peu-MIR2916-p3-enriched garlic exosomes ameliorate murine colitis by reshaping gut microbiota, especially by boosting the anti-colitic Bacteroides thetaiotaomicron.

Plant-derived exosome-like nanoparticles (ELNs) have drawn considerable attention for oral treatment of colonic diseases. However, the roles of ELNs derived from garlic on colitis remain unclear. Here, we demonstrate that garlic ELNs (GELNs), with desirable particle sizes (79.60 nm) and trafficking large amounts of functional proteins and microRNAs, stably roam in the gut and confer protection against ulcerative colitis (UC). In mice with DSS-induced colitis, orally administered GELNs effectively ameliorated bloody diarrhea, normalized the production of proinflammatory cytokines, and prevented colonic barrier impairment. Mechanistically, GELNs were taken up by gut microbes and reshaped DSS-induced gut microbiota dysbiosis, in which Bacteroides was the dominant respondent genus upon GELNs treatment. Notably, GELNs-enriched peu-MIR2916-p3 specifically promoted the growth of Bacteroides thetaiotaomicron, an intestinal symbiotic bacterium with palliative effects on colitis. Our findings provide new insights into the medicinal application of GELNs and highlight their potential as natural nanotherapeutic agents for preventing and treating UC.

Roundup-Induced Gut Dysbiosis, Irrelevant to Aromatic Amino Acid Deficiency, Impairs the Gut Function in Rats.

Glyphosate, the most popular herbicide globally, has long been considered safe for mammals. However, whether glyphosate can disturb gut microbiota via inhibiting aromatic amino acid (AAA) synthesis has been under debate recently. Here, we evaluated the impacts of chronic exposure to Roundup on gut health with the addition of AAA and explored the mechanism behind Roundup-induced gut dysfunction by performing fecal microbiota transplantation. 500 mg/kg·bw of Roundup, independent of AAA deficiency, caused severe damage to gut function, as characterized by gut microbial dysbiosis, oxidative stress damage, intestinal inflammation, and histopathological injury, particularly in female rats. Notably, similar to Roundup, Roundup-shaped gut microbiome evidently damaged serum, cecum, and colon profiling of oxidative stress biomarkers (malonaldehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH), and H2O2). Moreover, it induced 0.65-, 3.29-, and 2.36-fold increases in colonic IL-1ß, IL-6, and TNF-α levels, and 0.34-fold decreases in the IL-10 level. Upon transplanting healthy fecal microbiota to Roundup-treated rats, they exhibited a healthier gut microenvironment with mitigated inflammation, oxidative damage, and intestinal injury. Overall, our findings provide new insights into the safety of Roundup, highlight the crucial role of gut microbiota in Roundup-induced gut dysfunction, and pave the way for developing gut-microbiota-based strategies to address Roundup-related safety issues.

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

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.