南湖新闻网讯（通讯员 陶诗煜）近日，我校魏泓教授团队针对肠道微生物群体感应（QS）信号分子调控宫内生长受限（IUGR）仔猪肠道损伤这一领域开展系统深入的研究，在国际学术期刊Science of the Total Environment，Gut Microbes，Microbiology Spectrum，Frontiers in Immunology，Journal of Cellular Physiology和The Journal of Nutrition上发表了系列研究论文。揭示了IUGR仔猪肠腔中微生物QS信号分子的变化及其调控肠道屏障功能损伤的分子机制，为预防IUGR所致肠道疾病的发生提供了新思路，为IUGR仔猪营养生理调控关键靶点的筛选提供了理论依据。
Quorum sensing is a molecular signaling-based communication mechanism in prokaryotes. In the basic mode, signaling molecules released by certain bacteria are sensed by intracellular receptors or membrane-bound receptors of other members in the community, leading to the collective isogenic signaling molecule synthesis and synchronized activities. This regulation is important for the symbiosis of the bacterium with the host, as well as virulence and biofilm formation. Notably, quorum sensing signaling molecules are not only able to control microbial community behavior but can likewise regulate the physiological status of host cells. Here, we provide a comprehensive review of the importance of quorum sensing signaling molecules in gram-negative bacteria in regulating host cell function and gut health, and suggest possible opportunities for application in combating human and animal diseases by blocking the pathways through which quorum sensing signaling molecules exert their functions.
As a quorum sensing signal molecule, N-(3-oxododecanoyl)-homoserine lactone (3OC12) regulate the population behavior of microorganisms. Many studies have proved that 3OC12 harm the physiological function of host intestinal epithelial cells. However, the detrimental effects of 3OC12 on intestinal health need verification in animals. Besides, the role of gut microbiome in 3OC12-induced intestinal damage also needs further understanding. In our study, 3OC12 was first administered to specific pathogen-free (SPF) mice, then the fecal microbiome of SPF mice was transplanted into germ-free (GF) mice to reveal the effects of 3OC12 on intestinal health and regulatory mechanisms of the intestinal microbiome. 3OC12 treatment significantly decreased body weight, shortened colonic length, disrupted the morphology of the colonic epithelium and increased the histopathological score of the colon in SPF mice. The levels of diamine peroxidase, d-lactate, TNF-α, IL-1β, and IL-8 were found to be significantly elevated in the serum of 3OC12 mice, while the levels of IL-10 were significantly reduced. Besides, the fecal microbial community of mice was also altered in the 3OC12-treated SPF mice. The results of fecal microbial transplantation (FMT) experiment showed that the phenotypes in SPF mice were almost reproduced in GF mice, manifested by body weight loss, colon damage and changed in serum chemical markers. More importantly, a joint analysis of fecal microbes in SPF and GF mice revealed Feature14_Elizabethkingia spp. was common differential bacteria in the feces of two kinds of mice treated with and without FMT. Our results demonstrated that 3OC12 challenge led to systemic inflammation and body weight loss in mice by disrupting intestinal barrier function, in which gut microbiome played a key role. These findings increased our understanding of the mechanism of intestinal injury caused by 3CO12, providing new ideas for the prevention and therapy of diseases caused by bacterial infection from the perspective of intestinal microbiome.
Microbes employ autoinducers of quorum sensing (QS) for population communication. Although the autoinducer of Pseudomonas aeruginosa LasI-LasR system, N-(3-oxododecanoyl)- l -homoserine lactone (3OC12), has been reported with deleterious effects on host cells, its biological effects on integrity of the intestinal epithelium and epithelial barrier are still unclear and need further investigation. In the present study, flow cytometry, transcriptome analysis and western blot technology have been adopted to investigate the potential molecular mechanisms of 3OC12 and its structurally similar analogs damage to intestinal epithelial cells. Our results indicated that 3OC12 and 3OC14 trigger apoptosis rather than necrosis and ferroptosis in intestinal epithelial cells. RNA-sequencing combined with bioinformatics analysis showed that 3OC12 and 3OC14 reduced the expression of genes from extracellular matrix (ECM)-receptor interaction pathway. Consistently, protein expressions from ECM and tight junction-associated pathway were significantly reduced after 3OC12 and 3OC14 challenge. In addition, 3OC12 and 3OC14 led to blocked cell cycle, decreased mitochondrial membrane potential, increased reactive oxygen species level and elevated Ca2+ concentration. Reversely, the antioxidant NAC could effectively mitigate the reduced expression of ECM and tight junction proteins caused by 3OC12 and 3OC14 challenge. Collectively, this study demonstrated that QS autoinducer exposure to intestinal epithelial cells ablates the ECM and tight junctions by triggering oxidative stress and apoptosis, and finally disrupts the intestinal epithelial barrier. These findings provide a rationale for defensing QS-dependent bacterial infections and potential role of NAC for alleviating the syndrome.
Microbiological treatments are expected to have a role in the future management of inflammatory bowel disease (IBD).Clostridium butyricum(C. butyricum) is a probiotic microorganism that exhibits beneficial effects on various disease conditions. Although many studies have revealed thatC. butyricumprovides protective effects in mice with colitis, the wayC. butyricumestablishes beneficial results in the host remains unclear. In this study, we investigated the mechanisms by whichC. butyricummodifies the gut microbiota, produces bacterial metabolites that may be involved, and, specifically, how microbial extracellular vesicles (EVs) positively influence IBD, using a dextran sulfate sodium (DSS)-induced colitis murine model in mice. First, we showed thatC. butyricumprovides a protective effect against colitis, as evidenced by the prevention of body weight loss, a reduction in the disease activity index (DAI) score, a shortened colon length, decreased histology score, and an improved gut barrier function, accompanied by reduced levels of pathogenic bacteria, includingEscherichia/Shigella, and an increased relative abundance of butyrate-producingClostridium sensu stricto-1andButyricicoccus. Second, we also confirmed that the gut microbiota and metabolites produced byC. butyricumplayed key roles in the attenuation of DSS-induced experimental colitis, as supported by the profound alleviation of colitis effects following fecal transplantation or fecal filtrate insertion supplied fromC. butyricum-treated mice. Finally,C. butyricum-derived EVs protected the gut barrier function, improved gut microbiota homeostasis in ulcerative colitis, and contributed to overall colitis alleviation.