SIBO (Small Intestinal Bacterial Overgrowth) är ett tillstånd där tunntarmen koloniseras av bakterier som normalt finns i tjocktarmen. SIBO utvecklas när de normala homeostatiska mekanismerna som kontrollerar enteriska bakteriepopulationen störs. I tunntarmen ska det finnas väldigt liten mängd bakterier medan i tjocktarmen bör det finnas mycket större mängder bakterier. När bakterierna tar sig in i tunntarmen, resulterar det i SIBO. Denna bakteriella obalans i tunntarmen kan orsaka bland annat uppblåsthet, diarré och magsmärta, förstoppning och försämrat upptag av vitaminer och näringsämnen. Att behandla den underliggande orsaken bakom SIBO är det första steget i behandlingen och om detta inte räcker till, är antibiotikabehandlingen nästa steg. Syftet med denna litteraturstudie var att undersöka hur effektiv Rifaximin är vid behandling av bakteriell överväxt i tunntarmen (SIBO). Arbetet är en litteraturstudie och de vetenskapliga artiklarna är hämtade från databasen Pubmed. I detta arbete har fem studier analyserats. Studie I visade att högdosbehandling med rifaximin gav signifikant ökad behandlingseffekt jämfört med lågdosbehandling hos IBS-patienter. Studie II visade att kombination av amoxicillin och rifaximin kan vara en effektiv förstahandsbehandling för patienter som har både SIBO och H. pylori infektion. Studie III bekräftade att SIBO är underdiagnoserat hos Cystisk fibros patienter och är relaterad till en dålig näringsstatus. Rifaximin är en effektiv behandling av SIBO hos patienter som har Cystisk fibros. Studie IV visade att kombinationen av rifaximin tillsammans med hydrolyserat guargummi verkar vara mer effektivt vid utrotning av SIBO jämfört med enbart rifaximin hos SIBO patienter. Studie V studerade  rifaximinbehandlade IBS-patienter och fann att rifaximinbehandling var associerad med acceleration av kolontransitering samt hade svag påverkan på förändringar i mikrobiell artrikedom i feces. Baserat på de fem studierna föreligger det skäliga bevis att behandling med rifaxamin är en effektiv behandling vid SIBO. Mer forskning och studier behövs för att kunna bestämma den bästa dosen samt utvärdera rifaximin i kombination med andra läkemedel. / SIBO (Small Intestinal Bacterial Overgrowth) is a condition where the small intestine is colonized by bacteria normally found in the large intestine. SIBO develops when the normal homeostatic mechanisms controlling the enteric bacterial population are disrupted. In the small intestine, there should be very small number of bacteria while in the large intestine there should be much larger number of bacteria. When the bacteria colonizes the small intestine, it results in SIBO. This bacterial imbalance in the small intestine can cause bloating, diarrhea and stomach pain, constipation and impaired absorption of vitamins and nutrients. Treating the underlying cause of SIBO is the first step in the treatment and if this is not enough, antibiotic treatment is the next step. The purpose of this literature study was to investigate the effectiveness of Rifaximin in treatment of bacterial overgrowth in the small intestine (SIBO). The study is a literature study where the scientific articles were obtained from the database Pubmed. In this literature study, five studies have been analyzed. Study I showed that high-dose treatment with rifaximin significantly increased treatment efficacy compared to low-dose treatment. Study II showed that a combination of amoxicillin and rifaximin can be an effective first-line treatment for patients who have both SIBO and H. pylori infection. Study III confirmed that SIBO is underdiagnosed in CF patients, related to poor nutritional status. Rifaximin is an effective treatment for SIBO in patients who have CF. Study IV also showed a combination treatment where rifaximin together with hydrolyzed guar gum appears to be more effective in eradicating SIBO compared to rifaximin alone. Study V studied rifaximin-treated IBS patients, rifaximin treatment was associated with acceleration of colon transit, and a weak influence on changes in microbial species richness in faeces. Based on the five studies, there is reasonable evidence that a treatment with rifaximin is an effective treatment for SIBO. However, more research and studies are needed to determine the best dose and also rifaximin in combination with other drugs.