about every third patient with this functional gastrointestinal tract disease.

Impact of the Synbiotics and Urate-Lowering Therapy on Gut Microbiota and Cytokine Profile in Patients with Chronic Gouty Arthritis.

The main goal of our study is the impact evaluation of complex urate-lowering therapy with the synbiotic addition on fecal microbiota and cytokine profile in patients with primary gout. During our study, 130 men (mean age 55.5 ± 9.4 years) with gout (duration 7.7 ± 7.1 years) were examined. All patients were divided into two treatment groups. The main group (n = 68) was taking allopurinol at 300 mg per day dose and additionally a synbiotic. The comparison group (n = 62) received allopurinol monotherapy without synbiotic intake. The therapy duration was 3 months. Evaluation of therapy efficiency was marked by blood uric acid changes, cytokine levels, CRP and fecal microbiota condition. After treatment, stabilization of the gut microbiota parameters was observed, which was leading to normalization uricemia levels (40.3% vs. 21%, p <0.01) in the main group patients. Addition of synbiotic to allopurinol leads to a blood uric acid lowering (18.7% vs. 13.3%, p <0.01), CRP reduction (75% vs. 26.3%, p <0.01) as well as decrease of cytokines level: IL-1ß, IL-6, IL-8, IL-10 and TNFα (all p <0.001). After a 3-month gout treatment, a group of patients who received complex therapy with synbiotic inclusion showed signs of disease remission characterized by inflammation activity reducing, fecal microbiota condition normalization and a more pronounced decrease in laboratory markers comparing to control group.

Effectiveness of Saccharomyces boulardii and Metronidazole for Small Intestinal Bacterial Overgrowth in Systemic Sclerosis.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) affects up to 60% of patients with systemic sclerosis (SSc), and it improves with antibiotics. The addition of probiotics could lead to better results. AIMS: To evaluate the efficacy and safety of Saccharomyces boulardii (SB) versus metronidazole (M) versus M + SB for 2 months, to reduce gastrointestinal symptoms and SIBO assessed with hydrogen breath test in SSc. METHODS: An open pilot clinical trial performed in forty patients with SIBO and SSc (ACR-EULAR 2013) who signed informed consent. Three groups were assigned: M, SB, and M + SB, for 2 months. Hydrogen was measured in parts per million with a hydrogen breath test to evaluate SIBO. The National Institutes of Health Patient-Reported Outcomes Measurement Information System (NIH-PROMIS) questionnaire was applied to quantify gastrointestinal symptoms with a raw score of eight symptoms. This study is registered in ClinicalTrials.gov with the following ID: NCT03692299. RESULTS: Baseline characteristics were similar between groups. The average age was 53.2 ± 9.3 years, and the evolution of SSc was 13.5 (1-34) years. After 2 months of treatment, SIBO was eradicated in 55% of the M + SB group: 33% of SB, and 25% of M. The SB and M + SB groups had decreased diarrhea, abdominal pain, and gas/bloating/flatulence, but M remained unchanged. Reductions in expired hydrogen at 45 to 60 min were as follows: M + SB 48% and 44%, M 18% and 20%, and SB 53% and 60% at the first and second months, respectively (p < 0.01). Adverse effects were epigastric burning and constipation in M (53%) and M + SB (36%), and flatulence/diarrhea in SB (22%). CONCLUSIONS: Metronidazole treatment is partially effective in SIBO, but S. boulardii in monotherapy or in combination improves the gastrointestinal outcomes in SSc.

Microbiota, Microbial Metabolites, and Barrier Function in A Patient with Anorexia Nervosa after Fecal Microbiota Transplantation.

