Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment

• Published in: EMBO molecular medicine Vol. 3; no. 9; pp. 559 - 572
• Main Authors: Amar, Jacques, Chabo, Chantal, Waget, Aurélie, Klopp, Pascale, Vachoux, Christelle, Bermúdez‐Humarán, Luis G., Smirnova, Natalia, Bergé, Mathieu, Sulpice, Thierry, Lahtinen, Sampo, Ouwehand, Arthur, Langella, Philippe, Rautonen, Nina, Sansonetti, Philippe J., Burcelin, Rémy
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2011; WILEY‐VCH Verlag; EMBO Press; Wiley Open Access; WILEY-VCH Verlag
• Subjects: Adipose Tissue; Adipose Tissue - microbiology; Animals; Antigens; Bacteremia; Bacteremia - complications; Bacteria; Bacterial Adhesion; Bacterial Translocation; Bifidobacterium; Bifidobacterium - physiology; Bifidobacterium lactis 420; Blood; Blood - microbiology; CD14 antigen; Dendritic cells; Deoxyribonucleic acid; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - microbiology; Diabetes Mellitus, Type 2 - prevention & control; Diet; Diet, High-Fat; Diet, High-Fat - adverse effects; DNA; E coli; Escherichia coli; Escherichia coli - isolation & purification; Escherichia coli - pathogenicity; Experiments; High fat diet; Hyperglycemia; Inflammation; Insulin; Insulin resistance; Intestinal microflora; Intestinal Mucosa; Intestinal Mucosa - microbiology; Intestine; Kinases; Lamina propria; Life Sciences; Lipopolysaccharide Receptors; Lipopolysaccharide Receptors - genetics; Lipopolysaccharide Receptors - metabolism; Localization; Lymphatic system; Metabolic disorders; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiota; Molecular modelling; Mucosa; MyD88 protein; Myeloid Differentiation Factor 88; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Nod1 protein; Nod1 Signaling Adaptor Protein; Nod1 Signaling Adaptor Protein - genetics; Nod1 Signaling Adaptor Protein - metabolism; Obesity; pathogen‐associated molecular pattern receptors; Pattern recognition receptors; Probiotics; Probiotics - administration & dosage; Research Article; Therapeutic applications; France; 420; inflammation; pathogen‐associated molecular pattern receptors; diabetes; obesity; Bifidobacterium lactis 420
• ISSN: 1757-4676; 1757-4684; 1757-4684
• DOI: 10.1002/emmm.201100159

A fat‐enriched diet modifies intestinal microbiota and initiates a low‐grade inflammation, insulin resistance and type‐2 diabetes. Here, we demonstrate that before the onset of diabetes, after only one week of a high‐fat diet (HFD), live commensal intestinal bacteria are present in large numbers in the adipose tissue and the blood where they can induce inflammation. This translocation is prevented in mice lacking the microbial pattern recognition receptors Nod1 or CD14, but overtly increased in Myd88 knockout and ob / ob mouse. This ‘metabolic bacteremia’ is characterized by an increased co‐localization with dendritic cells from the intestinal lamina propria and by an augmented intestinal mucosal adherence of non‐pathogenic Escherichia coli . The bacterial translocation process from intestine towards tissue can be reversed by six weeks of treatment with the probiotic strain Bifidobacterium animalis subsp. lactis 420, which improves the animals' overall inflammatory and metabolic status. Altogether, these data demonstrate that the early onset of HFD‐induced hyperglycemia is characterized by an increased bacterial translocation from intestine towards tissues, fuelling a continuous metabolic bacteremia, which could represent new therapeutic targets.