Broccoli-Derived Exosome-like Nanoparticles Alleviate Loperamide-Induced Constipation, in Correlation with Regulation on Gut Microbiota and Tryptophan Metabolism

Abstract

Constipation, a common gastrointestinal dysfunction, damages patients' life quality and predisposes them to other serious diseases. Current strategies against constipation often cause drug dependency and side effects. Here, we demonstrated that broccoli-derived exosome-like nanoparticles (BENs), a natural product with high gastrointestinal stability, ameliorated LOP-induced constipation in mice. Specifically, orally administered BENs (17.5 mg/kg/d) effectively shortened defecation time, sped up intestinal propulsion rate, and increased feces amount in constipated mice. BENs also raised excitatory neurotransmitters SP and MTL and reduced inhibitory neurotransmitters VIP and ET-1. Mechanistically, BENs were taken up by gut microbes, restored LOP-disordered gut microbiota, and altered microbial metabolism of SCFAs and tryptophan, as evidenced by the results of fluorescence microscopy, 16S rRNA gene sequencing, and nontargeted metabolomics. Thereinto, BEN-enriched SCFA-producing microorganisms are closely associated with the feces amount and SP and VIP levels and BEN-elevated indole-3-pyruvic acid and 3-indoleacetic acid are highly linked to ET-1, SP, and MTL levels. Conclusively, BENs, mitigating constipation by regulating gut microbiota and microbial tryptophan metabolism, showed high potential to be developed as alternative regimens for constipation.

Causal relationship between gut microbiota and constipation: a bidirectional Mendelian randomization study

“…Additionally, the metabolism of bile acids (BAs) is essential for managing constipation-related symptoms. Bacteroidetes influence this process by stimulating colonic motility through alterations in the bile acid pool composition ( Duan et al, 2023 ). Our study indicates that a high abundance of Bacteroidetes is a risk factor for constipation.…”

Plant-derived extracellular vesicles: A novel approach for gastrointestinal tract diseases

“…Importantly, this approach seeks to minimize potential adverse reactions associated with the metabolic energy effects of AMPK. In another study, BDEVs were shown to alleviate LOP-induced constipation in mice by influencing gastrointestinal hormones, gut microbial structure, and intestinal metabolites [78]. These research findings underscore the promising potential of developing BDEVs as safe and effective nano-therapies for the treatment of constipation [78].…”

Exosomes as mediators of signal transmitters in biotoxins toxicity: a comprehensive review

“…Generally, they are extracted from edible plants, can be efficiently produced in large quantities, and can compensate for the limitations of mammal-derived exosomes, which have attracted more and more attention (Cao et al 2023 ). At present, there are exosomes from grape (Teng et al 2022 ), broccoli (Duan et al 2023 ), ginger (Zhu and He 2023 ), carrot (Mu et al 2014 ), and other sources (Record 2013 ), which are similar to general animal derived exosomes in terms of size distribution, morphology, and contents. They also have certain clinical applications.…”