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2015-05-25T13:09:16Z No. of bitstreams: 2 Tese - Felix André Sanches Penhavel - 2014.pdf: 2537517 bytes, checksum: 2edff02f8a1f3fa50c180c2222a53b17 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-05-25T13:34:49Z (GMT) No. of bitstreams: 2 Tese - Felix André Sanches Penhavel - 2014.pdf: 2537517 bytes, checksum: 2edff02f8a1f3fa50c180c2222a53b17 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-05-25T13:34:49Z (GMT). No. of bitstreams: 2 Tese - Felix André Sanches Penhavel - 2014.pdf: 2537517 bytes, checksum: 2edff02f8a1f3fa50c180c2222a53b17 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-12-15 / American Tripanosomiasis is one of the most prevalente tropical disease in Latin America. One third of brazilian territory is considered endemic for Chagas disease. Vectorial transmission is not complitely interrupted. In Central Brazil, specially Goiás State, digestive forms with megasyndormes have a high frequence. The involvement of small bowel has been discribed with functional disturbances. Patients with acquired megacolon may have normal bowel movements or long lasting constipation. Until now the influence of small bowel on the frequence of bowel movements is not clear. This prospective study addressed the small bowel motility measuring the orocecal transit time (OCTT) and the occurence of small bowel intestinal bacterial overgrowth (SIBO) by hydrogen breath test. 45 patients with positive serology for Chagas disease were divided into four groups: A – without megacolon and no constipation (17); B – with megacolon and no constipation (8); C – with megacolon and constipation (10) and D – without megacolon and constipation (10). Constipation was defined by at least 7 days without bowel movements. 15 healthy volunteers were taken as a control group (CG). Non hydrogen producers: 10/45 patients and 1/15 controls. The OCTT (medium time in minutes) was longer in patients than in controls: A=108.18, B=108.0, C=112.5, D=130.0 and CG=68.46. Patients together showed difference compared to controls (P=0.001). No difference was found among groups (P>0.05). The prevalence of SIBO was: 66.7% in constipated patients (C and D), 25% in non constipated patients (A and B) and 8.3% in controls. Significant statistical difference was found only comparing constipated patients and controls (P=0.017). The presence of megacolon did not show influence the frequence of SIBO (P=0.181). Lactose and D-xylose malabsorption was higher in controls. The number of patients with symptoms during the test was the same for chagasic and controls independently of the test result. Patients with Chagas disease have a prolonged OCTT and those with constipation showed a higher prevalence of SIBO and both factors are not related to megacolon. Chagasic patients showed a less frequency of lactose and D- xylose malabsorption. / A Tripanossomíase Americana é uma das doenças tropicais mais prevalentes na América Latina. Mais de um terço do território brasileiro é área endêmica, e a transmissão vetorial ainda não se interrompeu em todos os estados. Em Goiás, as megassíndromes do tubo digestivo são muito frequentes. O comprometimento do tubo digestivo não se restringe à víscera dilatada e alterações funcionais têm sido descritas no intestino delgado. O objetivo geral deste estudo foi investigar alterações de motilidade e de absorção de carboidratos no intestino delgado de pacientes chagásicos com e sem constipação e megacólon. Avaliou-se 45 pacientes com sorologia positiva para doença de Chagas, divididos em quatro grupos: A - sem constipação, sem megacólon (17); B - sem constipação, com megacólon (8); C - com constipação, com megacólon (10) e D - com constipação, sem megacólon (10). Quinze voluntários sadios foram usados como controles (GC). Todos os pacientes e controles realizaram três testes respiratórios com os substratos: lactulose, lactose e D-xilose. Identificou-se não produção de hidrogênio em 10 pacientes e um controle. O tempo de trânsito orocecal (TTOC) (média em minutos) foi maior nos pacientes do que nos controles: A=108,18; B=108,0; C=112,5; D=130,0 e GC=68,46 (P=0,001). Não houve diferença no TTOC entre os grupos de pacientes (P<0,05). A prevalência de supercrescimento bacteriano no intestino delgado (SBID) foi de 66,7% nos pacientes constipados (C e D), 25% nos não constipados (A e B) e de 8,3% nos controles (P=0,017). A presença de megacólon não influenciou a frequência de SBID (P=0,181). A má absorção de lactose foi maior entre os controles. O número de pacientes que apresentava sintomas ou não durante o teste da lactose foi igual para pacientes e controles, independentemente do resultado do teste. A má absorção de D-xilose foi mais frequente no grupo controle. Concluiu-se que os pacientes chagásicos têm o tempo de trânsito orocecal prolongado e que aqueles com constipação apresentam uma maior prevalência de SBID, ambos os fatores não sofrem influência da presença do megacólon. A má absorção de lactose e D-xilose foi maior entre controles.

