Resistant starch can improve insulin sensitivity independently of the gut microbiota.
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.



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.



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.
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA.
Laure B
LB
Bindels
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA.
Rafael R
RR
Segura Munoz
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA.
João Carlos
JC
Gomes-Neto
Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
Valentin
V
Mutemberezi
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Inés
I
Martínez
Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC), Asturias, Spain.
Nuria
N
Salazar
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA.
Elizabeth A
EA
Cody
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA.
Maria I
MI
Quintero-Villegas
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA.
Hatem
H
Kittana
Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias-Consejo Superior de Investigaciones Científicas (IPLA-CSIC), Asturias, Spain.
Clara G
CG
de Los Reyes-Gavilán
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA.
Robert J
RJ
Schmaltz
Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
Giulio G
GG
Muccioli
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.|Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
Jens
J
Walter
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA. aramer-tait2@unl.edu.
Amanda E
AE
Ramer-Tait
D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000502:physiology; D066273:Diet, Western; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D013213:Starch / Q000008:administration & dosage* / Q000737:chemistry*
D004040:Dietary Carbohydrates; D007328:Insulin; D013213:Starch
Adipose tissue macrophages; Gut microbiota; Insulin sensitivity; Resistant starch