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Micalis

Irene Millán - jeudi 17 novembre 2022 11h

jeudi 17 novembre 2022 11h - Micalis seminars auditorium 442

Irene Millán - jeudi 17 novembre 2022 11h
Gut microbiome depletion rescues pancreatic inflammation in Nr5a2+/- mice

Gut microbiome depletion rescues pancreatic inflammation in Nr5a2+/- mice

 Irene Millán

Spanish National Cancer Research Centre

 

Short abstract

Genome-wide association studies have identified pancreatic ductal adenocarcinoma susceptibility variants in the NR5A2 locus, which encodes an orphan nuclear receptor involved in acinar cell differentiation. In the last decade, our laboratory has worked under the assumption that these genetic variants lead to a partial loss of function, which can be modelled using Nr5a2 heterozygous mice (Nr5a2+/-). Nr5a2+/- mice display a pre-inflammatory state in the pancreas, experience a more severe damage upon induction of pancreatitis and are sensitized to pancreatic tumorigenesis.

The gut microbiome has recently emerged as a critical modulator of pancreatic disease. To determine the contribution of the gut microbiome to pancreatic inflammation in Nr5a2+/- mice, we depleted the gut microbiome using broad-spectrum antibiotics (ABX) and assessed the effects on the pancreas in basal conditions and upon induction of pancreatitis, through the use of histologic and transcriptomic analyses. ABX administration had no major effects on pancreas histology but it induced a transcriptomic sub-inflammatory state in the pancreas both in wt and in Nr5a2+/- mice. In addition, ABX-mediated gut microbiome depletion rescued pancreatitis at the histological and transcriptomic level in Nr5a2+/- mice. Transcriptomic analyses of the pancreas and blood/tissue immunoprofiling revealed that the protective effects of ABX could result from the modulation of mitochondrial and CD4+ T cell function.

Overall, our results indicate that the gut microbiota promotes basal inflammation in the pancreas, and reveal that a genetic defect that increases pancreatic cancer susceptibility can be rescued through modulation of the gut microbiota. Understanding the mechanisms involved may provide an opportunity to act on modifiable factors to prevent pancreatic disease.

 

Short CV

Irene Millán obtained her bachelor degree in general Biology at Universidad Autónoma de Madrid in 2015. During this time, she carried out one year abroad as an Erasmus student in Imperial College London, where she also pursued her Masters degree in Applied Biosciences and Biotechnology. In 2018, she was awarded a “la Caixa” Fellowship to join the Epithelial Carcinogenesis Group at the Spanish National Cancer Research Centre (CNIO), where she recently graduated as a doctor in Molecular Biology. Her talk will focus on the contribution of the gut microbiome to pancreatic inflammation in Nr5a2+/- mice.

jeudi 17 novembre 2022 11h

Auditorium 442

invitée par Sylvie Rabot