慢性暴露于微囊藻毒素-LR（MC-LR）对草鱼（Cyprinus carpio）免疫抑制及肠道炎症反应的影响

Abstract

MCs-exposure disrupted intestinal mucosal immunity by inducing gut microbiota dysbiosis, reducing butyric acid metabolism, and promoting LPS release. • MCs-exposure triggered local and systemic immune imbalance in the intestine of common carp. • Subchronic exposure to MCs promoted intestinal inflammation via activating the TLR4/MyD88/NF-κB pathway. Cyanobacterial blooms release microcystin-LR (MC-LR), which threaten aquatic organisms; yet the subchronic effects on fish intestinal mucosal immunity, and whether exposure route modulates injury progression, remain poorly understood, especially the key mechanism involved. Here, common carp were subjected to 21-day subchronic exposure via immersion in Microcystis aeruginosa PCC 7820 (10 9 cells/L) or intraperitoneal injection of MC-LR (3 μg/kg·bw). Both routes induced intestinal mucosal barrier damage, evidenced by disordered intestinal villi, impaired tight junctions, downregulated zo-1 , occludin , claudin-3 , and muc-2 expression, and reduced mucus secretion. 16S rRNA sequencing revealed gut microbiota dysbiosis with increased pathogenic bacteria, alongside elevated lipopolysaccharide and reduced butyric acid. Oxidative stress (elevated MDA but reduced GSH and T-SOD) and pro-inflammatory shifts (upregulated il-1β , tnf-α , il-6 but downregulated il-10 ) were observed. Mechanistically, the elevated LPS from gut dysbiosis activated the TLR4/MyD88/NF-κB signaling pathway at transcriptional and protein levels, suggesting a link between microbiota changes and intestinal inflammation in carp. Mucosal immunoglobulins (IgT and IgD) declined after 21 days of exposure, while IgM increased compensatorily. Injection induced earlier onset than immersion, yet both routes converged on similar endpoints by day 21, showing that exposure route affects timing more than final outcome severity. These findings not only elucidate a microbiota-LPS inflammatory axis underlying MC-LR immunotoxicity in fish, but also provide uniqu