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Sci Rep. 2018 Jul 27;8(1):11338. doi: 10.1038/s41598-018-29815-7.

Complementary intestinal mucosa and microbiota responses to caloric restriction.

Author information

1
Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, 308232, Singapore. kalina.duszka@univie.ac.at.
2
Center for Integrative Genomics, University of Lausanne, Lausanne, 1015, Switzerland. kalina.duszka@univie.ac.at.
3
Department of Nutritional Sciences, University of Vienna, Vienna, 1090, Austria. kalina.duszka@univie.ac.at.
4
Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, 31300, France.
5
Bioinformatics Institute, A*STAR Biomedical Sciences Institutes, Singapore, 13867, Singapore.
6
Quadram Institute Bioscience, , Norwich Science Park, Norwich, Norfolk, NR7UA, UK.
7
Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, 308232, Singapore.
8
Department of Nutritional Sciences, University of Vienna, Vienna, 1090, Austria.
9
Vienna Metabolomics Center (VIME), University of Vienna, Vienna, 1090, Austria.
10
SUNY Upstate Medical University Syracuse, Syracuse, NY, 13210, USA.
11
Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, 308232, Singapore. Walter.Wahli@ntu.edu.sg.
12
Center for Integrative Genomics, University of Lausanne, Lausanne, 1015, Switzerland. Walter.Wahli@ntu.edu.sg.
13
Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, 31300, France. Walter.Wahli@ntu.edu.sg.

Abstract

The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR.

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