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Aging and disease    2018, Vol. 9 Issue (4) : 566-577     DOI: 10.14336/AD.2017.1001
Orginal Article |
Effect of Aging and Glucagon-like Peptide 2 on Intestinal Microbiota in SD Rats
Wu Jiayu1, Ren Weiying1, Li Li2, Luo Man1, Xu Kan1, Shen Jiping1, Wang Jia1, Chang Guilin1, Lu Yi1, Qi Yiming2, Xu Binger1, He Yuting1, Hu Yu1,*
1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
2Department of Internal Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Abstract  

Recent research suggests that intestinal microbiota affect the aging process. Glucagon-like peptide 2 (GLP-2), a growth factor found in the intestinal mucosal epithelium, reduces intestinal permeability and affects intestinal microbiota. The relationship between aging, GLP-2, and intestinal microbiota are still not well understood. The current study examined the influence of aging and GLP-2 on the intestinal microbiota of rats. Twelve 3-month old male SD rats were randomly divided into two groups: a young control group (group C) and a young GLP-2 treatment group (group G). Twelve 26-month old male SD rats were randomly divided into two groups: an aged control group (group L) and an aged GLP-2 treatment group (group T). GLP-2 was intraperitoneally injected into rats from group G and group T for 14 days. Plasma GLP-2 concentration was evaluated by ELISA tests. Fresh intestinal stool samples were collected from each group and total fecal bacterial genomic DNA was extracted from the associated rats. The bacterial composition of fecal samples was analyzed by Miseq high-throughput sequencing and comparison with SRA databases. Overall, the diversity of intestinal microbiota significantly decreases with age in SD rats, while GLP-2 has no significant effect on the diversity of intestinal microbiota. Upon aging, there is a reduction in probiotic bacteria and a concomitant increase in pathogenic bacteria in rats. Treatment with GLP-2 results in a significant reduction in the prevalence of pathogenic bacterial genera and an increase in some potential benefit bacteria in aged rats. In addition, treatment with GLP-2 results in an increase in several probiotics and a reduction in the prevalence of pathogenic bacterial genera in young rats.

Keywords aging      GLP-2      intestinal microbiota      high-throughput sequencing     
Corresponding Authors: Hu Yu   
About author:

These authors contributed equally to this work.

Issue Date: 01 August 2018
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Wu Jiayu
Ren Weiying
Li Li
Luo Man
Xu Kan
Shen Jiping
Wang Jia
Chang Guilin
Lu Yi
Qi Yiming
Xu Binger
He Yuting
Hu Yu
Cite this article:   
Wu Jiayu,Ren Weiying,Li Li, et al. Effect of Aging and Glucagon-like Peptide 2 on Intestinal Microbiota in SD Rats[J]. Aging and disease, 2018, 9(4): 566-577.
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http://www.aginganddisease.org/EN/10.14336/AD.2017.1001     OR     http://www.aginganddisease.org/EN/Y2018/V9/I4/566
GroupNo. of readsNo. of OTUsRichness estimatorα-Diversity index

Ace95% CIChao95% CICoverageShannon
Group C699272124413393.1-431.9415384.9-445.80.98934.40
Group G723902111400386.5-414.1406392.3-419.70.99094.55
Group L780311848367345.3-388.4372336.0-408.00.99163.90
Group T716381912371339.0-402.7385345.7-424.30.99103.82
Table 1  Diversity estimation of the intestinal microbiota in SD rats.
Figure 1  Comparison of diversity indices, Venn diagram, rarefaction curve, PCoA, and plasma concentration of GLP-2 among the 4 groups

Comparison of diversity indices including the Shannon Curve (A) and Shannon Index (B). (C) Venn diagram illustrating overlap between the 4 groups. (D) Rarefaction curve. (E) PCoA was analyzed by unweighted Unifrac. (F) Plasma concentration of GLP-2 among the 4 groups. C denotes group C; G denotes group G; L denotes group L; T denotes group T; young denotes group C and group G; old denotes group L and group T; treat denotes treatment with GLP-2; * denotes P<0.05.

Figure 2  Relative abundance at the phylum level and the genus level in fecal microbiota

(A) Relative abundance at the phylum level in fecal microbiota. (B) Relative abundance at the genus level in fecal microbiota.

GroupBacteroidetesFirmicutesProteobacteriaVerrucomicrobiaSpirochaetae
(%)(%)(%)(%)(%)
Group C0.4574876170.457818830.0370454670.0298362420.000116522
Group G0.4222286420.4654884350.0438704020.0478687830.001192522
Group L0.5593298830.3896321820.0205497550.0000000000.015300716
Group T0.4708080050.4821633850.0277434440.00049830.007512288
Table 2  The relative abundance of microbial phyla in the microbiota of Groups C, G, L and T.
Figure 3  Comparison relative abundance of microbiota at the phylum level among the 4 groups

Relative abundance (at the phylum level) of Bacteroidetes (A), Firmicutes (B), Proteobacteria (C), Verrucomicrobia (D), and Spirochaetae (E) among the 4 groups. C denotes group C; G denotes group G; L denotes group L; T denotes group T; * denotes P<0.05.

SequenceGenusAbundance in Group C (%)Abundance in Group L (%)Trends in Group L
1Alistipes *0.0042280.000141
2Allobaculum *0.0208270.000000
3Anaerovibrio *0.0000000.003652
4Bifidobacterium *0.0005740.000000
5Christensenellaceae_uncultured *0.0085200.001827
6Clostridium_sensu_stricto_1 *0.0077290.000410
7Corynebacterium *0.0057290.000000
8Helicobacter *0.0100860.002609
9Jeotgalicoccus *0.0039660.000000
10Marvinbryantia *0.0066850.000059
11Paraprevotella *0.0016150.000000
12Parasutterella *0.0130600.000063
13Peptococcaceae_uncultured *0.0023930.000247
14Prevotellaceae_unclassified *0.0683510.355279
15Psychrobacter *0.0063870.000000
16RC9_gut_group *0.0000000.005918
17Ruminococcaceae_uncultured *0.1148760.060653
18S24-7_norank *0.2449960.029386
19Streptococcus *0.0011720.003484
20Thalassospira *0.0003410.001554
21Treponema *0.0001170.015301
22p-2534-18B5_gut_group_norank *0.0000000.007516
Table 3  The relative abundance of microbial genera in the microbiota of Group C and Group L.
Figure 4  Comparison relative abundance of microbiota at the genus level among the 4 groups

Relative abundance (at the genus level) of Anaerovibrio (A), Desulfovibrio (B), Helicobacter (C), Intestinimonas (D), Oscillibacter (E), Parasutterella (F), Prevotella (G), Psychrobacter (H), and Treponema (I) among the 4 groups. C denotes group C; G denotes group G; L denotes group L; T denotes group T; * denotes P<0.05.

Figure 5  The linear correlation between plasma concentrations of GLP-2 and relative abundance of microbiota

The linear correlation between plasma concentrations of GLP-2 and relative abundance of Spirochaetae (A), Intestinimonas (B), Desulfovibrio (C), Treponema (D).

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