Prebiotics from acorn and sago prevent high-fat-diet-induced insulin resistance via microbiome-gut-brain axis modulation - PubMed (original) (raw)

Prebiotics from acorn and sago prevent high-fat-diet-induced insulin resistance via microbiome-gut-brain axis modulation

Shokouh Ahmadi et al. J Nutr Biochem. 2019 May.

Abstract

Role of gut microbiome in obesity and type 2 diabetes (T2D) became apparent from several independent studies indicating that gut microbiome modulators like prebiotics may improve microbiome perturbations (dysbiosis) to ameliorate metabolic derangements. We herein isolate water soluble, nondigestible polysaccharides from five plant-based foods (acorn, quinoa, sunflower, pumpkin seeds and sago) and assess their impact on human fecal microbiome and amelioration of high-fat-diet (HFD)-induced obesity/T2D in mice. During polysaccharide isolation, purification, biochemical and digestion resistance characterization, and fermentation pattern by human fecal microbiome, we select acorn- and sago-derived prebiotics (on the basis of relatively higher purity and yield and lower protein contamination) and examine their effects in comparison to inulin. Prebiotics treatments in human fecal microbiome culture system not only preserve microbial diversity but also appear to foster beneficial bacteria and short-chain fatty acids (SCFAs). Feeding of acorn- and sago-derived prebiotics ameliorates HFD-induced glucose intolerance and insulin resistance in mice, with effects comparatively superior to those seen in inulin-fed mice. Feeding of both of novel prebiotics as well as inulin increases SCFAs levels in the mouse gut. Interestingly, gut hyperpermeability and mucosal inflammatory markers were significantly reduced upon prebiotics feeding in HFD-fed mice. Hypothalamic energy signaling in terms of increased expression of pro-opiomelanocortin was also modulated by prebiotics administration. Results demonstrate that these (and/or such) novel prebiotics can ameliorate HFD-induced defects in glucose metabolism via positive modulation of gut-microbiome-brain axis and hence could be useful in preventing/treating diet-induced obesity/T2D.

Keywords: Diabetes; Fibers; Metabolites; Microbiome; Obesity; Polysaccharides; Prebiotic.

Copyright © 2019 Elsevier Inc. All rights reserved.

PubMed Disclaimer

Figures

Figure 1.

Figure 1.. Effect of inoculation of prebiotics (inulin, acorn and sago) on the microbiome diversity and composition in the feces of healthy versus diseased (heart attack patients) subjects.

(a,b) PCoA analyses (a: unweighted unifrac; b: weighted unifrac) representing the β-diversity of microbiome; (c) Shannon index representing the α-diversity of microbiome; (d-f) relative abundance of major phyla (d), families (e) and genera (f); and (g,h) Linear discrimination analysis (LDA) using LDA effect size (LefSe) algorithm; in the fecal suspension from healthy and diseased subjects after 9h incubation with (treatment) or without (control) prebiotics. Each dot in PCoA analysis represents two replicates of fecal slurry collected from two different replication experiments of same group. CTL: Control, INU: inulin, ACO: acorn, and SAG: sago. Values are presented as mean ± SD/ SEM. *P<0.05; ** P<0.01; ***P<0.001.

Figure 2.

Figure 2.. Effects of inoculation of prebiotics (inulin, acorn and sago) on the metabolic activity of microbiome in the feces of healthy versus diseased subjects.

(a) Fecal pH of the fecal suspension from healthy and diseased subjects after 9h incubation with (treatment) or without (control) prebiotics. (b,c) Production of lactate, acetate, propionate and butyrate in the fecal suspension from healthy (b) and diseased (c) subjects after 9h incubation with (treatment) or without (control) prebiotics. (d) Correlation of microbial groups with pH and SCFAs levels in the fecal suspension from healthy and diseased subjects after 9h incubation with (treatment) or without (control) probiotics. Values are presented as mean ± SD/SEM of n=6 replicates per treatment group. P*<0.05; **P<0.01.

Figure 3.

Figure 3.. Prebiotics prevent high-fat diet (HFD)-induced obesity in mice.

(a) Body weight during HFD feeding with and without prebiotics up to 35 days/ 5 weeks. (b-d) Intraperitoneal glucose tolerance test (IPGTT; b), oral glucose tolerance tests (OGTT; c) and intraperitoneal insulin tolerance test (IPITT; d) in prebiotics-fed and control mice after 5 weeks of intervention. (e) Hematoxylin and eosin (H&E) staining of white adipose tissue (gonadal), brown adipose tissue and liver of prebiotics-fed and control mice. Values are presented as mean ± SD/SEM. P*<0.05; **P<0.01; NS: non-significant.

Figure 4.

Figure 4.. Prebiotics modulate the diversity and composition of gut microbiome in HFD-fed mice.

a) PCoA analyses presenting β-diversity (weighted unifrac) of the gut microbiome in prebiotics-fed and control mice after 5 weeks of intervention. (b) Shannon index representing the α-diversity of gut microbiome in prebiotics-fed and control mice after 5 weeks of intervention. (c,d) Relative abundances of major phyla (c) and genera (d) in prebiotics-fed and control mice after 5 weeks of intervention. (d) Linear discrimination analysis (LDA) using LDA effect Size (LefSe) algorithm of gut microbial taxa in prebiotics-fed and control mice after 5 weeks of intervention. Values are presented as mean ± SD/SEM. P*<0.05; **P<0.01.

Figure 5.

Figure 5.. Prebiotics modulate the metabolic activities of gut microbiome in HFD-fed mice.

(a,b) Fecal pH (a) and levels of lactate, acetate, propionate and butyrate (b) in the feces of prebiotics-fed and control mice after 5 weeks of intervention. (c) Correlation of microbial groups with pH and SCFAs levels in the feces of prebiotics-fed and control mice after 5 weeks of intervention. Values are presented as mean ± SD/SEM. P*<0.05; **P<0.01; ***P<0.001.

Figure 6.

Figure 6.. Prebiotics ameliorate gut permeability, reduce inflammation and modulate gut-brain axis.

(a) Gut permeability (in terms of the diffusion of 4kDa FITC dextran from gut to blood circulation) in prebiotics-fed and control mice after 5 weeks of intervention. (b) Zonulin-1 (ZO-1) and Occludin (Ocln) mRNA expression in prebiotics-fed and control mice after 5 weeks of intervention. (c) Gene (mRNA) expression of inflammatory markers including Interleukine-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and chemokine (C-C motif) ligand 2/ monocyte chemoattractant protein 1 (Ccl2/ MCP1) in prebiotics-fed and control mice after 5 weeks of intervention. (d) Gene (mRNA) expression of Agouti related protein (AgRP), neuropeptide Y (NPY) and Pro-opiomelanocortin (POMC) in the hypothalamus of (mRNA). Values are presented as mean ± SD/SEM. P*<0.05; **P<0.01; ***P<0.001.

Similar articles

Cited by

References

    1. Marti JM, Martinez-Martinez D, Rubio T, Gracia C, Pena M, Latorre A, et al. Health and Disease Imprinted in the Time Variability of the Human Microbiome. mSystems 2017;2. - PMC - PubMed
    1. Lynch SV, Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med 2016;375:2369–79. - PubMed
    1. Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet 2012;13:260–70. - PMC - PubMed
    1. Integrative HMPRNC. The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease. Cell Host Microbe 2014;16:276–89. - PMC - PubMed
    1. Kayshap PC, Quigley EM. Therapeutic implications of the gastrointestinal microbiome. Curr Opin Pharmacol 2018;38:90–6. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources