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Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders.

ABSTRACT: Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment.

SUBMITTER: Saffouri GB

PROVIDER: S-EPMC6494866 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders.

Saffouri George B GB Shields-Cutler Robin R RR Chen Jun J Yang Yi Y Lekatz Heather R HR Hale Vanessa L VL Cho Janice M JM Battaglioli Eric J EJ Bhattarai Yogesh Y Thompson Kevin J KJ Kalari Krishna K KK Behera Gaurav G Berry Jonathan C JC Peters Stephanie A SA Patel Robin R Schuetz Audrey N AN Faith Jeremiah J JJ Camilleri Michael M Sonnenburg Justin L JL Farrugia Gianrico G Swann Jonathan R JR Grover Madhusudan M Knights Dan D Kashyap Purna C PC

Nature communications 20190501 1

Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in sy ...[more]

PMID: 31043597

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Project description:Background/Objectives: The diagnosis of lower functional gastrointestinal disorders (FGIDs) is currently based on subjective and unreliable patient-reported symptoms, with significant clinical overlap between diagnosed phenotypes. Objective biomarkers are urgently sought. Gastrointestinal ultrasound (GIUS) can objectively and non-invasively assess luminal contents. This study aimed to assess the utility of GIUS in phenotyping patients with lower FGIDs. Methods: Patients with lower FGIDs underwent a GIUS and completed the Rome IV Diagnostic Questionnaire, SAGIS questionnaire, and 100 mm VAS score for overall symptom severity. The faecal loading score (FLS) was obtained using a modified Leech score, where an FLS of >37 was consistent with clinically significant constipation. Results: Eighty-eight patients fulfilled the study requirements. In total, 56 met the Rome IV criteria for irritable bowel syndrome (IBS) subtypes, while 23 met the criteria for functional constipation (FC), 4 for functional diarrhoea (FD), and 5 for other diagnoses. Patients reporting constipation-predominant symptoms had a significantly higher median FLS than those describing diarrhoea-predominant symptoms (FLS = 40 [IQR 20.0-53.3] vs. 13.3 [IQR 6.7-40.0], respectively). However, 27% of patients describing diarrhoea had significant faecal loading on GIUS, and of those who described constipation, 34% did not have significant faecal loading. Sensitivity and specificity for the detection of FLS-indicated constipation by the Rome IV criteria were low at 59% and 66%, respectively. Conclusions: The symptom-based diagnosis of FGID subtypes based on the Rome IV criteria is a poor predictor of faecal loading. These findings should prompt further exploration of the limitations of symptom-based assessment and a shift towards physiological assessment of patients with FGIDs such as gastrointestinal ultrasound to develop more targeted therapy. Future research is underway to determine if targeting objective physiological endpoints results in improved clinical outcomes.

Project description:We explored the metagenomic, metabolomic and trace metal makeup of intestinal microbiota and environment in healthy male participants during the run-in (5 day) and the following three 21-day interventions: normoxic bedrest (NBR), hypoxic bedrest (HBR) and hypoxic ambulation (HAmb) which were carried out within a controlled laboratory environment (circadian rhythm, fluid and dietary intakes, microbial bioburden, oxygen level, exercise). The fraction of inspired O2 (FiO2) and partial pressure of inspired O2 (PiO2) were 0.209 and 133.1 ± 0.3 mmHg for the NBR and 0.141 ± 0.004 and 90.0 ± 0.4 mmHg (~4,000 m simulated altitude) for HBR and HAmb interventions, respectively. Shotgun metagenomes were analyzed at various taxonomic and functional levels, 1H- and 13C -metabolomes were processed using standard quantitative and human expert approaches, whereas metals were assessed using X-ray fluorescence spectrometry. Inactivity and hypoxia resulted in a significant increase in the genus Bacteroides in HBR, in genes coding for proteins involved in iron acquisition and metabolism, cell wall, capsule, virulence, defense and mucin degradation, such as beta-galactosidase (EC3.2.1.23), α-L-fucosidase (EC3.2.1.51), Sialidase (EC3.2.1.18), and α-N-acetylglucosaminidase (EC3.2.1.50). In contrast, the microbial metabolomes, intestinal element and metal profiles, the diversity of bacterial, archaeal and fungal microbial communities were not significantly affected. The observed progressive decrease in defecation frequency and concomitant increase in the electrical conductivity (EC) preceded or took place in absence of significant changes at the taxonomic, functional gene, metabolome and intestinal metal profile levels. The fact that the genus Bacteroides and proteins involved in iron acquisition and metabolism, cell wall, capsule, virulence and mucin degradation were enriched at the end of HBR suggest that both constipation and EC decreased intestinal metal availability leading to modified expression of co-regulated genes in Bacteroides genomes. Bayesian network analysis was used to derive the first hierarchical model of initial inactivity mediated deconditioning steps over time. The PlanHab wash-out period corresponded to a profound life-style change (i.e., reintroduction of exercise) that resulted in stepwise amelioration of the negative physiological symptoms, indicating that exercise apparently prevented the crosstalk between the microbial physiology, mucin degradation and proinflammatory immune activities in the host.

Dataset Information

Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders.

Publications

Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders.

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