title: Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment.
abstract: 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.
authors: Rangueil Hospital, Department of Therapeutics, Toulouse, France. amar.j@chu-toulouse.fr
authors: Jacques
authors: J
authors: Amar
authors: Chantal
authors: C
authors: Chabo
authors: Aurélie
authors: A
authors: Waget
authors: Pascale
authors: P
authors: Klopp
authors: Christelle
authors: C
authors: Vachoux
authors: Luis G
authors: LG
authors: Bermúdez-Humarán
authors: Natalia
authors: N
authors: Smirnova
authors: Mathieu
authors: M
authors: Bergé
authors: Thierry
authors: T
authors: Sulpice
authors: Sampo
authors: S
authors: Lahtinen
authors: Arthur
authors: A
authors: Ouwehand
authors: Philippe
authors: P
authors: Langella
authors: Nina
authors: N
authors: Rautonen
authors: Philippe J
authors: PJ
authors: Sansonetti
authors: Rémy
authors: R
authors: Burcelin
mesh_terms: D000273:Adipose Tissue / Q000382:microbiology; D000818:Animals; D016470:Bacteremia / Q000150:complications*; D001422:Bacterial Adhesion; D018988:Bacterial Translocation; D001644:Bifidobacterium / Q000502:physiology; D001769:Blood / Q000382:microbiology; D003924:Diabetes Mellitus, Type 2 / Q000382:microbiology* / Q000517:prevention & control; D059305:Diet, High-Fat / Q000009:adverse effects*; D004926:Escherichia coli / Q000302:isolation & purification / Q000472:pathogenicity; D007413:Intestinal Mucosa / Q000382:microbiology*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D019936:Probiotics / Q000008:administration & dosage*
chemical_list: D018950:Lipopolysaccharide Receptors; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse