TY - JOUR
T1 - Resistant starch can improve insulin sensitivity independently of the gut microbiota
AU - Bindels, Laure B.
AU - Segura Munoz, Rafael R.
AU - Gomes-Neto, João Carlos
AU - Mutemberezi, Valentin
AU - Martínez, Inés
AU - Salazar, Nuria
AU - Cody, Elizabeth A.
AU - Quintero-Villegas, Maria I.
AU - Kittana, Hatem
AU - de los Reyes-Gavilán, Clara G.
AU - Schmaltz, Robert J.
AU - Muccioli, Giulio G.
AU - Walter, Jens
AU - Ramer-Tait, Amanda E.
N1 - Funding Information:
We thank Ody Maningat and Liming Cai (MGP Ingredients) for providing the RS, Dr. Jennifer Clarke (University of Nebraska-Lincoln) for expert advice on statistical analysis, Dr. Shawn Rigby (Iowa State University) for assistance with flow cytometry, Drs. Jun Han and Christoph H. Borchers (University of Victoria Genome British Columbia Proteomics Centre) for assistance with bile acids analysis, Dr. Junyi Yang and Maria Ximena Maldonaldo Gomez (University of Nebraska-Lincoln) for assistance with tissue processing, and Dr. Michael Pellizzon (Research Diets, Inc.) for assistance with diet formulations. ART and LBB would like to thank Drs. Andy Benson and Devin Rose (University of Nebraska-Lincoln) and Dr. Nathalie Delzenne (Universit? catholique de Louvain) for their helpful discussions and critical reading of the manuscript. We are all especially grateful for the technical expertise and skillful animal husbandry provided by Brandon White and the staffat the UNL Gnotobiotic Mouse Facility. This work was supported by the National Institute of General Medical Sciences of the National Institutes of Health (1P20GM104320), the Nebraska Corn Board, and start-up funding from the University of Nebraska-Lincoln to ART. LBB was supported by a complementary post-doctoral grant awarded by the "Fonds Sp?cial de Recherche, Universit? catholique de Louvain." VM is a research fellow of the "Fonds pour la recherche dans l'industrie et l'agriculture" (FRIA, Belgium). NS benefits from a Clar?n postdoctoral contract (Marie Curie European CoFund Program) co-financed by Plan Regional de Investigaci?n del Principado de Asturias, Spain. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
PY - 2017
Y1 - 2017
N2 - Background: Obesity-related diseases, including type 2 diabetes and cardiovascular disease, have reached epidemic proportions in industrialized nations, and dietary interventions for their prevention are therefore important. Resistant starches (RS) improve insulin sensitivity in clinical trials, but the mechanisms underlying this health benefit remain poorly understood. Because RS fermentation by the gut microbiota results in the formation of physiologically active metabolites, we chose to specifically determine the role of the gut microbiota in mediating the metabolic benefits of RS. To achieve this goal, we determined the effects of RS when added to a Western diet on host metabolism in mice with and without a microbiota. Results: RS feeding of conventionalized mice improved insulin sensitivity and redressed some of the Western diet-induced changes in microbiome composition. However, parallel experiments in germ-free littermates revealed that RS-mediated improvements in insulin levels also occurred in the absence of a microbiota. RS reduced gene expression of adipose tissue macrophage markers and altered cecal concentrations of several bile acids in both germ-free and conventionalized mice; these effects were strongly correlated with the metabolic benefits, providing a potential microbiota-independent mechanism to explain the physiological effects of RS. Conclusions: This study demonstrated that some metabolic benefits exerted by dietary RS, especially improvements in insulin levels, occur independently of the microbiota and could involve alterations in the bile acid cycle and adipose tissue immune modulation. This work also sets a precedent for future mechanistic studies aimed at establishing the causative role of the gut microbiota in mediating the benefits of bioactive compounds and functional foods.
AB - Background: Obesity-related diseases, including type 2 diabetes and cardiovascular disease, have reached epidemic proportions in industrialized nations, and dietary interventions for their prevention are therefore important. Resistant starches (RS) improve insulin sensitivity in clinical trials, but the mechanisms underlying this health benefit remain poorly understood. Because RS fermentation by the gut microbiota results in the formation of physiologically active metabolites, we chose to specifically determine the role of the gut microbiota in mediating the metabolic benefits of RS. To achieve this goal, we determined the effects of RS when added to a Western diet on host metabolism in mice with and without a microbiota. Results: RS feeding of conventionalized mice improved insulin sensitivity and redressed some of the Western diet-induced changes in microbiome composition. However, parallel experiments in germ-free littermates revealed that RS-mediated improvements in insulin levels also occurred in the absence of a microbiota. RS reduced gene expression of adipose tissue macrophage markers and altered cecal concentrations of several bile acids in both germ-free and conventionalized mice; these effects were strongly correlated with the metabolic benefits, providing a potential microbiota-independent mechanism to explain the physiological effects of RS. Conclusions: This study demonstrated that some metabolic benefits exerted by dietary RS, especially improvements in insulin levels, occur independently of the microbiota and could involve alterations in the bile acid cycle and adipose tissue immune modulation. This work also sets a precedent for future mechanistic studies aimed at establishing the causative role of the gut microbiota in mediating the benefits of bioactive compounds and functional foods.
KW - Adipose tissue macrophages
KW - Gut microbiota
KW - Insulin sensitivity
KW - Resistant starch
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U2 - 10.1186/s40168-017-0230-5
DO - 10.1186/s40168-017-0230-5
M3 - Article
C2 - 28166818
AN - SCOPUS:85016039483
VL - 5
JO - Microbiome
JF - Microbiome
SN - 2049-2618
IS - 1
M1 - 12
ER -