This study aimed to investigate the hypothesis that dietary konjac glucomannan (KGM) could alleviate Salmonella typhimurium-induced colitis by modulating intestinal microbiota. Mice were fed an isocaloric and isofibrous diet supplemented with either 7% KGM or cellulose and were treated with 5 × 108 CFU of S. typhimurium. The results showed that KGM had an average molecular weight of 936 kDa and predominantly consisted of mannose and glucose at a molar ratio of 1:1.22. In vivo studies demonstrated that dietary KGM effectively mitigated colonic lesions, oxidative stress, disruption of tight junction protein 2 and occludin, and the inflammatory response induced by S. typhimurium. Moreover, KGM administration alleviated the dramatic upregulation of toll-like receptor 2 (TLR2) and phosphonuclear factor κB (NF-κB) protein abundance, induced by Salmonella treatment. Notably, dietary KGM restored the reduced Muribaculaceae and Lactobacillus abundance and increased the abundance of Blautia and Salmonella in S. typhimurium-infected mice. Spearman correlation analysis revealed that the gut microbiota improved by KGM contribute to inhibit inflammation and oxidative stress. These results demonstrated the protective effects of dietary KGM against colitis by modulating the gut microbiota and the TLR2-NF-κB signaling pathway in response to Salmonella infection.

L-theanine is a natural bioactive component in tea leaves and has anti-inflammatory effects. The study aimed to investigated the effects and underlying mechanisms of L-theanine on lipopolysaccharide (LPS)-induced intestinal tight junction damage in IPEC-J2 cells. Results showed that LPS induced tight junction damage by increasing reactive oxygen species production and lactate dehydrogenase (LDH) release and decreasing the mRNA expression of tight junction proteins related genes zonula occludens-1 (ZO-1, also known as Tjp1), Occludin and Claudin-1, while L-theanine reversed such an effect and attenuated the increase of p38 mitogen-activated protein kinase (p38 MAPK) mRNA expression. The p38 MAPK inhibitor (SB203580) attenuated the mRNA expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (Nlrp3) inflammasome and interleukin-1β (Il-1β), and increased the mRNA expression of Tjp1, Occludin and Claudin-1, which showed a similar effect with L-theanine. In addition, NLRP3 inhibitor MCC950 attenuated the Il-1β expression and LDH release, while increased the expression of tight-junction protein-related genes. In conclusion, L-theanine could protect LPS-induced intestinal tight junction damage by inhibiting the activation of p38 MAPK-mediated NLRP3 inflammasome pathway.

This study was designed to investigate the hepatoprotective effects of Bacillus subtilis, a commensal bacterial species in the human gut, on ethanol-induced acute liver damage and the underlying mechanisms in mice. Male ICR mice challenged with three doses of ethanol (5.5 g/kg BW) exhibited a significant increase in serum aminotransferase activities and TNF-α level, liver fat accumulation, and activation of NF-κB signaling and NLRP3 inflammasome, which was suppressed by pretreatment with Bacillus subtilis. Besides, Bacillus subtilis inhibited acute ethanol-induced intestinal villi shortening and epithelial loss, the decline of protein levels of intestinal tight junction protein ZO-1 and occludin, and elevation of serum LPS level. Furthermore, the upregulation of mucin-2 (MUC2) and the downregulation of anti-microbial Reg3B and Reg3G levels induced by ethanol were repressed by Bacillus subtilis. Lastly, Bacillus subtilis pretreatment significantly increased the abundance of the intestinal Bacillus, but had no effects on the binge drinking-induced increase of Prevotellaceae abundance. These results demonstrate that Bacillus subtilis supplementation could ameliorate binge drinking-induced liver injury, and thus may serve as a functional dietary supplement for binge drinkers.

