Bifidobacterium Lactobacillus Triple Viable Alleviates Slow Transit Constipation by Regulating Gut Microbiota and Metabolism

Abstract

Background: Gut microbiota plays a crucial role in the pathogenesis and treatment of functional constipation (FC). The aim of this study was to explore the therapeutic effects of Bifidobacterium Lactobacillus triple viable on slow transit constipation (STC).

Methods: Patients with STC who met the Rome IV criteria received Bifidobacterium Lactobacillus triple viable. Gastrointestinal transit time (GITT) and constipation-related symptoms were assessed before and after receiving Bifidobacterium Lactobacillus triple viable. Additionally, a rat STC model was induced by loperamide and was treated with Bifidobacterium Lactobacillus triple viable to evaluate whether Bifidobacterium Lactobacillus triple viable could improve constipation in the rats and to explore the possible mechanisms involved.

Results: In patients with STC, Bifidobacterium Lactobacillus triple viable accelerated GITT and improved constipation-related symptoms, including bowel movement frequency, hard bowel movement, incomplete defecation, defecation time, purgative measures, and stool form. In addition, Bifidobacterium Lactobacillus triple viable improved body weight, food intake, bowel movement, the fecal water content, and the intestinal propulsion rate in STC rats. It regulates the gut microbiota structure in rats; increases serum acetylcholine (Ach), 5-hydroxytryptamine (5-HT), substance P (SP), and vasoactive intestinal peptide (VIP); increases fecal long-chain fatty acids (LCFAs); upregulates the mRNA expression of aquaporin 3 (AQP3) and aquaporin 3 (AQP8); and downregulates the mRNA expression of Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), and interleukin-1β (IL-1β).

Conclusions: Bifidobacterium Lactobacillus triple viable ameliorated the GITT and constipation-related symptoms of patients with STC and improved the STC in rats by regulating the gut microbiota and metabolism.

Keywords: Bifidobacterium Lactobacillus triple viable; gut microbiota; metabolism; slow transit constipation.

FIGURE 1

Abdominal x‐ray of a patient with STC before and after treatment with Bifidobacterium Lactobacillus triple viable. (A) Pretreatment. (B) Posttreatment.

FIGURE 2

The effects of Bifidobacterium Lactobacillus triple viable improves on the physiological indices in rats with STC. (A) Body weight. (B) Food intake. (C) Fecal number. (D) Fecal water content. (E) Intestinal propulsive rate. Data were represented as mean ± SD. *p < 0.05, **p < 0.01, *** p < 0.001, LOP versus CTR group; ^# p < 0.05, ^## p < 0.01, ^### p < 0.001, LOP versus BTV group.

FIGURE 3

The results of the analysis of the gut microbiota diversity in rats. (A) Rarefaction curves. (B) Shannon curves. (C) Sobs index. (D) Shannon index. (E) Principal coordinate analysis (PCoA). (F) Adonis analysis. The X‐axis represents the distance values within or between groups, the boxes corresponding to between represent the distance values of intergroup differences, and the remaining boxes represent the distance values of intragroup differences. The Y‐axis scale represents the size of the distance value. The data are presented as the means ± SD.

FIGURE 4

Composition of gut microbiota among the three groups. (A) Family level. (B) Genus level. (C) Specials level. (D) Major differential microbiota at the family level. (E–H) Major differential microbiota at the genus level. (I–L) Major differential microbiota at the specials level. Data were represented as mean ± SD.

FIGURE 5

Effects of Bifidobacterium Lactobacillus triple viable on the mRNA Expression of aquaporins and inflammatory cytokines in colon tissues of rats. (A,B) mRNA expression of aquaporins, including AQP3 (A) and AQP8 (B). (C–E) mRNA expression of inflammatory cytokines, including TLR2 (C), TLR4 (D), and IL‐1β (E). Data were represented as mean ± SD. *p < 0.05, **p < 0.01, LOP versus CTR group; ^# p < 0.05, ^## p < 0.01, LOP versus BTV group.

FIGURE 6

Effects of Bifidobacterium Lactobacillus triple viable on the serum metabolites in constipated rats. (A) Volcano plot of differential metabolites between CTR and LOP groups. (B) Volcano plot of differential metabolites between LOP and BTV groups. (C) Principal component analysis (PCA) based on all identified metabolites. (D) Heatmap of the compounds between three groups. (E) KEGG enrichment analysis of the differential metabolic pathways between the CTR, LOP, and BTV groups. (F) KEGG heatmap of the differential metabolic pathways between the CTR, LOP, and BTV groups.

FIGURE 7

The levels of neurotransmitters and LCFAs in the rats. (A–E) Neurotransmitters: 5‐HT (A), Ach (B), MTL (C), SP (D), and VIP (E). (F–J) LCFAs: C13:0 (F), C14:0 (G), C14:1 (H), C15:0 (I), and C17:0 (J). Data were represented as mean ± SD. ^ns p > 0.05, *p < 0.05, **p < 0.01, LOP versus CTR group; ^# p < 0.05, ^## p < 0.01, LOP versus BTV group.