The change in the gut microbiome and microbial metabolites in a patient suffering from severe and enduring anorexia nervosa (AN) and diagnosed with small intestinal bacterial overgrowth syndrome (SIBO) was investigated. Microbial gut dysbiosis is associated with both AN and SIBO, and therefore gut microbiome changes by serial fecal microbiota transplantation (FMT) is a possible therapeutic modality. This study assessed the effects of FMT on gut barrier function, microbiota composition, and the levels of bacterial metabolic products. The patient treatment with FMT led to the improvement of gut barrier function, which was altered prior to FMT. Very low bacterial alpha diversity, a lack of beneficial bacteria, together with a great abundance of fungal species were observed in the patient stool sample before FMT. After FMT, both bacterial species richness and gut microbiome evenness increased in the patient, while the fungal alpha diversity decreased. The total short-chain fatty acids (SCFAs) levels (molecules presenting an important source of energy for epithelial gut cells) gradually increased after FMT. Contrarily, one of the most abundant intestinal neurotransmitters, serotonin, tended to decrease throughout the observation period. Overall, gut microbial dysbiosis improvement after FMT was considered. However, there were no signs of patient clinical improvement. The need for an in-depth analysis of the donor´s stool and correct selection pre-FMT is evident.

[Non - alcoholic fatty liver disease and enteral insufficiency: comorbidity of their development].

The article reflects current literature data on the epidemiology and risk factors of non - alcoholic fatty liver disease. An important aspect is the description of the modern views of combined lesions of the hepatobiliary tract and small intestine. Disorders of the intestinal microbiota play a special role in the development of non - alcoholic fatty liver disease. The value of enterohepatic circulation of bile acids in the development of intestinal and liver diseases was shown. It seems relevant to further study the comorbidity of the development of non - alcoholic fatty liver disease and enteropathy for the development of pathogenetically substantiated therapy.

[Association of food patterns with different forms of small intestinal bacterial overgroth syndrome and treatment efficacy].

AIM: To assess food patterns in patients with different types of SIBO and their impact onto the course and treatment outcomes. MATERIALS AND METHODS: The data of 988 patients who signed informed consent surved as a source data. On the basis of lactulose breath test (LBT; GastroCH4eck, Bedfont, UK), the patients were selected into one of the studied groups: SIBO-H2, SIBO-CH4, SIBO-CH4-H2 and control. Twenty - four hours food recall test was used to analyze nutritional habits. In patients with SIBO-H2, standard treatment with Tilichinol 100 mg/Tilbrochinol 200 mg (Intetrix, Beaufour-Ipsen International, France) 2 caps BID for 10 days) was provided. Efficacy of treatment was assessed on the bass of the result of LBT 2 month after treatment completion. Mann-Whitney T test (Statistica 10, StatSoft, USA) was used to compare nutritional patterns in patients with or without SIBO, in different types of SIBO and in accordance to the results of treatment. RESULTS AND DISCUSSION: Nine hundred eighty eight patients were enrolled. On the basis of hydrogene breath test they were divided into 4 main groups: SIBO of hydrogen - producing flora (SIBO-H2, n=526), methane - producing flora (SIBO-CH4, n=129), SIBO with hyperproduction of methane and hydrogene (SIBO-CH4-H2, n=225). The control group consisted of 108 patients with no no excessive gas production on LBT. In contrast to controls, nutritional patterns of patients with SIBO were characterized by low dietary fiber and amount of red meat dishes in the rations. Those with SIBO-CH4 consumed more fruits (p=0.03), vegetables (p=0.003), and fish (p=0.026), compared to those with other variants of SIBO and the control group. Nutritional patterns of SIBO-H2 group were characterized by larger amount of poultry meat consumption (p=0.026) compared to other SIBO groups and controls. In SIBO-H2 "cured" group greater amounts of buckwheat (p.

Parkinson's Disease and Current Treatments for Its Gastrointestinal Neurogastromotility Effects.

