Improvement of loperamide-induced slow transit constipation by Bifidobacterium bifidum G9-1 is mediated by the correction of butyrate production and neurotransmitter profile due to improvement in dysbiosis

PLoS One. 2021 Mar 22;16(3):e0248584. doi: 10.1371/journal.pone.0248584. eCollection 2021.

Abstract

A treatment option for constipation that improves the quality of life is needed since available laxatives do not effectively improve the quality of life in patients with constipation. A significant association between gut dysbiosis and constipation is recognized, suggesting that probiotics may be an important option for management of constipation. The underlying mechanism by which probiotics improve constipation remains unclear. In this study, we aimed to evaluate the effects of the probiotic Bifidobacterium bifidum G9-1 (BBG9-1) on loperamide-induced delayed colonic transit constipation and to elucidate its mechanism of action. First, the effect of BBG9-1 was evaluated in a rat model of constipation induced by subcutaneous administration of loperamide. BBG9-1 improved constipation parameters (number of feces, fecal water content, and fecal hardness) in constipated rats. Next, the relationship of organic acids and neurotransmitters to gut microbiota was investigated. BBG9-1 improved dysbiosis and prevented a decrease in butyric acid concentration in the gut, increased serum serotonin, and suppressed an increase in dopamine and a decrease in acetylcholine in serum. Further, an increase in the expression level of tryptophan hydroxylase 1, a 5-HT-synthetizing enzyme, was observed. These results suggest that BBG9-1 improves dysbiosis, which results in an increase in organic acids and improvement of neurotransmission. These actions may increase intestinal mobility, finally leading to alleviating constipation. The probiotic BBG9-1 may, therefore, be a potential option for the treatment of constipation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bifidobacterium bifidum / chemistry*
  • Butyrates / metabolism
  • Butyric Acid / metabolism
  • Constipation / drug therapy*
  • Constipation / etiology
  • Constipation / pathology
  • Disease Models, Animal
  • Dopamine / biosynthesis
  • Dopamine / genetics
  • Dysbiosis / chemically induced
  • Dysbiosis / complications
  • Dysbiosis / microbiology*
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Motility / drug effects
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Laxatives / pharmacology
  • Loperamide / toxicity
  • Neurotransmitter Agents / metabolism
  • Probiotics / chemistry
  • Probiotics / pharmacology*
  • Quality of Life
  • Rats
  • Serotonin / blood
  • Tryptophan Hydroxylase / genetics*

Substances

  • Butyrates
  • Laxatives
  • Neurotransmitter Agents
  • Butyric Acid
  • Serotonin
  • Loperamide
  • Tryptophan Hydroxylase
  • Dopamine

Grants and funding

Biofermin Pharmaceutical Co., Ltd. provided support for this study in the form of salaries for YM, TU, HY, MY, YT, and HO. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.