Dataset Information

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 and 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.

OTHER RELATED OMICS DATASETS IN: GSE128189

INSTRUMENT(S): Nuclear Magnetic Resonance (NMR)

SUBMITTER: Yi Yang

PROVIDER: MTBLS876 | MetaboLights | 2019-04-30

REPOSITORIES: MetaboLights

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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:Neural control of visceral organ function is essential for homeostasis and health. Intestinal peristalsis is critical for digestive physiology and host defence and is often dysregulated in gastrointestinal (GI) disorders. Luminal factors, such as diet and microbiota regulate neurogenic programs of gut motility, but the underlying molecular mechanisms remain unclear. Here we show that the transcription factor Aryl hydrocarbon Receptor (AhR) functions as a biosensor in intestinal neural circuits linking their functional output to the microbial environment of the gut lumen. Using nuclear RNA sequencing of mouse enteric neurons representing distinct intestinal segments and microbiota states, we demonstrate that the intrinsic neural networks of the colon exhibit unique transcriptional profiles controlled by the combined effects of host genetic programmes and microbial colonisation. Microbiota-induced expression of AhR in neurons of the distal gastrointestinal tract enables them to respond to the luminal environment and induce expression of neuron-specific effector mechanisms. Neuron-specific deletion of Ahr or constitutive overexpression of its negative feedback regulator CYP1A1, results in reduced peristaltic activity of the colon, similar to that observed in microbiota-depleted mice. Finally, expression of Ahr in enteric neurons of antibiotic-treated mice partially restores intestinal motility. Taken together, our experiments identify AhR signalling in enteric neurons as a regulatory node that integrates the luminal environment with the physiological output of intestinal neural circuits towards gut homeostasis and health. The enteric nervous system (ENS) encompasses the intrinsic neural networks of the gastrointestinal (GI) tract, which regulate most aspects of intestinal physiology, including peristalsis. In addition to host-specific genetic programmes, microbiota and diet have emerged as critical regulators of gut tissue physiology and changes in the microbial composition of the lumen often accompany GI disorders. However the molecular mechanisms by which gut enviromental factors regulate ENS homeostasis remain unknown. In order to address this issue, we used RNA sequencing to identify genes specifically upregulated in mouse colonic neurons in response to microbial colonisation.

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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