PURPOSE OF REVIEW: Gastrointestinal disturbances are seen in nearly all patients with Parkinson's disease and lead to impaired quality of life, affect drug pharmacodynamics, and potentially worsen patient's existing motor fluctuations, leading to further disability. Recent evidence links abnormal accumulations of α-synuclein aggregates in the periphery (gut) as seen in the cortex which causes dysfunctions impacting every level of the gastrointestinal tract from the esophagus, to the stomach, small bowel, colon, and rectum and can even predate the onset of the central neurologic disorder itself. Many treatments exist for the clinical phenotypes that result from the autonomic dysfunction and neuropathy involved in this neurodegenerative disorder. The treatments for the gut dysfunction seen in Parkinson's disease (PD) depend on the specific area of the gastrointestinal tract affected. For dysphagia, behavioral therapies with speech pathology, neuromuscular electrical stimulation, or botulinum toxin injection may be helpful. For gastroparesis, domperidone may serve as an antiemetic while also blunting the hypotensive potential of Levodopa while new treatments such as ghrelin agonists may prove beneficial to help appetite, satiety, gastric emptying in those with constipation, and even improve constipation. Antibiotics such as rifaximin with poor systemic absorption may be used to treat small bacterial overgrowth also found in those with PD while the benefits of probiotics is yet to be determined. Finally, constipation in PD can be a reflection of pelvic floor dyssynergia, slow transit constipation, or both, thus treatments targeting the specific anorectal dysfunction is necessary for better outcomes.

Levothyroxine therapy and impaired clearance are the strongest contributors to small intestinal bacterial overgrowth: Results of a retrospective cohort study.

AIM: To identify a set of contributors, and weight and rank them on a pathophysiological basis. METHODS: Patients who have undergone a lactulose or glucose hydrogen breath test to rule out small intestinal bacterial overgrowth (SIBO) for various clinical symptoms, including diarrhoea, weight loss, abdominal pain, cramping or bloating, were seen as eligible for inclusion in a retrospective single-centre study. Clinical data such as co-morbidities, medication, laboratory parameters and other possible risk factors have been identified from the electronic data system. Cases lacking or with substantially incomplete clinical data were excluded from the analysis. Suspected contributors were summarised under four different pathophysiological pathways (impaired gastric acid barrier, impaired intestinal clearance, immunosuppression and miscellaneous factors including thyroid gland variables) and investigated using the χ2 test, Student's t-test and logistic regression models. RESULTS: A total of 1809 patients who had undergone hydrogen breath testing were analysed. Impairment of the gastric acid barrier (gastrectomy, odds ratio: OR = 3.5, PPI therapy OR = 1.4), impairment of intestinal clearance (any resecting gastric surgery OR = 2.6, any colonic resection OR = 1.9, stenosis OR = 3.4, gastroparesis OR = 3.4, neuropathy 2.2), immunological factors (any drug-induced immunosuppression OR = 1.8), altered thyroid gland metabolism (hypothyroidism OR = 2.6, levothyroxine therapy OR = 3.0) and diabetes mellitus (OR = 1.9) were associated significantly to SIBO. Any abdominal surgery, ileocecal resection, vagotomy or IgA-deficiency did not have any influence, and a history of appendectomy decreased the risk of SIBO. Multivariate analysis revealed gastric surgery, stenoses, medical immunosuppression and levothyroxine to be the strongest predictors. Levothyroxine therapy was the strongest contributor in a simplified model (OR = 3.0). CONCLUSION: The most important contributors for the development of SIBO in ascending order are immunosuppression, impairment of intestinal clearance and levothyroxine use, but they do not sufficiently explain its emergence.

Small Intestinal Bacterial Overgrowth in Patients with Refractory Functional Gastrointestinal Disorders.

