Aqueous Extract of Phyllanthus emblica L. Alleviates Functional Dyspepsia through Regulating Gastrointestinal Hormones and Gut Microbiome In Vivo

Abstract

Phyllanthus emblica L. fruits were extracted by a hot water assistant with ultrasonication to obtain aqueous Phyllanthus emblica L. extract (APE). The ameliorating functional dyspepsia (FD) effect of a low dose (150 mg/kg) and a high dose (300 mg/kg) of APE was exhibited by determining the gastrointestinal motility, gastrointestinal hormones, and gut microbiome shifts in reserpine induced FD male balb/c mice. APE increased the gastrointestinal motility including the gastric emptying (GE) rate and small intestinal transit (SIT) rate. The level of serum gastrointestinal hormones such as motilin (MTL) and gastrin (GAS) increased, and the vasoactive intestinal peptide (VIP) level decreased after the administration of APE. Furthermore, the gut microbiome analysis demonstrated that APE could regulate the microbiome structure and restore homeostasis by elevating useful bacterial abundance, while simultaneously decreasing harmful bacterial abundance. This study demonstrated the ameliorating FD effect of APE and its potential efficacy in curing functional gastrointestinal disorders and maintaining a healthy digestive tract.

Keywords: aqueous Phyllanthus emblica L. extract; functional dyspepsia; gastrointestinal hormones; gut microbiome.

Figure 1

The body weight (A) and food intake (B) changes of mice in the process of APE administration. (N, normal group; M, model group; APEL, 150 mg/kg APE group; APEH, 300 mg/kg APE group).

Figure 2

Effect of APE on GE ratio (A) and SIT ratio (B) in FD mice ((*) p < 0.05 and (**) p < 0.01 compared to the model group). (N, normal group; M, model group; APEL, 150 mg/kg APE group; APEH, 300 mg/kg APE group).

Figure 3

Effect of APE on serum gastrointestinal hormones MTL (A), GAS (B), VIP (C), and CCK (D) in FD mice ((*) p < 0.05 compared to the model group). (N, normal group; M, model group; APEL, 150 mg/kg APE group; APEH, 300 mg/kg APE group).

Figure 4

Effective sequence length distribution of intestinal microbial sequence tags in mice (A); Venn diagram of OTU distribution in the normal, model, APEL, and APEH groups (B); α diversity indicated by the (C) Shannon index and (D) Simpson index; PCA plots were used to visualize differences in weighted UniFrac distances of samples of OTUs from different groups (E). ((*) p < 0.05 compared to the model group). (N, normal group; M, model group; APEL, 150 mg/kg APE group; APEH, 300 mg/kg APE group).

Figure 5

Relative abundance plots displaying the differences in the microbial community structure at the phylum level (top 20) (A) and genus level (top 20) (B); relative abundance of Firmicutes (C), Bacteroidetes (D), Muribaculaceae (E), Lactobacillus (F), and Alistipes (G). ((*) p < 0.05 and (**) p < 0.01 compared to the model group). (N, normal group; M, model group; APEL, 150 mg/kg APE group; APEH, 300 mg/kg APE group).

Figure 6

Microbial taxa discrepancies among normal, model, and APE groups (LDA scores of >2.0 and adjusted p values of <0.05). (A) Histogram and (B) cladogram. (C) Correlation analysis (p value of <0.05 and |R2| of >0.7) based on Spearman’s rank-order correlation between the top 20 abundant gut microorganisms at the genera level and biochemical criterion.