Flavanones in Citrus unshiu peel (CUP) have been used as therapeutic agents to reduce intestinal inflammation; however, the anti-inflammatory effects of their biometabolites remain ambiguous. Here, we identified aglycone-type flavanones, such as hesperetin and naringenin, which were more abundant in the bioconversion of the CUP than in the ethanol extracts of the CUP. We found that the bioconversion of the CUP induced the canonical nuclear factor-κB pathway via degradation of IκB in Caco-2 cells. To check the immune suppressive capacity of the aglycones of the CUP in vivo, we orally administered the bioconversion of the CUP (500 mg/kg) to mice for two weeks prior to the 3% dextran sulfate sodium treatment. The CUP-pretreated group showed improved body weight loss, colon length shortage, and intestinal inflammation than the control mice. We also found a significant decrease in the population of lamina propria Th17 cells in the CUP-pretreated group following dextran sodium sulfate (DSS) treatment and an increase in mRNA levels of occludin in CUP-treated Caco-2 cells. Pyrosequencing analysis revealed a decreased abundance of Alistipes putredinis and an increased abundance of Muribaculum intestinale in the feces of the CUP-pretreated mice compared to those of the control mice. Overall, these findings suggest that the pre-administration of CUP biometabolites may inhibit the development of murine colitis by modulating intestinal permeability and the gut microbiome.

The relationship between inflammatory bowel disease and sleep disturbances is complicated and of increasing interest. We investigated the inflammatory and immunological consequences of EA in sleep-deprived colitis and found that dextran sulfate sodium (DSS)-induced colitis in sleep-fragmented (SF) mice was more severe than that in mice with normal sleep. This increase in the severity of colitis was accompanied by reduced body weight, shortened colon length, and deteriorated disease activity index. DSS with SF mice presented obvious diminished intestinal tight junction proteins (claudin-1 and occludin), elevated proinflammatory cytokines (CRP, IFN-γ, IL-6), lowered melatonin and adiponectin levels, downregulated vasoactive intestinal peptide (VIP) type 1 and 2 receptor (VPAC1, VPAC2) expression, and decreased diversity of gut bacteria. EA ameliorated colitis severity and preserved the performance of the epithelial tight junction proteins and VIP receptors, especially VPAC2. Meanwhile, the innate lymphoid cells-derived cytokines in both group 2 (IL-4, IL5, IL-9, IL-13) and group 3 (IL-22, GM-CSF) were elevated in mice colon tissue. Furthermore, dysbiosis was confirmed in the DSS group with and without SF, and EA could maintain the species diversity. Firmicutes could be restored, such as Lachnospiraceae, and Proteobacteria become rebalanced, mainly Enterobacteriaceae, after EA intervention. On the other hand, SF plays different roles in physiological and pathological conditions. In normal mice, interrupted sleep did not affect the expression of claudin-1 and occludin. But VPAC1, VPAC2, and gut microbiota diversity, including Burkholderiaceae and Rhodococcus, were opposite to mice in an inflamed state.

Salmonella enterica serovar Typhimurium (S. Typhimurium) continues to be a serious concern to the poultry industry as a bacterial foodborne zoonosis, which generally results in intestinal inflammation and barrier dysfunction or even death. Eugenol is a phenolic compound with various pharmacological activities involved antioxidant, anti-inflammatory, and antibacterial effects, which is expected to be an effective nonantibiotic therapy. The purpose of this study was to explore the protective effects of eugenol in the cellular and broiler models of S. Typhimurium infection and the possible underlying mechanisms. The results of animal infection showed that eugenol treatments enhanced the relative weight gains and survival rates of broilers with a reduction of the organ bacterial load and intestinal ultrastructural injury. Moreover, eugenol significantly inhibited the mRNA levels of myeloid differentiation factor 88 (MyD88) and toll-like receptor-4 (TLR4), then declined the phosphorylation of p65 and IκBα of NF-κB pathway and the expressions of inflammatory factors (TNF-α, IL-1β, IL-2, and IL-18) in duodenum tissues, while maintained the expressions of intestinal tight junction proteins (ZO-1, claudin-1, occludin). Further experiments in vitro revealed that eugenol markedly inhibited the adhesion and invasion of S. Typhimurium to RAW264.7 or IEC-6 cells, then reduce bacterial multiplication in IEC-6 or DF-1 cells. In conclusion, eugenol could defend broilers from S. Typhimurium infection by stabilizing the intestinal mucosal barrier and relieving inflammatory response, as well as inhibiting bacterial adhesion and invasion to cells.

