Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice. / Schroeder, Bjoern O.; Birchenough, George M. H.; Pradhan, Meenakshi; Nystrom, Elisabeth E. L.; Henricsson, Marcus; Hansson, Gunnar C.; Backhed, Fredrik.

In: Journal of Biological Chemistry, Vol. 295, No. 46, 2020, p. 15712-15726.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Schroeder, BO, Birchenough, GMH, Pradhan, M, Nystrom, EEL, Henricsson, M, Hansson, GC & Backhed, F 2020, 'Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice', Journal of Biological Chemistry, vol. 295, no. 46, pp. 15712-15726. https://doi.org/10.1074/jbc.RA120.015771

APA

Schroeder, B. O., Birchenough, G. M. H., Pradhan, M., Nystrom, E. E. L., Henricsson, M., Hansson, G. C., & Backhed, F. (2020). Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice. Journal of Biological Chemistry, 295(46), 15712-15726. https://doi.org/10.1074/jbc.RA120.015771

Vancouver

Schroeder BO, Birchenough GMH, Pradhan M, Nystrom EEL, Henricsson M, Hansson GC et al. Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice. Journal of Biological Chemistry. 2020;295(46):15712-15726. https://doi.org/10.1074/jbc.RA120.015771

Author

Schroeder, Bjoern O. ; Birchenough, George M. H. ; Pradhan, Meenakshi ; Nystrom, Elisabeth E. L. ; Henricsson, Marcus ; Hansson, Gunnar C. ; Backhed, Fredrik. / Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice. In: Journal of Biological Chemistry. 2020 ; Vol. 295, No. 46. pp. 15712-15726.

Bibtex

@article{38f62d7fddcf4e69822408e6d406d320,
title = "Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice",
abstract = "The intestinal mucus layer is a physical barrier separating the tremendous number of gut bacteria from the host epithelium. Defects in the mucus layer have been linked to metabolic diseases, but previous studies predominantly investigated mucus function during high-caloric/low-fiber dietary interventions, thus making it difficult to separate effects mediated directly through diet quality from potential obesity-dependent effects. As such, we decided to examine mucus function in mouse models with metabolic disease to distinguish these factors. Here we show that, in contrast to their lean littermates, genetically obese (ob/ob) mice have a defective inner colonic mucus layer that is characterized by increased penetrability and a reduced mucus growth rate. Exploiting the coprophagic behavior of mice, we next co-housed ob/ob and lean mice to investigate if the gut microbiota contributed to these phenotypes. Co-housing rescued the defect of the mucus growth rate, whereas mucus penetrability displayed an intermediate phenotype in both mouse groups. Of note, non-obese diabetic mice with high blood glucose levels displayed a healthy colonic mucus barrier, indicating that the mucus defect is obesity- rather than glucose-mediated. Thus, our data suggest that the gut microbiota community of obesity-prone mice may regulate obesity-associated defects in the colonic mucosal barrier, even in the presence of dietary fiber.",
keywords = "barrier dysfunction, gut microbiota, host defense, intestinal epithelium, metabolic disease, mucus, mucosal immunology, obesity, microbiome, metabolism, CHAIN FATTY-ACIDS, INTESTINAL MUCUS, DIETARY FIBER, COLON MUCUS, MOUSE, BACTERIAL, PROTECTS, BARRIER, CELLS",
author = "Schroeder, {Bjoern O.} and Birchenough, {George M. H.} and Meenakshi Pradhan and Nystrom, {Elisabeth E. L.} and Marcus Henricsson and Hansson, {Gunnar C.} and Fredrik Backhed",
year = "2020",
doi = "10.1074/jbc.RA120.015771",
language = "English",
volume = "295",
pages = "15712--15726",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "46",

}

RIS

TY - JOUR

T1 - Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice

AU - Schroeder, Bjoern O.

AU - Birchenough, George M. H.

AU - Pradhan, Meenakshi

AU - Nystrom, Elisabeth E. L.

AU - Henricsson, Marcus

AU - Hansson, Gunnar C.

AU - Backhed, Fredrik

PY - 2020

Y1 - 2020

N2 - The intestinal mucus layer is a physical barrier separating the tremendous number of gut bacteria from the host epithelium. Defects in the mucus layer have been linked to metabolic diseases, but previous studies predominantly investigated mucus function during high-caloric/low-fiber dietary interventions, thus making it difficult to separate effects mediated directly through diet quality from potential obesity-dependent effects. As such, we decided to examine mucus function in mouse models with metabolic disease to distinguish these factors. Here we show that, in contrast to their lean littermates, genetically obese (ob/ob) mice have a defective inner colonic mucus layer that is characterized by increased penetrability and a reduced mucus growth rate. Exploiting the coprophagic behavior of mice, we next co-housed ob/ob and lean mice to investigate if the gut microbiota contributed to these phenotypes. Co-housing rescued the defect of the mucus growth rate, whereas mucus penetrability displayed an intermediate phenotype in both mouse groups. Of note, non-obese diabetic mice with high blood glucose levels displayed a healthy colonic mucus barrier, indicating that the mucus defect is obesity- rather than glucose-mediated. Thus, our data suggest that the gut microbiota community of obesity-prone mice may regulate obesity-associated defects in the colonic mucosal barrier, even in the presence of dietary fiber.

AB - The intestinal mucus layer is a physical barrier separating the tremendous number of gut bacteria from the host epithelium. Defects in the mucus layer have been linked to metabolic diseases, but previous studies predominantly investigated mucus function during high-caloric/low-fiber dietary interventions, thus making it difficult to separate effects mediated directly through diet quality from potential obesity-dependent effects. As such, we decided to examine mucus function in mouse models with metabolic disease to distinguish these factors. Here we show that, in contrast to their lean littermates, genetically obese (ob/ob) mice have a defective inner colonic mucus layer that is characterized by increased penetrability and a reduced mucus growth rate. Exploiting the coprophagic behavior of mice, we next co-housed ob/ob and lean mice to investigate if the gut microbiota contributed to these phenotypes. Co-housing rescued the defect of the mucus growth rate, whereas mucus penetrability displayed an intermediate phenotype in both mouse groups. Of note, non-obese diabetic mice with high blood glucose levels displayed a healthy colonic mucus barrier, indicating that the mucus defect is obesity- rather than glucose-mediated. Thus, our data suggest that the gut microbiota community of obesity-prone mice may regulate obesity-associated defects in the colonic mucosal barrier, even in the presence of dietary fiber.

KW - barrier dysfunction

KW - gut microbiota

KW - host defense

KW - intestinal epithelium

KW - metabolic disease

KW - mucus

KW - mucosal immunology

KW - obesity

KW - microbiome

KW - metabolism

KW - CHAIN FATTY-ACIDS

KW - INTESTINAL MUCUS

KW - DIETARY FIBER

KW - COLON MUCUS

KW - MOUSE

KW - BACTERIAL

KW - PROTECTS

KW - BARRIER

KW - CELLS

U2 - 10.1074/jbc.RA120.015771

DO - 10.1074/jbc.RA120.015771

M3 - Journal article

C2 - 32900852

VL - 295

SP - 15712

EP - 15726

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 46

ER -

ID: 253444061