Fecal Microbiota Transplantation Can Alleviate Gastrointestinal Transit in Rats with High-Fat Diet-Induced Obesity via Regulation of Serotonin Biosynthesis

Abstract

Aim: We tested the hypothesis that fecal microbiota transplantation (FMT) could regulate the biotransformation of bile acids, such as deoxycholic acid (DCA) and cholic acid (CA), which in turn regulate the biosynthesis of serotonin in the gut and relieve gastrointestinal dysmotility in high-fat diet- (HFD-) induced obesity in rats.

Methods: Male Sprague-Dawley rats were randomly divided into the control diet group, HFD group, and HFD-fed with receiving FMT. HFD was fed for 12 weeks. At the end of two-week HFD, FMT was carried out for two weeks. The gastrointestinal transit, serotonin concentration, the expression of tryptophan hydroxylase 1 (TPH1) and serotonin reuptake transporter (SERT), and the levels of bile acids in intestinal contents were examined.

Results: Compared with the control group, the gastrointestinal transit and small intestinal serotonin concentration of HFD-fed rats were increased. In HFD-fed rats, TPH1 protein expression was increased significantly, while SERT protein expression was decreased, but not significant. The levels of CA and DCA in intestinal contents were also significantly increased in HFD-fed rats compared with the control group. After HFD-fed rats receiving FMT treatment, the gastrointestinal transit, small intestinal serotonin concentration, and TPH1 expression were decreased, while SERT expression was not affected. Moreover, the levels of CA and DCA in intestinal contents were also decreased.

Conclusions: FMT could alleviate small intestinal transit in the HFD-fed rats by regulating the serotonin biosynthesis. In this process, CA and DCA may be related to the regulation of synthesis of serotonin.

Figure 1

FMT alleviates the gastrointestinal transit in HFD-fed rats. (a) The flow chart of the experimental design. 30 male rats were randomly divided into the three groups (10 rats per group). (b) Body weight of the three group. (c) The small intestine and the gastrointestinal transit assay. Data were expressed as mean ± SEM (n=3~10), ∗ p<0.05 compared with the control group.

Figure 2

The concentration of serotonin in serum, small intestine, and colon among the three groups (n=6~8). ∗ p=0.020, compared with rats fed by control diet; ∗∗ p=0.030, compared with HFD-fed rats receiving FMT.

Figure 3

High-fat diets increased the levels of serotonin in small intestine. (a) Serotonin staining of small intestine in the three groups (×4). (b), (c) Brown areas show serotonin positive (×40). (d) The areas of serotonin positive in small intestine were measured in randomly selected fields from each slide. Statistical graph of quantified optical density is shown in (d). ∗p=0.012, compared with the control diet-fed rats.

Figure 4

The protein levels of TPH1 and SERT in small intestine among the three groups. (a) The protein levels of TPH1 and SERT were measured using Western blot. (b) and (c) Quantitative analysis of TPH1 and SERT protein expression. A, p=0.009, compared with the control diet rats. B, p=0.029, compared with the HFD-fed rats receiving FMT.

Figure 5

The levels of DCA and CA in intestinal contents of the three groups. (a) The CA levels of intestinal contents among the three groups (n=6~8). A, compared with control group, p<0.001; B, compared with HFD+FMT group, p=0.001. (b) The DCA levels of intestinal contents among the three groups (n=6~8). C, compared with control group, p<0.001; D, compared with HFD+FMT group, p=0.008.

Figure 6

HFD could increase the levels of CA and DCA, leading to upregulating the expression of small intestinal TPH1 and then increase the serotonin concentration of small intestine, which fastens the gastrointestinal motility. Furthermore, after receiving FMT, the decreased levels of CA and DCA could downregulate the expression of TPH1 and reduce the serotonin concentration in the gut and then relieve the gastrointestinal dysmotility. In addition, DCA can also promote gastrointestinal motility.