Mitigation of Dextran-Sodium-Sulfate-Induced Colitis in Mice through Oral Administration of Microbiome-Derived Inosine and Its Underlying Mechanisms

Abstract

Background: Colonic and serum inosine are significantly reduced in patients with inflammatory bowel disease (IBD). Methods: This study aimed to explore whether microbiome-derived inosine alleviates colitis and its underlying mechanisms. Results: An inosine intervention effectively improved the clinical signs in colitis mice, suppressed inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β) by regulating the nuclear factor-kappa B (NF-κB) pathway, and elevated the activities of anti-oxidative enzymes (including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) by regulating the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway. Additionally, the inosine intervention significantly elevated the expression of tight junction proteins (ZO-1, occudin, and claudin-1) in mice with colitis. High-throughput sequencing revealed that the inosine intervention also prevented gut microbiota disorder by increasing the abundance of beneficial bacteria (Lachnospiraceae NK4A136 group, Romboutsia, Marvinbryantia, Clostridium sensu stricto 1, and Bifidobacterium) and reducing the abundance of harmful bacteria (Pseudomonas, Acinetobacter, and Tyzzerella) in mice with colitis. Conclusions: Inosine played a significant role in mitigating colitis-related intestinal barrier injury and could potentially be used for therapy in clinical practice.

Dietary Supplementation with Bupleuri Radix Reduces Oxidative Stress Occurring during Growth by Regulating Rumen Microbes and Metabolites

“…Previous research has demonstrated that intestinal microbial disorders in colitis-affected mice can be prevented by microbiome-derived inosine. This is achieved by both decreasing the abundance of pathogenic bacteria ( Pseudomonas , Acinetobacter , and Tyzzerella ) and increasing the abundance of beneficial bacteria ( Lachnospiraceae NK4A136 group , Romboutsia , Marvinbryantia , and Bifidobacterium ) [ 43 ]. Therefore, we speculated that BR could intervene to boost the proportional abundance of advantageous bacteria to intervene in rumen microbiota disturbance and preserve the health of SFWS.…”

Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility

“…Bacteroides can produce SCFAs and are beneficial to the host; however, they can be opportunistic pathogens and are related to some pathological status (Shin et al, 2024). It could also be related to regulate the secretion of IL-6 and IL-17 in dendritic cells to associated with seizure severity (Xie et al, 2017).The functions of Marvinbryantia and Oscillibacter remain unclear, but they are often reported to be associated with health status or serve as protective factors (Fang et al, 2016;Xu et al, 2020;Crossland et al, 2023;Guo et al, 2023). This may be related to the production of SCFAs, which contribute to the maintenance of GM homeostasis.…”

Intestinal Membrane Function in Inflammatory Bowel Disease

“…Several non-clinical studies have revealed the healing of experimental colitis through the recovery of TJ proteins in parallel with the improved balance of the microbiota via the administration of sinapic acid and inosine [ 100 , 101 ]. In Caco-2 cells, Lactobacillus rhamnosus CY12, a favorable Gram-positive bacterial strain, was shown to ameliorate the loss of tight junctions through lipopolysaccharide treatment by improving the expression of the tight junction proteins claudin, ZO-1, and occludin [ 102 ].…”