###### Abstract  
Uleerative colitis is a chronic inflammatory bowel disease characterized by colonic mucosal inflammation, intestinal microflora imbalance, and intestinal permeability. It is essential to develop natural compounds with anti-inflammatory and intestinal bacterial imbalance correction properties. The brown alga _Sargassum horneri_ is rich in polyphenols, such as fucoxanthin and chromene, which have antioxidant, anti-inflammatory, and anti-cancer properties. In results, _S. horneri_ ethanol extract (SHE) reduced TNF-a and IL-6 levels as well as \(Pijk/M\)tor/_S6k_ mRNA expression in LPS-treated RAW264.7 and Caco-2 cells. In addition, SHE treatment decreased the expression of genes associated with inflammation and the mTOR axis in the co-culture system while increasing the expression of tight junction factors. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, SHE treatment improved intestinal length, histological scores, and the expression of genes related to tight junctions while decreasing the expression of genes related to inflammatory markers and the mTOR axis. The gut microbiota of mice treated with SHE exhibited a decrease in the ratio of Firmicutes to Bacteroidota, which had been increased by DSS treatment and an increase in beneficial bacteria. Therefore, SHE consumption may be a useful natural alternative, as it improves gut microbiota, alleviates colitis symptoms, and prevents their onset. Sargassum horneri; colitis; anti-inflammatory; mTOR pathway; gut microbiota +
Footnote †: journal: Medical  
and quercetin; chromenes; and carotenoids, such as fucoxanthin [7; 11]. Fucoxanthin, a carotenoid derived from brown seaweeds, possesses various health-promoting properties, including anti-inflammatory, anti-cancer, anti-obesity, and anti-diabetic effects [13]. Due to its potential to decrease COX-2 and iNOS levels, fucoxanthin decreased the expression of pro-inflammatory mediators such as PGE\({}_{2}\), IL-1\(\upbeta\), IL-6, and TNF-\(\upalpha\) in lipopolysaccharide-saccharide (LPS)-induced in vitro and in vivo models [14; 15]. In particular, in experiments related to the efficacy of fucoxanthin in UC, fucoxanthin treatment attenuated the dextran sulfate sodium (DSS)-induced increase of disease activity index and histological damage in the colon by inhibiting COX-2 and NF-\(\upkappa\)B expressions [16]. Chromenes isolated from seaweeds have also attracted attention due to their antioxidant and anti-inflammatory properties [17]. In particular, Sargachromenol, isolated from Sargassum, showed potent anti-inflammatory properties via the activation of Nrf2/HO-1 signaling [18; 19]. However, it remains unknown the underlying mechanism by which _S. horneri_, a mixture of these substances, regulates inflammation. The PI3K/Akt/mTOR pathway is essential for various cellular processes and is involved in inflammatory processes through modulation of the NF-\(\upkappa\)B and STAT3 pathways [20]. Inhibition of the PI3K/Akt/mTOR pathway may be regarded as a key regulator of intestinal inflammation in colitis [21], and several dietary polyphenols exert anti-inflammatory effects by modulating the mTOR signaling pathway [22]. Fucoxanthin has previously demonstrated a potential to regulate the PI3K/Akt/mTOR pathway [23]; however, no studies involving _S. horneri_ have been conducted. The gut microbiota of healthy individuals maintains gut homeostasis by fermenting indigestible polysaccharides to produce short-chain fatty acids (SCFAs), protecting the intestinal mucosa, and inhibiting pathogenic microorganisms [24; 25]. However, patients with IBD experience leaky gut and gut dysbiosis, and the most consistent observation of intestinal flora abnormalities in IBD patients is a decrease in the diversity of the gut microbiota and the ratio of Firmicutes to Bacteroidetes (F/B) [26; 27; 28].