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. 2020 May;41(5):678-685.
doi: 10.1038/s41401-019-0330-9. Epub 2020 Jan 14.

Fecal microbiota transplantation improves metabolism and gut microbiome composition in db/db mice

Pei-Pei Zhang #  1 , Lin-Lin Li #  1   2 , Xue Han  1 , Qin-Wei Li  3 , Xu-Hua Zhang  1 , Johnson J Liu  4 , Ye Wang  5
Affiliations

Fecal microbiota transplantation improves metabolism and gut microbiome composition in db/db mice

Pei-Pei Zhang et al. Acta Pharmacol Sin. 2020 May.

VSports注册入口 - Abstract

Fecal microbiota transplantation (FMT) has become an effective strategy to treat metabolic diseases, including type 2 diabetes mellitus (T2DM) VSports手机版. We previously reported that the intestinal microbiome had significant difference between individuals with normal glucose tolerance and T2DM in Chinese Kazak ethnic group. In this study, we investigated the effects of transplanted fecal bacteria from Kazaks with normal glucose tolerance (KNGT) in db/db mice. The mice were treated with 0. 2 mL of fecal bacteria solution from KNGT daily for 10 weeks. We showed that the fecal bacteria from KNGT successfully colonized in the intestinal tract of db/db mice detected on day 14. In the FMT-treated db/db mice, the levels of fasting blood glucose, postprandial glucose, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol were significantly downregulated, whereas high-density lipoprotein-cholesterol levels were upregulated. In the FMT-treated db/db mice, Desulfovibrio and Clostridium coccoides levels in gut were significantly decreased, but the fecal levels of Akkermansia muciniphila and colon histone deacetylase-3 (HDAC3) protein expression were increased. At 8 weeks, both intestinal target bacteria and HDAC3 were correlated with glycolipid levels; Akkermansia muciniphila level was positively correlated with HDAC3 protein expression (r = +0. 620, P = 0. 037). Our results suggest that fecal bacteria from KNGT could potentially be used to treat diabetic patients. .

Keywords: Akkermansia muciniphila; Chinese Kazak ethnic group; Clostridium coccoides; Desulfovibrio; colon histone deacetylase-3; db/db mice; fecal microbial transplantation; intestinal microbiome; metabolic diseases V体育安卓版. .

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Prepared feces from the donors were divided into several 5-mL cryopreservation tubes and fed to the db/db mice one tube per day.
Two tubes were randomly selected to determine the consistency of the composition of the daily administered fecal bacteria. HZR1: fecal bacteria of KNGT tube #1; HZR2: fecal bacteria of KNGT tube #2.
Fig. 2
Fig. 2. Staining of live bacteria in fecal samples from KNGT and mice.
a Fecal bacteria from KNGT. b Fecal bacteria from the intestinal tracts of mice, indicating colonization of KNGT bacteria on day 14.
Fig. 3
Fig. 3. Changes in body weight and plasma glycolipid levels in db/db mice treated with fecal bacteria from KNGT.
PPG (a), FBG (b), TC (c), TG (d), HDL–c (g), LDL–c (h), and body weight (k) in mice treated with KNGT. Area under the blood lipid-time curve (AUC) of TC (e), TG (f), HDL–c (i), and LDL–c (j) in mice treated with KNGT for 10 weeks. Differences between the groups were analyzed by using one-way ANOVA. **P < 0.01, ***P < 0.001 compared with the db/m + PBS mice. #P < 0.05, ##P < 0.01, ###P < 0.001 compared with the db/db + PBS mice.
Fig. 4
Fig. 4
Total OTU richness was evaluated by chao (a) or ace (b). The results were analyzed by using one-way ANOVA. *P < 0.05, **P < 0.01 compared with the db/m + PBS mice. Relative abundance ratio of the intestinal microbiome at the species (c) and genus (d) levels. Data are presented as the percentage of species, and the results were obtained by using the Kruskal–Wallis test. The same color in m6, D6, and H6 represents the same species. m6: db/m + PBS; D6: db/db + PBS; H6: db/db + KNGT. Mice were tested at 6 weeks.
Fig. 5
Fig. 5. Quantification of intestinal target bacteria in mice.
SQ represents the starting template quantity of Desulfovibrio (a), Clostridium coccoides (b), and Akkermansia muciniphila (c) at different time points. The results were analyzed by using one-way ANOVA. *P < 0.05, **P < 0.01, ***P < 0.001 compared with db/m + PBS mice. #P < 0.05, ##P < 0.01 compared with db/db + PBS mice.
Fig. 6
Fig. 6. HDAC3 protein expression in mouse colonic samples.
Total protein was extracted from mouse colon specimens at different time points (a: 0 weeks, b: 8 weeks), and the levels of HDAC3 were analyzed by using Western blot. The signal intensity was quantified by using densitometry and is expressed relative to β-actin expression (c). Values are the mean ± S.D. *P < 0.05 compared with db/m + PBS mice. #P < 0.05 compared with db/db + PBS mice.
Fig. 7
Fig. 7
Correlation between intestinal target bacteria and glycolipid metabolism parameters in db/db mice treated with fecal bacteria from KNGT on week 8 (a–f). Correlation between HDAC3 expression and glycolipid metabolism parameters (g–i). Correlation analysis between intestinal target bacteria and HDAC3 expression (j). The results were analyzed by using Pearson’s correlation analysis. P values  <  0.05 were considered significant.
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VSports注册入口 - References

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