Summary: | The Hylocereus undatus flower (HUF) is an herb with significant anti-inflammatory and immunomodulatory activity. It can be used as a food or a medicine and is beneficial to the gut and lung, which recent evidence has suggested interact through the gut–lung axis. This study investigated both the protective effect of HUF against DSS-induced colitis and its mechanism. The results showed that HUF significantly alleviated the symptoms of UC, maintained the normal functioning of the intestinal barrier, and ameliorated abnormally elevated inflammatory response, thereby repairing the damaged gut microenvironment and protecting the composition of the original gut microbiota. Interestingly, possibly related to the role of the gut–lung axis, HUF improved the disturbance of the lung microbiota and reduced lung injury in UC mice. To conclude, HUF alleviates colitis by restoring the integrity of the intestinal barrier, reducing the inflammatory response, and regulating gut and lung microbiota.
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