Inflammatory bowel disease (IBD) involves chronic inflammation, loss of epithelial integrity, and gastrointestinal microbiota dysbiosis, resulting in the development of a colon cancer known as colitis-associated colorectal cancer (CAC). In this study, we evaluated the effects of corylin in a mouse model of dextran sodium sulfate (DSS)-induced colitis. The results showed corylin could improved the survival rate and colon length, maintained body weight, and ameliorated the inflammatory response in the colon. Then, we further identified the possible antitumor effects after 30-day treatment of corylin on an azoxymethane (AOM)/DSS-induced CAC mouse model. Biomarkers associated with inflammation, the colon tissue barrier, macrophage polarization (CD11c, CCR7, CD163, and CD206), and microbiota dysbiosis were monitored in the AOM/DSS group versus corylin groups. Corylin downregulated pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) mRNA expression and inflammatory signaling-associated markers (TLR4, MyD88, AP-1, CD11b, and F4/80). In addition, a colon barrier experiment revealed that epithelial cell proliferation of the mucus layer (Lgr5, Cyclin D1, and Olfm4) was downregulated and tight junction proteins (claudin-1 and ZO-1) were upregulated. Furthermore, the Firmicutes/Bacteroidetes ratio changed with corylin intervention, and the microbial diversity and community richness of the AOM/DSS mice were improved by corylin. The comparative analysis of gut microbiota revealed that Bacteroidetes, Patescibacteria, Candidatus Saccharimonas, Erysipelatoclostridium, and Enterorhabdus were significantly increased but Firmicutes, Turicibacter, Romboutsia, and Blautia decreased after corylin treatment. Altogether, corylin administration showed cancer-ameliorating effects by reducing the risk of colitis-associated colon cancer via regulation of inflammation, carcinogenesis, and compositional change of gut microbiota. Therefore, corylin could be a novel, potential health-protective, natural agent against CAC.

Bisdemethoxycurcumin has good antioxidant and anti-inflammatory effects and has been widely used as food and feed supplements in the form of curcuminoids. However, the beneficial effect of individual bisdemethoxycurcumin on preventing lipopolysaccharide (LPS)-induced inflamed intestinal damage is unclear. The present study aimed to investigate whether dietary bisdemethoxycurcumin supplementation could attenuate LPS-induced intestinal damage and alteration of cecal microbiota in broiler chickens. In total, 320 one-day-old male Arbor Acres broiler chickens with a similar weight were randomly divided into four treatments. The treatments were designed as a 2 × 2 factorial arrangement: basal diet (CON); 150 mg/kg bisdemethoxycurcumin diet (BUR); LPS challenge + basal diet (LPS); LPS challenge + 150 mg/kg bisdemethoxycurcumin diet (L-BUR). Results showed that dietary bisdemethoxycurcumin supplementation attenuated the LPS-induced decrease of average daily feed intake. LPS challenge compromised the intestinal morphology and disrupted the intestinal tight junction barrier. Dietary bisdemethoxycurcumin supplementation significantly increased villus length:crypt depth ratio and upregulated the mRNA expression of intestinal tight junction proteins. Moreover, a remarkably reduced mRNA expression of inflammatory mediators was observed following bisdemethoxycurcumin supplementation. The cecal microbiota analysis showed that bisdemethoxycurcumin supplementation increased the relative abundance of the genus Faecalibacterium while decreased the relative abundance of the genera Bacteroides and Subdoligranulum. In conclusion, dietary bisdemethoxycurcumin supplementation could counteract LPS-induced inflamed intestinal damage in broiler chickens by improving intestinal morphology, maintaining intestinal tight junction, downregulating pro-inflammatory mediators, and restoring cecal microbiota.

