Type 2 diabetes influences bacterial tissue compartmentalisation in human obesity

Anhê, Fernando F.; Jensen, Benjamin Anderschou Holbech; Varin, Thibault; Servant, Florence; Blerk, Sebastian Van; Richard, Denis; Marceau, Simon; Surette, Michael G.; Biertho, Laurent; Lelouvier, Benjamin; Schertzer, Jonathan D.; Tchernof, André; Marette, André

doi:10.1038/s42255-020-0178-9

Cited by 180 publications

(200 citation statements)

References 43 publications

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“…This result is consistent changes in Enterococcaceae regulating insulin, since intermittent fasting lowers blood insulin and glucose and improved insulin sensitivity, coincident with a decreased relative abundance of Enterococcaceae in obese, diabetic, db/db mice [21]. Furthermore, while bacterial LPS has been shown to impair insulin clearance, we have recently shown that members of the Enterococcaceae family compartmentalize in the tissues of individuals with T2D, independently of obesity [22].…”

Section: Discussionsupporting

confidence: 78%

Gut microbiota impairs insulin clearance during obesity

Foley

Duggan

Barra

et al. 2020

Preprint

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Hyperinsulinemia can be a cause and consequence of obesity and insulin resistance. Increased insulin secretion and reduced insulin clearance can contribute to hyperinsulinemia. The triggers for changes in insulin clearance during obesity are ill-defined. We found that oral antibiotics mitigated impaired insulin clearance in mice fed a high fat diet (HFD) for 12 weeks or longer.Short-term HFD feeding and aging did not alter insulin clearance in mice. Germ-free mice colonized with microbes from HFD-fed mice had impaired insulin clearance, but not C-peptide clearance, and only after mice were colonized for 6 weeks and then HFD-fed. Five bacterial taxa predicted >90% of the variance in insulin clearance. Our data indicate that gut microbes are an independent and transmissible factor that regulates obesity-induced changes in insulin clearance.A small cluster of microbes may be a target for mitigating defects in insulin clearance and the progression of obesity and Type 2 Diabetes. We propose that a small community in the gut microbiota can impair insulin clearance and increase insulin load and the risk of complications from hyperinsulinemia.

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Section: Discussionsupporting

confidence: 78%

Gut microbiota impairs insulin clearance during obesity

Foley

Duggan

Barra

et al. 2020

Preprint

Self Cite

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“…Recent developments including multitechnical approaches [224] and more recently, contaminant-aware approaches [214,217] to evidence the existence of extra-intestinal bacteria and their relationship with metabolism point to the fact that one cannot simply repudiate the existence of tissue-specific bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…Whereas no differences in bacterial load were found within tissues between subjects with and without T2D, subjects without T2D displayed a significantly increased bacterial diversity in bacterial signature of mesenteric adipose tissue, pointing to a link between tissue-specific bacterial signature and glucose tolerance similar to observations of microbial diversity in gut microbiome studies. A specific strength of this study is the extensive inclusion of negative controls at each step of the preanalytical and experimental procedure accounting for operation field contamination at tissue collection, environmental contamination during tissue manipulation including air samples from surroundings and swab controls for used surfaces, as well as negative controls for DNA extraction, amplification, and sequencing, making it one of the first studies to present contamination-aware evidence of tissue-specific bacterial compartmentalization with a T2D extra-intestinal microbial signature, which was independent of obesity [214]. This evidence could further be expanded by recently published data from our group, where we succeeded in detecting adipose tissue borne living bacteria using catalyzed reporter deposition (CARD) -fluorescence in situ hybridization (FISH).…”

Section: Bacterial Presence In Remote Tissuesmentioning

confidence: 99%

Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders?

Chakaroun¹,

Massier²,

Kovacs³

2020

Nutrients

180

133

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The emerging evidence on the interconnectedness between the gut microbiome and host metabolism has led to a paradigm shift in the study of metabolic diseases such as obesity and type 2 diabetes with implications on both underlying pathophysiology and potential treatment. Mounting preclinical and clinical evidence of gut microbiota shifts, increased intestinal permeability in metabolic disease, and the critical positioning of the intestinal barrier at the interface between environment and internal milieu have led to the rekindling of the “leaky gut” concept. Although increased circulation of surrogate markers and directly measurable intestinal permeability have been linked to increased systemic inflammation in metabolic disease, mechanistic models behind this phenomenon are underdeveloped. Given repeated observations of microorganisms in several tissues with congruent phylogenetic findings, we review current evidence on these unanticipated niches, focusing specifically on the interaction between gut permeability and intestinal as well as extra-intestinal bacteria and their joint contributions to systemic inflammation and metabolism. We further address limitations of current studies and suggest strategies drawing on standard techniques for permeability measurement, recent advancements in microbial culture independent techniques and computational methodologies to robustly develop these concepts, which may be of considerable value for the development of prevention and treatment strategies.

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“…Bacterial translocation and tissue microbiota in humans are subjects of intense debate since several years ago [ 18 , 22 , 23 , 24 , 25 ]. Although some authors hypothesize that adipose tissue microbiota may come from the intestine when leaky gut occurs, there is still no reliable evidence in CD.…”

Section: Introductionmentioning

confidence: 99%

Microbial Signature in Adipose Tissue of Crohn’s Disease Patients

Serena

Queipo-Ortuño

Millán

et al. 2020

JCM

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Crohn’s disease (CD) is characterized by compromised immune tolerance to the intestinal commensal microbiota, intestinal barrier inflammation, and hyperplasia of creeping fat (CF) and mesenteric adipose tissue (AT), which seems to be directly related to disease activity. Gut microbiota dysbiosis might be a determining factor in CD etiology, manifesting as a low microbial diversity and a high abundance of potentially pathogenic bacteria. We tested the hypothesis that CF is a reservoir of bacteria through 16S-rRNA sequencing of several AT depots of patients with active and inactive disease and controls. We found a microbiome signature within CF and mesenteric AT from patients, but not in subcutaneous fat. We failed to detect bacterial DNA in any fat depot of controls. Proteobacteria was the most abundant phylum in both CF and mesenteric AT, and positively correlated with fecal calprotectin/C-reactive protein. Notably, the clinical status of patients seemed to be related to the microbiome signature, as those with the inactive disease showed a reduction in the abundance of pathogenic bacteria. Predictive functional profiling revealed many metabolic pathways including lipopolysaccharide biosynthesis and sulfur metabolism overrepresented in active CD relative to that in inactive CD. Our findings demonstrate that microbiota dysbiosis associated with CD pathophysiology is reflected in AT and might contribute to disease severity.

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Type 2 diabetes influences bacterial tissue compartmentalisation in human obesity

Cited by 180 publications

References 43 publications

Gut microbiota impairs insulin clearance during obesity

Gut microbiota impairs insulin clearance during obesity

Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders?

Microbial Signature in Adipose Tissue of Crohn’s Disease Patients

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