Bypass or resection of the stomach and oesophagus, has long been recognised to result in profound changes in the handling of ingested nutrients. This results in significant morbidity after radical surgery for oesophago-gastric cancer, in particular post-prandial hypoglycaemia, altered appetite, early satiety and noxious post-prandial symptoms. By profiling and challenging the gut hormone axis in healthy volunteers and patients who had undergone total or subtotal gastrectomy, or oesophagectomy, this thesis explores the possible causative mechanisms for the challenges faced by this patient population. In the surgical groups, an oral glucose tolerance test (OGTT) resulted in enhanced secretion of satiety and incretin gut hormones (GLP-1, GIP, PYY) and insulin, followed by hypoglycaemia in a cohort of patients. Continuous glucose monitoring of gastrectomy participants over two weeks of normal lifestyle identified an increased incidence of day and night time hypoglycaemia. RNAseq and mass spectrometry based peptidomics of human and murine enteroendocrine cells in the pre- and post-operative populations revealed no significant change in the underlying cellular pathways for nutrient sensing and gut hormone secretion, indicating that the altered hormone secretion is primarily driven by accelerated nutrient transit, rather than adaptive changes in the gut. Finally, specific blockade of the GLP-1 receptor in post-gastrectomy patients using Exendin 9-39 normalised insulin secretion and prevented reactive hypoglycaemia after an OGTT. In conclusion, profound changes in gut hormone secretion as a result of enhanced nutrient transit after foregut surgery likely underlie the early and late post-prandial symptoms seen in this group, and therapies specifically targeting the gut hormone axis, and GLP-1 in particular, could be the first targeted treatments for post-gastrectomy syndromes.

This thesis investigates how air pollution, both natural and anthropogenic, affects changes in the proximal small intestine and ileum microbiota profile, as well as intestinal barrier integrity, histological changes, and inflammation. APO-E KO mice on a high fat diet were randomly selected to be exposed by whole body inhalation to either wood smoke (WS) or mixed vehicular exhaust (MVE), with filtered air (FA) acting as the control. Intestinal integrity and histology were assessed by observing expression of well- known structural components tight junction proteins (TJPs), matrix metallopeptidase-9 (MMP-9), and gel-forming mucin (MUC2), as well known inflammatory related factors: TNF-α, IL-1β, and toll-like receptor (TLR)-4. Bacterial profiling was done using DNA analysis of microbiota within the ileum, utilizing 16S metagenomics sequencing (Illumina miSeq) technique. Overall results of this experiment suggest that air pollution, both anthropogenic and natural, cause a breach in the intestinal barrier with an increase in inflammatory factors and a decrease in beneficial bacteria. This evidence suggests the possibility of air pollution being a potential causative agent of intestinal disease as well as a possible contributing mechanism for induction of systemic inflammation.