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

By J. Amar, C. Chabo, A. Waget, P. Klopp, C. Vachoux, L. Bermúdez-Humarán, N. Smirnova, M. Bergé, T. Sulpice, Sampo J. Lahtinen and 5 more. EMBO Molecular Medicine, 2011

775 citations recorded by the source corpus.

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.

Subfields: Food Science, Gastroenterology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2d49ddf180b00111a96c5030748315cb6677f72b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Food Science

In Gastroenterology

In Molecular Biology

Citations in the corpus

The gut microbiome: Relationships with disease and opportunities for therapy (2018, background): “lactis Restores the integrity of the intestinal barrier, thus reducing bacterial translocation and insulin sensitivity (Amar et al., 2011)”
Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance. (2016, background): “The breakdown of tightjunction function leads to LPS translocation, which may be an early factor in the development of inflammation and insulin resistance in humans and mice (4, 12, 13, 17, 18) (FIGURE 2).”
Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice (2014, background): “All strains significantly attenuated HFD-induced weight gain, improved glucose– insulin homeostasis and reduced hepatic steatosis, consistent with other studies of Lactobacillus and Bifidobacterium probiotic strains tested individually or as cocktails (Lee et al., 2006; Ma et al., 2008; Aronsson et ”
Inflammatory mechanisms linking obesity and metabolic disease (2017, background): “For example, obesity gives rise to increased intestinal permeability, which results in higher circulating levels of LPS from intestinal Gram-positive bacterial species (14).”
Next-Generation Beneficial Microbes: The Case of Akkermansia muciniphila (2017, background): “…September 2017 | Volume 8 | Article 1765 Knowing that these metabolic features can be caused by an increased plasma LPS level (i.e., metabolic endotoxemia) or bacterial translocation (Cani et al., 2007; Amar et al., 2011), we next investigated the gut barrier function by measuring several markers.”
Impacts of Gut Bacteria on Human Health and Diseases (2015, background): “since glucose intolerance was moderately blunted, and insulin sensitivity and fasting hyperinsulinemia were completely normalized [89].”
Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation (2015, background): “Proteobacteria are generally not considered to be beneficial due to their proinflammatory properties (Amar et al., 2011; Cani et al., 2007; Mukhopadhya et al., 2012).”
Role of intestinal microbiota and metabolites on gut homeostasis and human diseases (2017, background): “The receptors for foreign nucleic acids involve members of TLRs including TLR3, TLR7, TLR8, and TLR9, and intracellular DNA sensors [17].”
Intestinal permeability – a new target for disease prevention and therapy (2014, background): “Western style diet rich in fat and sugars alters the intestinal barrier in a way resulting in enhanced permeability and elevated endotoxin levels in the portal vein [104,150,227].”
The Hologenome Concept: Human, Animal and Plant Microbiota (2014, background): “Bacteremia has also (potentially) been implicated in this process (Amar et al. 2011).”