Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal barrier

Gut Microbes. 2022 Jan-Dec;14(1):2013764. doi: 10.1080/19490976.2021.2013764.

Abstract

With the rapid development and high therapeutic efficiency and biosafety of gas-involving theranostics, hydrogen medicine has been particularly outstanding because hydrogen gas (H2), a microbial-derived gas, has potent anti-oxidative, anti-apoptotic, and anti-inflammatory activities in many disease models. Studies have suggested that H2-enriched saline/water alleviates colitis in murine models; however, the underlying mechanism remains poorly understood. Despite evidence demonstrating the importance of the microbial hydrogen economy, which reflects the balance between H2-producing (hydrogenogenic) and H2-utilizing (hydrogenotrophic) microbes in maintaining colonic mucosal ecosystems, minimal efforts have been exerted to manipulate relevant H2-microbe interactions for colonic health. Consistent with previous studies, we found that administration of hydrogen-rich saline (HS) ameliorated dextran sulfate sodium-induced acute colitis in a mouse model. Furthermore, we demonstrated that HS administration can increase the abundance of intestinal-specific short-chain fatty acid (SCFA)-producing bacteria and SCFA production, thereby activating the intracellular butyrate sensor peroxisome proliferator-activated receptor γ signaling and decreasing the epithelial expression of Nos2, consequently promoting the recovery of the colonic anaerobic environment. Our results also indicated that HS administration ameliorated disrupted intestinal barrier functions by modulating specific mucosa-associated mucolytic bacteria, leading to substantial inhibition of opportunistic pathogenic Escherichia coli expansion as well as a significant increase in the expression of interepithelial tight junction proteins and a decrease in intestinal barrier permeability in mice with colitis. Exogenous H2 reprograms colonocyte metabolism by regulating the H2-gut microbiota-SCFAs axis and strengthens the intestinal barrier by modulating specific mucosa-associated mucolytic bacteria, wherein improved microbial hydrogen economy alleviates colitis.

Keywords: Microbial hydrogen economy; colitis; colonocyte metabolism; hydrogen-rich saline; intestinal barrier; microbiome; short-chain fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / classification
  • Bacteria / drug effects
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colitis / microbiology*
  • Colon / drug effects
  • Colon / metabolism
  • Colon / microbiology
  • Dextran Sulfate / adverse effects
  • Fatty Acids, Volatile / metabolism
  • Gastrointestinal Microbiome* / drug effects
  • Humans
  • Hydrogen / administration & dosage*
  • Hydrogen / metabolism
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Male
  • Mice
  • Mice, Inbred C57BL

Substances

  • Fatty Acids, Volatile
  • Hydrogen
  • Dextran Sulfate

Grants and funding

This work was supported by the National Natural Science Foundation of China under Grant 81771711; the Natural Science Foundation of Shandong Province under Grant ZR2019MH123; the Open Project of Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention under Grant ABDC-201901; the Shandong Provincial Integrated Traditional Chinese and Western Medicine Special Disease Prevention Project under Grant SDPR-2020-0230007; and Academic Promotion Programme of Shandong FirstMedical University under Grant 2019QL007, YS22-0001817.