Astragalus alters gut-microbiota composition in type 2 diabetes mice: clues to its pharmacology

Abstract

Background: Astragalus possesses therapeutic effects for type 2 diabetes (T2D), while its action mechanisms remain to be elucidated. In view of the pathogenic associations between gut microbiota and T2D, we explored the effect of astragalus on gut-microbiota composition of T2D mice. Materials and methods: Modulation effects of astragalus on gut microbiota of T2D-model mice were assessed by 16S rRNA gene sequencing. Results: Inhibited blood-glucose and body-weight levels of T2D mice by astragalus were accompanied by gut microbiota-composition alteration. Astragalus administration significantly increased gut-microbiota richness and diversity in T2D mice and significantly altered the abundance of several bacterial taxa, inducing increased abundance of Lactobacillus and Bifidobacterium. PICRUSt software revealed the relationship between astragalus and T2D. Conclusion: Due to previously reported decreased gut-microbiota richness and diversity and reduced abundance of key species of Lactobacillus and Bifidobacterium, more studies are encouraged to explore the contribution of gut-microbiota alteration by astragalus to its anti-T2D effect.

Keywords: 16S rRNA gene sequencing; alteration; astragalus; gut microbiota; type 2 diabetes.

Figure 1

Effect of astragalus on fasting blood-glucose (A) and body-weight (B) levels in type 2 diabetes mice. Values represent mean ± SE (n=5).

Figure 2

Evaluation of Illumina MiSeq data showing that astragalus altered the overall composition of gut microbiota in type 2 diabetes mice. Notes: (A) Venn diagram of shared operational taxonomic units in astragalus-administered and control groups; (B) rarefaction curves determined at the 97% similarity level.

Figure 3

Comparisons of bacterial community abundance between the control and astragalus- administered groups. Notes: (A) Abundance bar plot at phylum level; (B) significance of top ten bacterial community abundance at phylum level; (C) abundance bar plot at genus level. (D) significance of top 20 bacterial community abundance at genus level. *P<0.05; **P<0.01.

Figure 4

Linear discriminant analysis (LDA) combined with effect-size measurements at all levels of control and astragalus-administered groups. Notes: LDA scores that were greater in astragalus males shown in red, whereas the one (Clostridium XI) LDA score that was elevated in control males is depicted in blue. The LDA score of Lactobacillus and Bifidobacterium were greater in astragalus males than control males. Only LDA scores ≥2 are listed.

Figure 5

Predicted functions for the altered metagenome of gut microbiota in each group shown with Kyoto Encyclopedia of Gene and Genomes pathways. Notes: These data were obtained with PICRUSt. (A) There were 13 markedly altered pathways at level 2 in the astragalus group compared with that in the control group and (B) 31 significantly changed pathways through astragalus supplementation in type 2 diabetes mice.