Oral, but not rectal delivery of epigallocatechin-3-gallate alleviates colitis by regulating the gut microbiota, oxidative stress, inflammation, and barrier integrity

Abstract

Background: Alteration of the gut microbiota may contribute to the development of inflammatory bowel diseases (IBDs). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBDs alleviation. However, it is unclear whether EGCG attenuates IBDs through direct improvement of gastrointestinal function or indirect alteration of the structure and function of the gut microbiota.Results: We first investigated the therapeutic effects of EGCG on disease severity, oxidative stress, inflammation, barrier function, and gut microbiota in murine colitis model, and further demonstrate it via EGCG pre-supplementation. We revealed that, oral, but not rectal, delivery of EGCG alleviated the severity of colitis through attenuation of anti-oxidative and anti-inflammatory response. Mucin-secreting goblet cell number, barrier function gene expression levels, and the integrity of tight junctions in the colon were also enhanced by oral EGCG. Additionally, we observed distinct EGCG-mediated alternation in the gut microbiome, as highlighted by increased Akkermansia abundance and butyrate production. Furthermore, we revealed that prophylactic oral application of EGCG for 21 days prior to the onset of dextran sodium sulfate (DSS)-induced colitis also ameliorated colonic damage, oxidative stress, and inflammatory response. Prophylactic EGCG significantly enriched Akkermansia, Faecalibaculum, and Bifidobacterium and enhanced acetate, propionate and butyrate production in DSS-treated mice. Moreover, scores of differential microbes, in particular Akkermansia, showed a strong positive correlation with short-chain fatty acids (SCFAs) and antioxidant enzyme levels in both the plasma and colon, but a negative association with inflammatory cytokines and malondialdehyde.Conclusions: EGCG is capable of treating DSS-induced colitis both therapeutically and prophylactically by inducing a pronounced anti-oxidative and anti-inflammatory response. Attenuation of colitis by oral, but not rectal administration of, EGCG suggests an intimate involvement of the gut microbiota. Increased Akkermansia and subsequent protective SCFAs production may be largely responsible for the anti-inflammatory and anti-oxidative function of EGCG, leading to restoration of intestinal epithelial homeostasis of the host. These findings provide novel insights into EGCG-mediated remission of IBDs and the rationale for devising more effective therapeutic strategies for IBDs.

Liposomal Epigallocatechin-3-Gallate for the Treatment of Intestinal Dysbiosis in Children with Autism Spectrum Disorder: A Comprehensive Review

“…EGCG modulates intestinal microbiota and its metabolites, enriching the population of short-chain fatty acid (SCFA)-producing bacteria such as Akkermansia spp., resulting in an improvement in the production of acetate, propionate, and butyrate in a sodium dextran sulfate (SDS)-induced colitis mouse model, where levels of these metabolites were significantly reduced [ 88 , 89 ]; this promotes an anti-inflammatory and antioxidant state in the intestine. [ 88 ].…”