Background: The progression of liver disorders is frequently associated with inflammatory bowel disease through the gut-liver axis. However, no direct evidence showed the mechanisms of ulcerative colitis (UC) in the development of liver fibrosis per se. Thus, this study aimed to evaluate the effects of UC on liver fibrosis and its potential mechanism in the experimental model. Methods: Male C57BL/6 mice were allocated into five groups (n = 10 per group) to receive either drinking water (control), 2% dextran sulfate sodium (DSS), olive oil, carbon tetrachloride (CCl4) or DSS + CCl4 for 4 cycles. Blood was collected for biochemical analysis. Colons were excised for the evaluation of colon length and morphological score. Liver, colon, and mesenteric lymph nodes (MLNs) were collected for histopathological staining, expression analysis, and bacterial translocation assay to evaluate the inflammation, fibrosis, the activation of hepatic stellate cells (HSCs), and gut barrier function. Results: DSS caused severe colitis in mice treated or treated with CCl4, as evident from the elevation of disease activity index (DAI), histological abnormalities, and increased pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-17A). Histopathological staining revealed that DSS treatment aggravated the CCl4-induced extracellular matrix deposition, liver fibrosis, and inflammation in mice. Additionally, biochemical and expression analysis indicated the DSS treatment caused the increase of hydroxyproline and pro-inflammatory cytokines, as well as the abnormal liver function indexes in CCl4-induced mice. Gut barrier function was impaired in DSS- and DSS + CCl4-treated mice, manifesting as the increase in bacterial translocation and lipopolysaccharide level, and the reduction in tight junction proteins (occluding, claudin-1 and ZO-1) expression. Further, the activations of HSCs and TLR4 signaling pathway were observed after DSS + CCl4 treatment, presenting with the increase in expression of α-SMA, vimentin, TGF-β, collagen type I, collagen type II, TIMP-2, TLR4, TRAF6, and NF-κB p65, and a decrease in GFAP and MMP-2 expression. Conclusion: The present study verified that UC aggravated CCl4-induced liver injury, inflammation, and fibrosis in mice through the gut-liver axis. Gut barrier dysfunction in UC leads to bacterial translocation and elevated lipopolysaccharide, which may promote the activation of TLR4 signaling and HSCs in the liver.

Ammonia is an important environmental pollutant and can induce serious damages to the organs of aquatic animals, especially the intestine which is mostly exposed to external environment. As important species of aquatic ecosystems, turtles may be potential risk targets of ammonia. However, it is not clear whether ammonia shows toxic effects on the intestines of turtles. Therefore, the worldwide species red-eared slider (Trachemys scripta elegans) was selected, to investigate the effects of ammonia on intestinal health and the composition of microbiota. Results showed that ammonia significantly changed the structure of intestines by decreasing the thickness of intestinal wall, shortening the length of intestinal villus, extending lamina proprias, and inducing inflammatory cells appearance when the turtles were exposed to ammonia (1.418 mg NH3 L-1) for 30 d. In addition, the downregulation of epithelial tight junction genes indicated that ammonia increased selective paracellular permeability. Simultaneously, the upregulation of cytokines suggested that ammonia induced intestinal immune and inflammatory responses. Furthermore, ammonia altered the dominant bacterial composition, and decreased the abundance of beneficial intestinal bacteria in the host. Our results demonstrated that ammonia impaired the intestinal health and changed the composition of residential microbiota in T. s. elegans. This study provides a new insight to evaluate the toxic effects of ammonia on aquatic turtles and helps to build a framework for the effective conservation of turtles.