This study evaluated the inhibitory activity of quercetin at sub-inhibitory concentrations on quorum-sensing (QS) molecules in vitro and the effects of dietary supplementation with quercetin (for 24 consecutive days) on enterotoxigenic Escherichia coli (ETEC)-induced inflammatory and oxidative stress responses in weaned piglets. The piglets were fed one of three diets: the basal diet (Con), ETEC challenge (K88) after the basal diet, or ETEC challenge (quercetin + K88) after the basal diet supplemented with 0.2% quercetin. In vitro experiments revealed that 5 mg/mL quercetin exhibited the strongest QS inhibitory activity and reduced pigment production by Chromobacterium violaceum ATCC12472 by 67.70%. In vivo experiments revealed that quercetin + K88 significantly increased immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) levels in the serum, ileum mucosa, and colon mucosa; increased glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) levels in the serum, liver, and colon mucosa; and decreased cluster of differentiation 3 (CD3) and cluster of differentiation 8 (CD8)activity in the serum compared with K88 alone. Quercetin + K88 significantly alleviated pathological damage to the liver and spleen and upregulated antioxidant genes (nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1(HO-1), CAT, SOD, and glutathione s-transferase (GST)). Inducible nitric oxide synthase (iNOS) and kelch-like ech-associated protein 1 (Keap1), which cause oxidative damage to the liver and spleen, were significantly downregulated. The acetic acid content in the cecum was significantly increased, and the E. coli count and QS signal molecule autoinducer-2 (AI-2) yield were significantly reduced. In conclusion, 0.2% dietary quercetin can alleviate ETEC-induced inflammation and oxidative stress in weaned piglets.

Background/Objectives: The effect of proanthocyanidins (PAs) on neuroinflammation through the modulation of colonic microflora and their metabolites was investigated in obese mice fed a high-fat diet (HFD). Methods: Thirty healthy male C57BL/6J mice of similar body weight were randomly divided into control (CON), high-fat diet (HFD), and proanthocyanidin (PA_HFD) groups. HFD and PA_HFD groups were fed an HFD, whereas the CON group was fed a basic diet for 8 weeks. Subsequently, the CON and HFD groups were administered equal doses of saline, and the PA_HFD group was administered PA (100 mg/kg/day) daily. We evaluated microbial changes through gut microbiota richness and probiotic relative abundance, analyzed metabolite variations via non-targeted metabolomics and pathway enrichment, assessed neuroinflammation via related gene expression, and measured cognitive function using platform crossing frequency and target quadrant time in the Morris water maze, where longer duration and more crossings indicate better cognition. Results: Body weight was significantly lower in the PA_HFD group than in the HFD group. In the PA_HFD group, fewer inflammatory and hepatic fat cells were observed, and hepatocellular edema was alleviated. PA significantly decreased total cholesterol, low-density lipoprotein, IL-1β, TNF-α, lipopolysaccharide, and Lc3 expression and increased Sirt1 and FGF21 expression in hippocampal tissue (p < 0.01). PA significantly altered the abundance of colonic microbiota (p < 0.01), including phyla Patescibacteria and Bacteroidota and genera Lactobacillus and Akkermansia. KEGG analysis revealed that differences in metabolite profiles between CON and HFD groups were reflected in glycerophospholipid metabolism, while those between HFD and PA_HFD groups were in steroid hormone biosynthesis and tryptophan metabolism. Metabolomic analysis demonstrated that changes in metabolites and microbiota were significantly correlated with neuroinflammation. Conclusions: In conclusion, PAs play a role in modulating neuroinflammation, colonic microflora, and colonic metabolites in mice and have a mitigating effect on cognitive decline in HFD-induced obese mice.

This study systematically compared the effects of dietary supplementation with glutamine (Gln) and its precursors, including glutamic acid (GA) and α-ketoglutarate (AKG), on growth performance, serum antioxidant and immune parameters, and multi-region gastrointestinal microbiota in suckling lambs. Forty healthy suckling Hu lambs with similar body weight (7.37 ± 1.18 kg) and age (7 ± 0.8 d) were selected and randomly allocated into four groups (n = 10 per group): a control group (CON, without additive), and three treatment groups (GA, AKG, and Gln), each receiving 2 g per animal per day of the corresponding additive. The experimental period lasted for 42 d. All three additives showed a tendency to increase the final body weight (p = 0.056) and significantly increased the average daily gain (ADG) of lambs (p < 0.05). GA supplementation increased the dry matter intake throughout the entire trial (p < 0.05), whereas the addition of AKG and Gln increased the dry matter intake only during the later period (d 21–42) (p < 0.05). The feed-to-gain ratios did not differ among all groups (p > 0.05). Compared with the CON group, all three treatment groups showed elevated serum activities of catalase, glutathione peroxidase, and total antioxidant capacity, as well as increased IgA and IgG contents (p < 0.05). In addition, malondialdehyde concentration was decreased in all three treatment groups (p < 0.05). Moreover, GA supplementation reduced the ruminal alpha diversity while increasing the abundance of butyrate-producing bacteria (Ruminococcaceae UCG-014) (p < 0.05). All three interventions consistently decreased the abundance of the intestinal pathogen Escherichia-Shigella in the ileum (p < 0.05). Correlation analyses showed that ruminal Treponema 2 abundance was negatively correlated with ADG, whereas jejunal Methylobacterium and ileal [Eubacterium] coprostanoligenes group were positively correlated with final body weight or ADG. In conclusion, glutamine and its precursors play an important role in modulating gastrointestinal bacterial diversity and composition, enhancing antioxidant and immune functions, and improving the growth performance of suckling lambs.