Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway

Authors
Journal
World Journal of Gastroenterology
Year
DOI
10.3748/wjg.v30.i20.2709
Study Type
Rat
Outcome
Positive
Peer Reviewed
Yes
Country
China
Health Condition
Constipation
Body System
Gastrointestinal system

TL;DR

Drinking hydrogen-rich water (HRW) may help relieve constipation by reducing oxidative stress in the intestines and improving gut health.

Key Finding

Hydrogen-rich water improved constipation symptoms in rats by reducing intestinal oxidative stress through activation of a specific cellular pathway (SIRT1/Nrf2/HO-1) and by modifying gut bacteria composition.

Summary

Researchers gave constipated rats hydrogen-rich water and found it improved bowel movements and reduced damage from harmful molecules (oxidative stress) in the intestines. The study identified a specific cellular pathway (SIRT1/Nrf2/HO-1) through which hydrogen water appeared to work, and also found that it changed the balance of bacteria in the gut and altered certain chemicals in the blood.

Practical Takeaway

This rat study suggests hydrogen-rich water may help with constipation by reducing cellular damage in the intestines, but human studies are needed to confirm whether these effects apply to people. The study's findings are promising but preliminary, and anyone considering hydrogen water for constipation should consult a healthcare provider.

Abstract

Background: Constipation, a highly prevalent functional gastrointestinal disorder, induces a significant burden on the quality of patients' life and is associated with substantial healthcare expenditures. Therefore, identifying efficient therapeutic modalities for constipation is of paramount importance. Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms. Consequently, we postulate that hydrogen therapy, an emerging and promising intervention, can serve as a safe and efficacious treatment for constipation. Aim: To determine whether hydrogen-rich water (HRW) alleviates constipation and its potential mechanism. Methods: Constipation models were established by orally loperamide to Sprague-Dawley rats. Rats freely consumed HRW, and were recorded their 24 h total stool weight, fecal water content, and charcoal propulsion rate. Fecal samples were subjected to 16S rDNA gene sequencing. Serum non-targeted metabolomic analysis, malondialdehyde, and superoxide dismutase levels were determined. Colonic tissues were stained with hematoxylin and eosin, Alcian blue-periodic acid-Schiff, reactive oxygen species (ROS) immunofluorescence, and immunohistochemistry for cell growth factor receptor kit (c-kit), PGP 9.5, sirtuin1 (SIRT1), nuclear factor-erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1, Nrf2 and HO-1. A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor, EX527, into constipated rats. NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression. Results: HRW alleviated constipation symptoms by improving the total amount of stool over 24 h, fecal water content, charcoal propulsion rate, thickness of the intestinal mucus layer, c-kit expression, and the number of intestinal neurons. HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism. HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway. This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats. The serum metabolites, β-leucine (β-Leu) and traumatic acid, were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1. Conclusion: HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway, modulating gut microbiota and serum metabolites. β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.