(-)-Epicatechin targets gut microbiota-barrier crosstalk to ameliorate colitis-induced cognitive defects

Inflammatory bowel disease is closely linked to neuroinflammation and cognitive dysfunction via the gut-brain axis, yet strategies targeting this interplay remain limited. This study investigated the therapeutic potential of (−)-epicatechin, a bioactive flavonoid, in alleviating colitis-associated brain functional impairments and explored its underlying mechanisms. We demonstrated that (−)-epicatechin treatment significantly mitigated colitis symptoms, restored colon morphology, and improved intestinal barrier integrity in dextran sulfate sodium (DSS)-induced colitis mice. Furthermore, (−)-epicatechin normalized brain oxidative stress and neuroinflammation and suppressed the glial cell activation. These improvements in the neuroimmune environment contributed to reduced neuronal apoptosis and maintenance of synaptic integrity, which was accompanied by enhanced cognitive performance. Gut microbiota profiling revealed reversed DSS-induced dysbiosis by (−)-epicatechin, as reflected by the altered alpha diversity indices and relative abundance of pathogenic and beneficial taxa. Notably, the increased abundance of barrier-disrupting genera, such as Escherichia_Shigella and Mucispirillum were strongly correlated with the weakened intestinal barriers and brain functions, which were reversed by (−)-epicatechin treatment. These findings suggest that (−)-epicatechin attenuates colitis-associated brain dysfunction by restoring gut microbial balance, reinforcing intestinal barrier integrity, and dampening systemic and neuroinflammation. This study highlights the pivotal role of the microbiota-gut-brain axis in mediating the beneficial effects of (−)-epicatechin, positioning it as a promising prebiotic for managing neurological complications associated with IBD.