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Author Notes:

Address correspondence to: Andrew T. Gewirtz, PhD, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30303. e-mail: agewirtz@gsu.edu; fax: (404) 413–3580.

Benoit Chassaing and Andrew T. Gewirtz conceived the project, designed the experiments, interpreted the results, and wrote the manuscript.

Shanthi Srinivasan and Shreya M. Raja collected biopsies and critically revised the manuscript.

Benoit Chassaing performed experiments and analysis.

James D. Lewis performed statistical analysis and helped interpret data.

The authors disclose no conflicts.

Research Funding:

This work was supported by National Institutes of Health grants DK099071 and DK083890 (A.T.G.), National Institutes of Health grant DK080684 (S.S.), and VA-MERIT (S.S.). B.C. is a recipient of the Career Development Award from the Crohn’s and Colitis Foundation of America.

Keywords:

  • BMI, body mass index
  • HPF, high-powered field
  • IBD, inflammatory bowel disease
  • Metabolic Syndrome
  • Microbiota
  • Mucus Layer
  • PBS, phosphate-buffered saline
  • TLR, Toll-like receptor

Colonic Microbiota Encroachment Correlates With Dysglycemia in Humans.

Tools:

Journal Title:

Cellular and Molecular Gastroenterology and Hepatology

Volume:

Volume 4, Number 2

Publisher:

, Pages 205-221

Type of Work:

Article | Final Publisher PDF

Abstract:

BACKGROUND AND AIMS: Mucoid structures that coat the epithelium play an essential role in keeping the intestinal microbiota at a safe distance from host cells. Encroachment of bacteria into the normally almost-sterile inner mucus layer has been observed in inflammatory bowel disease and in mouse models of colitis. Moreover, such microbiota encroachment has also been observed in mouse models of metabolic syndrome, which are associated low-grade intestinal inflammation. Hence, we investigated if microbiota encroachment might correlate with indices of metabolic syndrome in humans. METHODS: Confocal microscopy was used to measure bacterial-epithelial distance of the closest bacteria per high-powered field in colonic biopsies of all willing participants undergoing cancer screening colonoscopies. RESULTS: We observed that, among all subjects, bacterial-epithelial distance was inversely correlated with body mass index, fasting glucose levels, and hemoglobin A1C. However, this correlation was driven by dysglycemic subjects, irrespective of body mass index, whereas the difference in bacterial-epithelial distance between obese and nonobese subjects was eliminated by removal of dysglycemic subjects. CONCLUSIONS: We conclude that microbiota encroachment is a feature of insulin resistance-associated dysglycemia in humans.

Copyright information:

© 2017 The Authors

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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