BACKGROUND/AIMS: Small intestinal bacterial overgrowth (SIBO) is considered to be involved in the pathogenesis of functional gastrointestinal disorders (FGID). However, the prevalence and clinical conditions of SIBO in patients with FGID remain to be fully elucidated. Here, we examined the frequency of SIBO in patients with refractory FGID. METHODS: We prospectively enrolled patients with refractory FGID based on Rome III criteria. A glucose hydrogen breath test (GHBT) was performed using a gas analyzer after an overnight fast, with breath hydrogen concentration measured at baseline and every 15 minutes after administration of glucose for a total of 3 hours. A peak hydrogen value ≥ 10 ppm above the basal value between 60 and 120 minutes after administration of glucose was diagnosed as SIBO. RESULTS: A total of 38 FGID patients, including 11 with functional dyspepsia (FD), 10 with irritable bowel syndrome (IBS), and 17 with overlapping with FD and IBS, were enrolled. Of those, 2 (5.3%) were diagnosed with SIBO (one patient diagnosed with FD; the other with overlapping FD and IBS). Their symptoms were clearly improved and breath hydrogen levels decreased to normal following levofloxacin administration for 7 days. CONCLUSIONS: Two patients initially diagnosed with FD and IBS were also diagnosed with SIBO as assessed by GHBT. Although the frequency of SIBO is low among patients with FGID, it may be important to be aware of SIBO as differential diagnosis when examining patients with refractory gastrointestinal symptoms, especially bloating, as a part of routine clinical care.

Small Intestinal Bacterial Overgrowth in Patients with Refractory Functional Gastrointestinal Disorders

BACKGROUND/AIMS: Small intestinal bacterial overgrowth (SIBO) is considered to be involved in the pathogenesis of functional gastrointestinal disorders (FGID). However, the prevalence and clinical conditions of SIBO in patients with FGID remain to be fully elucidated. Here, we examined the frequency of SIBO in patients with refractory FGID. METHODS: We prospectively enrolled patients with refractory FGID based on Rome III criteria. A glucose hydrogen breath test (GHBT) was performed using a gas analyzer after an overnight fast, with breath hydrogen concentration measured at baseline and every 15 minutes after administration of glucose for a total of 3 hours. A peak hydrogen value > or = 10 ppm above the basal value between 60 and 120 minutes after administration of glucose was diagnosed as SIBO. RESULTS: A total of 38 FGID patients, including 11 with functional dyspepsia (FD), 10 with irritable bowel syndrome (IBS), and 17 with overlapping with FD and IBS, were enrolled. Of those, 2 (5.3%) were diagnosed with SIBO (one patient diagnosed with FD; the other with overlapping FD and IBS). Their symptoms were clearly improved and breath hydrogen levels decreased to normal following levofloxacin administration for 7 days. CONCLUSIONS: Two patients initially diagnosed with FD and IBS were also diagnosed with SIBO as assessed by GHBT. Although the frequency of SIBO is low among patients with FGID, it may be important to be aware of SIBO as differential diagnosis when examining patients with refractory gastrointestinal symptoms, especially bloating, as a part of routine clinical care.

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.

Small intestinal bacterial overgrowth syndrome in children.

INTRODUCTION: Small intestinal bacterial overgrowth syndrome (SIBO) is defined as an increased number of nonpathogenic bacteria over 10(5) organisms in 1 millilitre of small intestine content. The most common predisposing factors include, among others, gut motility disorders and chronic use of proton pump inhibitors. The results of recent studies indicate the importance of SIBO in gastrointestinal diseases. AIM: To assess the prevalence of SIBO in children with abdominal pain. MATERIAL AND METHODS: One hundred children (59 girls and 41 boys) aged from 4 to 17 years (mean age: 10.47 ±3.73 years), hospitalised due to abdominal pain, were enrolled in the study. Hydrogen breath test (HBT) with lactulose was established among all patients. Expired air was analysed using a Gastrolyzer (Bedfont). RESULTS: The HBT result was positive in 63 (63%) children with abdominal pain; including 40 girls (67.8%) and 23 boys (56.1%). The test was positive in the group of 29 (46%) children aged under 10 years and in the group of 34 (54%) children aged over 10 years. Among the patients who reported for the control study 88% achieved a normalisation of HBT after treatment. CONCLUSIONS: The prevalence of positive HBT results in the group of patients with abdominal pain is over 60%. Small intestinal bacterial overgrowth syndrome should be considered as one of the causes of abdominal pain in children. The SIBO in children shows a good response to treatment.