Levels of type 2
cytokines are elevated in the blood and intestinal tissues of
ulcerative colitis (UC) patients in the active phase; this phenomenon indicates the participation of type 2 immune response in UC progression. The beneficial effects of
melatonin in
dextran sodium sulfate (DSS) and
2,4,6-trinitrobenzene sulfonic acid (TNBS)
colitis models have been illustrated, but its role in the
oxazolone (Oxa)-induced
colitis model (driven by type 2 immune response) remains relatively unknown. We investigated the relationship between
melatonin concentration and the severity of UC, revealing a significantly negative correlation. Subsequently, we investigated the effects of
melatonin in Oxa-induced
colitis mice and the potential underlying mechanisms. Administration of
melatonin significantly counteracted
body weight loss, colon shortening, and neutrophil infiltration in Oxa-induced
colitis mice.
Melatonin treatment mitigated Oxa-induced
colitis by suppressing type 2 immune response. In addition,
melatonin attenuated intestinal permeability by enhancing the expression of ZO-1 and
occludin in
colitis mice. Interestingly, the protective effect of
melatonin was abolished when the mice were co-housed, indicating that the regulation of gut microbiota by
melatonin was critical in alleviating Oxa-induced
colitis. Subsequently,
16S rRNA sequencing was performed to explore the microbiota composition. Decreased richness and diversity of intestinal microbiota at the operational taxonomic unit (OTU) level resulted from
melatonin treatment.
Melatonin also elevated the abundance of Bifidobacterium, a well-known probiotic, and reduced proportions of several harmful bacterial genera, such as Desulfovibrio, Peptococcaceae, and Lachnospiraceae.
Fecal microbiota transplantation (FMT) was used to explore the role of microbiota in the function of
melatonin in Oxa-induced
colitis. Microbiota
transplantation from
melatonin-treated mice alleviated Oxa-induced
colitis, suggesting that the microbiome participates in the relief of Oxa-induced
colitis by
melatonin. Our findings demonstrate that
melatonin ameliorates Oxa-induced
colitis in a microbiota-dependent manner, suggesting the therapeutic potential of
melatonin in treating type 2 immunity-associated UC.